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The Role of Podocyte Cells in Diabetic Nephropathy: A Narrative Literature Review Azhari, Fauzan; Novadian; Ian Effendi; Zulkhair Ali; Suprapti; Ratna Maila Dewi Anggraini; Yulianto Kusnadi; Alwi Shahab
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 7 No. 12 (2023): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v7i12.893

The main cells affected in diabetic nephropathy are podocytes and proximal tubular cells. One of the main functional proteins in the podocyte slit diaphragm is podocin which podocytes need to express together with several specific proteins in the correct way for their differentiation, as well as to maintain their complex anatomy. Podocytes are highly specialized epithelial cells. They line the urinary surface of the glomerular capillary bundles. Podocytes are part of the filtration barrier along with capillary endothelial cells and GBM. Podocytes ensure selective permeability of the glomerular capillary walls. Podocin is a membrane protein with a molecular weight of 42kD which is located in the foot processes, and also forms part of the SD with the nephrin protein. Urinary podocin levels more specifically indicate ongoing glomerular damage because they were significantly increased in the normoalbuminuria group compared with the control group.

The Shadow of Deficiency: Vitamin D Status as a Critical Determinant of Antithyroid Drug Efficacy in Graves’ Disease – Insights from an Indonesian Cohort Ratna Maila Dewi Anggraini; Intan Fajrin Karimah; Eddy Yuristo; Yulianto Kusnadi; Erwin Sukandi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 8 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i8.1356

Background: Graves' disease (GD), an autoimmune hyperthyroid condition, presents significant management challenges, particularly concerning variable remission rates with antithyroid drugs (ATDs). Vitamin D, with its established immunomodulatory properties, is hypothesized to influence autoimmune processes, including those in GD. However, its precise impact on ATD treatment outcomes in diverse populations, especially in regions like Indonesia with high vitamin D deficiency prevalence, remains insufficiently elucidated. Methods: This retrospective cohort study was conducted at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia, analyzing data from 73 newly diagnosed adult GD patients (diagnosed January 2022 - December 2023). Patients had confirmed GD based on hyperthyroidism with orbitopathy or positive TRAb and were followed until May 2025. Baseline serum 25-hydroxyvitamin D [25(OH)D], free T4 (fT4), and TSH levels were recorded. Vitamin D deficiency (VDD) was defined as <20 ng/mL. The primary outcome was non-remission after ATD therapy, defined as failure to achieve stable euthyroidism for ≥6 months on minimal ATD doses. Multivariate Poisson regression was used to assess predictors of non-remission. Results: Of 73 patients (mean age 36.2 years; 62% female), 55 (75.3%) exhibited VDD. Multivariate analysis identified VDD as a significant independent predictor of non-remission (adjusted Relative Risk [aRR] 11.81; 95% CI 1.88–74.20; p=0.008). Elevated baseline fT4 levels (≥5 ng/dL; aRR 4.61; 95% CI 1.13–18.70; p=0.032) and older age (>48 years; aRR 0.078; 95% CI 0.06–0.95, indicating a protective effect of older age against non-remission) were also significant predictors. Conclusion: Baseline vitamin D deficiency is a potent independent risk factor for non-remission in Indonesian Graves' disease patients receiving antithyroid drug therapy. These findings underscore the potential importance of assessing and addressing vitamin D status in the management of Graves' disease to optimize therapeutic outcomes.

The Dual Role of Hypoxia-Inducible Factor-1α in Sepsis-Induced Immunomodulation and Organ Dysfunction: A Systematic Review and Meta-Analysis Hudari, Harun; Mega Permata; Ratna Maila Dewi Anggraini; Raden Ayu Linda Andriani
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1378

Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a leading cause of global mortality. Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of the cellular adaptive response to hypoxia but plays a complex, paradoxical role in sepsis. While essential for innate immune function, its sustained activation may amplify inflammation and drive organ damage. This meta-analysis was conducted to synthesize the evidence on the association of HIF-1α with key markers of immunomodulation and organ dysfunction in sepsis. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science was conducted for studies published between January 2014 and December 2024. We included observational studies that measured HIF-1α levels in adult sepsis patients and reported outcomes related to organ dysfunction (Sequential Organ Failure Assessment [SOFA] score) or mortality, and immunomodulation (Interleukin-6 [IL-6] levels). Seven studies meeting the inclusion criteria were included in the final analysis. Data were pooled using a random-effects model. Standardized Mean Difference (SMD) and Odds Ratios (OR) with 95% confidence intervals (CI) were calculated. Results: The seven included studies comprised 1,288 patients. The overall quality of the included studies was moderate to high as per the Newcastle-Ottawa Scale. The pooled analysis revealed that HIF-1α levels were significantly elevated in sepsis patients who died compared to those who survived (OR = 2.68, 95% CI: 1.55–4.64, p < 0.001), with moderate heterogeneity (I² = 45%). Furthermore, HIF-1α levels were strongly associated with greater organ dysfunction, as measured by the SOFA score (5 studies; SMD = 0.92, 95% CI: 0.51–1.33, p < 0.0001), with substantial heterogeneity (I² = 78%). HIF-1α levels also showed a significant positive correlation with the pro-inflammatory cytokine IL-6 (4 studies; SMD = 1.15, 95% CI: 0.65–1.65, p < 0.00001), with high heterogeneity (I² = 82%). Conclusion: This meta-analysis provides robust evidence that elevated HIF-1α levels are significantly associated with increased sepsis severity, characterized by greater organ dysfunction, a heightened pro-inflammatory state, and a higher risk of mortality. These findings underscore the maladaptive consequences of sustained HIF-1α activation in sepsis, positioning it as a critical prognostic biomarker and a complex, high-value target for future therapeutic modulation.

The Shadow of Deficiency: Vitamin D Status as a Critical Determinant of Antithyroid Drug Efficacy in Graves’ Disease – Insights from an Indonesian Cohort Ratna Maila Dewi Anggraini; Intan Fajrin Karimah; Eddy Yuristo; Yulianto Kusnadi; Erwin Sukandi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 8 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i8.1356

Background: Graves' disease (GD), an autoimmune hyperthyroid condition, presents significant management challenges, particularly concerning variable remission rates with antithyroid drugs (ATDs). Vitamin D, with its established immunomodulatory properties, is hypothesized to influence autoimmune processes, including those in GD. However, its precise impact on ATD treatment outcomes in diverse populations, especially in regions like Indonesia with high vitamin D deficiency prevalence, remains insufficiently elucidated. Methods: This retrospective cohort study was conducted at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia, analyzing data from 73 newly diagnosed adult GD patients (diagnosed January 2022 - December 2023). Patients had confirmed GD based on hyperthyroidism with orbitopathy or positive TRAb and were followed until May 2025. Baseline serum 25-hydroxyvitamin D [25(OH)D], free T4 (fT4), and TSH levels were recorded. Vitamin D deficiency (VDD) was defined as <20 ng/mL. The primary outcome was non-remission after ATD therapy, defined as failure to achieve stable euthyroidism for ≥6 months on minimal ATD doses. Multivariate Poisson regression was used to assess predictors of non-remission. Results: Of 73 patients (mean age 36.2 years; 62% female), 55 (75.3%) exhibited VDD. Multivariate analysis identified VDD as a significant independent predictor of non-remission (adjusted Relative Risk [aRR] 11.81; 95% CI 1.88–74.20; p=0.008). Elevated baseline fT4 levels (≥5 ng/dL; aRR 4.61; 95% CI 1.13–18.70; p=0.032) and older age (>48 years; aRR 0.078; 95% CI 0.06–0.95, indicating a protective effect of older age against non-remission) were also significant predictors. Conclusion: Baseline vitamin D deficiency is a potent independent risk factor for non-remission in Indonesian Graves' disease patients receiving antithyroid drug therapy. These findings underscore the potential importance of assessing and addressing vitamin D status in the management of Graves' disease to optimize therapeutic outcomes.

The Dual Role of Hypoxia-Inducible Factor-1α in Sepsis-Induced Immunomodulation and Organ Dysfunction: A Systematic Review and Meta-Analysis Hudari, Harun; Mega Permata; Ratna Maila Dewi Anggraini; Raden Ayu Linda Andriani
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1378

Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a leading cause of global mortality. Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of the cellular adaptive response to hypoxia but plays a complex, paradoxical role in sepsis. While essential for innate immune function, its sustained activation may amplify inflammation and drive organ damage. This meta-analysis was conducted to synthesize the evidence on the association of HIF-1α with key markers of immunomodulation and organ dysfunction in sepsis. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science was conducted for studies published between January 2014 and December 2024. We included observational studies that measured HIF-1α levels in adult sepsis patients and reported outcomes related to organ dysfunction (Sequential Organ Failure Assessment [SOFA] score) or mortality, and immunomodulation (Interleukin-6 [IL-6] levels). Seven studies meeting the inclusion criteria were included in the final analysis. Data were pooled using a random-effects model. Standardized Mean Difference (SMD) and Odds Ratios (OR) with 95% confidence intervals (CI) were calculated. Results: The seven included studies comprised 1,288 patients. The overall quality of the included studies was moderate to high as per the Newcastle-Ottawa Scale. The pooled analysis revealed that HIF-1α levels were significantly elevated in sepsis patients who died compared to those who survived (OR = 2.68, 95% CI: 1.55–4.64, p < 0.001), with moderate heterogeneity (I² = 45%). Furthermore, HIF-1α levels were strongly associated with greater organ dysfunction, as measured by the SOFA score (5 studies; SMD = 0.92, 95% CI: 0.51–1.33, p < 0.0001), with substantial heterogeneity (I² = 78%). HIF-1α levels also showed a significant positive correlation with the pro-inflammatory cytokine IL-6 (4 studies; SMD = 1.15, 95% CI: 0.65–1.65, p < 0.00001), with high heterogeneity (I² = 82%). Conclusion: This meta-analysis provides robust evidence that elevated HIF-1α levels are significantly associated with increased sepsis severity, characterized by greater organ dysfunction, a heightened pro-inflammatory state, and a higher risk of mortality. These findings underscore the maladaptive consequences of sustained HIF-1α activation in sepsis, positioning it as a critical prognostic biomarker and a complex, high-value target for future therapeutic modulation.

Efficacy and Safety of IL-5 Pathway-Targeting Biologics (Mepolizumab, Reslizumab, Benralizumab) in the Management of Hypereosinophilic Syndromes: A Systematic Review and Meta-Analysis Yuniza; Melani; Ratna Maila Dewi Anggraini; Yenny Dian Andayani
Open Access Indonesian Journal of Medical Reviews Vol. 5 No. 5 (2025): Open Access Indonesian Journal of Medical Reviews
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/oaijmr.v5i5.780

Hypereosinophilic syndromes (HES) are rare disorders defined by persistent eosinophilia and eosinophil-driven organ damage. Interleukin-5 (IL-5) is the central cytokine governing eosinophil maturation and survival, establishing its pathway as a critical therapeutic target. While individual trials of biologics targeting the IL-5 pathway—mepolizumab, reslizumab, and benralizumab—have shown promise, a quantitative synthesis of their class-wide efficacy and safety in HES is needed. This study aimed to meta-analyze the evidence for these agents in managing HES. Following PRISMA guidelines, we systematically searched PubMed, Embase, and Cochrane Library through December 2024 for randomized controlled trials (RCTs) and prospective observational studies of IL-5 pathway biologics in patients with HES. Primary outcomes were the proportion of patients achieving hematologic response and the annualized rate of clinical exacerbations. Key secondary outcomes included oral corticosteroid (OCS) dose reduction and adverse events (AEs). Data were pooled using a random-effects model, with extensive, pre-planned subgroup and sensitivity analyses to explore heterogeneity. Seven studies (3 RCTs, 4 observational) involving 388 patients were included. Patients receiving IL-5 pathway biologics had significantly higher odds of achieving hematologic response (Odds Ratio [OR] 9.85; 95% Confidence Interval [CI] 5.12-18.96; p<0.0001), a finding robust to sensitivity analyses of different response definitions. The annualized exacerbation rate was reduced by 64% (Rate Ratio 0.36; 95% CI 0.25-0.52; p<0.0001). The intervention led to a mean daily OCS reduction of 12.5 mg (95% CI -15.8 to -9.2 mg; p<0.0001). Subgroup analysis revealed this effect was more pronounced in observational studies than in RCTs. The overall risk of AEs was not significantly increased. This meta-analysis provides robust evidence that biologics targeting the IL-5 pathway are highly effective and generally safe for managing PDGFRA-negative HES. They induce high rates of hematologic remission, substantially reduce clinical exacerbations, and facilitate a significant corticosteroid-sparing effect. These findings strongly support their role as a foundational component of modern HES therapy, though long-term safety and efficacy within distinct HES subtypes warrant further investigation.

Impaired Stimulated Pancreatic β-Cell Responsiveness is a Dominant Feature of Bisphenol A-Associated Metabolic Dysfunction in Type 2 Diabetes: A Cross-Sectional Analysis of Adjusted Associations in an Indonesian Cohort Yulianto Kusnadi; Ardianto Ardianto; Ratna Maila Dewi Anggraini; Sudarto Sudarto; Imran Imran
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 10 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i10.1410

Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is a suspected contributor to the type 2 diabetes mellitus (T2DM) pandemic. This study aimed to move beyond simple correlation and investigate the adjusted association between urinary BPA and the dual pathophysiological defects of T2DM—insulin resistance and pancreatic β-cell failure—with a novel emphasis on contrasting basal versus stimulated β-cell function in an understudied Indonesian cohort. Methods: In a cross-sectional study, 40 patients with T2DM were recruited from a tertiary hospital in Palembang, Indonesia. Urinary BPA was quantified by liquid chromatography–mass spectrometry (LCMS). Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). β-cell function was evaluated using the C-peptide index (CPI) at fasting and 1-hour post-75g oral glucose tolerance test (OGTT). Multivariable linear regression models were constructed to determine the association between urinary BPA (log-transformed) and metabolic indices, adjusting for age, gender, and body mass index (BMI). Results: After adjusting for confounders, higher log-urinary BPA remained a significant independent predictor of higher log-HOMA-IR (β = 0.58, 95% CI: 0.31-0.85, p < 0.001). BPA was also independently associated with poorer β-cell function, showing a significant inverse association with the fasting CPI (β = -0.45, 95% CI: -0.73 to -0.17, p = 0.003). Critically, this association was markedly stronger and more profound with the 1-hour stimulated CPI (β = -0.79, 95% CI: -0.99 to -0.59, p < 0.001). The variance in stimulated CPI explained by the model (R2) was substantially higher than for other indices. Conclusion: Higher environmental BPA exposure is independently associated with both heightened insulin resistance and compromised β-cell function in T2DM. The distinctly stronger association with impaired stimulated β-cell secretion, even after adjusting for key confounders, identifies a critical mechanism by which BPA may accelerate functional β-cell exhaustion, the pivotal event in T2DM progression.

Impaired Stimulated Pancreatic β-Cell Responsiveness is a Dominant Feature of Bisphenol A-Associated Metabolic Dysfunction in Type 2 Diabetes: A Cross-Sectional Analysis of Adjusted Associations in an Indonesian Cohort Yulianto Kusnadi; Ardianto Ardianto; Ratna Maila Dewi Anggraini; Sudarto Sudarto; Imran Imran
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 10 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i10.1410

Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is a suspected contributor to the type 2 diabetes mellitus (T2DM) pandemic. This study aimed to move beyond simple correlation and investigate the adjusted association between urinary BPA and the dual pathophysiological defects of T2DM—insulin resistance and pancreatic β-cell failure—with a novel emphasis on contrasting basal versus stimulated β-cell function in an understudied Indonesian cohort. Methods: In a cross-sectional study, 40 patients with T2DM were recruited from a tertiary hospital in Palembang, Indonesia. Urinary BPA was quantified by liquid chromatography–mass spectrometry (LCMS). Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). β-cell function was evaluated using the C-peptide index (CPI) at fasting and 1-hour post-75g oral glucose tolerance test (OGTT). Multivariable linear regression models were constructed to determine the association between urinary BPA (log-transformed) and metabolic indices, adjusting for age, gender, and body mass index (BMI). Results: After adjusting for confounders, higher log-urinary BPA remained a significant independent predictor of higher log-HOMA-IR (β = 0.58, 95% CI: 0.31-0.85, p < 0.001). BPA was also independently associated with poorer β-cell function, showing a significant inverse association with the fasting CPI (β = -0.45, 95% CI: -0.73 to -0.17, p = 0.003). Critically, this association was markedly stronger and more profound with the 1-hour stimulated CPI (β = -0.79, 95% CI: -0.99 to -0.59, p < 0.001). The variance in stimulated CPI explained by the model (R2) was substantially higher than for other indices. Conclusion: Higher environmental BPA exposure is independently associated with both heightened insulin resistance and compromised β-cell function in T2DM. The distinctly stronger association with impaired stimulated β-cell secretion, even after adjusting for key confounders, identifies a critical mechanism by which BPA may accelerate functional β-cell exhaustion, the pivotal event in T2DM progression.

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