The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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miR-29 Family as Epigenetic Regulators of DNMTs in Prostate Cancer and Benign Prostatic Hyperplasia
Get PDFBACKGROUND: The miR-29 family (miR-29a/b/c) is recognized as a tumor suppressor, directly targeting DNA methyltransferases (DNMTs), key regulators of epigenetic gene silencing. Even though miR-29 has been implicated in tumor progression, its regulatory interaction with DNMT3A/3B, particularly in prostate cancer (PCa), has not been elucidated well. This study was conducted to explore the potential of miR-29a/b/c in targeting DNMT3A/3B in PCa and benign prostatic hyperplasia (BPH), addressing a critical gap in understanding their epigenetic role.METHODS: This study used tissue samples that were taken surgically from 30 subjects that consisted of 15 diagnosed PCa and 15 BPH patients (as the control group), aged between 18-75 years, with urinary system disorders and had a prostate specific antigen (PSA) value between 1.18 and 56.15 ng/dL. The miR-29a/b/c and DNMT3A/3B expressions were measured using quantitative real-time PCR (qRT-PCR). The variations in mean values across groups, the associations between miR-29a/b/c and DNMT3A/3B expression levels parameters, as well as the correlation between miR-29 levels and DNMT3A/3B variables were then statistically analyzed.RESULTS: The expression levels of miR-29a/b/c were significantly downregulated in the PCa subjects compared to the BPH subjects (p<0.05), and negative correlations were observed between miR-29a/b/c and DNMT3A/3B in the PCa subjects (p<0.001). In addition, a significant inverse correlation was detected only between miR-29a and DNMT3B in BPH subjects (p<0.05).CONCLUSION: The results of this study indicated that miR-29a/b/c in PCa may act as a negative regulator directly targeting DNMT3A/3B. These findings support the role of miR-29s in developing miRNA-based strategies for treating PCa.KEYWORDS: prostate cancer, benign prostatic hyperplasia, epigenetic, DNA methyltransferases-3A/3B, miR-29a/b/
Opuntia cochenillifera Cream Accelerates Incision and Burn Wound Healing in Streptozotocin-Induced Diabetic Mice by Enhancing Fibroblast
Get PDFBACKGROUND: Diabetes mellitus (DM) often leads to chronic, slow-healing wounds due to impaired tissue regeneration and sustained inflammation, which can progress to diabetic ulcers. Opuntia cochenillifera has been reported to possess antioxidant and anti-inflammatory potential, making it a promising candidate for natural wound therapies. However, standardized topical formulations and in vivo evaluations are limited. This study was conducted to develop and assess the wound-healing effects of Opuntia cochenillifera cream in diabetic mice.METHODS: Forty-eight male Balb/C mice were randomly assigned to different groups: healthy control (HC), negative control (C−), positive control (C+), and treatment (T) groups. DM was induced by a single intraperitoneal injection of 180 mg/kgBW streptozotocin. After confirming hyperglycemia, incisions and burn wounds were created and monitored for 7 and 14 days. Wound healing was assessed macroscopically (incision length, width, and burn diameter) and microscopically (fibroblast proliferation and re-epithelialization). The formulated Opuntia cochenillifera cream was evaluated for pH, homogeneity, adhesion, and spreadability using standard topical formulation tests.RESULTS: The formulated cream exhibited good homogeneity, adhesion (4.97 s), spreadability (5.10 cm), and skin-compatible pH (6.44). Phytochemical analysis confirmed the presence of flavonoids, tannins, terpenoids and alkaloids. In vivo, Opuntia cochenillifera cream significantly accelerated wound closure and increased fibroblast proliferation compared to the C− group (p<0.05). Its effects were comparable to those of the standard treatment for burn wounds and superior for incision wounds, demonstrating enhanced fibroblast activity and more organized re-epithelialization.CONCLUSION: Opuntia cochenillifera cream effectively improves wound healing in diabetic mice through the enchantment fibroblast activity and organized re-epithelialization. These findings support the potential of this formulation as a natural topical therapy for diabetic wounds, warranting further mechanistic investigation.KEYWORDS: Opuntia cochenillifera, diabetic wound, wound healing, topical cream, phytochemica
Long Noncoding RNAs TYMSOS, VASH1-AS1, and LINC01001 Expressions as Biomarkers of β-thalassaemia Severity Among the Malaysian Patients
Get PDFBACKGROUND: β-thalassaemia has heterogeneous disease severities ranging from mild to trait, and major. Long noncoding RNAs (lncRNAs) are known to regulate microRNAs (miRNAs) and genes, possibly modifying the disease phenotypes. However, limited data exist on the lncRNAs in β-thalassaemia, and no study has yet addressed this gap in Malaysia. Therefore, this study aimed to identify the expression profile of lncRNAs in β-thalassaemia major and trait among Malaysians.METHODS: Case-control study was conducted in two phases at Tunku Azizah Women and Children's Hospital and the Institute of Medical Research, from September 2019 to November 2021. Total of 141 individuals were recruited, comprising β-thalassemia major (MAJOR, n=11), β-thalassemia trait (TRAIT, n=17), and healthy controls (CON, n=113). All participants were genotyped for thalassaemia and assessed for their haemoglobin and red blood cells (RBC) indices. In the first phase, discovery of lncRNA was performed using microarray, and differential expression of lncRNAs (DEL) in MAJOR, TRAIT, and CON groups was identified. Significant lncRNAs were subjected to lncRNA-miRNA prediction, and gene ontology and biological pathway were analyzed. In validation phase, six potential lncRNAs were further validated via using lncRNA polymerase chain reaction (PCR) custom array.RESULTS: Total of 364 DELs were identified in MAJOR group, and 128 DELs were identified in TRAIT group. Between the MAJOR and TRAIT groups, 100 DELs were dysregulated in MAJOR group. Two molecular networks comprising the lncRNA interactions with miRNAs were identified and associated with traits and major phenotypes, resulting in six potential lncRNAs for validation. Among these six lncRNAs, three lncRNAs (TYMSOS, VASH1-AS1, and LINC01001) were reduced in the MAJOR group (fold change (FC)=-6.67, p=0.026; FC=-8.33, p=0.022; and FC=-8.33, p=0.021, respectively).CONCLUSION: Expressions of TYMSOS, VASH1-AS1, and LINC01001 lncRNAs were altered differently between β-thalassaemia major and trait patients. Therefore these lncRNAs may serve as novel biomarkers for β-thalassaemia disease severity in Malaysian population.KEYWORDS: β-thalassaemia, lncRNAs, miRNAs, severity, major, trait, molecular networ
Design and Stability Evaluation of Active Peptides from Indonesian Echinozoa as Acetylcholinesterase (AChE) Inhibitors for Alzheimer’s Therapy
Get PDFBACKGROUND: Alzheimer’s disease is characterized by cognitive decline resulting from decreased acetylcholine (ACh) levels due to excessive acetylcholinesterase (AChE) activity. Current therapies, such as galantamine, have several side effects. Bioactive peptides derived from marine Echinozoa (sea urchins and sea cucumbers) have emerged as promising therapeutic agents owing to their structural diversity and diverse bioactivities. Previous studies identified peptides from sea cucumbers and sea urchins collected along the southern coast of Gunung Kidul, Yogyakarta (VLCAGDLR, SWIGLK, MNGKKITVRPR, and KTKDLK), which exhibit acetylcholinesterase (AChE) inhibitory activity. However, the therapeutic use of these peptides is challenged by blood–brain barrier (BBB) penetration and stability issues. Therefore, this study was conducted to identify candidate peptides through in silico analysis and to evaluate their stability in phosphate-buffered saline (PBS) as potential AChE inhibitors.METHODS: Molecular docking was conducted to evaluate peptide binding affinity to the active site. The best candidate peptides were synthesized and tested in vitro for AChE inhibition using a colorimetric method. Stability was assessed in PBS by monitoring aggregation through turbidity and Congo Red assays.RESULTS: The sea cucumber peptide SWIGLK showed strong binding affinity (–10.2 kcal/mol) and 12.11% inhibition at 0.19 mM, while the sea urchin peptide KTKDLK exhibited –8.2 kcal/mol and 11.50% inhibition at 0.19 mM. Both peptides remained stable in PBS without aggregation for up to 48 h.CONCLUSION: SWIGLK and KTKDLK demonstrate the most significant AChE inhibitory activity and maintained structural stability, hence supporting their potential as peptide-based candidates for Alzheimer’s therapy.KEYWORDS: Alzheimer, AChE inhibitor, holothuroidea, echinoidea, bioactive peptide, peptide stabilit
APOA2–265 T>C Polymorphism as A Genetic Marker Associated with Lipid Profiles and Cardiovascular Risk in A Healthy Indonesian Population
Get PDFBACKGROUND: Apolipoprotein A (APOA)2–265 T>C polymorphism significantly affects lipid metabolism and body composition, as well as plays a key role in cardiovascular diseases (CVD) and metabolic syndrome. In this study, association between the APOA2 polymorphism, lipid profiles, body composition, and cardiovascular disease (CVD) risk in a healthy Indonesian population was investigated. Although similar studies have been conducted in other populations, this study addresses the urgent need to understand genetic factors influencing lipid profiles in Southeast and East Asia, where hypercholesterolemia rate keep rising, particularly in Indonesia.METHODS: A cross-sectional study involving 84 healthy participants was performed. Genotyping for the APOA2–265 T>C polymorphism was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of APOA2 and APOB100 were measured with enzyme-linked immunosorbent assay (ELISA), and APOB100/APOA2 ratio was calculated to assess CVD risk. Lipid profiles were evaluated with enzymatic methods, and body fat percentage was measured using calipers.RESULTS: CT/CC genotypes showed significantly lower plasma APOA2 levels compared to the TT genotype (p=0.0215). APOB100/APOA2 ratio was significantly higher in CT/CC genotypes (p=0.0020) and remained significant after Bonferroni correction. No significant differences were found in lipid profiles and body fat percentages between genotypes after correction, although trends suggested higher cholesterol and low-density lipoprotein (LDL) levels in TT genotypes and higher median body fat percentages in CC/CT genotypes.CONCLUSION: APOA2–265 T>C polymorphism is linked to changes in lipid profiles and body composition, potentially raising CVD risk in CT/CC genotypes. However, limited sample size and modest effect sizes suggest that the practical use of APOA2 genotyping for risk assessment might require further investigation.KEYWORDS: APOA2 polymorphism, APOB100, hypercholesterolemia, cardiovascular disease, lipid profile, body fat percentag
Trends in CTGF Expression in Renal and Chorioretinal Tissues Following Metformin and SGLT2 Inhibitor Treatment in Diabetic Rats
Get PDFBACKGROUND: Connective tissue growth factor (CTGF) plays a central role in fibrotic processes affecting both renal and retinal tissues in diabetes. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to exert renoprotective and antifibrotic effects, their impact on CTGF expression in renal and retinal tissues has not been clearly established. This preliminary study was conducted to evaluate whether SGLT2 inhibitors (SGLT2i) could influence CTGF expression in the kidneys and eyes of diabetes-induced rats.METHODS: After two weeks of adaptation, 24 rats were randomized and distributed equally into four groups (n=6 each): 1) Healthy Control, healthy rats without diabetic induction; 2) Negative Control, diabetic rats induced with streptozotocin (STZ) without treatment; 3) Metformin Group, diabetic rats treated with metformin; and 4) SGLT2i Group, diabetic rats treated with empagliflozin. Following eight weeks of intervention, CTGF expression was analyzed by Western blot in renal tissue (right kidney) and chorioretinal tissue (right eye). Four samples per group yielded analyzable bands and were included in the final quantification.RESULTS: In renal tissue, CTGF levels (mean±SD) were highest in Negative Control Group (0.81±0.06). Both the Metformin Group (0.58±0.14) and SGLT2i Group (0.57±0.33) demonstrated a trend toward reduced CTGF expression. In chorioretinal tissue, CTGF values were relatively similar across groups (Healthy Control: 0.67±0.05; Negative Control: 0.63±0.12), with Metformin Group (0.61±0.12) and SGLT2i Group (0.64±0.22) showing a modest reduction trend.CONCLUSION: In diabetic rats, CTGF expression levels are markedly increased. Following treatment with metformin and SGLT2i, CTGF expression demonstrates a noticeable reduction trend.KEYWORDS: SGLT2 inhibitor, metformin, connective tissue growth factor, cellular communication network factor 2, renal, retin
MCM6 rs4988235 Allele G, AGT rs699 Allele C, ACE rs4343 Allele A, FADS1 rs174547 Allele C, DCHR7 rs12785878 Allele G, and GC rs7041 Allele T: Candidate Genes for Preeclampsia Prevention
Get PDFBACKGROUND: Preeclampsia is the primary cause of maternal and neonatal morbidity and mortality; however, currently there is no definitive method exists to prevent preeclampsia. Recent findings indicate a possible genetic influence on preeclampsia. Therefore, this study was conducted to assess nutrigenomic patterns in preeclampsia as a potential mechanism for identifying appropriate preventive strategies through a nutrigenomic approach.METHODS: This descriptive study focused on 15 primiparous pregnant women diagnosed with preeclampsia. The nutrigenomic test was performed using DNA microarray method to examine variant genes associated with food response and nutrient metabolites. The genetic tendencies were categorized as "low," "average," and "high." The frequencies of alleles and probabilities were assessed for gene variants expressing "high" and "low" genotypic tendencies.RESULTS: The identified genetic variations were MCM6 rs4988235 allele G that indicated lactose intolerance (allele frequency 100%), AGT rs699 allele C and ACE rs4343 allele A that were associated with sodium metabolism (allele frequency 82% and 90%, respectively), as well as FADS1 rs174547 allele C that was pertained to omega metabolism (allele frequency 85%). Likewise, DCHR7 rs12785878 allele G and GC rs7041 allele T were relevant for vitamin D (allele frequencies 82% and 77%, respectively). However, MCM6 rs4988235 allele G, FADS1 rs174547 allele C, DCHR7 rs12785878 allele G, and GC rs7041 allele T had not been explicitly linked to preeclampsia.CONCLUSION: MCM6 rs4988235 allele G, AGT rs699 allele C, ACE rs4343 allele A, FADS1 rs174547 allele C, DCHR7 rs12785878 allele G, and GC rs7041 allele T are the dominant variant genes observed. The associations between preeclampsia and AGT rs699 allele C and ACE rs4343 allele A are consistent with other study.KEYWORDS: preeclampsia, nutrigenomics, nutrition metabolis
Lower Ferrum, Selenium, and Cadmium; Higher Chromium and Lead Levels in Preeclampsia Patients’ Erythrocyte: A Cross-Sectional Study
Get PDFBACKGROUND: Oxidative stress and trace elements in erythrocytes are linked to impaired nitric oxide that can lead to endothelial dysfunction in preeclampsia patients. The morphology of erythrocytes could also be affected by oxidative stress and trace elements. While the relationships between erythrocyte index, superoxide dismutase (SOD) activity, and oxidative stress in preeclampsia have been well established, less attention has been given to the erythrocyte trace elements and their role in disease progression. This study was performed to examine the erythrocyte trace element profile in women with preeclampsia, comparing it with controls. Additionally, it will explore the correlations between erythrocyte trace element levels, the erythrocyte index, and SOD activity.METHODS: A cross-sectional study was conducted involving 40 pregnant women consisting of those with severe preeclampsia and normotensive. Erythrocytes was isolated from blood samples, and analysis of erythrocyte SOD activity and trace elements were performed using the enzyme linked immunosorbent assay (ELISA) and inductively coupled plasma mass spectrometry (ICP-MS), respectively.RESULTS: Among 15 examined erythrocyte trace elements, the levels of ferrum (Fe), selenium (Se), and cadmium (Cd) were significantly lower, meanwhile, the levels of chromium (Cr) and lead (Pb) were significantly higher in preeclampsia subjects. Additionally, preeclampsia subjects exhibited smaller erythrocyte sizes compared to the normotensive subjects. The erythrocyte SOD activity was significantly elevated in the preeclampsia subjects than the normotensive subjects.CONCLUSION: Erythrocyte trace element levels of Fe, Se, Cd, Cr, and Pb were significantly altered in preeclampsia compared to normotensive controls. These findings suggest that these trace elements may serve as potential predictors for preeclampsia.KEYWORDS: preeclampsia, trace elements, antioxidant, oxidative stress, superoxide dismutase, erythrocyte inde
Tempeh Smoothie Consumption Reduces Triglyceride Levels and Body Mass Index of Menopausal Women
Get PDFBACKGROUND: To reduce the risk of dyslipidemia, increasing the consumption of fiber-rich foods, such tempeh, is necessary. Tempeh contains abundant isoflavones that support lipid metabolism and vascular function, prompting researchers to develop methods for producing tempeh with more practical consumption compared to conventional tempeh. In current study, tempeh smoothie was produced and its effects on body composition and lipid profiles in menopausal women was evaluated.METHODS: A quasi-experimental study was conducted including 16 menopause women as subjects. The tempeh smoothie was prepared using tempeh blended with water until smooth and creamy. The tempeh smoothie was consumed by the subjects five times a week for six weeks, and then the subjects’ body composition and lipid profiles were measured before and after the intervention.RESULTS: There were some improvements in subjects’ body composition, specifically in muscle mass, and a few subjects shifted their body mass index (BMI) status from obesity to overweight. However, these changes were not statistically significant. Even though the consumption of tempeh smoothie did not improve total cholesterol level, which increased by 12.31 mg/dL); low-density lipoprotein (LDL) cholesterol, which increased by 32.81 mg/dL; and high-density lipoprotein HDL cholesterol, which decreased by 5.12 mg/dL; however, it is significantly reduced triglyceride levels by 75.00 mg/dL from baseline to post-intervention.CONCLUSION: Consuming tempeh smoothie regularly shows a trend towards BMI reduction and a slight improvement in muscle mass among menopausal women. This consumption also significantly lowers the triglyceride levels, indicating that it might be potential in preventing dyslipidemia in menopausal women.KEYWORDS: tempeh smoothie, menopausal women, body composition, lipid profil
Anti-thrombocytopenic Activities of 15 Selected Indonesian Medicinal Plants: Psidium guajava Leaves, Phyllanthus niruri Aerial Parts, and Andrographis paniculata Leaves as Potential Sources in Enhancing Platelet Levels in Rats
Get PDFBACKGROUND: Thrombocytopenia is a medical condition characterized by a low platelet count in the blood, which can cause excessive bleeding and serious complications. Current conventional treatments for thrombocytopenia often present significant side effects and limitations, necessitating the exploration of alternative therapeutic options. Therefore, this study was conducted to evaluate the potential of Indonesian ethnomedicinal plants as alternative therapies.METHODS: The research was conducted by ethanol maceration of 15 medicinal plants selected based on their use in traditional Indonesian medicine to treat thrombocytopenia. Male white rats, aged three month and weighing between 150 and 250 g, were divided into four groups, which each group consists of five rats: the negative control group, group receiving 250 mg/kg BW extract, group receiving 500 mg/kg BW extract, and the normal control group. The effects of the test preparations on platelet count, erythrocyte count, and hematocrit were observed after 7 days of treatment.RESULTS: Among of 15 medicinal plants extract tested at a dose of 500 mg/kg BW, Psidium guajava L. leaves extract showed to increase blood platelets counts in thrombocytopenic mice by 60.82% (p<0.01) followed by Phyllanthus niruri L. aerial parts extract at (48.22%; p<0.01), and Andrographis paniculata (Burm.f.) Wall. ex Nees leaves extract (47.14%; p<0.01).CONCLUSION: The extracts of P. guajava leaves, aerial parts of P. niruri, and A. paniculata leaves exhibited significant potential in enhancing platelet levels. These findings suggest that some Indonesian medicinal plants can be used as alternative therapy for thrombocytopenia.KEYWORDS: dengue hemorrhagic fever, Phyllanthus niruri, Psidium guajava, Andrographis paniculata, thrombocytopeni