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Team</li> </ul> </div> </div> </li> <li> <div class="img-profile"> <div class="imgthumb"><img src="https://narraj.org/public/site/images/auliasyarif/chosy-alvais.jpg" alt="Profile Image" width="75" height="100" /></div> </div> <div class="team-content"> <div class="team-aff"> <ul class="list-unstyled"> <li><strong>Chosy Alvais</strong></li> <li>Production Team</li> </ul> </div> </div> </li> <li> <div class="img-profile"> <div class="imgthumb"><img src="https://narraj.org/public/site/images/auliasyarif/aulia-syarif-aziz.JPG" alt="Profile Image" width="75" height="100" /></div> </div> <div class="team-content"> <div class="team-aff"> <ul class="list-unstyled"> <li><strong>Aulia Syarif Aziz</strong></li> <li>Web Administrator</li> </ul> </div> </div> </li> </ul> </div> </div> </div> </div> </div> </div> en-US admin@narraj.org (Narra J Editorial Office) m.iqhram@narraj.org (Muhammad Iqhrammullah, PhD) Mon, 21 Apr 2025 00:00:00 +0700 OJS 3.2.1.3 http://blogs.law.harvard.edu/tech/rss 60 Cryotherapy on exfoliative cytological changes for oral mucositis in cancer patients undergoing chemotherapy: A randomized control trial https://narraj.org/main/article/view/1644 <p>Oral mucositis is a common complication of chemotherapy that significantly impacts quality of life and may reduce treatment efficacy. While oral cryotherapy has been widely studied as a preventive intervention due to its cost-effectiveness, safety, and ease of use, most research focused on clinical outcomes without incorporating objective cytological assessments of mucosal changes. The aim of this study was to evaluate the effectiveness of oral cryotherapy in managing chemotherapy-induced mucositis using exfoliative cytology to monitor oral mucosal changes. A single-blinded, randomized controlled trial was conducted involving 50 cancer patients undergoing chemotherapy, who were randomly assigned to either the intervention or control group. The control group (n=25) received standard oral hygiene care, while the intervention group (n=25) received oral cryotherapy in addition to routine oral hygiene. A 20-minute oral cryotherapy was administered twice daily after breakfast (09:00 A.M.) and lunch (01:00 P.M.) for 14 days. This study found a significant reduction in mucositis scores was observed in both groups (p&lt;0.05). However, post-hoc analysis indicated that mucositis severity declined earlier in the cryotherapy group, whereas improvement in the control group was noted only after 14 days. Serial oral mucosal smears analyzed via exfoliative cytology revealed a reduction in inflammatory cells and the absence of coccus microorganisms by days 7 and 14 in the intervention group. In conclusion, this study demonstrated that oral cryotherapy effectively reduces the severity and duration of mucositis and accelerates recovery in cancer patients undergoing chemotherapy. Oral cryotherapy can be applied as a viable alternative to mitigate the severity of oral mucositis in this patient population.</p> Kadek A. Erika, Mulhaeriah Mulhaeriah, Upik A. Miskad, Eli Zuraida, Moh S. Sangkala, Ika Magfirah, Harun Achmad Copyright (c) 2025 Kadek Ayu Erika, Mulhaeriah, Upik A. Miskad, Eli Zuraida, Moh S. Sangkala, Ika Magfirah, Harun Achmad https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1644 Tue, 06 May 2025 00:00:00 +0700 Impact of walking exercise intensity on cartilage IL-1, TNF-α, IL-4, MMP-13 and pain threshold in osteoarthritis rat models https://narraj.org/main/article/view/2109 <p>Pro-inflammatory cytokines produced by chondrocytes play a crucial role in activating matrix metalloproteinase-13 (MMP-13), leading to an imbalance between the synthesis and degradation of the extracellular matrix (ECM) in osteoarthritis (OA). Although regular walking exercise has been shown to reduce inflammatory cytokine levels in OA animal models, the optimal exercise intensity remains underexplored. Therefore, the aim of this study was to investigate the effects of different intensities of regular walking exercise on the levels of pro-inflammatory cytokines (interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α)), anti-inflammatory cytokine (interleukin-4 (IL-4)), as well as MMP-13 expression in cartilage and pain thresholds in an OA animal model. A total of 30 adult male <em>Rattus norvegicus</em> (6–8 weeks old) were divided into five groups: (1) healthy control; (2) monosodium iodoacetate (MIA)-induce OA model; (3) OA with light-intensity walking (OA1); (4) OA with moderate-intensity walking (OA2); (5) and OA with high-intensity walking (OA3). The exercise intervention began one week after MIA injection and continued for six weeks. Pain threshold, inflammatory cytokine (IL-1, TNF-α, IL-4) levels, and MMP-13 expression were measured using an analgesymeter, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. The results demonstrated a significant reduction in IL-1 and TNF-α levels, along with decreased MMP-13 expression and increased IL-4 levels, in all exercise groups (OA1, OA2, OA3) compared to the untreated OA group. Additionally, pain thresholds improved following exercise. However, no significant differences were observed among the three exercise intensities in terms of cytokine levels, MMP-13 expression, or pain threshold. This study highlights that the light-intensity regular walking exercise effectively reduces inflammation, MMP-13 expression, and pain in OA. Further research is needed to elucidate the underlying mechanisms of exercise in OA management.</p> Kusworini Handono, Dwi A. Prasetyo, Nia Kurnianingsih, Cesarius S. Wahono, Thoha M. Albaar Copyright (c) 2025 Kusworini Handono, Dwi A. Prasetyo, Nia Kurnianingsih, Cesarius S. Wahono, Thoha M. Albaar https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2109 Fri, 25 Apr 2025 00:00:00 +0700 Hybrid function of light fraction patchouli oil in hair care formulations for effective hair and anti-dandruff treatment https://narraj.org/main/article/view/1622 <p>Hair issues, such as hair loss and dandruff, pose significant challenges in hair care. Patchouli oil, rich in bioactive components, has emerged as a promising candidate for addressing these concerns. The aim of this study was to investigate the hybrid functionality of fractionated patchouli oil in hair care formulations designed to promote hair growth and control dandruff caused by <em>Malassezia globosa</em>. Crude patchouli oil (CPO) was fractionated to enhance its efficacy, producing light fraction patchouli oil (LFPO), which was then characterized using gas chromatography-mass spectrometry (GC-MS) analysis. Hair tonic formulations containing three different LFPO concentrations (0.5%, 1.0%, and 1.5%) were developed and evaluated for stability, pH, viscosity, and antifungal activity against <em>M. globosa</em>. The results showed that LFPO contained 2.51% acid number, 0.70% ester number, 0.71 mg/kg iron content, and 25.88% patchoulol. The formulations exhibited stable physicochemical properties, with pH levels of 5.36–5.51 and viscosity ranging from 3.94 to 4.08 centipoise (cP), suitable for hair tonic applications. Formulation of 1.5% LFPO demonstrated the strongest antifungal activity, producing a 31.18±1.37 mm inhibition zone against <em>M. globosa</em>, surpassing ketoconazole (21.72±0.28 mm), suggesting potential as a natural antifungal agent. Histological analysis in rabbits revealed that 1.5% LFPO formulation reduced epidermal cell shedding, increased hair length by 41.6±0.35 mm after six weeks, and promoted dense hair follicle growth. This research provides a foundation for developing natural, effective, and stable hair care formulations. Despite these promising results, the efficacy and safety of LFPO formulations in humans remain unexplored. Therefore, a clinical human trial is necessary to assess skin tolerance, irritation risks, and long-term effects under real-world conditions.</p> Nadia Isnaini, Syaifullah Muhammad, Vicky Prajaputra, Indra Indra, Elly Sufriadi, Ernawati Ernawati, Cantika D. Riski Copyright (c) 2025 Nadia Isnaini, Syaifullah Muhammad, Vicky Prajaputra, Indra Indra, Elly Sufriadi, Ernawati Ernawati, Cantika D. Riski https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1622 Mon, 28 Apr 2025 00:00:00 +0700 Impact of anthropometric adiposity and excessive daytime sleepiness on endothelial function in healthcare workers: A cross-sectional analysis https://narraj.org/main/article/view/2003 <p>Obesity and excessive daytime sleepiness (EDS) are known contributors to cardiovascular risk through their impact on endothelial function. Healthcare workers, frequently exposed to shift work, are particularly vulnerable to these risk factors. The aim of this study was to assess the relationship between anthropometric adiposity measures and EDS with endothelial function, measured via flow-mediated dilation (FMD), in healthcare workers. This cross-sectional study included 82 healthcare workers aged 20–50 years without pre-existing cardiovascular conditions. Anthropometric measures such as body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were collected to assess adiposity. EDS was evaluated using the Epworth sleepiness scale (ESS), with a score ≥10 indicating EDS. Endothelial function was measured via FMD, with values &lt;7.1% indicating dysfunction. Multivariate logistic regression was used to identify predictors of endothelial dysfunction, adjusting for confounders such as age and sex. Collinearity diagnostics, including the Belsley–Kuh–Welsch method, were applied to confirm multicollinearity and refine the regression model. Overweight and obesity, high-risk WC, and increased risk WHtR were associated with endothelial dysfunction (p&lt;0.001), with WHtR showing an independent association (adjusted odds ratio (AOR): 8.48; 95%CI: 2.58–27.86; p&lt;0.001). EDS also showed a significant independent association with impaired FMD outcomes (AOR: 3.73; 95%CI: 1.23–11.26; p=0.020). Pearson correlation analysis revealed significant negative correlations between BMI (r=-0.483, p&lt;0.001), WC (r=-0.473, p&lt;0.001), and WHtR (r=-0.432, p&lt;0.001) with FMD, indicating that higher adiposity levels were linked to poorer endothelial function. Obesity and poor sleep quality, even in the absence of cardiovascular disease, are associated with an increased risk of endothelial dysfunction in healthcare workers. Early intervention focusing on weight management and improving sleep quality could mitigate future cardiovascular risks in this population.</p> Vito Damay, Ignatius Ivan, Nadhira A. Islami, Kenza Y. Rubismo Copyright (c) 2025 Vito Damay, Ignatius Ivan, Nadhira Azra Islami, Kenza Yogasvara Rubismo https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2003 Mon, 21 Apr 2025 00:00:00 +0700 Ivermectin and dexamethasone combination induces apoptosis in SUP-B15 cell line https://narraj.org/main/article/view/1975 <p>The development of glucocorticoid resistance has complicated the management of acute lymphoblastic leukemia (ALL), leading to increased mortality rates. Ivermectin, a low-cost and well-established anthelmintic, exhibits anticancer potential and may enhance glucocorticoid toxicity in ALL, offering a possible strategy to overcome resistance. The aim of this study was to evaluate the apoptotic effect of combining ivermectin with dexamethasone in ALL. ALL SUP-B15 cells were cultured under standard conditions before treatment with dexamethasone (200 nM) alone or combined with ivermectin (5, 10, and 20 µM), with an untreated group serving as the control. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay by measuring cell viability and inhibition. Apoptosis was evaluated through BAX, BCL-2, and CASP3 gene expression analysis using reverse transcription-polymerase chain reaction (RT-PCR). The findings revealed that the combination of ivermectin and dexamethasone was superior in the repression of ALL cell viability compared to control (<em>p</em>&lt;0.001). The combination of dexamethasone 200 nM + ivermectin 20 μM demonstrated the most significant cell inhibition of 38.16±0.04% (<em>p</em>&lt;0.001) and produced the lowest cell viability of 61.84±0.05% (<em>p</em>&lt;0.001). Moreover, the combination of dexamethasone 200 nM + ivermectin 20 μM demonstrated superior upregulations of <em>BAX</em> (<em>p</em>&lt;0.001) and <em>CASP3</em> (<em>p</em>&lt;0.001). In conclusion, the addition of ivermectin (5 µM) to dexamethasone regimen (200 nM) increases its cytotoxic and apoptotic activities against SUP-B15 cell line as observed by the <em>CASP3</em> and <em>BAX</em> upregulation. Studies to confirm the enhanced anticancer activity by this combination by observing the protein levels and animal studies are warranted.</p> Olga R. Siregar, Arlinda S. Wahyuni, Ayodhia P. Pasaribu, Deri Edianto, I DG. Ugrasena, Rina Amelia, Inke ND. Lubis, Muhammad Rusda Copyright (c) 2025 Olga R. Siregar, Arlinda S. Wahyuni, Ayodhia P. Pasaribu, Deri Edianto, I DG. Ugrasena, Rina Amelia, Inke ND. Lubis, Muhammad Rusda https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1975 Thu, 24 Apr 2025 00:00:00 +0700 Adherence to iron supplementation and associated factors among pregnant women in Cambodia: Insights from the 2021–2022 Demographic and Health Survey https://narraj.org/main/article/view/1659 <p>Iron deficiency is the leading cause of anemia during pregnancy, a major public health concern in many developing countries. To mitigate anemia, iron supplementation for at least 90 days is recommended for pregnant women. The aim of this study was to evaluate adherence to iron supplementation during pregnancy and to identify its key determinants in Cambodia. A cross-sectional study was conducted using secondary data from the 2021–2022 Cambodia National Demographic and Health Survey. Key variables assessed included maternal age, education level, ethnicity, wealth index, number of pregnancies, age at first pregnancy, prenatal care provider, timing of the first antenatal care (ANC) visit, and frequency of ANC visits. Multivariate logistic regression was employed to evaluate associations between adherence and independent variables. A total of 4,475 women aged 15–49 years who had been pregnant in the past five years were included in the analysis, with 91.2% adhering to iron supplementation for at least 90 days. Multivariate logistic regression showed that those with primary and higher education had greater odds of adherence (odds ratio (OR)=1.38; 95%CI: 1.00–1.90; OR=3.07; 95%CI: 1.39–6.79, respectively) compared to women with no education. There was a positive relationship between education level and adherence. Women who attended four or more ANC visits were more likely to adhere (OR=2.93; 95%CI: 2.27–3.77), and those who initiated ANC in the first trimester had higher adherence compared to those who started later (OR=1.78; 95%CI: 1.35–2.36). This study highlights that education level, frequency, and timing of ANC visits significantly influenced adherence to iron supplementation. Strengthening maternal education and promoting early and regular ANC follow-up should be prioritized to improve adherence and prevent anemia during pregnancy.</p> Annas Buanasita, Sri Sumarmi, Trias Mahmudiono, Soenarnatalina Melaniani, Lutfi A. Salim, Ma Sokvy, Nur MW. Sari Copyright (c) 2025 Annas Buanasita, Sri Sumarmi, Trias Mahmudiono, Soenarnatalina Melaniani, Lutfi A. Salim, Ma Sokvy, Nur MW. Sari https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1659 Mon, 28 Apr 2025 00:00:00 +0700 Striving for smoke-free families: Wives’ role in Gayo Lues, Aceh-Indonesia https://narraj.org/main/article/view/1960 <p>Smoking remains a prevalent habit in many households, particularly in regions where cultural norms strongly accept tobacco use. The aim of this study was to examine the influential role of wives in Gayo Lues, Aceh, Indonesia, in promoting smoking cessation within their families. Amidst cultural norms that widely accept smoking, these wives employed both persuasive and, occasionally, coercive methods to encourage healthier behaviors among family members. Utilizing a qualitative approach with Participatory Action Research (PAR), data were collected through in-depth interviews with seven wives who have firsthand experience with smoking behaviors in their families. The findings revealed that wives in Gayo Lues act as both health monitors and guardians, balancing emotional support with firm boundaries to foster a smoke-free home environment. Their roles extended beyond traditional caregiving, as they actively shape family health outcomes. In conclusion, this study underscored the importance of empowering wives as health advocates in public health efforts, particularly in culturally conservative settings. Future research could further explore the broader socio-cultural dynamics influencing wives’ health advocacy roles and assess the sustainability of these behaviors over time.</p> Hasrizal Saffutra, Mustanir Yahya, Rizanna Rosemary, Rosaria Indah, Dedy Syahrizal Copyright (c) 2025 Hasrizal Saffutra, Mustanir Yahya, Rizanna Rosemary, Rosaria Indah, Dedy Syahrizal https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1960 Wed, 30 Apr 2025 00:00:00 +0700 Genetic variations of the L2 gene in human papillomavirus (HPV) type 16 from cervical cancer patients in Sumatra region, Indonesia https://narraj.org/main/article/view/1653 <p>The L2 protein, a minor capsid component of human papillomavirus (HPV), plays a critical role in the HPV life cycle by packaging the viral genome with the L1 protein and facilitating DNA transport to the nucleus. Identifying genetic variations in the <em>L2</em> gene is essential for improving vaccine development, diagnostic accuracy, and understanding viral evolution, potentially contributing to more effective HPV vaccines. The aim of this study was to investigate the genetic variation of the <em>L2</em> gene in cervical cancer specimens collected from patients in Riau Province, Indonesia. A single-center, cross-sectional study was conducted at Arifin Achmad General Hospital, Riau Province, involving cervical cancer patients with confirmed HPV16 infection between January 2018 and August 2020. Demographic, clinical, and risk factor data were collected through structured interviews and direct assessments. Cervical biopsy specimens were collected, and viral DNA was extracted for <em>L2</em> gene amplification using polymerase chain reaction (PCR). Sequencing was conducted on PCR products, followed by single-nucleotide polymorphism (SNP) identification through alignment with the HPV16 reference genome. The amplification and sequencing of the HPV16 <em>L2</em> gene from 22 cervical cancer specimens revealed 36 SNPs, including 31 nonsynonymous and five synonymous mutations. High-frequency mutations were observed at nucleotide positions 4,074 and 4,177, each detected in 95.45% of the samples. Notable insertions were found at positions 3,668–3,669 and 4,275–4,276, indicating substantial sequence variation. Phylogenetic analysis grouped the sequences into three clusters, with most belonging to sub-lineage A2 (European), while others aligned with A4 (Asian) and East Asian lineages. The observed genetic diversity in the HPV16 <em>L2</em> gene may reflect regional viral evolution and has potential implications for future vaccine development.</p> Maya Savira, Arnaldi Farniga, Zidny Ilmiah, Rachmadina Rachmadina, Ika A. Rini, Rahmat A. Kemal, Azza E. Mahargyarani, Muhammad Z. Admiral, Amru Sofian, Renardy R. Razali, Donel Suhaimi, Andani E. Putra Copyright (c) 2025 Maya Savira, Arnaldi Farniga, Zidny Ilmiah, Rachmadina, Ika A. Rini, Rahmat A. Kemal, Azza E. Mahargyarani, Muhammad Z. Admiral, Amru Sofian, Renardy R. Razali, Donel Suhaimi, Andani E. Putra https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1653 Thu, 24 Apr 2025 00:00:00 +0700 Network pharmacology, molecular docking, and molecular dynamics analyses to explore the molecular mechanism of paclitaxel in atherosclerosis therapy https://narraj.org/main/article/view/2140 <p>Atherosclerosis is a chronic arterial disease and the leading cause of vascular death. Paclitaxel has long been recognized as an anticancer agent, but recent studies have shown that paclitaxel can also potentially reduce the progression of atherosclerosis. The aim of this study was to explore the molecular mechanism of paclitaxel as an atherosclerosis therapy using in silico study. Pharmacokinetic and pharmacodynamic analyses of paclitaxel were conducted using SwissADME, ProTox v3.0, and SCFbio websites. Cytoscape software was used to construct a network of protein-protein interactions, and the key proteins involved in paclitaxel-related atherosclerosis were identified, including AKT serine/threonine kinase 1 (AKT1), Jun N-terminal kinase (JNK), and Endothelin 1 (ET1). These key proteins were then subjected to molecular docking and molecular dynamic simulation using MOE and Yasara applications. Pharmacokinetic and pharmacodynamic analyses revealed that paclitaxel has good distribution, metabolism, and excretion properties. However, paclitaxel has shortcomings in absorption, toxicity, and water solubility. According to the results of molecular docking, paclitaxel showed consistent results as the most potential inhibitor of AKT1 (-9.59 kcal/mol), ET1 (-9.16 kcal/mol), JNK (-8.72 kcal/mol) when compared to the control ligands. Molecular dynamics simulations also confirmed the interaction stability between paclitaxel with AKT1, ET1, and JNK, with paclitaxel-AKT1 demonstrating the highest conformational stability (Carbon-α Root Mean Square Deviation &lt;3.0 Å). Even though our in-silico results are promising, more experimental studies are required to confirm the efficacy of paclitaxel as an atherosclerosis therapy.</p> Biomechy Oktomalioputri, Afriwardi Afriwardi, Eryati Darwin, Rauza S. Rita Copyright (c) 2025 Biomechy Oktomalioputri, Afriwardi Afriwardi, Eryati Darwin, Rauza S. Rita https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2140 Mon, 28 Apr 2025 00:00:00 +0700 DOCA and L-NAME hydrochloride: Their impact on T regulatory cells, macrophage activity, and pro- and anti-inflammatory cytokine profiles in pre-eclampsia animal model https://narraj.org/main/article/view/1872 <p>Deoxycorticosterone acetate (DOCA) and N-nitro-L-arginine methyl ester (L-NAME) hydrochloride have been well-reported as pre-eclampsia inducers due to their ability to mimic hypertension, endothelial dysfunction, and inflammatory response. However, no study has compared the two inducers in developing a mice model of preeclampsia characterized by proinflammatory and anti-inflammatory parameters. The aim of this study was to investigate the efficacy of DOCA and L-NAME hydrochloride in inducing pre-eclampsia in pregnant mice, focusing on the expression of regulatory T cells (Tregs), macrophages, anti-inflammatory cytokines TGF-β, and pro-inflammatory cytokines (IL-6 and IL-1β). Twenty-seven female BALB/c mice were grouped into three groups (n=9): healthy pregnant mice (NP), pregnant mice induced with DOCA (PD), and pregnant mice induced with L-NAME hydrochloride (PL). L-NAME hydrochloride was orally given to the pregnant mice at 4.464 mg/30 g body weight (BW) every day after five days of gestation. DOCA was injected subcutaneously in 0.1 mL of corn oil at 0.74 mg/30 g BW before mating and 0.38 mg/30 g BW once a week until dissection. Drinking water for PD and PL groups was replaced with 0.9% saline. On day 16 of pregnancy, the lymphocytes were isolated from the spleen to determine the profile of Tregs, macrophages, TGF-β, IL-6, and IL-1β using flow cytometry analysis. The results showed that administering L-NAME hydrochloride in pregnant mice exhibited a significant increase in the relative number of IL-1β and macrophages compared to DOCA (<em>p</em>&lt;0.05). L-NAME hydrochloride significantly reduced the production of TGF-β compared to DOCA (<em>p</em>&lt;0.05). Both DOCA and L-NAME hydrochloride could decrease Tregs and IL-6 levels. This study also found that L-NAME hydrochloride was more effective in inducing pre-eclampsia in pregnant BALB/c mice than DOCA indicated by the highest increase in pro-inflammatory cytokines and macrophage activity and a low anti-inflammatory cytokine. The present study provides a foundation for understanding the pathophysiological mechanisms of preeclampsia in the inflammatory pathway; however, further exploration of other mechanisms, markers, and target proteins can deepen insights into its development.</p> Shella ZK. Azmi, Yuyun I. Christina, Dinia R. Dwijayanti, Sri Rahayu, Muhammad S. Djati Copyright (c) 2025 Shella ZK. Azmi, Yuyun I. Christina, Dinia R. Dwijayanti, Sri Rahayu, Muhammad S. Djati https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1872 Mon, 21 Apr 2025 00:00:00 +0700 Beetroot (Beta vulgaris) potential in preventing colorectal cancer using in-silico analysis https://narraj.org/main/article/view/1578 <p>Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, necessitating the need for an effective therapeutic strategy. Beta vulgaris (beetroot) possesses active compounds that exert anti-cancer properties. The aim of this study was to evaluate the potential of beetroot as a preventative agent against the progression of CRC using differentially expressed gene (DEG) analysis and network pharmacology approaches. The protein-protein interaction network and molecular docking analyses were employed to assess the key interactions of beetroot active compounds with CRC-related target protein. Cytotoxicity of beetroot extract was experimentally evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay on the HT29 cell line. The result of this study showed that protein in the cell cycle was significantly enriched in CRC, with cyclin-dependent kinase 4 (CDK4) gene as one of the specific genes. Quercetin, galangin, hesperidin, farrerol, and betanin were the most typical compounds of beetroot based on the Comparative Toxicogenomics Database (CTD). Molecular docking studies revealed the strong binding affinity between quercetin (-7.04 kcal/mol) and bentanin (-8.11 kcal/mol) with CDK4. Beetroot demonstrated anticancer properties against the HT29 cell line with IC50 value of 39.03±1.4 µg/mL. In conclusion, the beetroot extract has inhibitory activity against HT29 cell line proliferation, highlighting its potential in preventing the development of CRC through the substantial suppression of gene expression within the cell cycle pathway.</p> Adisti Dwijayanti, Norma N. Azizah, Linda Erlina, Kusmardi Kusmardi, Sri S. Ningsih, Fadilah Fadilah, Najihah M. Hashim Copyright (c) 2025 Adisti Dwijayanti, Norma N. Azizah, Linda Erlina, Kusmardi Kusmardi, Sri S. Ningsih, Fadilah Fadilah, Najihah M. Hashim https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1578 Fri, 02 May 2025 00:00:00 +0700 Coenzyme Q10 as adjuvant therapy could reduce oxidative stress and enhance sperm quality in cryptorchidism animal models https://narraj.org/main/article/view/2474 <p>The role of coenzyme Q10 (CoQ10) as an antioxidant in the context of cryptorchidism is increasingly recognized due to its potential protective effects against oxidative stress, a key contributor to testicular dysfunction in this condition. The aim of this study was to evaluate the antioxidant activity of CoQ10 and its impact on sperm parameters as an adjuvant therapy in a cryptorchidism mouse model. A total of 36 male Sprague Dawley mice were divided into six groups: control (negative control), cryptorchidism (positive control), orchidopexy only, and orchidopexy treated with CoQ10 at 5, 10 and 20 mg/kg body weight (BW). After seven days of induction into the cryptorchidism model, the mice underwent orchidopexy, and CoQ10 was administered orally from day 1 to day 7 post-orchidopexy. At the end of the treatment period, all mice were euthanized, and the left testes were collected for immunohistochemical analysis of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as histological examination and sperm parameter assessment. Testicular tissue damage was assessed using the Cosentino grade, while spermatogenesis was evaluated using the Johnsen scoring system. Additionally, sperm parameters were analyzed from the left testis. MDA expression in the cryptorchidism group was significantly lower than in all CoQ10-treated groups (<em>p</em>&lt;0.001). In contrast, SOD expression was significantly higher in the cryptorchidism group compared to the 10 mg/kg BW and 20 mg/kg BW CoQ10 groups (both had <em>p</em>&lt;0.001). Cosentino grade and Johnsen score showed no significant differences between the control group and the group treated with 20 mg/kg BW CoQ10 (<em>p</em>=0.891 and <em>p</em>=0.123, respectively). Furthermore, the 20 mg/kg BW CoQ10 group had significantly greater sperm concentration and motility compared to the cryptorchidism group (<em>p</em>&lt;0.001 for both). These findings demonstrated that CoQ10 had significant antioxidant activity as an adjuvant therapy in a cryptorchidism mouse model. CoQ10 supplementation could reduce oxidative stress markers, enhance antioxidant enzyme expression, and improve sperm parameters, supporting its potential to mitigate testicular damage associated with cryptorchidism.</p> Pradana Nurhadi, Besut Daryanto, Fauzan K. Dhani, Athaya F. Purnomo, Kusworini Kusworini, Tommy N. Alfandy Copyright (c) 2025 Pradana Nurhadi, Besut Daryanto, Fauzan K. Dhani, Athaya F. Purnomo, Kusworini Kusworini, Tommy N. Alfandy https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2474 Fri, 09 May 2025 00:00:00 +0700 Lichen substances from Teloschistes flavicans (Sw.) Norman: Isolation, crystal structure, and evaluation of their antibacterial activities https://narraj.org/main/article/view/1463 <p><em>Teloschistes flavicans </em>(Sw.) Norman is a lichen known as the golden-haired lichen<em>.</em> This lichen has been recognized and used in herbal medicine mixtures as an antimicrobial and bioindicator of air pollution that plays a role in ecological systems. The aim of this study was to explore the potential of its secondary metabolites as antibacterial and anticancer agents, particularly against bacterial pneumonia. Two main compounds (vicacinin and parietin) were isolated with chromatography and identified by spectrometry and single-crystal X-ray diffraction. The crystallographic data of vicanicin are reported for the first time. Chromatography and recrystallization methods were used to obtain both compounds with orange (parietin) and white (vicanicin) crystals. Furthermore, these compounds were evaluated for cytotoxicity on keratinocytes (HaCaT) cells and antibacterial activity against pneumonia pathogens (<em>Klebsiella pneumoniae </em>ATCC 1706, <em>Streptococcus pneumoniae </em>ATCC 49619, <em>Moraxella catarhalis </em>ATCC 25240, and <em>Staphylococcus pyogenes </em>ATCC 19615). The cytotoxic activity of these compounds was moderate at the concentration of 50-100 µM. The antibacterial pneumonia activity was relatively weak compared to chloramphenicol. Between the two compounds, vicanicin showed stronger activity than parietin against all strains. Vicanicin was more active against <em>Klebsiella pneumoniae</em> and <em>Staphylococcus pyogenes</em> with minimum inhibitory concentrations of 156±0.77 µM and 156±0.91 µM, respectively. In this study, comprehensive molecular structures of parietin and vicanicin have been successfully elucidated, and their antibacterial and cytotoxic activities have been provided.</p> Friardi Ismed, Nurwahidatul Arifa, Mentari Q. Nissa, Deddi P. Putra, Analia IC. Orue, Jack K. Clegg, Isabelle Rouaud, Françoise L. Dévéhat Copyright (c) 2025 Friardi Ismed, Nurwahidatul Arifa, Mentari Q. Nissa, Deddi P. Putra, Analia IC. Orue, Jack K. Clegg, Isabelle Rouaud, Françoise L. Dévéhat https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1463 Mon, 21 Apr 2025 00:00:00 +0700 Effects of doxazosin as adjuvant to abiraterone on viability and apoptosis of metastatic castration-resistant prostate cells cancer (mCRPC) PC3 https://narraj.org/main/article/view/1961 <p>Prostate cancer is a leading cause of death among men worldwide, with limited therapeutic options for castration-resistant metastatic prostate cancer (mCRPC). The aim of this study was to investigate the potential role of doxazosin, an α1-blocker, as an adjunctive therapy for mCRPC in combination with abiraterone. Using mCRPC PC3 cells, the effects of doxazosin on cell viability and apoptosis were assessed. The experimental design was an in vitro study with post-test-only control design. Experimental groups were divided into four groups: control group, doxazosin group, abiraterone group, and combination group (doxazosin and abiraterone). Cell viability was analyzed using the cell counting kit-8 (CCK-8) assay, while apoptosis was analyzed using Fluorescence-activated cell sorting (FACS). This study found that the IC<sub>50</sub> value for doxazosin was 25.42±1.42 µM (mean ± standard error). The results indicated that doxazosin significantly reduced cell viability, with effects varying based on the dose administered, and doxazosin was able to induce apoptosis in mCRPC PC3 cells. The combined treatment of doxazosin and abiraterone in mCRPC PC3 cells demonstrated a significantly higher mean apoptosis percentage compared to the control group (16.27%; 95% confidence interval (CI): 11.89–20.65; <em>p</em>=0.001). Furthermore, the combined treatment showed a significantly higher mean apoptosis percentage compared to abiraterone alone (4.79%; 95%CI: 0.41–9.18; <em>p</em>=0.029), and doxazosin alone (10.99%; 95%CI: 6.61–15.38; <em>p</em>=0.001). These findings suggest that doxazosin, traditionally used as an α1-blocker for lower urinary tract symptoms (LUTS), could offer a novel therapeutic approach for mCRPC patients.</p> Putu KD. Pratama, Zakaria A. Rahman, Furqan Hidayatullah, Tetuka B. Laksita, Lukman Hakim Copyright (c) 2025 Putu KD. Pratama, Zakaria A. Rahman, Furqan Hidayatullah, Tetuka B. Laksita, Lukman Hakim https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1961 Thu, 24 Apr 2025 00:00:00 +0700 CTLA-4 +6230G>A polymorphism and its impact on CTLA-4 level and risk of hepatocellular carcinoma: A case-control study in Batak patients with chronic hepatitis B https://narraj.org/main/article/view/1959 <p>Genetic polymorphisms in cytotoxic T-lymphocyte-associated protein 4 gene (<em>CTLA-4</em>) vary by ethnic background, necessitating population-specific studies. The aim of this study was to assess the association between the <em>CTLA-4</em> +6230G&gt;A polymorphism, serum CTLA-4 level, and hepatocellular carcinoma (HCC) in Batak patients with chronic hepatitis B, a group with high hepatitis B virus (HBV) endemicity. A case-control study was conducted among cases (Batak patients with chronic hepatitis B and HCC) and controls (chronic hepatitis B without HCC). Genotyping of the <em>CTLA-4 +6230G&gt;A</em> polymorphism was performed using the TaqMan SNP Genotyping Assay. Serum CTLA-4 level was quantified using enzyme-linked immunosorbent assay (ELISA). Patient’s demographic, clinical and laboratory data were recorded and assessed including age, sex, body mass index (BMI), smoking history, cirrhosis status, HBV DNA level, liver function markers (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), hepatitis B e-antigen (HBeAg) status, smoking history, and alcohol consumption. This study found that G allele was significantly associated with an increased risk of HCC (OR: 2.69; 95%CI: 1.21–6.00; <em>p</em>=0.013). Individuals with GG/AG genotypes had a 2.89-fold higher risk of developing HCC compared to those with the AA genotype (<em>p</em>=0.032). Serum CTLA-4 level was significantly elevated in G allele carriers (GG: 159.9±57.1 pg/mL vs AA: 83.7±44.7 pg/mL; <em>p</em>&lt;0.001). Multivariate analysis identified cirrhosis as the strongest predictor of HCC (OR: 7.60; <em>p</em>&lt;0.001), followed by elevated ALT (OR: 3.42; <em>p</em>=0.018) and high HBV DNA levels (OR: 2.31; <em>p</em>=0.024). In conclusion, the <em>CTLA-4 +6230G&gt;A</em> GG/AG genotype and elevated serum CTLA-4 level were significantly associated with an increased risk of HCC in Batak individuals with chronic HBV infection. Further research is needed to explore additional <em>CTLA-4</em> polymorphisms and immune regulatory mechanisms in HBV-related HCC to improve risk stratification and therapeutic strategies.</p> Darmadi Darmadi, Imelda Rey, Masrul Lubis, Dharma Lindarto, Riri A. Muzasti Copyright (c) 2025 Darmadi Darmadi, Imelda Rey, Masrul Lubis, Dharma Lindarto, Riri A. Muzasti https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1959 Tue, 13 May 2025 00:00:00 +0700 Mortality and associated factors among community-acquired pneumonia patients: A cross-sectional study in a provincial referral hospital in Indonesia https://narraj.org/main/article/view/1649 <p>Community-acquired pneumonia (CAP) poses a significant impact on the healthcare system due to rehospitalization and mortality. About one-third of hospitalized CAP patients died within one year. In addition to advanced age, vulnerable groups with comorbidities such as cancer, diabetes, and cerebrovascular disease (CVD) are more likely to suffer from severe CAP. The aim of this study was to investigate the factors linked to mortality in adult hospitalized CAP patients. The study extracted the medical records of patients aged ≥18 years, admitted to a referral hospital in Riau Province, who were diagnosed with CAP between January and December 2023. Multiple logistic regression step-wise analysis was employed to determine the factors associated with mortality in CAP patients. The study involved 334 patients with a median age of 58 years. Based on the confusion, urea, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score, 11.9% of patients had severe CAP (CURB-65 scores 3 and 4). Age was a significant predictor of severe CAP (<em>p≤</em>0.001). The most prevalent comorbidities were malignancy (33.2%), CVD (30.2%), and diabetes (28.4%). Mortality incidence during hospitalization reached 35.9%. Significant factors associated with mortality in hospitalized CAP patients included renal dysfunction/elevated serum urea levels (<em>p</em>=0.031), CURB-65 score (<em>p</em>=0.023), vasopressor use (<em>p≤</em>0.001), mechanical ventilator use (<em>p≤</em>0.01) and steroid use (p=0.029). However, CVD was associated with a decreased risk of mortality (<em>p</em>=0.019). Gram-negative bacteria predominated, accounting for 50.6% of all positive isolates. Several significant factors were associated with mortality in adult patients hospitalized with CAP at referral Hospital in Riau, including renal dysfunction, CURB-65 score, vasopressor use, mechanical ventilator use, and steroid use. This finding underscored the importance of early identification factors in CAP patients.</p> Dani Rosdiana, Fajri M. Siregar, Nabila C. Ediwi, Rahmi T. Putri, Zuyyina ER. Nurrahma, Adinda Elisabet, Rosantia Sarassari, Dodi Safari, Cimi Ilmiawati, Aisyah Elliyanti Copyright (c) 2025 Dani Rosdiana, Fajri M. Siregar, Nabila C. Ediwi, Rahmi T. Putri, Zuyyina ER. Nurrahma, Adinda Elisabet, Rosantia Sarassari, Dodi Safari, Cimi Ilmiawati, Aisyah Elliyanti https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1649 Wed, 04 Jun 2025 00:00:00 +0700 Biomarkers for predicting COVID-19 mortality: A study at Sulianti Saroso Infectious Disease Hospital, Indonesia https://narraj.org/main/article/view/1936 <p>The high transmissibility and mortality rates of the COVID-19 pandemic pose significant challenges. Patients can deteriorate rapidly, making it crucial to identify laboratory biomarkers for high-risk individuals. The aim of this study was to evaluate the predictive value of various laboratory parameters, including C-reactive protein (CRP), D-dimer, ferritin, neutrophil-to-lymphocyte ratio (NLR), prothrombin time (PT), and procalcitonin (PCT), in predicting COVID-19 mortality. A retrospective cohort study was conducted at Sulianti Saroso Infectious Disease Hospital, where COVID-19 patients were categorized into survivors and non-survivors. The Mann-Whitney test was used to assess group differences, while receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of each biomarker, with Youden's index (J) determining optimal cut-off values. Kaplan-Meier analysis was used to compare median survival times, and Cox regression assessed hazard rates and the relationship between biomarkers and mortality. A total of 1,598 patients were analyzed, the majority of whom were admitted with oxygen saturation levels &gt;95% and classified as having mild to moderate disease severity. Among them, 216 patients died, resulting in a mortality rate of 13.52%. Significant variations in mortality rates were observed along the survival functions for NLR, ferritin, D-dimer, CRP, and PCT (<em>p</em>&lt;0.001). The survival curves for these biomarkers demonstrated distinct trends across tertiles over time. Among hematological markers, NLR was significantly associated with mortality (<em>p</em>&lt;0.001), with a 1.5–2.2% increased risk per unit increase. Biochemical markers (complete blood count) proved to be more effective than hematological parameters (NLR, ferritin, PT, D-dimer, CRP, PCT) when evaluating individual prognostic performance. Bivariate analysis of CRP, D-dimer, ferritin, NLR, PT, and PCT between survivors and non-survivors showed significant differences. Notably, NLR and PCT were highly relevant for predicting disease prognosis and mortality, with sensitivity and specificity values exceeding 80%.</p> Siti Maemun, Aninda D. Widiantari, Farida Murtiani, Herlina Herlina, Dian W. Tanjungsari, Kunti Wijiarti, Tiara Z. Pratiwi, Faisal Matondang, Adria Rusli, Rivaldiansyah Rivaldiansyah, Maria L. Tampubolon, Nina Mariana, Vivi Setiawaty, Tri B. Purnama Copyright (c) 2025 Siti Maemun, Aninda D. Widiantari, Farida Murtiani, Herlina Herlina, Dian W. Tanjungsari, Kunti Wijiarti, Tiara Z. Pratiwi, Faisal Matondang, Adria Rusli, Rivaldiansyah Rivaldiansyah, Maria L. Tampubolon, Nina Mariana, Vivi Setiawaty, Tri B. Purnama https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1936 Sat, 26 Apr 2025 00:00:00 +0700 Comparative analysis of hemotoxic, myotoxic, and inflammatory profiles of Calloselasma rhodostoma and Trimeresurus insularis venoms in mice https://narraj.org/main/article/view/1874 <p>Snakebite envenomation remains a significant medical concern, particularly in tropical regions where venomous snakes such as <em>Calloselasma rhodostoma</em> and <em>Trimeresurus insularis</em> are prevalent. Both venoms are known for their potent hemotoxic, myotoxic, and inflammatory effects, yet their differential impacts on systemic physiological pathways remain unclear. The aim of this study was to characterize the hematological, myotoxic, and inflammatory effects of <em>C. rhodostoma</em> and <em>T. insularis</em> venoms in a murine model and to explore their influence on systemic factors such as insulin-like growth factor 1 (IGF-1), which is critical for muscle repair and inflammation regulation. Mice were exposed to varying doses (20–100 µg) of <em>C. rhodostoma</em> and <em>T. insularis</em> venoms. Hematological parameters, muscle degeneration, inflammatory cell infiltration, and plasma IGF-1 levels were assessed to evaluate the venoms' systemic and local effects. Our data indicated that <em>C. rhodostoma</em> venom induced significant changes in blood coagulation, muscle edema, and inflammatory infiltration, with pronounced effects even at lower doses. Conversely, <em>T. insularis</em> venom showed a dose-dependent suppression of IGF-1 levels, highlighting its unique systemic impact. Both venoms caused severe muscle damage, characterized by structural disintegration and increased leukocyte infiltration, with <em>C. rhodostoma</em> eliciting a stronger inflammatory response at lower doses.Snakebite envenomation remains a significant medical concern, particularly in tropical regions where venomous snakes such as <em>Calloselasma rhodostoma</em> and <em>Trimeresurus insularis</em> are prevalent. Both venoms are known for their potent hemotoxic, myotoxic, and inflammatory effects, yet their differential impacts on systemic physiological pathways remain unclear. The aim of this study was to characterize the hematological, myotoxic, and inflammatory effects of <em>C. rhodostoma</em> and <em>T. insularis</em> venoms in a murine model and to explore their influence on systemic factors such as insulin-like growth factor 1 (IGF-1), which is critical for muscle repair and inflammation regulation. Mice were exposed to varying doses (20–100 µg) of <em>C. rhodostoma</em> and <em>T. insularis</em> venoms. Hematological parameters, muscle degeneration, inflammatory cell infiltration, and plasma IGF-1 levels were assessed to evaluate the venoms' systemic and local effects. Our data indicated that <em>C. rhodostoma</em> venom induced significant changes in blood coagulation, muscle edema, and inflammatory infiltration, with pronounced effects even at lower doses. Conversely, <em>T. insularis</em> venom showed a dose-dependent suppression of IGF-1 levels, highlighting its unique systemic impact. Both venoms caused severe muscle damage, characterized by structural disintegration and increased leukocyte infiltration, with <em>C. rhodostoma</em> eliciting a stronger inflammatory response at lower doses.</p> Adiva Aphrodita, Diva N. Sentono, Donan S. Yudha, Yekti A. Purwestri, Tri R. Nuringtyas, Slamet Raharjo, Isra Wahid, Sri N. Rahmi, Setyanto T. Wahyudi, Fajar Sofyantoro Copyright (c) 2025 Adiva Aphrodita, Diva N. Sentono, Donan S. Yudha, Yekti A. Purwestri, Tri R. Nuringtyas, Slamet Raharjo, Isra Wahid, Sri N. Rahmi, Setyanto T. Wahyudi, Fajar Sofyantoro https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1874 Mon, 21 Apr 2025 00:00:00 +0700 Enhancing dermoscopic pigmented skin lesion classification: A refined approach using the pre-trained Inception-V3 architecture https://narraj.org/main/article/view/1852 <p>Skin cancer is one of the most prevalent cancers worldwide, with early diagnosis being critical for improving survival rates. Dermoscopy, a non-invasive imaging tool, is widely used for identifying pigmented skin lesions. However, its accuracy is heavily dependent on expert interpretation, which introduces variability and limits accessibility in resource-constrained settings. This highlighted the need for automated solutions to enhance diagnostic consistency and aid in early detection. The aim of this study was to develop a refined machine-learning framework for classifying pigmented skin lesions using dermoscopy images. We employed an enhanced Inception-V3 model, a state-of-the-art convolutional neural network, integrated with a simplified soft-attention mechanism, advanced data augmentation techniques, and Bayesian hyperparameter tuning. These innovations improved the model’s ability to accurately focus on and identify relevant lesion features, marking a significant advancement in the field. Using the ISIC-2019 dataset, a publicly available resource containing dermoscopy images classified into eight diagnostic categories, we implemented preprocessing steps such as resizing, cleaning, and data balancing. Additionally, ImageNet transfer learning and Bayesian optimization were applied to refine the model. The inclusion of a soft-attention mechanism further enhanced the model’s capacity to identify patterns within lesion images. Our model exhibited outstanding performance on the ISIC-2019 dataset, achieving a sensitivity of 98.5%, specificity of 99.62%, precision of 97.42%, accuracy of 97.38%, an F1 score of 97.34%, and an area under the curve (AUC) of 0.99. These metrics underscored the model’s superior capability in accurate and reliable classification of pigmented skin lesions, surpassing current benchmarks and demonstrating significant advancements over existing methodologies.</p> Erwin S. Nugroho, Igi Ardiyanto, Hanung A. Nugroho Copyright (c) 2025 Erwin S. Nugroho, Igi Ardiyanto, Hanung A. Nugroho https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1852 Mon, 21 Apr 2025 00:00:00 +0700 Exploring the potential effects of Lactococcus lactis D4 on the proliferation, apoptosis, and inflammatory responses in colorectal cancer cells https://narraj.org/main/article/view/1596 <p><em>Lactococcus lactis</em> D4 is a probiotic produced through the fermentation of buffalo milk in bamboo, namely "<em>dadih</em>", a traditional food from West Sumatera, Indonesia. To the best of our knowledge, no specific research has investigated the effects of <em>L. lactis</em> D4, derived from <em>dadih</em> extraction, on colorectal cancer or its potential clinical applications. Therefore, the aim of this study was to evaluate the potential of <em>L. lactis</em> D4 from <em>dadih</em> to inhibit colorectal cancer growth in rat models, with a focus on its effects on cell proliferation, apoptosis, and inflammatory responses. An in vivo study was conducted using 37 male Sprague-Dawley rats, allocated into five groups: (1) control (no treatment), (2) dysplasia (induced with 1,2-dimethylhydrazine until dysplasia developed), (3) dysplasia + <em>L. lactis</em> D4 (induced with 1,2-dimethylhydrazine, then treated with <em>L. lactis</em> D4 after dysplasia confirmation), (4) cancer (induced with 1,2-dimethylhydrazine until cancer was confirmed), and (5) cancer + <em>L. lactis</em> D4 (induced with 1,2-dimethylhydrazine until cancer was confirmed, then treated with <em>L. lactis</em> D4 for 15 days). The effects of <em>L. lactis</em> D4 on cancer progression were assessed through immunohistochemical analysis of cell proliferation (cyclin D1, Bcl-2), apoptosis (p53, caspase-3), and inflammation (nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2)). This study found that <em>L. lactis</em> D4 treatment reduced adenocarcinoma and dysplasia severity in colorectal cancer models through significant reduction in cyclin D1, Bcl-2, NF-κB, and COX-2 expression observed across all groups (<em>p</em>&lt;0.01), although changes in dysplasia and cancer subgroups were not statistically significant (<em>p</em>&gt;0.05). No statistically significant change was noted in p53 expression (<em>p</em>=0.518), whereas caspase-3 expression varied significantly across groups (<em>p</em>=0.010). In conclusion, <em>L. lactis</em> D4 reduces the expression of cyclin D1, Bcl-2, NF-κB, and COX-2 proteins, offering insights into its potential to modulating proliferation and inflammation in colorectal cancer growth.</p> Muhammad I. Rivai, Ronald E. Lusikooy, Andani E. Putra, Aisyah Elliyanti, Ade Sukma Copyright (c) 2025 Muhammad I. Rivai, Ronald E. Lusikooy, Andani E. Putra, Aisyah Elliyanti, Ade Sukma https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1596 Mon, 28 Apr 2025 00:00:00 +0700 Cytoarchitectural changes in the developing cerebellar cortex of the laggard mutant mouse https://narraj.org/main/article/view/2075 <p>The laggard (lag) mutant mouse, which arises from a mutation in the Kif14 gene, begins to exhibit ataxia and impaired growth after the first postnatal week and subsequently dies prematurely around two weeks of age. In this mutant mouse, the layered architecture of the cerebellar cortex, cerebral cortex, dentate gyrus, and olfactory bulb is disrupted at the cellular level. The aim of this study was to identify the effect of Kif14 mutation on the development of the cerebellar cortex. Abnormalities in the cytoarchitectonics of the developing cerebellar cortex were assessed using hematoxylin-eosin (HE) staining and immunohistochemistry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and bromodeoxyuridine (BrdU) assays were performed to identify apoptotic and proliferating cells. Macroscopic observation of the lag mutant cerebellum reveals a marked reduction in size compared to wild-type mice. HE staining displays a normal foliation and lamination pattern in the lag mutant cerebellum, but detailed analysis has shown morphological disorganization in the cytoarchitectonics of the cerebellar cortex. The mutant internal granular layer is poorly defined and contains significantly fewer granule cells. Meanwhile, Purkinje cells form multilayer arrangements instead of a monolayer arrangement, as observed in wild-type mice, with their dendritic arborization being severely underdeveloped. Some Purkinje cells exhibit multiple nuclei, suggesting that the Kif14 mutation disrupts normal cell division. These phenotypes are already recognized during early postnatal days, although no difference is determined before birth. TUNEL-positive cells are significantly more numerous in the mutant external granular layer, indicating that increased apoptotic cell death contributes to the diminished granule cell population in the lag mutant mouse. In conclusion, the lag mutant cerebellar cortex shows distinct structural abnormalities, suggesting that the Kif14-encoded protein exerts multifaceted roles in the development of the brain laminated structures as well as in myelin formation.</p> Junaedy Yunus, Tomiyoshi Setsu, Satoshi Kikkawa, Toshio Terashima Copyright (c) 2025 Junaedy Yunus, Tomiyoshi Setsu, Satoshi Kikkawa, Toshio Terashima https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2075 Mon, 21 Apr 2025 00:00:00 +0700 Mesenchymal stem cell-derived secretome accelerates third-degree burn wound healing: Effects on proliferation, angiogenesis, and fibrosis regulation https://narraj.org/main/article/view/1828 <p>Mesenchymal stem cell-derived secretome (MSC-derived secretome) has shown promise in regenerative medicine; however, research specifically evaluating its efficacy in third-degree burn wounds remains scarce. The aim of this study was to investigate the effects of MSC-derived secretome on cellular proliferation, angiogenesis, myofibroblast activity, and collagen synthesis in a third-degree burn wound model. A total of 20 Wistar rats were randomly assigned to four groups: a healthy control group, a negative control group with untreated third-degree burn wounds, and two treatment groups receiving MSC-derived secretome at doses of 100 µL and 200 µL for 14 days. The wound healing was assessed 14 days post-treatment. Proliferating cell nuclear antigen (PCNA) protein expression was quantified via Western blot to assess cell proliferation; <em>vascular endothelial growth factor</em> (<em>VEGF</em>) gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to examine angiogenesis; alpha-smooth muscle actin (α-SMA) expression was assessed through immunohistochemistry to evaluate myofibroblast activity; and collagen density was measured using Masson's trichrome staining to determine tissue remodeling. Our data indicated that MSC-derived secretome treatment significantly enhanced multiple aspects of the healing process in a dose-dependent manner. PCNA expression increased by 2.8-fold in the 200 µL MSC-derived secretome group compared to the negative control (<em>p</em>&lt;0.05). <em>VEGF</em> gene expression was upregulated by 2.14-fold in the 200 µL secretome group compared to the negative control (<em>p</em>&lt;0.05). α-SMA protein expression increased by 12.67% in the 200 µL secretome group, while collagen density demonstrated the most pronounced improvement at the 200 µL dose, reaching an increase of 81.26% (<em>p</em>&lt;0.05). In conclusion, MSC-derived secretome significantly accelerates burn wound healing by promoting cell proliferation, enhancing angiogenesis, and increasing collagen synthesis while modulating myofibroblast activity. This highlights the potential of MSC-derived secretome as a therapeutic option for optimizing burn wound repair and reducing fibrotic complications.</p> Bayu T. Dirja, Agung Putra, Nur D. Amalina Copyright (c) 2025 Bayu T. Dirja, Agung Putra, Nur D. Amalina https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1828 Mon, 19 May 2025 00:00:00 +0700 Medical cost inflation and its drivers in Indonesian employer-sponsored health insurance for retiree families https://narraj.org/main/article/view/2528 <p>Rising life expectancy and changes in disease patterns have led to an increase in retiree medical costs. Understanding these trends is essential for ensuring the financial sustainability of retiree healthcare programs. The aim of this study was to analyze medical cost inflation and its drivers in Indonesia's employer-sponsored retiree health insurance program from 2020 to 2023. A retrospective cohort study using total sampling included 29,695 retirees, analyzing medical records and insurance claims to examine demographic transition, cost analysis and relative risk of cost drivers. The study found that the retiree population is aging, characterized by longer life expectancy and a growing proportion of individuals aged above 71 years. Medical cost inflation among retirees is higher compared to the general population, driven by aging, high-cost diseases, increased healthcare utilization, and rising treatment costs. Cardiovascular diseases, diabetes, and chronic kidney disease are major drivers of high medical costs. Inpatient care is the most significant cost component, with a cost risk 14.39 times higher than clinic visits. Medicine and medical treatment are leading cost contributors in the retired population. The rising cost of retiree healthcare necessitates sustainable financing strategies. The study highlights that medical cost inflation in retirees was higher than in the general population, driven by aging, high-cost diseases, increased utilization, and rising treatment costs. Strengthening preventive care, optimizing primary care, and diversifying funding sources are recommended to ensure long-term financial stability.</p> Cahya E. Prastyo, Ascobat Gani Copyright (c) 2025 Cahya E. Prastyo, Ascobat Gani https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2528 Thu, 08 May 2025 00:00:00 +0700 Plant-based synthesis of gold and silver nanoparticles using Artocarpus heterophyllus aqueous leaf extract and its anticancer activities https://narraj.org/main/article/view/1770 <p>Green synthesis of nanoparticles has garnered significant attention for its sustainable and environmentally friendly approach. Despite extensive research on <em>Artocarpus heterophyllus</em>-derived nanoparticles using seeds, fruits, and rind, the therapeutic potential of its leaf extract remains largely unexplored, particularly in MCF-7 breast cancer cells. The aim of this study was to investigate the potential of aqueous leaf extract from <em>A. heterophyllus</em> as a reducing and capping agent to synthesize silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), as well as to evaluate their anticancer efficacy. The nanoparticles were characterized using ultraviolet-visible spectroscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and particle size analysis to confirm the formation. To evaluate anticancer potential, key oncogenes associated with cancer proliferation and survival were analyzed, including <em>c-Myc</em>, <em>cyclin D1</em>,<em> human epidermal growth factor receptor-2 (HER-2), </em><em>microRNA-622</em> (<em>miR-622</em>)<em>, </em>and <em>cyclooxygenase-2 (COX-2)</em>. The present study demonstrated that AgNPs and AuNPs synthesized from <em>A. heterophyllus</em> extract had distinct sizes and shapes, with AgNPs averaging approximately 12.75 nm and exhibiting a spherical morphology, while AuNPs averaged 109.26 nm and had a pentagonal shape. Furthermore, AuNPs had no anticancer activity. In contrast, AgNPs showed potent anticancer effects, with inhibitory concentration (IC<sub>50)</sub> values of 124.626 and 54.981 µg/mL at 48 and 72 hours, respectively. The AgNPs treatment increased the proportion of cells in G2/M phase, indicating the induction of mitotic catastrophe leading to cell death. AgNPs downregulated the expression of several oncogenes associated with cancer cell proliferation and survival (<em>cyclin D1, COX-2, HER-2</em>, and <em>miR622), </em>but did not significantly reduce <em>c-Myc</em> expression. In conclusion, AgNPs derived from <em>A. heterophyllus</em> leaf extract have significant potential as a novel therapeutic agent in cancer treatment while preserving its biocompatibility, emphasizing the promise of sustainable and cost-effective synthesis of plant-based nanoparticles.</p> Firli RP. Dewi, Aulia U. Rohmatika, Arniza KM. Jamil, Turan Demircan, Muhammad F. Idris, Litazkiyyah Litazkiyyah, Muhammad Fahmi, A'liyatur Rosyidah, Alfiah Hayati, Sugiharto Sugiharto Copyright (c) 2025 Firli RP. Dewi, Aulia U. Rohmatika, Arniza KM. Jamil, Turan Demircan, Muhammad F. Idris, Litazkiyyah Litazkiyyah, Muhammad Fahmi, A'liyatur Rosyidah, Alfiah Hayati, Sugiharto Sugiharto https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1770 Sun, 27 Apr 2025 00:00:00 +0700 Thymoquinone and madecassoside improve motor function in a rotenone-induced mouse model of early Parkinson’s disease: Role of dopamine, alpha-synuclein and mBDNF https://narraj.org/main/article/view/2439 <p>Parkinson’s disease is a progressive, incurable neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and pathological aggregation of α-synuclein in the midbrain, leading to motor dysfunction. Thymoquinone (TQ), an active compound from Nigella sativa, has demonstrated antioxidant properties that may reduce dopamine degradation, while madecassoside (MA), a triterpenoid component of Centella asiatica, exhibits neuroprotective effects. To date, no study has investigated the combined effects of TQ and MA in a Parkinson’s disease model. The aim of this study was to evaluate the synergistic neuroprotective potential of TQ and MA on motor function, dopamine levels, α-synuclein accumulation, and mature brain-derived neurotrophic factor (mBDNF) expression in a rotenone (ROT)-induced mouse model of early Parkinson’s disease. Rotenone (2.5 mg/kg BW) was administered subcutaneously for two weeks to induce Parkinson’s disease, while TQ alone, MA alone and combination of TQ and MA at various doses, as well as a reference drug (pramipexole) were given every 48 hours concurrently with rotenone. Motor symptoms were assessed through behavioral tests, including the open field test (OFT), beam walking test, and hanging wire test; midbrain dopamine levels were quantified via enzyme-linked immunosorbent assay (ELISA), α-synuclein expression was assessed using Western blotting, and immunohistochemistry was used to detect mBDNF-positive cells in the cerebral cortex. The combination of TQ and MA significantly increased midbrain dopamine levels and improved locomotor activity, as shown by increased total distance traveled and mean velocity in ROT-induced mice. Biochemically, this combined treatment reduced α-synuclein expression, suggesting attenuation of early pathological aggregation typically observed in Parkinson’s disease. Although the increase in mBDNF expression in the cerebral cortex was not statistically significant, it was higher in the TQ-MA treatment group compared to controls and other groups. Collectively, these results highlight the therapeutic potential of TQ and MA in combination to counteract both motor deficits and early neurochemical disruptions in a ROT-induced model of Parkinson’s disease.</p> Shinta Kusumawati, Agustina T. Endharti, Farhad Balafif, Shahdevi N. Kurniawan, Aris Rosidah, Rabjhany Anaqah, Izzunazel A. Barqillah, Husnul Khotimah Copyright (c) 2025 Shinta Kusumawati, Agustina T. Endharti, Farhad Balafif, Shahdevi N. Kurniawan, Aris Rosidah, Rabjhany Anaqah, Izzunazel A. Barqillah, Husnul Khotimah https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2439 Fri, 09 May 2025 00:00:00 +0700 Stigma and health-related quality of life (HRQoL) among people with multidrug-resistant tuberculosis (MDR-TB): A cross-sectional study in Indonesia https://narraj.org/main/article/view/1317 <p>Stigma often accompanies people with multidrug-resistant tuberculosis (MDR-TB) and potentially affects their health-related quality of life (HRQoL). The aim of this study was to investigate the stigma faced by patients with MDR-TB, both from the patients' and community's perspective, and its relationship with HRQoL. Data was gathered at the provincial hospital in Makassar, South Sulawesi, Indonesia. The instrument employed in this research was the Indonesian version of the tuberculosis (TB) stigma instrument to assess MDR-TB stigma from the patient and community perspectives. The patient perspective represents how individuals with TB perceive and experience stigma, including the fear of disclosure, isolation, and guilt (feeling responsible for the burden on their family or their own risky behaviors). Meanwhile, the community perspective reflects how individuals with TB perceive societal attitudes towards them, such as social distancing, avoidance, and reluctance to interact. HRQoL was measured using the European quality of life-5 dimensions-5 level version (EQ-5D-5L) instrument. Notably, the evaluation of anxiety and depression is centered on the fifth dimension of the EQ-5D-5L instrument. A total of 210 patients with MDR-TB were included in the study, all of whom reported experiencing stigma. Most participants perceived stigma at a moderate level, with 76% from the patient perspective and 71% from the community perspective. The average EQ-5D-5L index score was 0.72 (95% confidence interval (95%CI): 0.68–0.76). Measurements from both perspectives show similar scores. There is a substantial negative association between the level of stigma and HRQoL, both from the patient's perspective (<em>R</em><sup>2</sup>=-0.33; F=102.52; <em>p</em>&lt;0.001) and the community's (<em>R</em><sup>2</sup>=-0.32; F=96.76; <em>p</em>&lt;0.001). The study highlights that the stigma of MDR-TB significantly affects the HRQoL from the patient and community perspective.</p> Bustanul Arifin, Muhamad G. Sarwadan, Elly Wahyudin, Latifah M. Sarifah, Ahmad Fuady, Fredrick D. Purba, Sylmina D. Alkaff, Akhmad Ardiansyah, Jamaluddin Madolangan Copyright (c) 2025 Bustanul Arifin, Muhamad G. Sarwadan, Elly Wahyudin, Latifah M. Sarifah, Ahmad Fuady, Fredrick D. Purba, Sylmina D. Alkaff, Akhmad Ardiansyah, Jamaluddin Madolangan https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1317 Mon, 21 Apr 2025 00:00:00 +0700 Comparative assessment of smartphone‐based digital planimetry for wound area measurement https://narraj.org/main/article/view/1987 <p>Accurate wound area measurement is essential for effective wound care as it helps determine the progression of healing in patients. The aim of this study was to compare two wound area measurement techniques wound tracing (manual planimetry) and imitoMeasure (smartphone-based digital planimetry) with standard ImageJ-based digital image analysis in a rabbit wound healing study. The study involved 291 wounds categorized into small, intermediate, and large wounds. ImageJ was used as the reference method for comparisons. The intraclass correlation coefficient (ICC) was computed to assess the agreement and reliability between different wound measurement techniques. A mountain plot was used to assess the agreement between measurement methods, and a Bland-Altman plot was used to evaluate the agreement and concordance between measurement methods. The time required for analysis (processing time) was also compared. The study revealed that the imitoMeasure consistently demonstrated a greater level of agreement with ImageJ, especially in small and intermediate wounds. The ICC values indicated substantial agreement between ImageJ and imitoMeasure, with an exceptionally high ICC value for small wounds. Mountain plots revealed that the imitoMeasure had better agreement with ImageJ across all wound sizes. Bland-Altman plots further supported these findings, with wound tracing exhibiting wider limits of agreement and greater variability than imitoMeasure. ImitoMeasure consistently proved to be the quickest method across all wound sizes, whereas wound tracing required the longest processing time. These findings indicate that the imitoMeasure is a more reliable and consistent method for measuring the wound area, in particular for small and intermediate wounds.</p> Khan Sharun, Shajahan A. Banu, Merlin Mamachan, Obli R. Vinodhkumar, Kallemuchikal M. Manjusha, Rohit Kumar, Abhijit M. Pawde, Kuldeep Dhama, Amar Pal Copyright (c) 2025 Sharun Khan, Shajahan A. Banu, Merlin Mamachan, Obli R. Vinodhkumar, Kallemuchikal M. Manjusha, Rohit Kumar, Abhijit M. Pawde, Kuldeep Dhama, Amar pal https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1987 Thu, 24 Apr 2025 00:00:00 +0700 Development and validation of clinical prediction score for mortality in tuberculosis patients https://narraj.org/main/article/view/1701 <p>Tuberculosis (TB) remains a global and national public health concern, with mortality posing a significant challenge in treatment programs. The aim of this study was to develop a simple risk-scoring system to predict mortality among TB patients and assess its applicability in resource-limited settings. Data from TB patient registries in Phichit Province, Thailand, covering from January 1, 2017, to December 31, 2020, were used. Eligible participants were aged ≥18 years, having completed treatment or death. A risk score was developed and internally validated using logistic regression. Coefficients were used to assign weighted points to predictors and applied to a validation cohort to assess diagnostic performance. The performance was evaluated by generating a receiver operating characteristic (ROC) curve. The study included 2,196 participants, randomly allocated into derivation (n=1,600) and validation (n=596) cohorts. The risk score included Charlson Comorbidity Index scores (1–2 points and ≥3 points) and TB meningitis. It showed an area under ROC curve (AuROC) of 74.34% (95%CI: 70.80–77.88%) with good calibration (Hosmer-Lemeshow χ<sup>2</sup>: 0.53; <em>p</em>= 0.97). Positive likelihood ratios for low (≤3) and high (≥6) risk were 1.06 (95%CI: 1.03–1.09) and 31.62 (95%CI: 7.23–138.37), respectively. In the validation cohort, AuROC was 79.50% (95%CI: 74.40–84.60%), with 75% and 100% certainty in low- and high-risk groups. In conclusion, this simple risk score, using routine data and two predictors, can predict mortality in TB patients. It may aid clinicians in planning appropriate care strategies. Nevertheless, the tool should undergo external validation before being implemented in clinical practice.</p> Pattama Saisudjarit, Surasak Saokaew, Acharaporn Duangjai, Anurak Prasatkhetragarn, Sukrit Kanchanasurakit, Pochamana Phisalprapa Copyright (c) 2025 Pattama Saisudjarit, Surasak Saokaew, Acharaporn Duangjai, Anurak Prasatkhetragarn, Sukrit Kanchanasurakit, Pochamana Phisalprapa https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1701 Mon, 21 Apr 2025 00:00:00 +0700 Therapeutic potential of hUC-MSC secretome preconditioned with IFN-γ and/or TNF-α: An in vitro study on Alzheimer’s neuronal cell models https://narraj.org/main/article/view/2281 <p>Alzheimer's disease is a progressive neurodegenerative disease that is characterized by toxic Amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Treatment options include the use of human umbilical cord mesenchymal stem cell (hUC-MSC)-based therapy. Its secretome contains healing substances such as neprilysin (CD10), which breaks down Aβ42; anti-inflammatory cytokines, which lower inflammation; and growth factors, which promote neuronal regeneration. The aim of this study was to produce hUC-MSC secretomes preconditioned with tumor necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ) to enhance the secretion of these healing substances. hUC-MSCs were sub-cultured in T-25 flasks at a seeding density of 5×10³ cells/cm² in 10 mL xeno-free medium. hUC-MSCs were preconditioned with TNF-α only, IFN-γ only, and a combination of TNF-α and IFN-γ. This study used 10 ng/mL TNF-α and 20 ng/mL IFN-γ. The secretome was harvested after 48 hours of preconditioning and then filtered through a 0.22 µm filter. In vitro tests were conducted to assess the effects of the secretome on neuronal survival using the neuroblastoma SH-SY5Y cell line. These cells were differentiated with retinoic acid (RA) and then exposed to Aβ42 to mimic Alzheimer's disease neurons. Secretome therapy was applied at concentrations of 5%, 10%, and 20% to evaluate neuroprotective effects. Four types of secretome were tested: unpreconditioned, TNF-α preconditioned, IFN-γ preconditioned, and a combination of TNF-α and IFN-γ. High levels of CD10 (neprilysin) expression were observed in hUC-MSCs treated with IFN-γ and TNF-α, although they did not release sufficient soluble neprilysin (sNEP). Viability results indicated that secretomes preconditioned with IFN-γ at 10% and 20% concentrations provided the highest increase in cell viability after 72 hours post-therapy. The combination of TNF-α and IFN-γ preconditioned secretome exhibited synergistic effects, particularly at 5% and 10% doses at 24- and 72-hours post-therapy. In conclusion, preconditioned hUC-MSC secretome represents a promising therapeutic approach for Alzheimer's disease, as it enhances neuronal cell viability and promotes neuronal regeneration. However, further studies are required to optimize sNEP release and maximize therapeutic efficacy in in vivo models.</p> Edhijanto Widaja, Jeanne A. Pawitan, Yetty Ramli Copyright (c) 2025 Edhijanto Widaja, Jeanne A. Pawitan, Yetty Ramli https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2281 Sat, 24 May 2025 00:00:00 +0700 Peptide-based drug as atherosclerosis multitarget therapy from Lytechinus variegatus spine: An in silico study https://narraj.org/main/article/view/1152 <p>Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from <em>Lytechinus variegatus</em> spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD<sub>50</sub>) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from <em>Lytechinus variegatus</em> spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.</p> Dessy Arisanty, Salsabila P. Khairani, Kevin Nathaniel, Dhyani P. Wahyudi, Isna C. Kamila, Malya CS. Maharani, Eillen Theodora, Raymond E. Budianto, Alifya R. Shofiy, Ikwandi C. Nugraha, Zaki S. Aaliyya, Awalil RK. Rahman, Al H. Ariouso Copyright (c) 2025 Dessy Arisanty, Salsabila P. Khairani, Kevin Nathaniel, Dhyani P. Wahyudi, Isna C. Kamila, Malya CS. Maharani, Eillen Theodora, Raymond E. Budianto, Alifya R. Shofiy, Ikwandi C. Nugraha, Zaki S. Aaliyya, Awalil RK. Rahman, Al H. Ariouso https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1152 Mon, 21 Apr 2025 00:00:00 +0700 Colchicine attenuates chemical hypoxia-induced pyroptosis through downregulation of nuclear factor kappa B and caspase-1 in cardiomyocytes https://narraj.org/main/article/view/2245 <p>Myocardial infarction (MI) is the leading cause of mortality worldwide. During MI, cardiomyocyte necrosis and inflammation are crucial in the post-MI cardiac remodeling process, including pyroptosis. Although colchicine is a well-known anti-inflammatory drug that has been clinically studied in the context of MI, its role in cardiac pyroptosis remains unclear. The aim of this study was to investigate the role of colchicine in pyroptosis in vitro, using CoCl<sub>2</sub>-induced H9c2 cells. Prior to the primary experiment, the hypoxic model in H9c2 cells was optimized by evaluating hypoxia-inducible factor-1 alpha (HIF-1α) expression and viability in cells exposed to various concentrations of CoCl<sub>2</sub> at different time intervals. Subsequently, an in vitro hypoxia model was established by treating H9c2 cells with CoCl<sub>2</sub> (600 µM), with or without colchicine (1 µM), for 3 hours. Flow cytometry was used to measure the expression of nuclear factor-kappa beta (NF-κB), interleukin 18 (IL-18), caspase-1, and HIF-1α in pyroptotic cells. Immunofluorescence was used to assess caspase-1 localization and its colocalization with propidium iodide during late-stage pyroptosis. Our data indicated that CoCl<sub>2</sub>-induced hypoxia significantly upregulated NF-κB, caspase-1, and IL-18 expression, and increased pyroptotic cell death in H9c2 cells. Colchicine treatment attenuated these effects, leading to a marked reduction in NF-κB, caspase-1, and IL-18 expression in hypoxic cells. Colchicine treatment significantly decreased the number of late pyroptotic cells. The protective effect of colchicine was more pronounced in late hypoxia (24-hour) setting compared to early hypoxia (3-hour). These findings suggest that colchicine attenuates cardiac pyroptosis in hypoxic H9c2 cells, as evidenced by the significant downregulation of key proteins involved in this pathway, including NF-κB, caspase-1, and IL-18. This protective effect appeared to be more effective in late hypoxia.</p> Budi Satrijo, Mohammad S. Rohman, Aulanni'am Aulanni'am, Hidayat Sujuti, Bayu Lestari Copyright (c) 2025 Budi Satrijo, Mohammad S. Rohman, Aulanni'am Aulanni'am, Hidayat Sujuti, Bayu Lestari https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2245 Mon, 21 Apr 2025 00:00:00 +0700 Prevalence and risk factors of adult attention deficit hyperactivity disorder in university students: A study from the United Arab Emirates https://narraj.org/main/article/view/1950 <p>Attention deficit hyperactivity disorder (ADHD), once considered primarily a childhood condition, is now increasingly recognized as a disorder that persists into adulthood and significantly impacts academic and professional success. The aim of this study was to investigate the prevalence of ADHD and identify associated risk factors among university students. A cross-sectional study was conducted over a period of six months at Ras Al Khaimah Medical and Health Sciences University, United Arab Emirates. Data were collected through a self-report questionnaire addressing sociodemographic, lifestyle, and family environment factors. ADHD symptoms were assessed using the World Health Organization Adult ADHD Self-Report Scale version 1.1, based on the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition criteria. The study sample included 472 students, with a mean age of 19.9±1.85 years. The overall prevalence of ADHD was 13.6% (n=64). Logistic regression analysis revealed significant associations between the mother's smoking status (odds ratio (OR): 2.35; 95% confidence interval (95%CI): 1.949–5.862, <em>p</em>=0.050) and living in shared housing (OR: 3.35; 95%CI: 1.674–6.723, <em>p</em>=0.001) with increased odds of ADHD. Conversely, being male (OR: 0.4; 95%CI: 0.216–0.891, <em>p</em>=0.02) and being born full-term (OR: 0.331; 95%CI: 0.138–0.794, <em>p</em>=0.013) were associated with decreased odds of ADHD. Other factors, such as college affiliation, smoking status, exercise habits, maternal employment, mode of delivery, and pregnancy complications, were not significant risk factors. These findings highlight the need for targeted interventions in university settings, including early screening, tailored support services, and increased staff awareness, to support students with ADHD and enhance their academic success and well-being.</p> Rasha A. Salama, Talaat M. Tadross, Ali R. Ammar, Haya T. Manasrah, Rishana A. Razack, Shameena M. Koya, Nihal A. Wadid, Mohamed AF. Patni, Shehla S. Khan Copyright (c) 2025 Rasha A. Salama, Talaat M. Tadross, Ali R. Ammar, Haya T. Manasrah, Rishana A. Razack, Shameena M. Koya, Nihal A. Wadid, Mohamed AF. Patni, Shehla S. Khan https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1950 Wed, 07 May 2025 00:00:00 +0700 Metabolomic profiling and antimicrobial investigation of Aspergillus fumigatus LBKURCC269 and Bacillus paramycoides LBKURCC218 co-culture https://narraj.org/main/article/view/1647 <p>The increasing resistance of pathogenic microbes to antibiotics is a major public health concern, necessitating the discovery of effective antimicrobial compounds. The aim of this study was to assess the bioactive metabolites produced by Aspergillus fumigatus LBKURCC269 and Bacillus paramycoides LBKURCC218 under three fermentation conditions: monoculture of each microorganism and their co-culture. Metabolite analyses initiated with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) followed with molecular networking–Global Natural Products Social Molecular Networking (GNPS) and molecular docking. Antimicrobial activity of the extracts was then conducted. Metabolite analysis using GC-MS identified key antimicrobial compounds, including 2,6-bis(1,1-dimethylethyl)-4-methylphenol, pentadecanoic acid, cyclopropane pentanoic acid, and 3-piperidinol. LC-HRMS, combined with multivariate analysis and GNPS molecular networking, revealed additional antimicrobial compounds, including novel pyrazine derivatives induced in co-culture fermentation. Molecular docking analysis of 3-(propan-2-yl)-octahydropyrrolo[1,2-a]pyrazine-1,4-dione demonstrated its potential as an antimicrobial agent by inhibiting topoisomerase IV and cytochrome monooxygenase with binding affinity of -5.34 kcal/mol and -5.6 kcal/mol, respectively. The antimicrobial assays showed that the co-culture fermentation extract had the strongest activity, with inhibition zones of 20.33±0.59 mm (Escherichia coli), 14.33±0.59 mm (Staphylococcus aureus), and 25.67±0.59 mm (Candida albicans). This study highlights the advantages of co-culture fermentation in enhancing the discovery of antimicrobial compounds. The findings underscore the potential of this approach to simplify chemical isolation and accelerate the identification of novel antimicrobial agents for pharmaceutical development.</p> Zona Octarya, Titania T. Nugroho, Yuana Nurulita, Nabella Suraya, Saryono Saryono Copyright (c) 2025 Zona Octarya, Titania T. Nugroho, Yuana Nurulita, Nabella Suraya, Saryono Saryono https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1647 Tue, 22 Apr 2025 00:00:00 +0700 Helicobacter pylori sabA, hopQ and hom genotypes as potential genetic biomarkers for gastric mucosal inflammation https://narraj.org/main/article/view/1917 <p><em>Helicobacter pylori</em> infection drives heterogeneous gastric pathologies, yet genotype-phenotype correlations in diverse populations remain underexplored. The aim of this cross-sectional study was to investigate the associations between <em>H. pylori</em> virulence genotypes (<em>sabA</em>, <em>hopQ</em>, <em>hom</em> family) and histopathological severity in gastric mucosa among 113 Indonesian dyspepsia patients (mean age: 49.6 years; male predominance: 64.6%). Whole-genome sequencing characterized virulence genotypes, while histopathological grading system using the Updated Sydney System assessed inflammation, atrophy, and bacterial density in the antral and corporal gastric regions. Phylogenetic analysis elucidated strain relatedness. Key genotype frequencies included <em>sabA</em> "on" (40.6%, 43/106), <em>hopQ</em> type I (53.7%, 43/80), and <em>homC<sup>L</sup></em><sup> </sup>(82.4%, 75/91). Statistical analysis revealed <em>sabA</em> "on" status significantly associated with elevated antral bacterial density (odds ratio (OR) 2.70 and 95% confidence interval (95%CI) 1.10–6.60, <em>p</em>=0.027). The <em>homC</em> variants (<em>homC<sup>L</sup></em>/<em>homC<sup>S</sup></em>) demonstrated robust associations with chronic inflammation severity (OR: 3.04; 95%CI: 0.99–9.36, <em>p</em>=0.046) and atrophy progression (OR: 4.78; 95%CI: 1.00–22.86, <em>p</em>=0.035), in contrast to the <em>hopQ</em> genotype, which showed no histopathological association. These findings indicated that <em>sabA</em> and <em>homC</em> as critical determinants of gastric microenvironment modulation, potentially through <em>sabA</em>-mediated colonization efficiency and <em>homC<sup>L</sup></em>-<em>babA</em> synergistic interactions. While histological profiles predominantly indicated mild atrophy, widespread severe chronic inflammation signals latent progression risks.</p> Ramdan Hunowu, Kartika A. Fauzia, Ricky I. Alfaray, Selva R. Dewi, Juniastuti Juniastuti, Yoshio Yamaoka, Muhammad Miftahussurur Copyright (c) 2025 Ramdan Hunowu, Kartika A. Fauzia, Ricky I. Alfaray, Selva R. Dewi, Juniastuti Juniastuti, Yoshio Yamaoka, Muhammad Miftahussurur https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1917 Mon, 28 Apr 2025 00:00:00 +0700 Designing the CORI score for COVID-19 diagnosis in parallel with deep learning-based imaging models https://narraj.org/main/article/view/1606 <p>The coronavirus disease 2019 (COVID-19) pandemic has triggered a global health crisis and placed unprecedented strain on healthcare systems, particularly in resource-limited settings where access to RT-PCR testing is often restricted. Alternative diagnostic strategies are therefore critical. Chest X-rays, when integrated with artificial intelligence (AI), offers a promising approach for COVID-19 detection. The aim of this study was to develop an AI-assisted diagnostic model that combines chest X-ray images and clinical data to generate a COVID-19 Risk Index (CORI) Score and to implement a deep learning model based on ResNet architecture. Between April 2020 and July 2021, a multicenter cohort study was conducted across three hospitals in Jakarta, Indonesia, involving 367 participants categorized into three groups: 100 COVID-19 positive, 100 with non-COVID-19 pneumonia, and 100 healthy individuals. Clinical parameters (e.g., fever, cough, oxygen saturation) and laboratory findings (e.g., D-dimer and C-reactive protein levels) were collected alongside chest X-ray images. Both the CORI Score and the ResNet model were trained using this integrated dataset. During internal validation, the ResNet model achieved 91% accuracy, 94% sensitivity, and 92% specificity. In external validation, it correctly identified 82 of 100 COVID-19 cases. The combined use of imaging, clinical, and laboratory data yielded an area under the ROC curve of 0.98 and a sensitivity exceeding 95%. The CORI Score demonstrated strong diagnostic performance, with 96.6% accuracy, 98% sensitivity, 95.4% specificity, a 99.5% negative predictive value, and a 91.1% positive predictive value. Despite limitations—including retrospective data collection, inter-hospital variability, and limited external validation—the ResNet-based AI model and the CORI Score show substantial promise as diagnostic tools for COVID-19, with performance comparable to that of experienced thoracic radiologists in Indonesia.</p> Telly Kamelia, Benny Zulkarnaien, Wita Septiyanti, Rahmi Afifi, Adila Krisnadhi, Cleopas M. Rumende, Ari Wibisono, Gladhi Guarddin, Dina Chahyati, Reyhan E. Yunus, Dhita P. Pratama, Irda N. Rahmawati, Dewi Nareswari, Maharani Falerisya, Raissa Salsabila, Bagus DI. Baruna, Anggraini Iriani, Finny Nandipinto, Ceva Wicaksono, Ivan R. Sini Copyright (c) 2025 Telly Kamelia, Benny Zulkarnaien, Wita Septiyanti, Rahmi Afifi, Adila Krisnadhi, Cleopas M. Rumende, Ari Wibisono, Gladhi Guarddin, Dina Chahyati, Reyhan E. Yunus, Dhita P. Pratama, Irda N. Rahmawati, Dewi Nareswari, Maharani Falerisya, Raissa Salsabila, Bagus DI. Baruna, Anggraini Iriani, Finny Nandipinto, Ceva Wicaksono, Ivan R. Sini https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1606 Mon, 05 May 2025 00:00:00 +0700 Role of LBX1 rs11190870 polymorphism in adolescent idiopathic scoliosis in the Acehnese population: A preliminary study https://narraj.org/main/article/view/2038 <p>Genome-wide association studies (GWAS) have identified the single nucleotide polymorphism (SNP) rs11190870 near the <em>ladybird homeobox 1</em> (<em>LBX1</em>) gene as being associated with the susceptibility and severity of adolescent idiopathic scoliosis (AIS). However, no such genetic studies have been conducted in the Indonesian population. The aim of this study was to investigate the genetic profile of AIS patients in the Acehnese population, with a focus on<em> LBX1 </em>rs11190870, and to assess its association with disease severity. A total of 30 female AIS patients were included. Genetic analysis was performed to determine the rs11190870 genotype in each subject. The association between rs11190870 and curve progression, measured by Cobb angle, was analyzed using the Mann–Whitney U test. The T allele was found to be more prevalent (73.3%), with the TC genotype being the most common (53.3%). A significant association was observed between <em>LBX1</em> rs11190870 and curve progression, where patients with the TT genotype exhibited a larger Cobb angle compared to those with TC or CC genotypes (<em>p</em>=0.01). This is the first study to characterize the genetic profile of AIS and its association with curve severity in the Acehnese population. These findings suggest that <em>LBX1</em> rs11190870 may act as a disease modifier in AIS. Further studies with larger sample sizes are warranted to confirm the role of <em>LBX1</em> rs11190870 in AIS susceptibility and severity in the Indonesian population.</p> Teuku N. Aulia, Luthfi Gatam, Aman Yaman, Djufri Djufri Copyright (c) 2025 Teuku N. Aulia, Luthfi Gatam, Aman Yaman, Djufri Djufri https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2038 Tue, 13 May 2025 00:00:00 +0700 Effects of patin fish-based nutritional intervention on biochemical and physiological recovery in malnourished rats: An in vivo study and its implications for clinical nutrition https://narraj.org/main/article/view/1811 <p>Malnutrition is a major global health concern, especially in developing countries. Although patin fish oil and protein offer benefits, their individual and combined effects on maternal physiology remain unclear, particularly during early pregnancy. The aim of this study was to assess the effect of patin-based nutritional intervention on total serum protein, albumin, hemoglobin levels, body weight during pregnancy, body weight during lactation, heart rate, respiratory rate, body temperature, external appearance, behavioral activity, and milk production in malnourished rats. An in vivo study was conducted using <em>Rattus norvegicus</em> rats. The rats were divided into six groups: (1) healthy control, receiving standard feed; (2) malnourished control, receiving an 8% low-protein diet; (3) malnourished group, receiving standard feed; (4) malnourished treated with patin oil; (5) malnourished treated with patin meat; and (6) malnourished treated with a combination of patin oil and meat. The treatment consisted of 21 days during pregnancy and 23 days during lactation, for a total of 44 days. Our data indicated that patin-based intervention significantly increased total protein (<em>p</em>=0.044), albumin (<em>p</em>=0.001), and hemoglobin levels (<em>p</em>=0.034) compared to malnourished control group. The malnourished animals treated with patin oil showed the highest increases in total protein (1.67%), albumin (17.75%), and hemoglobin (24.26%). Body weight gain improved significantly in patin-treated group in both pregnancy (<em>p</em>=0.032) and lactation (<em>p</em>&lt;0.001) compared to the malnourished control, with the highest gains observed in the patin oil group. Milk production also increased significantly (<em>p</em>&lt;0.05), reaching its peak in the patin oil and meat combination group (6.97 g). Physiological parameters, including heart rate (<em>p</em>=0.021), respiratory rate (<em>p</em>=0.025), and body temperature (<em>p</em>=0.023), were significantly different among groups, of which patin oil and meat groups had the most optimal parameters compared to malnourished control group. In conclusion, patin-based nutritional intervention effectively enhances protein metabolism, hematological parameters, and physiological health in malnourished maternal rats, with patin oil demonstrating the most pronounced effects.</p> Hidayaturrahmah Hidayaturrahmah, Agik Suprayogi, Huda S. Darusman, Katrin Roosita, Novriyandi Hanif Copyright (c) 2025 Hidayaturrahmah Hidayaturrahmah, Agik Suprayogi, Huda S. Darusman, Katrin Roosita, Novriyandi Hanif https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1811 Mon, 12 May 2025 00:00:00 +0700 Fecal ingestion rate based on worker activity patterns during stool handling in a ruminant farm https://narraj.org/main/article/view/1989 <p>Farm workers who handle livestock stools face an increased risk of infection by pathogenic bacteria, such as <em>Escherichia coli</em> O157 and <em>Salmonella spp</em>., leading to millions of severe health issues and thousands of fatalities annually. The aim of this study was to assess the impact of these pathogens by measuring their concentrations, determining rates of unintentional fecal consumption, and conducting a quantitative assessment of microbial risk. An integrated farm in Sukabumi City, Indonesia, was examined for <em>E. coli</em> O157 and <em>Salmonella spp</em>. in livestock stools. Additionally, the study monitored the rate of incidental fecal ingestion among farm workers. Stool samples were collected (n= 40) from ruminants and analyzed following ISO 16649-1:2018, ISO 9308-1:2014, and ISO 6579-1:2017/Amd.1:2020. The study tracked worker’s behavior daily to determine the contact time. The fecal ingestion rate was calculated by multiplying the estimated stool weight ingested by the contact time workers spent cleaning livestock stools in the barn each day. Microbial analysis revealed that the highest concentration of <em>E. coli</em> O157 in beef cattle stools was 2.49 log<sub>10</sub> CFU/g. The study determined mean fecal ingestion rates during the dry season (8.64 mg/day) and rainy season (6.84 mg/day). Results from the quantitative microbial risk assessment showed that stool from beef cattle posed a higher risk of <em>E. coli</em> O157 infection compared to other ruminants, with an estimated disease burden of 9.8 × 10<sup>-3</sup> pppy. This study represents the first comprehensive quantitative evaluation of fecal ingestion by farm workers during animal husbandry. The findings underscore the need for improved worker safety measures, such as enhanced sanitation practices and protective equipment, to mitigate the risks of handling livestock stools.</p> Yudith V. Paramitadevi, Cindy R. Priadi, Iftita Rahmatika, Andriansjah Rukmana Copyright (c) 2025 Yudith V. Paramitadevi, Cindy R. Priadi, Iftita Rahmatika, Andriansjah Rukmana https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1989 Fri, 20 Jun 2025 00:00:00 +0700 Spectrum of rare EGFR mutations in Indonesian lung adenocarcinoma: Findings from an 8-year analysis of 4,778 cases highlighting the need for advanced targeted therapies https://narraj.org/main/article/view/1721 <p>Lung cancer patients in Indonesia exhibit a high prevalence of epidermal growth factor receptor (<em>EGFR</em>) mutations, with a substantial proportion attributed to rare or uncommon variants. The clinical significance of rare <em>EGFR </em>mutations lies in their differential sensitivity to tyrosine kinase inhibitors (TKIs). While they are frequently resistant to first- and second- generation TKIs, they often respond to third-generation TKIs, necessitating tailored treatment options. The need for improving access to advanced targeted therapies in Indonesia also highlights the importance of conducting research on rare <em>EGFR</em> mutations. The aim of this study was to identify the spectrum and frequency of <em>EGFR</em> mutations in patients with lung adenocarcinoma in Indonesia. A cross-sectional observational study with total sampling was conducted from January 2016 to April 2024 to investigate <em>EGFR</em> mutation profiles in lung adenocarcinoma patients. Samples were acquired from patients with a confirmed anatomical pathology diagnosis from various healthcare centers across Indonesia. A total of 4,778 samples were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) on various specimen types to determine <em>EGFR</em> mutation prevalence and patterns. Associations between demographic data and <em>EGFR</em> mutation status were assessed. <em>EGFR</em> mutations were detected in 54.6% of samples, with common mutations (exon 19 deletions/insertions and point mutation L858R) comprising 76.2% of positive cases and rare mutations (exon 20 insertions, point mutation G719X, S768I, T790M, and L861Q) accounted for 20.3%. Significant associations were found between geographic origin, age, and sex with <em>EGFR</em> mutation status. This study confirms substantial genetic variability and geographical differences in <em>EGFR</em> mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.</p> Didik S. Heriyanto, Ika Trisnawati, Lisnawati Rachmadi, Jeffry B. Tenggara, Vincent Lau, Andrew N. Gunawan, Brigitta N. Halim, Fara S. Yuliani, Vincent Laiman, Soehartati Gondhowiardjo, Hsiao-Chi Chuang Copyright (c) 2025 Didik S. Heriyanto, Ika Trisnawati, Lisnawati Rachmadi, Jeffry B. Tenggara, Vincent Lau, Andrew N. Gunawan, Brigitta N. Halim, Fara S. Yuliani, Vincent Laiman, Soehartati Gondhowiardjo, Hsiao-Chi Chuang https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1721 Mon, 21 Apr 2025 00:00:00 +0700 Exploring the hypoglycemic potential of fresh, semangit, and bosok tempe: A comparative metabolite profile https://narraj.org/main/article/view/2327 <p>Tempe, a traditional Indonesian fermented soybean product made with <em>Rhizopus</em> spp., is classified based on fermentation duration into fresh (two days), <em>semangit</em> (five days), and <em>bosok</em> (seven days) varieties, fermented at room temperature (28–30°C). Longer fermentation is believed to enhance its antidiabetic properties. The aim of this study was to compare the metabolite profiles and hypoglycemic activities of fresh, <em>semangit</em>, and <em>bosok</em> tempe made from germinated and non-germinated soybeans. Diabetic rat models were used to assess the effects of these tempe types on body weight, blood glucose levels, serum insulin, pancreatic β-cell count, and glycogen content in liver and muscle tissues. Metabolomic profiling was conducted using gas chromatography-mass spectrometry (GC-MS), followed by principal component analysis (PCA) to assess the influence of fermentation stage and germination. Fresh tempe, especially from germinated soybeans, had the highest moisture content. Fermentation duration significantly influenced color, texture, and pH, with <em>bosok</em> tempe showing the most notable changes. Tempe and gliclazide significantly reduced blood glucose in diabetic rats in vivo, with <em>semangit</em> and <em>bosok</em> tempe restoring levels close to normal. However, weight loss was not reversed. <em>Bosok</em> non-germinated tempe induced the highest insulin levels among tempe treatments and improved β-cell count and density to levels comparable with gliclazide. Glycogen stores in the liver and muscle were significantly restored by tempe, with <em>bosok</em> non-germinated tempe showing the greatest effect. GC-MS profiling identified 154 metabolites, of which 63 were annotated. Fermentation and germination shifted the metabolite profile, with <em>bosok</em> non-germinated tempe showing the highest diversity, including amino acids, sugars, and amines. PCA separated samples by fermentation stage, highlighting metabolite accumulation with prolonged fermentation. The findings revealed that <em>bosok </em>tempe from non-germinated soybeans had the highest abundance of bioactive metabolites, including isoflavones, which likely contributed to its superior antioxidant and hypoglycemic potential compared to other tempe types.</p> Made Astawan, Zaid Adurrasyid, Rias R. Novita, Aprilia F. Damayanti, Saraswati Saraswati, Tutik Wresdiyati, Pramuan Saithong, Wanida T. Chitisankul, Sastia P. Putri Copyright (c) 2025 Made Astawan, Zaid Adurrasyid, Rias R. Novita, Aprilia F. Damayanti, Saraswati Saraswati, Tutik Wresdiyati, Pramuan Saithong, Wanida T. Chitisankul, Sastia P. Putri https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2327 Thu, 24 Apr 2025 00:00:00 +0700 Assessing health-related quality of life in schizophrenia patients using EQ-5D-5L index: Insights from patients and caregivers https://narraj.org/main/article/view/1314 <p>Schizophrenia is a prevalent mental health disorder often marked by relapses, significantly affecting the health-related quality of life (HRQoL) of both patients and their families. The aim of this study was to compare the EuroQol 5-Dimension 5-level (EQ-5D-5L) responses of schizophrenia patients and their caregivers. Using an observational cross-sectional design, HRQoL was assessed among schizophrenia patients and their family caregivers recruited from a provincial referral hospital. Sociodemographic (age, sex, education, marital status, income) and clinical variables (diagnosis, treatment duration, comorbidities) were analyzed alongside HRQoL using structured interviews, medical record reviews, and the EQ-5D-5L instrument (self-report by patients and proxy-reported by family caregivers). Statistical analyses included chi-square tests for associations, Wilcoxon tests for patient-family caregiver comparisons, and multivariate modeling of HRQoL determinants. A total of 526 participants (263 patients and 263 accompanying family caregivers) were included. Significant differences were observed between patients and family caregivers in two domains: pain/discomfort and anxiety/depression. Also, the agreement between patients' and family caregivers’ reports showed good results. A substantial agreement was observed between patient-reported and family caregiver-assessed HRQoL, as indicated by a Cohen’s Kappa value of 0.8. This result suggests a strong level of consistency between the two assessments, supporting the potential use of family caregivers as reliable proxies for evaluating patient HRQoL when self-reports are unavailable or unreliable. In the self-care domain, mobility, and daily activities, patient and caregiver assessments show high agreement. In conclusion, the closeness between patients and caregivers significantly influences patients' HRQoL, providing critical insights for evaluating treatment effectiveness in schizophrenia cases. While discrepancies exist between patient and caregiver assessments, these interactions are particularly impactful in subjective domains like pain/discomfort and anxiety/depression, but not for other domains that are visible.</p> Nugraha A. Prasetiyo, Elly Wahyudin, Iman Setiawan, Mayamariska Sanusi, Fredrick D. Purba, Bustanul Arifin, Sylmina D. Alkaff Copyright (c) 2025 Nugraha A. Prasetiyo, Elly Wahyudin, Iman Setiawan, Mayamariska Sanusi, Fredrick D. Purba, Bustanul Arifin, Sylmina D. Alkaff https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1314 Mon, 28 Apr 2025 00:00:00 +0700 Developing a maturity-level model for interprofessional collaboration in elective surgery preparation https://narraj.org/main/article/view/2213 <p class="Abstract-Narra">Interprofessional collaboration plays a crucial role in the preparation for elective surgeries to enhance the quality, safety, and efficiency of patient care. However, its implementation continues to encounter substantial obstacles, which require the creation of a customized maturity model to effectively resolve these concerns. The aim of this study was to develop an interprofessional collaboration maturity model that is specifically designed for the context of elective surgery preparation. This qualitative study employed a case study approach, conducted in 2024. This maturity model was developed through four stages: (1) a literature study to identify key interprofessional collaboration indicators in surgery; (2) in-depth interviews with ten healthcare professionals at Universitas Muhammadiyah Malang Hospital, Malang, Indonesia; (3) adaptation of existing maturity models (Fleming, Hudson, collaboration maturity model, and quality management system) as a framework for synthesizing data from the findings of stage 2 (in-depth interviews); and (4) expert panel review to evaluate the maturity model. We successfully developed an interprofessional collaboration maturity model specifically applied to elective surgery preparation, Preoperative Interprofessional Collaboration Maturity Model (P-ICMM), consisting of five maturity levels: emerging, developing, coordinated, integrated, and optimized. Each level’s assessment criteria are based on indicators of interprofessional collaboration. This maturity model has been evaluated by the experts in elective surgery preparation to ensure its validity and applicability. This maturity model is expected to help hospitals identify the level of interprofessional collaboration, design strategies to enhance collaboration, and ultimately improve the quality of healthcare services and patient safety in the preparation for elective surgeries.</p> Else Agustina, Respati S. Dradjat, Viera Wardhani, Kuswantoro R. Putra Copyright (c) 2025 Else Agustina, Respati S. Dradjat, Viera Wardhani, Kuswantoro R. Putra https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2213 Mon, 21 Apr 2025 00:00:00 +0700 Healing the healers: Unlocking psychological well-being through meaningful work and quality of work life https://narraj.org/main/article/view/2152 <p>Healthcare workers in developing countries, such as Indonesia, experience significant psychological stress due to heavy workloads, limited resources, and systemic inefficiencies, all of which negatively impact their psychological well-being (PWB). The aim of this study was to investigate the direct and indirect effects of quality of work life (QWL) on PWB, with meaningful work (MW) as a mediating variable. A cross-sectional survey was conducted with 285 healthcare professionals from various healthcare facilities, including specialists, general practitioners, and nurses. Data were collected using validated scales to assess QWL, MW, and PWB. Pearson correlation analysis was employed to examine relationships among variables, while mediation analysis tested direct and indirect effects. The results indicate that QWL positively influences PWB both directly (β=0.22, <em>p</em>&lt;0.001) and indirectly through MW (β=0.13, <em>p</em>&lt;0.001). Furthermore, MW was found to be a strong mediator (β=0.61, <em>p</em>&lt;0.001), underscoring its critical role in enhancing purpose and resilience. Specialists reported the highest QWL and PWB, whereas nurses exhibited the lowest levels, highlighting occupational disparities. These findings suggest that enhancing the QWL and fostering MW can significantly improve healthcare professionals' PWB. Accordingly, organizations should prioritize strategies that promote MW and improve work-life conditions to support mental well-being and job satisfaction.</p> Eka D. Aprilia, Muhammad Adam, Zulkarnain Zulkarnain, Marty Mawarpury Copyright (c) 2025 Eka D. Aprilia, Muhammad Adam, Zulkarnain Zulkarnain, Marty Mawarpury https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2152 Wed, 14 May 2025 00:00:00 +0700 Zero-fluoroscopy versus fluoroscopy-guided catheter ablation in ventricular arrhythmia: A systematic review and meta-analysis https://narraj.org/main/article/view/2094 <p>Catheter ablation has been the go-to treatment for ventricular arrhythmia, with traditional fluoroscopy-guided and non-zero fluoroscopy (NZF) catheter ablation posing high radiation risk for operators and patients. Zero-fluoroscopy technique offers elimination of radiation risk; however, its efficacy and safety in ventricular arrhythmia patients are not well explored. The aim of this study was to systematically evaluate the effectiveness, safety, and feasibility of zero-fluoroscopy ablation on ventricular arrhythmia patients. This study only included relevant studies comparing zero-fluoroscopy and NZF in ventricular arrhythmia ablation that were identified from Scopus, PubMed, and ScienceDirect (up to June 20, 2024). The quality of the study was assessed using the ROBINS-I tool, and the meta-analysis was conducted using a random-effect model. Out of 383 studies found, nine cohort studies were included with 1.408 patients. There was no significant difference in the acute procedural success rate of the zero-fluoroscopy and NZF (relative risk: 1.01; 95%CI: 0.95–1.07; p=0.69), with a similar recurrence rate (p=0.88; for four studies; n=374), and comparable procedural time (mean difference: -19.22 minutes; 95%CI: -41.16–2.72; p=0.09). Adverse events such as pericardial effusion, pseudoaneurysm, and hematoma were similar between zero-fluoroscopy and NZF. Overall, zero-fluoroscopy catheter ablation has demonstrated non-inferiority as a treatment option for ventricular arrhythmia ablation. As zero-fluoroscopy eliminates radiation risk without compromising procedural efficacy, zero-fluoroscopy has the potential to become a widely adopted approach for catheter ablation in ventricular arrhythmia.</p> Irnizarifka Irnizarifka, Christopher D. Tristan, Matthew A. Wijayanto, Risalina Myrtha, Kyra Modesty, Annisa A. Rahma, Enrico A. Budiono, Awalil R. K. Rahman, Muhammad Farid Hamka, Muhana F. Ilyas Copyright (c) 2025 Irnizarifka Irnizarifka, Christopher D. Tristan, Matthew A. Wijayanto, Risalina Myrtha, Kyra Modesty, Annisa A. Rahma, Enrico A. Budiono, Awalil R. K. Rahman, Muhammad Farid Hamka, Muhana F. Ilyas https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2094 Thu, 24 Apr 2025 00:00:00 +0700 Probiotic Lactobacillus sp. as a strategy for modulation of non-comorbid obesity: A systematic meta-analysis and GRADE assessment of randomized controlled trials https://narraj.org/main/article/view/1562 <p class="Abstract-Narra">Given the high prevalence of obesity worldwide, effective therapeutic strategies are crucial to prevent and manage obesity-related health conditions. Existing studies indicate that <em>Lactobacillus</em> sp. showed beneficial effects on body weight and adiposity by modifying the gut microbiota; however, no meta-analysis has been conducted assessing the efficacy of <em>Lactobacillus</em> sp-based probiotics on anthropometric parameters, leptin and adiponectin levels, and gut microbiota composition. The aim of this study was to evaluate the efficacy and safety of probiotic supplementation with <em>Lactobacillus </em>sp. in obese individuals without comorbidities. A systematic search was conducted on November 28, 2024, using five databases: PubMed, Wiley, ScienceDirect, Epistemonikos, and Cochrane. Primary outcomes included changes in body mass index (BMI), body weight, waist and hip circumferences, visceral and subcutaneous fat areas, and total body fat content. Secondary outcomes included alterations in leptin and adiponectin levels, gut microbiota composition, and the incidence of adverse events. A total of 1,058 individuals were included across 12 clinical trials. Significant reductions were observed in BMI (mean difference (MD): -0.40 kg/m²; 95%CI: -0.48–(-0.32), <em>p</em>&lt;0.00001), body weight (MD: -1.16 kg; 95%CI: -1.79–(-0.53), <em>p</em>=0.0003), waist circumference (MD: -1.41 cm; 95%CI: -1.75–(-1.08), <em>p</em>&lt;0.00001), and hip circumference (MD: -0.85 cm; 95%CI: -1.09–(-0.61), <em>p</em>&lt;0.00001) compared to controls. Additionally, compared to control group, significant reductions were observed in visceral and subcutaneous fat mass (MD: -7.35; 95%CI: -9.95–(-4.75); <em>p</em>&lt;0.00001) and overall body fat (MD: -1.11; 95%CI: -1.31–(-0.91); <em>p</em>&lt;0.00001). Leptin levels significantly decreased (MD: -2.11 μg/mL; 95%CI: -3.59–(-0.64), <em>p</em>=0.005) compared to before <em>Lactobacillus </em>sp. supplementation, while adiponectin levels increased (MD: 0.71 μg/mL; 95%CI: 0.22–1.20, <em>p</em>=0.004) following <em>Lactobacillus</em> sp. supplementation compared to placebo group. No significant adverse events were reported in either the intervention or control groups. In conclusion, <em>Lactobacillus</em> sp. probiotic supplementation may serve as an adjuvant therapy to enhance obesity management in non-comorbid obese individuals.</p> Juan AJMN. Lele, Karlos B. Sihaloho, Dewa Vighneswara, Derren DCH. Rampengan , Chrisandi Y. Rizqiansyah, Happy K. Permatasari, Nelly Mayulu, Trina E. Tallei, Nurpudji A. Taslim, Bonglee Kim, Immanuelle Kezia, Fahrul Nurkolis, Rony A. Syahputra Copyright (c) 2025 Juan AJMN. Lele, Karlos B. Sihaloho, Dewa Vighneswara, Derren DCH. Rampengan , Chrisandi Y. Rizqiansyah, Happy K. Permatasari, Nelly Mayulu, Trina E. Tallei, Nurpudji A. Taslim, Bonglee Kim, Immanuelle Kezia, Fahrul Nurkolis, Rony A. Syahputra https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1562 Wed, 23 Apr 2025 00:00:00 +0700 Outcomes of first-generation versus second-generation drug-eluting stents in calcified coronary lesions: A meta-analysis https://narraj.org/main/article/view/2100 <p>The choice between first-generation drug-eluting stents (DES) and second-generation DES in managing calcified coronary lesions remains a topic of debate. The aim of this study was to compare outcomes between first-generation DES and second-generation DES in patients with calcified coronary lesions. This meta-analysis study was conducted from October to November 2024. The databases used were Embase, Scopus, and PubMed. Relevant articles were collated, and data regarding outcomes in patients with calcified coronary lesions treated with first-generation and second-generation DES were included to calculate the pooled effect size. The statistical analysis was performed using the Mantel-Haenszel method. Six articles were included in the study. The results indicated that calcified coronary lesions treated with first-generation DES were associated with increased risks of all-cause mortality (Odd ratios (OR): 1.23; 95% confidence interval (95%CI): 1.05–1.45; <em>p</em>-Egger= 0.9346; <em>p-</em>Heterogeneity: 0.9720; <em>p=</em>0.0120), myocardial infarction (OR: 1.48; 95%CI: 1.22–1.80; <em>p</em>-Egger: 0.6472; <em>p</em>-Heterogeneity: 0.5890; <em>p</em>&lt;0.0001); and target lesion revascularization (TLR) (OR: 1.47; 95%CI: 1.24–1.74; <em>p-</em>Egger: 0.9982; <em>p-</em>Heterogeneity: 0.5950; <em>p</em>&lt;0.0001), in comparison with second-generation DES. In contrast, when comparing first- and second-generation DES in terms of cardiac death and major adverse cardiovascular events, a similar risk was depicted. This study compared the outcomes of first-generation and second-generation DES in the management of patients with calcified coronary lesions, which may serve as a reference for selecting DES in the patient population.</p> Mohammad S. Rohman, Jonny K. Fajar, Melly C. Widyaningsih, Yusnia N. Aziizah, Uswatun A. Khasanah, Farid EB. Nendro, Euphrasiane G. Beting, Vini S. Tanaem, Desi Jannati, Wanda M. Putri, Fredo Tamara Copyright (c) 2025 Mohammad S. Rohman, Jonny K. Fajar, Melly C. Widyaningsih, Yusnia N. Aziizah, Uswatun A. Khasanah, Farid EB. Nendro, Euphrasiane G. Beting, Vini S. Tanaem, Desi Jannati, Wanda M. Putri, Fredo Tamara https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2100 Mon, 02 Jun 2025 00:00:00 +0700 Key contents of health education and their impact on improving medication adherence among hypertensive patients: A systematic review and meta-analysis https://narraj.org/main/article/view/2080 <p>Hypertension is a global health issue with significant effects on morbidity and mortality, and medication adherence is crucial for effective management. Despite its importance, adherence remains low among hypertensive patients. Health education has been shown to improve medication adherence, though its effectiveness varies across studies. The aim of this study was to systematically synthesize evidence on the impact of health education in enhancing medication adherence among hypertensive patients. This study followed preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and employed the population, intervention, control, and outcome (PICO) approach to develop keywords for a search across five databases: Emerald, ProQuest, PubMed, ScienceDirect, and Scopus. All randomized control trials published between 2019 and 2024 in English, evaluating health education's impact on medication adherence in hypertensive patients aged ≥18 years were included. The protocol was registered on PROSPERO (CRD42024532890), and study quality was assessed using the CEBMa scale. Twelve high-quality articles (CEBMa score of ≥7) involving 1,827 participants were included, identifying four key themes in health education for hypertension: an overview of hypertension and complications, medication and side-effect management, healthy lifestyle modification, and medication adherence strategies. Health education significantly improved medication adherence by 33% (risk ratio (RR): 1.33; 95%CI: 1.08–1.64; <em>p</em>=0.008), with a medium-large effect on improving medication adherence (<em>d</em>=0.70; 95%CI: 0.34–1.05; <em>p</em>&lt;0.0001) and a small-medium effect on reducing non-adherence (<em>d</em>=-0.45; 95%CI: -0.66–(-0.24); <em>p</em>&lt;0.0001). Health education delivered 1 to 3 months and with individualized approaches showed better adherence outcomes compared to more than three months and group-based methods. Face-to-face education was more effective than the digital method. In conclusion, health education improves medication adherence in hypertensive patients when delivered comprehensively over 1–3 months through individualized face-to-face sessions. These findings support its integration as a key strategy in hypertension management to enhance adherence.</p> Mustara Mustara, Hartono Hartono, Eti P. Pamungkasari Copyright (c) 2025 Mustara Mustara, Hartono Hartono, Eti P. Pamungkasari https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2080 Mon, 21 Apr 2025 00:00:00 +0700 Impact of vitamin D supplementation on post-stroke rehabilitation outcomes: A systematic review and meta-analysis https://narraj.org/main/article/view/1848 <p>Each year, there are approximately 12.2 million new stroke cases and 6.5 million stroke-related deaths, with low- and middle-income countries shouldering a disproportionately high financial burden. Studies have associated vitamin D deficiency with arteriosclerosis, left ventricular hypertrophy, and vascular dysfunction, contributing to an elevated risk of stroke. The aim of this study was to evaluate how vitamin D supplementation affects post-stroke outcomes. A comprehensive literature search was performed across PubMed, Scopus, the Cochrane Library, ScienceDirect, Springer Link, ProQuest, and Epistemonikos from April to May 2024. This study focused on comparing the efficacy of vitamin D supplementation versus no supplementation in stroke patients of all ages. Outcome measures included the Functional Ambulation Classification (FAC), Brunnstrom Recovery Stage (BRS), Modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS). Case reports, reviews, and research on other cardiovascular or metabolic issues were excluded. Five authors extracted data and analyzed bias separately using the Risk of Bias Version 2 (RoB V2) algorithms. The results of continuous variables were pooled into the mean difference (MD) along with 95% confidence intervals (CI) using random-effect models. Review Manager 5.4 was used to evaluate the data. Out of the 1,152,449 papers evaluated, six met the inclusion criteria, with a sample size ranging from 42 to 123 patients. Vitamin D supplementation was found to yield better outcomes after stroke. BRS in lower extremities showed better results (MD: 0.59 (95%CI: 0.27–0.91)), NIHSS improved with an MD of -1.47 (95%CI: -2.03–(-0.90)). Furthermore, there was also an improvement in mRS, with an MD of -0.91 (95%CI: -1.25–(-0.56)). In conclusion, vitamin D improved post-stroke outcomes, which supported its supplementation as a part of stroke rehabilitation.</p> Etisa A. Murbawani, Dodik T. Pramukarso, Siti F. Muis, Dwi Pudjonarko, Hertanto W. Subagio, Kevin C. Tjandra, Danendra RP. Respati, Laksmana AK. Nugraha, Ghifarie A. Ramadhany, Stephano Pranoto Copyright (c) 2025 Etisa A. Murbawani, Dodik T. Pramukarso, Siti F. Muis, Dwi Pudjonarko, Hertanto W. Subagio, Kevin C. Tjandra, Danendra RP. Respati, Laksmana AK. Nugraha, Ghifarie A. Ramadhany, Stephano Pranoto https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1848 Mon, 28 Apr 2025 00:00:00 +0700 Comparative efficacy of solifenacin and tamsulosin in alleviating stent-related symptoms: A systematic review and meta-analysis https://narraj.org/main/article/view/1683 <p>Ureteral stents, commonly used in urology, can cause side effects affecting patient quality of life. However, studies on managing lower urinary tract symptoms showed inconsistencies due to the use of various alpha-blockers and antimuscarinic drugs. The aim of this study was to evaluate the effectiveness of combining tamsulosin and solifenacin therapy compared to tamsulosin and solifenacin monotherapy for treating stent-related symptoms. Randomized controlled trials assessing tamsulosin, solifenacin, or their combination for stent-related symptoms treatment were identified through a comprehensive search of four databases (PubMed, Scopus, Web of Science, and Cochrane) from January 2018 to December 2023. Ureteral stent symptom questionnaire (USSQ), international prostate symptom score (IPSS), visual analog scale (VAS), and quality of life (QoL) were pooled for meta-analysis. Eleven studies with a total of 1,627 patients were included in the quantitative analysis. Solifenacin significantly improved urinary symptoms (MD: 15.31; 95%CI: 0.36–30.26; <em>p</em>=0.040) and reduced the IPSS (MD: -2.52; 95%CI: -3.68–-1.36; <em>p</em>&lt;0.00001) compared to the control group. Tamsulosin reduced urinary symptoms on the USSQ (MD: 14.27; 95%CI: 8.68–19.86; <em>p</em>&lt;0.00001), general health problems (MD: 4.53; 95%CI: 2.13­–6.94; <em>p</em>=0.0002), and IPSS (MD: -0.95; 95%CI: -1.86–-0.03; <em>p</em>&lt;0.00001) compared to the control group. Solifenacin demonstrated a more significant reduction in the overall IPSS compared to tamsulosin (MD: -1.57; 95%CI: -2.85–-0.29; <em>p</em>=0.020). The combination of solifenacin and tamsulosin resulted in a significantly superior reduction in IPSS compared to solifenacin monotherapies (MD: -2.30; 95%CI: -3.23–-1.37; <em>p</em>&lt;0.00001) and tamsulosin monotherapy (MD -3.17; 95%CI: -5.07­–-1.27; <em>p</em>=0.00001). No significant differences were found between tamsulosin and solifenacin in terms of QoL (MD: 0.12; 95%CI: -0.01–0.26; <em>p</em>=0.070) and VAS (MD: 0.25; 95%CI: -0.95–1.44; <em>p</em>=0.690). In conclusion, solifenacin was more effective than tamsulosin in reducing stent-related symptoms, and the combination of tamsulosin and solifenacin was superior to either monotherapy in alleviating stent-related symptoms.</p> Dianita H. Harahap, Kharisma P. Adhyatma, Elbert Elbert, Felix Khosasi, Muhammad H. Warli Copyright (c) 2025 Dianita H. Harahap, Kharisma P. Adhyatma, Elbert Elbert, Felix Khosasi, Muhammad H. Warli https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1683 Mon, 21 Apr 2025 00:00:00 +0700 Associations between plasma beta amyloid and cognitive decline: A systematic review and meta-analysis https://narraj.org/main/article/view/2268 <p>Alzheimer’s disease is a leading neurodegenerative disorder characterized by progressive cognitive decline. Early prediction is crucial for enabling timely interventions. Plasma amyloid β-peptides (Aβ), particularly the Aβ-42/Aβ-40 ratio, have been proposed as potential non-invasive biomarkers for cognitive decline and Alzheimer’s disease risk. However, conflicting findings and methodological variability have hindered consensus regarding their clinical utility. The aim of this study was to evaluate whether the plasma Aβ levels predict dementia, Alzheimer’s disease, and cognitive decline. Studies were eligible for inclusion if they measured at least one plasma Aβ species (Aβ-40, Aβ-42, or the Aβ-42/Aβ-40 ratio) and reported outcomes related to dementia, Alzheimer’s disease, or cognitive change. Only human studies published in peer-reviewed journals were included. A comprehensive search of six databases (PubMed, PMC, SSRN, Scopus, BioRxiv, and MedRxiv) was conducted up to December 1, 2024. Risk of bias was assessed using the ROBINS-E tool, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects meta-analysis. A total of 25 studies were included in the systematic review, with four contributing to the meta-analysis. Lower plasma Aβ-42/Aβ-40 ratio was not significantly associated with Alzheimer’s disease risk (pooled HR=0.8; 95%CI: 0.62–1.04), and substantial heterogeneity was observed (<em>I²</em>=70%, <em>p</em>=0.02). Individual studies varied in their findings: while some reported that lower Aβ-42/Aβ-40 ratio predicted increased Alzheimer’s disease risk, others found no association or even opposing trends. Methodological heterogeneity—including differences in sample handling, measurement techniques, and study designs—likely contributed to these inconsistencies. Overall, this review suggests that plasma Aβ-42/Aβ-40 ratio is not reliable predictors for the onset of Alzheimer’s disease or dementia. However, the substantial heterogeneity observed underscores the need for further research to clarify the potential of plasma Aβ as a preclinical biomarker.</p> Cynthia Cynthia, Jusak Nugraha, Muhammad Hamdan, Rahajuningsih Dharma, Silvia F. Lumempouw Copyright (c) 2025 Cynthia Cynthia, Jusak Nugraha, Muhammad Hamdan, Rahajuningsih Dharma, Silvia F. Lumempouw https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2268 Tue, 13 May 2025 00:00:00 +0700 Effectiveness of digital health in improving pregnancy quality among preconception women: A systematic review https://narraj.org/main/article/view/993 <p>Improving nutrition in women prior to conception represents an alternative approach to enhancing the quality of pregnancy. Increased knowledge and self-efficacy among preconception women positively impact changes in health behavior. The rapid development of technology provides an opportunity to implement innovative interventions, including digital health. The aim of this study was to systematically review the efficacy of digital health interventions in modifying the behavior of preconception women. The data were obtained by searching relevant articles published from 2015 to 2023 in electronic databases, including Google Scholar, Science Direct, Web of Science (WoS), Biomed Central, and PubMed. The following keywords were used: "digital health" OR "mobile health" OR "e-health" AND "preconception women" OR "pre-marriage women." Of the 266 studies identified in the search phase, only those that met the inclusion criteria were included in the review. These criteria included 10 articles that assessed the effectiveness of digital health interventions on the behavior change of preconception women. The articles included in this study originated from diverse countries and addressed various digital health interventions. The findings of the review indicated that ten articles reported an increase in pregnant women's knowledge, nine articles demonstrated an enhancement in self-efficacy, and nine articles documented behavioral changes. The behavioral changes observed included the initiation of folic acid consumption before pregnancy, an increase in vegetable and fruit consumption, and a reduction in unhealthy dietary behaviors, such as maintaining a normal weight, smoking cessation, and reduced alcohol consumption. In conclusion, digital health literacy interventions, delivered via web-based platforms or mobile applications, demonstrate effectiveness in promoting positive preconception health behaviors among women, ultimately contributing to improved pregnancy outcomes.</p> Nurleli Nurleli, Veni Hadju, Rahayu Indriasari, Intan S. Areni, Masni Masni, Shanti Riskyani Copyright (c) 2025 Nurleli Nurleli, Veni Hadju, Rahayu Indriasari, Intan S. Areni, Masni Masni, Shanti Riskyani https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/993 Mon, 28 Apr 2025 00:00:00 +0700 Determinants of safety performance in healthcare settings: A meta-analysis https://narraj.org/main/article/view/1654 <p>Safety performance among healthcare workers is an important issue, and currently, the factors related to it remain unclear. The aim of this study was to identify the factors related to safety performance among the healthcare worker population. This meta-analysis study was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Data on the factors affecting safety performance in the healthcare population were collected from each article to determine pooled point estimates. Data heterogeneity was evaluated using the Q statistic. Numerical data were analyzed using the inverse variance test, and the Mantel-Haenszel test was used for categorical data analysis. Pooled point estimates were presented as mean difference (MD) or odds ratio (OR) along with a 95% confidence interval (95%CI). Fifty articles were included in this study. Our results showed that nurses had lower safety performance compared to other professions (OR: 0.66; 95%CI: 0.56–0.79; <em>p</em>-Egger: 0.3739; <em>p</em>-Heterogeneity &lt;0.0001; <em>p</em>&lt;0.0001). On the other hand, it was also identified that housekeepers were associated with better safety performance compared to other professions (OR: 1.90; 95%CI: 1.08–3.35; <em>p</em>-Egger: 0.1577; <em>p</em>-Heterogeneity: 0.0950; <em>p</em>=0.0220). Furthermore, our findings revealed that healthcare workers who had undergone work safety training had better safety performance compared to those who had not (OR: 1.40; 95%CI: 1.01–1.95; <em>p</em>-Egger: 0.6124; <em>p</em>-Heterogeneity &lt;0.0001; <em>p</em>=0.0430). In conclusion, this study has identified the factors contributing to safety performance in the healthcare population. These findings can inform policymakers in developing regulatory improvements regarding safety performance in healthcare workers.</p> Septyani Prihatiningsih, Tri Martiana, Noeroel Widajati, Jonny K. Fajar Copyright (c) 2025 Septyani Prihatiningsih, Tri Martiana, Noeroel Widajati, Jonny K. Fajar https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1654 Mon, 12 May 2025 00:00:00 +0700 Customized feeding plate for nutritional and respiratory support in an infant with Pierre Robin sequence and cleft palate complicated by severe respiratory infections: A case report https://narraj.org/main/article/view/2175 <p>Pierre Robin sequence (PRS) is a congenital condition characterized by micrognathia, glossoptosis, and airway obstruction, often accompanied by cleft palate. Feeding difficulties and respiratory compromise pose significant challenges in early management. While feeding plates are commonly used to improve feeding and airway stability, their application in infants with severe respiratory infections remains underreported. The aim of this study was to describe the challenges of impression-taking and feeding plate fabrication in an infant with PRS complicated by multiple congenital anomalies and severe respiratory complications, including bilateral pneumonia. A 23-day-old male infant was referred to the pediatric dentistry department of Pandega General Hospital, Pangandaran, Indonesia, with the chief complaints of feeding difficulties, recurrent choking episodes, and respiratory distress. The patient was diagnosed with PRS with a cleft palate, complicated by congenital tuberculosis and bilateral pneumonia, exacerbating respiratory compromise. Given the patient's fragile condition, impression-taking was performed with strict airway precautions, including lateral positioning, continuous oxygen monitoring, and suction readiness. High-viscosity alginate and a perforated stock tray were used to minimize aspiration risk. Two clinicians ensured airway security throughout the procedure. A customized acrylic feeding plate was fabricated with a palatal extension to prevent nasal regurgitation and a contoured surface to aid tongue positioning. The plate was polished for comfort, adjusted for retention, and fitted to accommodate maxillary growth, ensuring safe and effective feeding support. Within one month, the infant’s weight increased from 2,200 g to 3,100 g, choking episodes significantly decreased, and a transition from orogastric tube to bottle feeding was achieved. In conclusion, this case highlights the feasibility and benefits of feeding plate adaptation in PRS management, even in the presence of severe respiratory infections. A non-invasive approach using a feeding plate can serve as an initial intervention before surgical correction, particularly in fragile neonates.</p> Claudia NR. Jayanti, Evelyn Anugerah, Willyanti Soewondo, Asep K. Pasha, Galuhafiar Puratmaja Copyright (c) 2025 Claudia NR. Jayanti, Evelyn Anugerah, Willyanti Soewondo, Asep K. Pasha, Galuhafiar Puratmaja https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/2175 Mon, 28 Apr 2025 00:00:00 +0700 Challenges in maritime evacuation during pre-hospital emergency anesthesia on a remote island in Indonesia: A case report https://narraj.org/main/article/view/1643 <p>Preeclampsia and eclampsia remain significant contributors to maternal and perinatal mortality. Managing these conditions is particularly challenging in remote areas in many islands of Indonesia, where access to medical care is severely limited. The aim of this study was to analyze the pre-hospital anesthetic management of an eclampsia patient during maritime evacuation to a higher-level facility, highlighting the complexities of medical transport in resource-limited settings. A 38-year-old multiparous woman from a remote village on Pagerungan Island, Indonesia, at 37 weeks of gestation, presented with tonic-clonic seizures consistent with eclampsia. The absence of antenatal care necessitated urgent intervention. Upon presentation, the patient had a Glasgow Coma Scale (GCS) score of 5, tachycardia, and irregular breathing, requiring rapid-sequence intubation and magnesium sulfate administration. Given the geographic constraints, the patient was evacuated by sea under challenging conditions. Despite significant waves, a multidisciplinary team successfully performed an emergency cesarean section onboard, delivering a male infant who required neonatal resuscitation. Postoperatively, both mother and neonate were transferred to a higher-level facility. However, engine failure extended the journey to 18 hours, leading to depletion of oxygen and essential medications, necessitating critical decision-making. This case underscores the significant challenges of emergency eclampsia management in remote settings, particularly during maritime evacuation. Effective stabilization, anesthesia, monitoring, and timely transport are crucial. This case highlights the need for optimized evacuation protocols and increased healthcare resource allocation to enhance maternal and neonatal outcomes in maritime and other resource-limited settings.</p> Airi Mutiar, Kun Arifi Abbas Copyright (c) 2025 Airi Mutiar, Kun Arifi Abbas https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1643 Mon, 21 Apr 2025 00:00:00 +0700 Tackling the ST elevation in leptospirosis: A double-edged sword between bleeding and thrombosis – A case report https://narraj.org/main/article/view/1978 <p>Although leptospirosis is a well-recognized zoonotic disease, the occurrence of ST-segment-elevation myocardial infarction (STEMI)-mimicking leptospiral myocarditis, accompanied by subsequent bleeding and thrombocytopenia is an exceptionally rare finding. The dual risks of bleeding and thrombosis further complicate the management of anticoagulation and thrombolytic therapy amidst competing risks. The aim of this study was to present leptospirosis complicated by myocarditis, which mimicked STEMI, followed by bleeding and thrombocytopenia. A 61-year-old male patient was referred from a community health center to the hospital with primary complaints of chest discomfort and diaphoresis, which had started 11 hours prior to admission. These symptoms were associated with a 12-day history of intermittent fever, nausea, and vomiting. Upon physical examination, the patient appeared lethargic, with a blood pressure of 86/63 mmHg, heart rate of 107 bpm, respiratory rate of 22 breaths per minute, and temperature of 39.8°C. Electrocardiography revealed widespread ST-segment elevation. Echocardiography showed global hypokinesia with a reduced ejection fraction of 48%. Laboratory tests confirmed the presence of IgM and IgG anti-<em>Leptospira</em> antibodies, along with elevated high-sensitivity cardiac troponin levels. The patient was diagnosed with Weil's disease (Faine's score 32), with leptospiral myocarditis and STEMI considered as differential diagnoses. Initial management involved a loading dose of dual antiplatelet therapy (aspirin 320 mg and clopidogrel 300 mg) due to the suspected diagnosis of STEMI. However, it was later discontinued on the second day of admission due to the development of severe thrombocytopenia and minor bleeding manifestations. Following the administration of ceftriaxone 2 g every 12 hours and doxycycline 100 mg every 12 hours, the patient's condition improved. This case highlights the importance of recognizing leptospirosis as a potential cause of myocarditis and thrombocytopenia, especially when clinical signs resemble those of STEMI. Early diagnosis and careful management, including the suspension of dual antiplatelet therapy and initiation of targeted antibiotic therapy, were pivotal in preventing further complications and improving the patient's outcomes.</p> Ivana P. Dewi, Kadex RS. Damayanti, Andreas M. Anggitama, Arya T. Bagaskara, Kristin P. Dewi, Teuku Yusrizal Copyright (c) 2025 Ivana P. Dewi, Kadex RS. Damayanti, Andreas M. Anggitama, Arya T. Bagaskara, Kristin P. Dewi, Teuku Yusrizal https://creativecommons.org/licenses/by-nc/4.0 https://narraj.org/main/article/view/1978 Mon, 21 Apr 2025 00:00:00 +0700