Narra J (Journal)
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Perindopril and losartan affect ACE-2 and IL-6 expression in obese rat model
Get PDFObesity has emerged as a worldwide health concern due to its increasing prevalence. Adipocytes have the ability to express angiotensin-converting enzyme 2 receptors (ACE2) and several adipocytokines. These expressions could lead to the activation of a cytokine storm, which in turn promotes the development of cardiovascular diseases. The aim of this study was to investigate the impact of perindopril and losartan exposure on the ACE2 and interleukin 6 (IL-6) levels in adipocyte cells. This study used an in vivo true experimental design utilizing a post-test-only control group. A total of 24 adult male albino rats were divided into four groups, one group served as the non-obese (negative control), while the other three groups were obese: (1) the positive control (untreated obese rats); (2) perindopril group (2 mg/kg BW/day orally for 4 weeks); and (3) losartan group (20 mg/kg BW/day for 4 weeks). Afterwards, the rats were euthanized, and the visceral fat tissue were obtained during dissection. The levels of ACE2 and IL-6 were measured using the enzyme-linked immunosorbent assay (ELISA). Losartan administration in obese rats resulted in a notable elevation in ACE2 levels compared to both the perindopril group (losartan vs perindopril, p=0.011) and the positive control (p=0.004). In addition, the treatment of perindopril and losartan in obese rats resulted in a significant reduction in IL-6 levels when compared to the positive control (perindopril vs positive control, p=0.020; losartan vs positive control, p=0.002, respectively). This study provides insight into the administration of perindopril and losartan, which could suppress the pro-inflammatory (IL-6) but increase the ACE2 levels in adipose tissue
Finding the new potential research on diabetic kidney disease and hemodialysis in healthcare insurance databases: A bibliometric analysis
Get PDFTo the best of our knowledge, bibliometric analysis has not been performed for studies related to diabetic kidney disease (DKD) and hemodialysis using healthcare big data. Herein, the aim of this bibliometric analysis was to identify emerging research trends in DKD and hemodialysis within healthcare insurance databases by exploring authors, co-author networks, and countries to discover new potential research areas. A bibliometric study was conducted, utilizing data obtained from the Scopus database. Keywords such as diabetic kidney disease, hemodialysis, insurance or big data, and prediction were employed. Inclusion criteria were original articles and review articles written in English published between 2010 and 2022. VOSviewer and the Bibliometrix package in R were used for comprehensive bibliometric analysis. VOSviewer facilitated keyword co-occurrence analysis to identify clusters and visualize relationships among keywords, emphasizing distinct research themes, keyword density, and network visualization. Meanwhile, Bibliometrix allowed exploration of key metrics such as prolific authors and institutions, publication trends, co-authorship networks, citations, document types, emerging trends through keyword analysis, and network visualizations, including co-authorship and keyword co-occurrence. Results from both tools were integrated for a thorough analysis. The present study yielded 2,199 articles, which was reduced to 1,828 after removing duplicates and applying inclusion criteria. This bibliometric analysis found that machine learning and artificial intelligence are emerging yet remain relatively under-researched in the context of hemodialysis and DKD. The prominence of topics such as diabetic nephropathy, non-insulin treatments, and lifestyle modifications highlighted ongoing research priorities in DKD and hemodialysis. Taiwan's dominance in publications suggested robust research activity in this field, while international collaboration underscored global interest and the potential for diverse research perspectives. The need for similar research development in Indonesia, leveraging big data and machine learning, indicates opportunities for advancing the understanding and management of DKD and hemodialysis within the region
Burden of osteoarthritis in Indonesia: A Global Burden of Disease (GBD) study 2019
Get PDFOsteoarthritis (OA) is a complex and common condition, especially affecting the knees due to their weight-bearing role. Traditionally seen as a degenerative disease, OA is now understood to have both mechanical and inflammatory causes. Despite its increasing prevalence, there is limited data on OA in Indonesia, resulting in low awareness among clinicians and the public. The aim of this study was to describe the OA burden in Indonesia, focusing on its prevalence, incidence, and years lived with disability (YLD) from 1990 to 2019, using data from the Global Burden of Disease (GBD) study 2019. A descriptive cross-sectional study was conducted to examine the prevalence, incidence, and YLD of OA in Indonesia from the GBD study 2019. OA prevalence and YLD were compared to other countries according to similar social demographics and geographical proximity. OA YLD was also compared to the top causes of death and disability YLD in Indonesia. The study found that OA cases in Indonesia more than doubled from 1990 to 2019, with increases of 153.12% in males and 143.36% in females. Similar trends were observed for knee OA. The age-standardized prevalence rate in Indonesia increased by 10.03% in males and 8.42% in females, and these were higher compared to China, India, Singapore, and the global average. Younger people had a higher OA prevalence rate growth than older groups. The incidence rate for OA also rose significantly, with males seeing a 10.89% increase to 290 per 100,000 people and females with an 8.57% increase to 384 per 100,000 people. Despite lower overall burden rates compared to some countries, Indonesia experienced significant growth in YLD due to OA (12.16% in males and 9.65% in females) since 1990. Although OA was less burdensome than stroke, diabetes, low back pain, and chronic obstructive pulmonary disease (COPD), its YLD growth rate was higher. In conclusion, OA prevalence and incidence in Indonesia significantly increased from 1990 to 2019, with a notable rise among younger populations. OA had a higher YLD growth compared to several other major diseases in Indonesia, highlighting the need for early detection and preventive measures, particularly for the younger population
Evaluation of phenolic compounds as cross-linkers to improve the qualities of halal gelatin from milkfish scales (Chanos chanos)
Get PDFGelatin is a versatile substance extensively used in medical and pharmaceutical industries for many applications, including capsule shells, X-ray film, infusion for plasma substitute, and the fabricating of artificial tissue. Fish scale gelatin is a profitable alternative source as a halal material despite its inferior quality. An addition of phenolic cross-linker may enhance the qualities of fish scale gelatin. The aim of this study was to determine the ability of phenolics to act as cross-linkers for fish scale gelatin and to identify the factors affecting this process. Gelatin production from fish scales (Chanos chanos) was carried out through basic pre-extraction and acidic pre-extraction. Thereafter, the gelatin was reacted with 10 different phenolics (phenol, pyrocatechol, resorcinol, α-naphthol, vanillin, L-tyrosine, curcumin, gallic acid, quercetin, and tannic acid). The resultant gelatins were characterized by infrared spectrum, X-ray diffraction pattern, swelling index, degree of cross-linking, viscosity, gel strength, mechanical profile, thermal profile, and water vapor permeability. Gelatin with the most favorable characteristics was further investigated for the effects of acidity (pH 4, 7, and 10) and cross-linker concentrations (2.5–10%). The findings revealed the formation of cross-linkage through shifted vibrational peaks of amide A, amide B, and amide II in the infrared spectrum. Shifted X-ray diffraction peaks in the gelatin with phenol addition also indicated the formation of cross-linkage. Significant improvement in the gelatin characteristics, such as swelling index, degree of cross-linking, viscosity, gel strength, mechanical profile, thermal profile, and water vapor permeability, could be attributed to the addition of phenolics cross-linkers. The highest improvement was observed in gelatin added with basic tannic acid 10%. Gelatin cross-linked with basic tannic acid 10% had a moisture content of 9.24±0.14%, swelling index of 323±17%, degree of cross-linking of 69.99±0.84%, viscosity of 8.48±0.23 cP, gel strength of 151.5±6.9 Bloom, melting temperature of 213.5°C, tensile strength of 7.00±0.54 N.cm-2, elongation at the break of 114.08±14.63%, elastic modulus of 58.45±8.20 N.cm-2 and water vapor permeability of 0.57±0.07 g.mm.m-2.h-1. kPa-1. The qualities of tannic acid-cross-linked gelatin films and film-forming gel increased when manufactured under basic conditions in comparison to acidic or neutral conditions. Furthermore, increasing the quantity of tannic acid to 10% improved the overall characteristics as compared to non-cross-linked gelatin. In conclusion, tannic acid has the ability to cross-link the fish gelatin, thereby enhancing its qualities
A network pharmacology approach to elucidate the anti-inflammatory and antioxidant effects of bitter leaf (Vernonia amygdalina Del.)
Get PDFThe therapeutic potential of bitter leaf (Vernonia amygdalina Del.) has been established both empirically and in various scientific investigations. However, the molecular pathways related to its possible anti-inflammatory and antioxidant properties remain unclear. Therefore, the aim of this study was to elucidate the molecular interactions between bitter leaf's bioactive compounds and cellular targets involved in these activities. The compounds in bitter leaf were identified using gas chromatography-mass spectrometry (GC-MS) analysis, and subsequently, a network pharmacology approach was employed together with molecular docking and dynamics simulations. Acetonitrile (4.5%) and dimethylamine (4.972%) were the most prevalent compounds among the 38 identified by the GC-MS analysis of bitter leaf extract. The proto-oncogene tyrosine-protein kinase (SRC) demonstrated significant connectivity within the antioxidant network, highlighting its pivotal role in facilitating inter-protein communication. It also exhibited strategic positioning in anti-inflammatory mechanisms based on closeness centrality (0.385). The enrichment analysis suggested multifaceted mechanisms of bitter leaf compounds, including transcriptional regulation and diverse cellular targeting, indicating broad antioxidant and anti-inflammatory effects. Eicosapentaenoyl ethanolamide (EPEA) displayed strong interactions with multiple proteins, including SRC (-7.17 kcal/mol) and CYP3A4 (-6.88 kcal/mol). Moreover, EPEA demonstrated to form a stable interaction with SRC during a 100 ns simulation. In conclusion, the computational simulations revealed that the hypothetical antioxidant and anti-inflammatory actions of bitter leaf compounds were achieved by specifically targeting SRC. However, confirmation using either in vitro or in vivo techniques is necessary
Role of mothers in preventing tuberculosis in children: A scoping review
Get PDFTuberculosis (TB) remains a significant global health challenge, especially for children. The aim of this scoping review was to investigate the role of mothers in preventing childhood TB transmission and highlight effective strategies and associated barriers. A systematic literature search was conducted using PubMed, Web of Science, and Scopus, covering articles up to January 17, 2024. The search included keywords like “mother,” “parents,” “care,” “prevention,” and “tuberculosis.” Eligibility criteria included peer-reviewed articles on maternal health interventions for TB prevention in children and published in English. The study selection process involved screening titles and abstracts, followed by full-text reviews by Rayyan Artificial Intelligence (AI). Eighteen studies were analyzed, revealing the crucial roles of mothers and healthcare workers in TB prevention. The results indicated that in South Africa, only 47% of eligible pregnant women underwent Mantoux testing, with lower rates in rural areas. The isoniazid preventive therapy (IPT) uptake rate was 79%, with geographical variations. Barriers included insufficient patient information, inadequate screening facilities, and healthcare providers' knowledge gaps. Parental involvement, particularly by mothers, is vital for adherence to TB preventive measures. Challenges in integrating TB case-finding with antenatal care and prevention of mother-to-child transmission (PMTCT) services included inconsistent screening and healthcare worker shortages. Enhancing health services, reducing stigma, and integrating TB prevention into existing programs are essential. In conclusion, this review underscores that effective childhood TB prevention requires a coordinated approach that incorporates the efforts of the mother and healthcare worker. Addressing barriers such as contact tracing gaps and diagnostic delays, alongside enhancing maternal health education and support, is essential for improving TB prevention and management. Targeted interventions and collaborative efforts are needed to reduce transmission and improve health outcomes, particularly in bridging rural-urban disparities
Challenges in diagnosing and treating Liddle syndrome in resource-limited settings: A case report from Indonesia
Get PDFLiddle syndrome, a rare form of monogenic hypertension, poses significant diagnostic and therapeutic challenges due to its phenotypic variability and the need for genetic testing. The rarity of the condition, coupled with the limited availability of first-line treatments such as epithelial sodium channel (ENaC) blockers, makes this case report particularly urgent and novel, highlighting alternative management strategies in resource-limited settings. The aim of this case report was to present the diagnostic challenges, therapeutic strategies, and clinical outcomes of a patient with Liddle syndrome who did not have access to ENaC blockers, emphasizing the importance of early recognition and personalized treatment. A 35-year-old female presented with resistant hypertension (190/100 mmHg) and bilateral limb weakness. Laboratory results revealed persistent hypokalemia, hypernatremia, and metabolic alkalosis. Low aldosterone levels, alongside clinical and family history, led to the diagnosis of Liddle syndrome. Genetic testing was not conducted due to resource limitations, and ENaC blockers were unavailable. The patients were managed with a combination of alternative antihypertensive agents, potassium supplementation, and a low-sodium diet. Although this approach led to modest improvements in blood pressure and motor strength, persistent hypokalemia and hypernatremia underscored the suboptimal control of the syndrome's underlying pathophysiology in the absence of ENaC blockers. This case highlights the challenges faced in resource-limited settings and the need for innovative strategies to manage rare conditions like Liddle syndrome. Liddle syndrome's diagnostic and therapeutic challenges underscore the critical importance of early recognition and access to targeted therapies. In the absence of ENaC blockers, alternative treatment strategies can provide some benefit, but they often fall short of optimal management. This case emphasizes the need for enhanced clinical awareness, improved access to genetic testing, and the development of personalized treatment approaches to achieve better patient outcomes
Exploring the promising therapeutic benefits of iodine and radioiodine in breast cancer cell lines
Get PDFIodine has an anti-proliferative effect on cancer cells; however, its effects have not been explored adequately. The aim of this study was to evaluate the therapeutic potential of iodine and radioiodine by assessing their effects on the viability of various breast cancer cell lines: MCF7, SKBR3, and MDA-MB231. The viability of cells was measured in treated cells exposed to six doses of iodine (5, 10, 20, 40, 60, 80 µM) and two doses of radioiodine (3.7×104 and 3.7×105 Bq). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and modified clonogenic assays were used to assess cell viability. Exposure to 80 µM of iodine significantly reduced the viability of all cell types. The cells were then exposed to a 50% inhibitory concentration (IC50) dose. When the cells were exposed to the IC50 dose of iodine, the MCF7 cell viability was reduced by 42.6±0.14% (IC50 dose 12.88 µM), 40.2±0.08% for SKBR3 (IC50 dose 11.03 µM) and 47.0±0.02% for MDA-MB231 (IC50 dose 14.09 µM). All cells were also exposed to 3.7×104 Bq and 3.7×105 Bq radioiodine. Both doses significantly reduced the cell viability of MCF7 and SKBR3 cells compared to the unexposed control cells (all had p<0.05), while MDA-MB231 cell viability only reduced significantly after 3.7×105 Bq of radioiodine exposure compared to the unexposed control cells (p<0.05). This study highlighted that iodine had a toxic effect on breast cancer cells, and radioiodine enhanced the toxicity to breast cancer cells. The types of cancer cells and doses of iodine and radioiodine influenced the effect. These findings suggest that iodine and radioiodine hold promise as therapeutic agents for breast cancer, similar to their established use in thyroid disease treatment. However, further in vivo studies are important to provide more evidence
GSTA1 gene polymorphisms are associated with cyclophosphamide effectiveness in lupus nephritis patients: A case-control study in Indonesia
Get PDFGlutathione-S-transferase alpha-1 (GSTA1) is an enzyme with high conjugation activity against aldophosphamide, a metabolite of cyclophosphamide and promoter polymorphisms in GSTA1 may influence the cyclophosphamide effectiveness. The aim of this study was to evaluate the effectiveness and side effects of cyclophosphamide in lupus nephritis patients, using GSTA1 variants as predictors. A case-control study was conducted at Hasan Sadikin Hospital, Bandung, Indonesia, involving 100 lupus nephritis patients from February 2023 to January 2024. The PCR-Sanger sequencing was used to genotype five selected single nucleotide polymorphisms (SNPs) in the GSTA1 promoter: -52 A>G, -69 T>C, -513 A>G, -567 G>T, and -631 G>T. The endpoint was assessed after six doses of cyclophosphamide by evaluating renal function, disease activity and side effects. Results indicated that six doses of intravenous cyclophosphamide treatment improved renal function and disease activity in the patients, as evidenced by significant changes in serum creatinine (0.79 vs 0.69 mg/dL), dipstick proteinuria (3.00 vs 1.50), creatinine clearance (98.50 vs 109.50 mL/min), and Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (M-SLEDAI-2K) score (8.61 vs 6.95). The AG genotype at -513 A>G was associated with reduced cyclophosphamide effectiveness (odds ratio (OR): 0.19; 95%CI: 0.19–0.60; p=0.019). The GT genotype at -631 G>T independently increased the progression of anemia (OR: 2.41; 95%CI: 0.26–22.12; p=0.040). This study highlights that the presence of GSTA1 variants affected cyclophosphamide effectiveness in lupus nephritis patients, with heterozygous polymorphisms at -513 (AA to AG) and -631 (TT to GT) predicting reduced effectiveness of cyclophosphamide by enhancing GSTA1 promoter activity, while anemia further exacerbated lupus nephritis disease severity. GSTA1 polymorphism was not associated with the presence of alopecia, amenorrhea, gastrointestinal disorders, and leukopenia during cyclophosphamide therapy
Efficacy of angiotensin receptor neprilysin inhibitor in hypertension management: A systematic review and meta-analysis of clinical trials
Get PDFDysregulation of renin-angiotensin-aldosterone system (RAAS) often leads to hypertension and severe cardiorenal complications. Although RAAS-targeted therapies have proven effective, it remains yet optimal in reducing cardiovascular events. The aim of this study was to evaluate the efficacy and safety of angiotensin receptor neprilysin inhibitor (ARNI) compared to control in patients with hypertension. The primary outcomes were systolic and diastolic blood pressure (BP) control, along with the incidence of adverse events. A systematic review and meta-analysis was conducted according following PRISMA guidelines. A comprehensive literature search was performed across five databases: PubMed, ScienceDirect, EBSCO, Cochrane, and ProQuest, with studies identified up until 3 October 2024. The study included nine clinical trials that met the predefined eligibility criteria: (1) randomized clinical trials; (2) adult patients diagnosed with hypertension; and (3) comparison of ARNI versus control, reporting either BP control or adverse events. Quality appraisal using RoB 2.0 revealed that eight studies had a low risk of bias, and one had a high risk of bias. The pooled analysis demonstrated that ARNI is significantly more efficacious in achieving targeted systolic BP as compared to the control group (OR: 1.80; 95%CI: 1.41-2.30; p<0.001; I²=0%), and there was no statistical difference for the efficacy on diastolic BP compared to control (OR: 0.92; 95%CI: 0.75–1.13; p=0.45; I²=75%). The incidence of adverse events was not associated with ARNI (OR: 1.07; 95%CI: 0.90–1.27; p=0.46; I²=72%). In conclusion, ARNI demonstrated a favorable outcome only in systolic BP, but in diastolic BP which could be associated with inadequate duration of observation. Further studies are warranted to assess BP-lowering effect and safety profile of ARNI in a longer observation time