The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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Resveratrol: The Multifaceted Roles and Mechanisms of Polyphenol to Improve Longevity, Immunomodulation, and Age-related Diseases
Full text linkHigh in polyphenols diet has been known to protect human against chronic metabolic diseases including cancer, diabetes, neurological and cardiovascular disorders. Resveratrol (RSV) is a natural polyphenol that presents in fruits, vegetables, and nuts. The polyphenols content of RSV possesses anti-inflammatory, antioxidant, immunomodulatory, and anticancer properties by influencing the nuclear factor-kappaB (NF-κB), p53, adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways, enzymatic antioxidants expressions, and the levels of microRNAs. Therefore, this review article will focus on the potential of RSV in improving aging and metabolic diseases, which mostly induced by low-chronic inflammation and oxidative stress. RSV is also known as calorie restriction (CR)-mimetics to activate sirtuins family which improve mitochondrial function, repair DNA and genomic stability and reduce inflammation thus become a promising substance to extend health span and longevity. RSV can be useful as a supplement to prevent aging-related diseases, with a dose range between 250–1,000 mg depending on the intended health benefit and individual factors. More clinical data is needed to determine the impact of RSV metabolites and the relationship between dose, concentration, and effect, particularly in the context of chronic illness.KEYWORDS: mesenchymal stem cell, extracellular vesicle, exosome, cancer therapy, drug deliver
Lifestyle Modifications and Nutraceutical Interventions in the Prevention and Management of Metabolic Syndrome
Full text linkAbdominal obesity, dyslipidemia, hypertension, and hyperglycemia are metabolic risk factors that are grouped together to define metabolic syndrome (MetS). It is now widely recognized that MetS is linked to a higher risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Overall, the pathophysiology of MetS initiated by the imbalance of nutrition intake and physical activity. It involves a complex interplay of insulin resistance (IR), inflammation, dysregulated adipocyte function, and genetic susceptibility, all of which contribute to the metabolic dysfunction. Lifestyle modifications play a crucial role in managing and preventing MetS. Key strategies include adopting a balanced diet like Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), or caloric restriction (CR), engaging in regular physical activity, and maintaining a healthy weight. Nutraceuticals, including polyphenols and CR-mimetic agents, improve insulin sensitivity, reduce inflammation, lower blood pressure and cholesterol levels, reducing oxidative stress, and promoting autophagy. In addition to lifestyle changes, drug therapy may be necessary for some individuals to manage specific risk factors, such as diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), calcium channel blockers, and beta blockers for hypertension; biguanides, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1(GLP-1) receptor agonists, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and thiazolidinediones for hyperglycemia; and statins for dyslipidemia. Early diagnosis, including waist circumference and blood pressure measurement, serum cholesterol and glucose testing, and intervention, is essential to effectively manage MetS and prevent the progression of associated diseases. In conclusion, understanding the risk factors and associated risks of MetS, along with the implementation of lifestyle modifications such as dietary and nutraceutical interventions including polyphenols and CR-mimetic agents, is vital for reducing the burden of this syndrome. Early diagnosis and proactive management are key to improving long-term health outcomes.KEYWORDS: metabolic syndrome, abdominal obesity, insulin resistance, diet, nutraceutical
Non-Invasive Prenatal Testing with Next Generation Sequencing Methods in Birth Defect Pregnancy: A Pilot Study
Full text linkBACKGROUND: Identification of cell-free foetal DNA (cffDNA) in maternal blood, combined with next-generation sequencing (NGS) advancement, has paved the way for non-invasive prenatal screening to detect foetal aneuploidies. However, there is limited evidence on its diagnostic accuracy when compared with gold-standard invasive tests specifically in pregnancies complicated by birth defects in Indonesia. This study was conducted to evaluate the precision of non-invasive prenatal testing (NIPT) using NGS and ultrasound findings compared with the established benchmarks of amniocentesis and neonatal karyotyping through G-banding analysis, which is an invasive procedures, in a private laboratory setting for pregnancies with birth defect.METHODS: An observational cohort study involving pregnant women with foetal birth defects in central nervous system, facial, heart, gastrointestinal tract, urinary tract abnormalities and suspected Down Syndrome was conducted. The foetal birth defects were identified in the first trimester with ultrasound screening. Venous blood was drawn from the mother for NGS-based NIPT examination. As a gold standard, amniocentesis or neonatal G-banding karyotyping was conducted.RESULTS: Using G-banding karyotyping as gold standard, the results indicated that NIPT using the NGS method and ultrasound findings achieved 100% sensitivity, 100% specificity, and 100% accuracy in detecting trisomy 13, 18, and 21, as well as foetal sex chromosome abnormalities. Additionally, a case of tetrasomy 9p was identified through G-banding karyotyping, which was associated with multiple clinical abnormalities.CONCLUSION: NIPT with NGS methods and ultrasound findings demonstrated 100% accuracy for the screening of trisomy 13, 18, and 21 in birth defect pregnancy, which is comparable with G-banding analysis as a gold standard. Therefore, this suggest that these approaches offer a safe early detection, highly accurate alternative in high risk setting, compared to invasive procedure in Indonesia where access to such testing may be limited. KEYWORDS: G-banding karyotyping, next generation sequencing, non-invasive prenatal testin
Immunomodulatory Effect of Dioscorea esculenta L. on NF-κB, TLR-4, TNF-α, and IL-10 Expressions in LPS-stimulated RAW 264.7 Mouse Macrophages
Full text linkBACKGROUND: Gene expressions of toll-like receptor 4 (TLR)-4, nuclear factor-kappaB (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 are known to have roles in the inflammatory process and affect the regulation of the immune system. A preliminary study showed that Dioscorea esculenta L. tuber has immunomodulatory activity against macrophage phagocytosis activity and lymphocyte proliferation. However, the immunomodulatory activity of aqueous extract (AE), polysaccharide fraction (PF), and non-polysaccharide fraction (NPF) of D. esculenta L. tubers on these gene expressions have not been elucidated well. Therefore, this study was performed to determine its immunomodulatory activity by utilizing RAW 264.7 cell culture induced by lipopolysaccharide (LPS).METHODS: RAW 264.7 cells were stimulated with LPS at a concentration of 1 µg/mL for 30 minutes before incubation with non-toxic concentrations of AE, PF, NPF, positive control, and inulin at 25 and 50 µg/mL. TNF-α, IL-10, TLR-4, NF-κB, and β-actin expressions were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and were normalized with β-actin as an internal control. Triplicate experiments were performed throughout this study.RESULTS: Treatment with 25 µg/mL NPF significantly decreased the expression of NF-κB, TLR-4, and TNF-α (p<0.05). In contrast, treatment of 25 and 50 µg/mL PF significantly decreased the NF-κB expression (p<0.05). Moreover, only treatment with 50 µg/mL AE exhibited a significant increase in IL-10 expression (p<0.05).CONCLUSION: Treatment with D. esculenta L. tuber stimulated macrophage RAW 264.7 cells via NF-κB, TLR-4, TNF-α, and IL-10 expressions. NPF at 25 µg/mL has stronger immunomodulatory activity in reducing the expression of genes involved in the inflammatory process that plays a role in regulating the immune system.KEYWORDS: Dioscorea esculenta L., Immunomodulator, IL-10, NF-κB, TLR-4, TNF-α, RAW 264.7 cel
Therapeutic Potential of Gut Microbiota in Hypertension: Mechanisms of Immune Modulation and Inflammation
Full text linkEmerging evidence links gut dysbiosis to numerous ailments, including hypertension and metabolic diseases. Multi-omics techniques have revealed that hypertensive individuals exhibit distinct alterations in their gut bacterial composition and metabolite profiles. The gut microbiome influences blood pressure through several mechanisms. For instance, microbiota-derived metabolites can have beneficial effects, such as those from short-chain fatty acids (SCFAs), or detrimental ones, like trimethylamine N-oxide (TMAO). These molecules modulate downstream signaling pathways via G protein-coupled receptors or direct immune cell activation. Furthermore, dysbiosis can compromise the gut epithelial barrier, leading to systemic inflammation that activates key regulatory pathways like the renin-angiotensin-aldosterone system (RAAS), the autonomic nervous system, and the immune system. Given these connections, the gut microbiome is a promising therapeutic target for hypertension. This review explores the potential of modulating the gut microbiota to manage blood pressure, focusing on the underlying mechanisms of immune modulation, inflammation, and microbial metabolites. By focusing on the 'how' rather than the 'what' of hypertension, it is identified that immune-mediated inflammation is orchestrated by the gut microbiota, as the core mechanism driving the disease. Gut dysbiosis is triggered by environmental factors like high-salt diets, perpetuates a pro-inflammatory state that undermines the efficacy of conventional antihypertensive drugs and contributes to treatment-resistant hypertension. Consequently, modulating the gut microbiota through targeted interventions, including dietary fiber, probiotics, and fecal transplantation, might represents a critical evolution in treatment. This approach moves beyond managing symptoms to directly correcting the inflammatory dysfunction at the heart of the disease, offering a powerful strategy to complement existing therapies.KEYWORDS: hypertension, inflammation, gut microbiota, metabolit
Liposome-based Nanoparticles Encapsulating Vitamin D3 Attenuate IL-6 and TNF-α in a Menopausal Mouse Model
Full text linkBACKGROUND: Vitamin D3 is an essential regulator of immune function, however its bioavailability is limited. Liposomes as nanocarriers can enhance vitamin D3 absorption and delivery, however the application of liposomal vitamin D3 in postmenopausal remains underexplored, particularly in preclinical models. Estrogen deficiency during menopause promotes immune dysregulation and elevates proinflammatory cytokines, including interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This study was conducted to evaluate the effects of liposomal vitamin D3 supplementation on serum vitamin D3, IL-6, and TNF-α levels in an ovariectomy-induced menopausal mouse model.METHODS: Mice were randomly divided into four groups comprising non-surgical control (N), ovariectomized without treatment (D−), conventional vitamin D3-treated (D+), and liposomal vitamin D3-treated (LD). Treatments were administered daily via oral gavage for two months. Serum vitamin D3, IL-6, and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA). IL-6 and TNF-α data were analyzed by ANOVA with Duncan’s post-hoc test, while vitamin D3 data were analyzed using the Brown-Forsythe test with Games-Howell post-hoc test (p<0.01).RESULTS: Ovariectomy significantly decreased vitamin D3 levels and increased IL-6 and TNF-α levels in the D− group. Conventional vitamin D3 supplementation (D+) significantly decreased serum vitamin D3 levels and slightly decreased IL-6 and TNF-α levels. Liposomal vitamin D3 (LD3) significantly increased vitamin D3 levels and decreased TNF-α, only slightly decreasing IL-6. Correlation analysis showed a negative association between serum vitamin D3 levels and both cytokines.CONCLUSION: Administration of vitamin D3 liposomes was able to increase vitamin D3 levels and suppress IL-6 and TNF-α towards normal levels. LD3 offers enhanced bioavailability and anti-inflammatory effects, making it a promising therapeutic strategy for managing menopause-associated inflammation and related systemic disorders.KEYWORDS: menopause, liposomal VD3, inflammation, IL-6, TNF-
Modified High-Fat High-Sucrose Diet Promotes Obesity and Alters Colonic Cytokines
Full text linkBACKGROUND: Western dietary patterns are often associated with increasing non-communicable diseases, including inflammatory bowel disease (IBD). In experimental models, a high-fat high-sucrose (HFHS) diet is used to mimic metabolic and inflammatory effects of such diets, however the data regarding colonic inflammation in Indonesia remain limited. Therefore, this study was conducted evaluated the impact of HFHS feeding on colonic interleukin (IL)-6, IL-10 expression, and the IL-6/IL-10 ratio.METHODS: Six weeks old male C57BL/6 mice were randomly assigned to a normal fat diet (NFD) or HFHS diet group and fed ad libitum for 8 weeks. Colonic tissues were collected, and IL-6 and IL-10 expression was analyzed by immunohistochemistry.RESULTS: HFHS-fed mice showed significant increases in body weight (increased by 22.44%, p=0.0047) and caloric intake (increased by 125.17%, p=0.0000), confirming obesity induction. Colitis was also evident, with higher histological colitis scores (p=0.0072). However, colonic IL-6 (increased by 9.12%, p=0.1236), IL-10 (increased by 1.49%, p=0.8013), and the IL-6/IL-10 ratio (increased by 7.38%, p=0.4000) showed no significant differences compared to NFD.CONCLUSION: In C57BL/6 mice, an 8-week modified HFHS diet induced obesity, increased caloric intake, and mucosal injury, but did not significantly alter colonic IL-6, IL-10, or their ratio. This suggests preserved mucosal immune homeostasis consistent with an early compensatory phase rather than overt cytokine-driven inflammation. Longer or more intensive exposure may disrupt this balance, highlighting the need for further studies to define the temporal threshold and clarify immune microbiome interactions in colitis progression.KEYWORDS: high-fat high-sucrose diet, colon inflammation, IL-6, IL-10, obesity mic
FOXO1 and FYN Expression Trends in Breast Cancer Stem Cells: An Integrative Study of Single Nucleotide Polymorphism (SNP) Array and Quantitative PCR (qPCR) Analysis
Full text linkBACKGROUND: Currently, identification of breast cancer stem cells (BCSCs) commonly relies on CD24-/CD44+ expression profiles. However, few studies have integrated genomic mutation data with experimental gene expression validation in CSC and non-CSC populations. Genotyping results of CD24-/CD44+ MDAMB-231 cells revealed 36 mutations in BCSCs compared to non-BCSCs, with upregulated FOXO1 and FYN that might represent promising candidate biomarkers for this subpopulation. Therefore, in this study, single nucleotide polymorphism (SNP) and quantitative polymerase chain reaction (qPCR) analysis were performed to assess the association between mutations and expression trends of FOXO1 and FYN in MDAMB-231 cell, as breast cancer cell model with stem-like traits and well-characterized profile.METHODS: Genomic DNA was isolated from BCSC and non-BCSC DNA from the MDAMB-231 cell line. Mutation analysis was conducted using PLINK, while gene expressions of FOXO1 and FYN were quantified by one-step SYBR Green-based qPCR, using 18s rRNA as a reference. Data was then analyzed with the Livak (2−∆∆Ct) method.RESULTS: Among 36 mutations found in BCSCs of the MDAMB-231 cell line, PTEN (rs786204914) and CHEK2 (rs587782401) were identified as pathogenic. While FOXO1 (2.989±2.817 vs. 1.072±0.388) and FYN (1.405±0.072 vs. 0.855±0.140) mRNA levels were found to be higher in CSCs compared to non-CSCs, though these differences was not statistically significant.CONCLUSION: Pathogenic mutations in CHEK2 and PTEN were detected within BCSC population, implying a potential influence on the expression of FOXO1 and FYN, though not statistically significant. These findings suggest a possible, but as yet unverified, association between gene mutations and expression patterns, emphasizing the importance of further functional studies to validate FOXO1 and FYN as biomarkers for BCSCs.KEYWORDS: breast cancer stem cells, FOXO1, FYN, PTEN, CHEK2, mutation, biomarke
Impact of GFR Stratification on Tc-99m DTPA Dose Distribution in Target and Non-Target Organs: A MIRD-Based Comparative Study in Renogram Imaging
Full text linkBACKGROUND: Renogram using Technetium-99m Diethylene Triamine Pentaacetic Acid (Tc-99m DTPA) is applied to evaluate renal perfusion, glomerular filtration rate (GFR), and urinary excretion. In patients with impaired renal function, delayed tracer elimination may increase accumulation in non-target organs such as the heart and liver, resulting in greater radiation exposure and reduced image quality. Studies examining the relationship between renal function and Tc-99m DTPA dose distribution remain limited, particularly in clinical settings in Indonesia. Therefore, in this study, an organ-level quantitative analysis of Tc-99m DTPA radiopharmaceutical dose distribution and absorbed dose using the Medical Internal Radiation Dose (MIRD) approach based on Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging was performed.METHODS: Thirty adult patients undergoing renogram were categorized into low-GFR (<60 mL/min/1.73 m²) and high-GFR (≥60 mL/min/1.73 m²) groups. Each patient received 4–5 mCi of Tc-99m DTPA intravenously. Organ activities were obtained from regions of interest (ROIs) on SPECT/CT images, and organ-level absorbed doses (mGy) were calculated using the MIRD formalism.RESULTS: In the low-GFR group, tracer retention in non-target organs increased, with absorbed doses up to twofold higher in the heart (0.0002–0.0136 mGy) and liver (0.0010–0.0178 mGy) compared to the high-GFR group. Renal absorbed doses ranged from 0.0001–0.0694 mGy, showing no significant difference between the left and right kidneys, while significant differences were observed in the heart and liver.CONCLUSION: GFR significantly affects the radiopharmaceutical dose distribution and absorbed dose of Tc-99m DTPA. Reduced renal function increases radiation exposure in non-target organs, whereas normal function results in a more localized renal dose distribution.KEYWORDS: Tc-99m DTPA, renogram, MIRD, glomerular filtration rate, absorbed dose, SPECT/CT, nuclear medicin
Renoprotective Effects of Hydroxychloroquine and Folinic Acid via ET-1 and NLRP3 Modulation in Reducing Tubular Injury in A Rabbit Model of Methanol-induced Acute Kidney Injury
Full text linkBACKGROUND: Methanol intoxication is associated with significant morbidity and mortality, particularly when acute kidney injury (AKI) developed. Emerging evidence implicates Endothelin-1 (ET-1) and Nucleotide-binding domain leucine-rich repeat-containing pyrin receptor 3 (NLRP3) inflammasome in renal injury, but their roles in methanol-induced AKI remain unclear. To date, no studies have examined whether hydroxychloroquine or folinic acid, which are known to modulate ET-1 and NLRP3 signaling, could mitigate renal injury in this setting. This study evaluated their therapeutic effects in a rabbit model of methanol-induced AKI.METHODS: The animals subjects were randomly assigned to four groups: control group receiving aquabidest, folinic acid group receiving 2 mg/kg body weight (BW) intraperitoneal folinic acid, hydroxychloroquine group receiving 30 mg/kg BW oral hydroxychloroquine phosphate, and combination group receiving both folinic acid and hydroxychloroquine at the same dosages. Histopathological evaluation of tubular injury scores and immunohistochemical analysis of ET-1 and NLRP3 expression were then conducted.RESULTS: Expressions of ET-1, NLRP3, and tubular injury scores were significantly lower in the hydroxychloroquine, folinic acid, and combination therapy groups compared to the control group (p<0.001). Expression of ET-1 was lowest in folinic acid group (59.38±0.71%), followed by combination group (62.23±1.98%) and hydroxychloroquine group (62.43±1.81%), compared to control group (72.14±1.02%). Expression of NLRP3 was lowest in combination group (58.94±1.05%), followed by folinic acid and hydroxychloroquine group, which showed equal values (60.57±1.38%), compared to control group (72.15±1.02%). Tubular injury scores were also lowest in combination group (27.07±3.16%), followed by hydroxychloroquine group (45.29±1.75%) and folinic acid group (48.38±2.49%), compared to control group (77.15±1.66%).CONCLUSION: Expression of ET-1 and NLRP3, as well as tubular injury scores, are significantly lower in all treatment groups compared to control, suggesting hydroxychloroquine and folinic acid demonstrated renoprotective effects in methanol-induced AKI, likely through modulation of ET-1 and NLRP3 pathways.KEYWORDS: methanol intoxication, acute kidney injury, hydroxychloroquine, folinic acid, endothelin-1, NLRP3 inflammasome, experimental animal models, rabbit