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INDONESIA
The Indonesian Biomedical Journal
Published by The Prodia Education and Research Institute
ISSN : -     EISSN : -     DOI : -
Core Subject : Health, Science,
Biochemistry, Genetics & Molecular Biology Public Health
Arjuna Subject : -
Articles 621 Documents
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The Regulation of SPRY4 Intronic Transcript 1 (SPRY4-IT1) on KIT Signaling and Imatinib Resistance of Gastrointestinal Stromal Tumor (GIST) Cells Yuanyuan Yu; Zongying Jiang; Sien Zhao; Cuiyun Liu; Jinhai Ma; Shujing Li
The Indonesian Biomedical Journal Vol 16, No 4 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i4.3084

Abstract

BACKGROUND: SPRY4 intronic transcript 1 (SPRY4-IT1), is a long non-coding RNA coded by the intron of SPRY4. SPRY4 is highly expressed in gastrointestinal stromal tumor (GIST) and inhibits the tumorigenesis of GIST, but whether SPRY4-IT1 regulates the tumorigenesis of GIST or not remains unclear. Therefore, in this study, the regulation of SPRY4-IT1 expression and its role in GIST will be investigated.METHODS: GIST-T1 cells, and Ba/F3 cells which express KIT proto-oncogene (KIT) and SPRY4-IT1 were used as cell models. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to examine mRNA expression, while the protein expression and signal transduction were examined by western blot. The association between SPRY4-IT1 and KIT was examined by pull down of KIT and PCR. Cell proliferation, survival, and cell cycle progression were examined by cell counting kit-8 (CCK8) and flow cytometry.RESULTS: KIT mutants increased the expression of SPRY4-IT1 in GIST. SPRY4-IT1 bound to KIT, also enhanced the activation and expression of both wild-type KIT and primary KIT mutants, therefore increasing the activation of downstream signaling proteins AKT and ERK of KIT, GIST cell survival, and proliferation. In addition, SPRY4-IT1 reduced the sensitivity of wild-type KIT, or primary KIT mutants to the first-line targeted therapeutic drug of GIST, imatinib, which can inhibit KIT activation. Gaining drug-resistant secondary KIT mutants might be one of the main reasons of GIST recurrence after targeted therapy. Similar to wild-type KIT and primary KIT mutants, the activation and expression of secondary KIT mutants and their resistance to imatinib were also increased by SPRY4-IT1.CONCLUSION: The results indicated positive feedback between SPRY4-IT1 and wild-type KIT, primary KIT mutants or secondary KIT mutants, and the upregulation of AKT and ERK activation by SPRY4-IT1 in GIST cells, providing a new insight in the KIT signaling regulation in GIST, and the resistance of GIST to targeted therapy.KEYWORDS: SPRY4-IT1, KIT, GIST, SPRY4, signaling
Mesenchymal Stem Cell Therapy for Ischemic Stroke in Animal Model: A Systematic Review Muhammad Agus Aulia; Keri Lestari; Ahmad Faried; Cynthia Retna Sartika; Andi Wijaya; Achmad Adam; Hanna Gunawan; Rima Haifa; Nabilla Farah Naura; Billy Yosua Costantin Pongajow
The Indonesian Biomedical Journal Vol 15, No 6 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i6.2460

Abstract

BACKGROUND: Stroke is one of many leading causes of death and disability worldwide. Despite decades of research, treatment for stroke recovery is still inadequate. Recently, mesenchymal stem cell (MSC) therapy is considered as one of the potential treatments for stroke due to their capabilities to repair or regenerate damaged tissues, as well as immunomodulators in inflammatory conditions. Many pre-clinical and clinical trials have shown MSC therapy feasibility, safety, and efficacy in treating stroke. However, evidence regarding the optimal treatment plan and factors that can improve stem cell functional outcomes in treating stroke needs to be further explored. Therefore, a systematic review was conducted.METHODS: Recent literatures from 2015-2022 regarding stem cell therapies, specifically MSC on ischemic stroke, were collected from two reliable databases: PubMed and PubMed Central. Collected literatures were properly applied to inclusion-exclusion criteria and appraised critically. Keyword strategies on databases were employed, including both medical subject headings (MeSH).RESULTS: Five literatures from 726 were identified and used for systematic review. All animal model in the literatures were prepared to have middle cerebral artery occlusion. All studies indicated that MSC therapy is a safe and reliable procedure despite the variety of transplantation routes. No report of toxicity, rejection reaction, nor infection on MSC treated groups.CONCLUSION: Stem cell sources, dosages, and delivery routes could be resourceful for future translational studies to ensure the safety and efficacy of MSC therapy for ischemic stroke.KEYWORDS: ischemic stroke, mesenchymal stem cells, regenerative medicine, immunomodulator
Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway Novi Dewi Tanjung; Nieka Adhara Wahono; Ninik Mudjihartini; Ani Retno Prijanti
The Indonesian Biomedical Journal Vol 16, No 3 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i3.3021

Abstract

BACKGROUND: Zinc released into the synaptic cleft able to modulate various signaling pathways, including brain derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). Zinc binding to its receptor, G-protein coupled receptor 39 (GPR39), may trigger biochemical pathways leading to cAMP response element binding protein (CREB)-dependent gene transcription that subsequently promotes BDNF upregulation. Therefore, zinc dyshomeostasis should be considered as a condition that induces disruption of CREB/BDNF signaling. This study was conducted to examine the effect of maternal zinc diet on hippocampal expression levels of CREB and BDNF in offspring.METHODS: One-day pregnant rats were randomly divided into five groups: zinc-deficient (D), zinc-restricted (R), zinc-adequate (A), zinc-supplemented (S), and excess zinc-supplemented (ES). The groups had different zinc diets during pregnancy and lactation. The behavioral function of the offspring was tested with Y-maze at the 43th postnatal. Hippocampus was isolated, BDNF was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and CREB was examined using sandwich enzyme-linked immunosorbent assay (ELISA).RESULTS: Spatial working memory measurement demonstrated that D and ES group exhibited a significantly lower spontaneous alternation than other groups. The qRT-PCR and ELISA analysis revealed the hippocampal expression level of BDNF and CREB decreased in groups D and ES, but tended to increase in groups R and S, until the highest expression peak was found in group A.CONCLUSION: High and low intake of zinc induces lower expression of BDNF and CREB in hippocampus, which further impairs learning and memory. Our findings suggest the signaling pathway of CREB/BDNF is involved in zinc dyshomeostasis-induced cognitive impairments.KEYWORDS: hippocampus, BDNF, CREB, TrkB, GPR39, zinc, diet, LTP
The Powdered Red Macroalgae (Eucheuma spinosum) Supplementation Potentially Enhanced Bone Structure in Osteoporotic Mice Jusniar Patandung; Ika Yustisia; Rosdiana Natzir; Gita Vita Soraya; Lia Hafiyani; Sulfahri Sulfahri
The Indonesian Biomedical Journal Vol 16, No 2 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i2.2752

Abstract

BACKGROUND: Red macroalgae, such as Eucheuma spinosum, have been found to have potential benefits for bone health due to their unique bioactive compounds, including proteins, polyphenols, polysaccharides, vitamins, and minerals. Therefore, this study was conducted to evaluate the benefits of powdered E. spinosum supplementation in osteoporosis-induced mice.METHODS: Thirty middle-aged mice were divided into 6 groups, namely: healthy control group (HC), negative control group (NC), positive control group (PC), and treatment groups supplemented with 1.25 mg/gBW (T1), 2.5 mg/gBW (T2), and 5 mg/gBW (T3) of E. spinosum powder for twenty days. Mice in NC, PC, T1, T2, and T3 groups were induced with 0.0029 mg/gBW of dexamethasone for 30 days to create osteoporosis mice models. Alkaline phosphatase (ALP) levels were measured by colorimetric methods before and after the intervention. Bone structures were evaluated using X-ray images and histological examination.RESULTS: After the intervention, PC, T1, T2, and T3 groups showed a significant decrease (p≤0.01) in serum ALP levels compared to the NC group, which experienced an increase in ALP levels. The X-ray images revealed that the PC, T1, T2, and T3 showed radiopaque bone density. For bone histology, PC, T2, and T3 showed an improvement with thickened and intact trabeculae, but T1 still had visible osteoporosis cavities.CONCLUSION: Supplementation of 2.5 and 5 mg/gBW of E. spinosum powder were able to improve bone density as well bone histology. Therefore, E. spinosum powder supplementation might potentially improve bone structure in osteoporosis.KEYWORDS: Eucheuma spinosum, red macroalgae, alkaline phosphatase, osteoporosis
Effects of SGLT2-inhibitor on The Expression of MicroRNA-21, Transforming Growth Factor-β1, and Matrix Metalloproteinase-2 in The Process of Cardiac Fibrosis in Hyperglycemic Model Rats Muhammad Ridwan; Herlina Dimiati; Maimun Syukri; Ronny Lesmana; Lia Meuthia Zaini
The Indonesian Biomedical Journal Vol 16, No 1 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i1.2776

Abstract

BACKGROUND: Sodium glucose co-transporter-2 inhibitor (SGLT2-i), a new oral antidiabetic drug, has been recommended for its morbidity and mortality benefits in patients with heart failure. This study aimed to determine the effect of acute SGLT2-i therapy on the relative ratio expression of microRNA-21 (miR-21), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-2 (MMP-2) in the process of cardiac fibrosis in the hyperglycemia Wistar rat models compared to biguanide (metformin) therapy.METHODS: We used Streptozotocin (STZ) to induce hyperglycemia in Wistar rats (n=31), randomly divided into four groups: negative control (NC, n=4), positive control (PC, n=10), hyperglycemia plus metformin (M, n=8), and hyperglycemia plus empagliflozin (E, n=9). After seven weeks, the rats were sacrificed and the heart tissue was taken for microRNA and messenger RNA (mRNA) extraction, followed by reverse transcription quantitative real time polymerase chain reaction (RT-qPCR) examination. The data was analyzed using One-way ANOVA.RESULTS: Results showed a decreasing trend in the gene expression relative ratio of miR-21 (1.0 vs. 1.9; p=0.079) and TGF-β1 (0.9 vs. 3.2; p=0.145), but a significant increase in MMP-2 gene expression (1.3 vs. 0.7; p=0.002) in the SGLT2-i (empagliflozin) vs. biguanide (metformin) groups.CONCLUSION: Empagliflozin administration may play a significant role in preventing the occurrence of cardiac fibrosis in hyperglycemia.KEYWORDS: sodium glucose co-transporter-2 inhibitor, microRNA-21, transforming growth factor-β1, matrix metalloproteinase-2, cardiac fibrosis
Normal Value of Thrombocytes Indices in Indonesian Adults: Focus on Gender and Ages Usi Sukorini; Adika Zhulhi Arjana; Tri Ratnaningsih; Rahmat Dani Satria
The Indonesian Biomedical Journal Vol 16, No 4 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i4.3205

Abstract

BACKGROUND: Monitoring platelet count and related indices is crucial for managing hematological disorders. No studies are reporting normal platelet indices in the adult Indonesian population. Therefore, this study was conducted to establish normal reference values for platelet count and indices in a healthy population in Indonesia and investigate their association with platelet count and each parameter.METHODS: This cross-sectional study included healthy adults from both sexes who underwent hematological testing in our laboratory. Two mL of venous blood was drawn and analyzed using an automated machine ADVIA 2120 to identify platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), mean platelet component (MPC), platelet component distribution width (PCDW), mean platelet mass (MPM), platelet mass distribution width (PMDW), and large platelet count.RESULTS: This study included 1037 subjects with median of 27 (18–58) years old. Normal reference range values for platelet indices in adult Indonesians was established, which was significantly different between males and females (p<0.05) in following parameters: platelet count (191.77–400.37 vs. 203.00–433.00 ×109/L), MPV (7.30–9.91 vs. 7.20–10.00 fL), PDW (38.09–59.83 vs. 37.10–58.50%), PCT (0.17–0.33 vs. 0.17–0.35%), PMDW (0.68–1.06 vs. 0.67–1.04 pg) for males vs. females, respectively. However, other parameters such as MPC, PCDW, MPM, and large platelet, did not show any significant differences.CONCLUSION: The reference intervals of platelet indices in the adult Indonesian population were different from previously established reference values, indicating the importance of dedicated reference interval determination with gender consideration.KEYWORDS: thrombocyte indices, platelet count, hematology reference values, blood platelet analysis 
AvrA Salmonella Increases TLR4/NF-κB/β-catenin/TGF-β Expressions of Colorectal Cancer Mice Model Bogi Pratomo Wibowo; Handono Kalim; Husnul Khotimah; Hidayat Sujuti; Ettie Rukmigarsari; Nabila Erina Erwan
The Indonesian Biomedical Journal Vol 15, No 6 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i6.2607

Abstract

BACKGROUND: Colorectal cancer (CRC) is reported as the third most frequently diagnosed cancer worldwide. Salmonella infection plays a role in developing this cancer, which is chronically related to the avirulence protein A (AvrA) effector protein produced by the bacteria. This study was conducted to point out the effect of AvrA Salmonella on the occurrence of CRC through the regulation of TLR4/NF-κB/β-catenin/TGF-β expressions in the azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model.METHODS: A randomized control group post-test-only study was conducted using male Balb/c mice with 30-gram body weight (10-12 weeks), which were divided into three groups, namely the negative control (normal mice without any treatment), positive control (AOM/DSS-treated mice), treatment 1 (T1) (AOM/DSS-treated mice + AvrA Salmonella) groups. Colon tissue was collected and then prepared for immunohistochemistry staining using TLR4, β-catenin, NF-κB, TGF-β, and Ki67 antibodies, whereas apoptotic cells were stained using TUNEL assay.RESULTS: The expressions of TLR4, β-catenin, NF-κB, TGF-β, Ki67, and apoptosis percentage indicated significant differences among the three groups, which statistically showed p<0.05 in all observed parameters. The mean of all parameters was far more significant in the T1 group than in the negative and positive control groups.CONCLUSION: The findings revealed that AvrA Salmonella could increase the expressions of TLR4, β-catenin, NF-κB, TGF-β, and Ki67 and decrease the apoptotic percentage. Thus, AvrA Salmonella influences CRC tumorigenesis through TLR4/NF-κB/β-catenin/TGF-β and is suggested as a potential target in future preventive and curative management for CRC.KEYWORDS: AvrA Salmonella, carcinogenesis, colorectal cancer 
A Potential Pathogenic SRD5A2 Mutation and rs632148, rs523349 and rs522638 Polymorphisms in Increasing the Risk of Syndromic Hypospadias in Indonesian Population Rizki Diposarosa; Yunisa Pamela; Herry Herman; Yunia Sribudiani
The Indonesian Biomedical Journal Vol 16, No 3 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i3.2968

Abstract

BACKGROUND: Hypospadias, a congenital birth defect in male, is the opening of the urethra located on the ventral side of the penis. Several mutations in SRD5A2 encoding steroid 5 alpha-reductase type 2 protein have been identified in hypospadias and polymorphisms in this gene have been known to be associated with an increased risk of hypospadias. In this study, several crucial molecular analyses of the SRD5A2 gene and the association of the identified variants to the risk of syndromic hypospadias in Indonesian population were conducted.METHODS: Thirty-two isolated and 29 syndromic hypospadias patients were enrolled in this study. DNA was isolated from whole blood for the amplification of all exons and exon-intron boundaries of SRD5A2 by polymerase chain reaction (PCR), followed by Sanger sequencing. In silico analysis was performed using PolyPhen-2, Sorting Intolerant from Tolerant (SIFT) and Align GVGD. Statistical analysis was performed using Chi-squared test.RESULTS: A novel missense mutation c.32T>C/p.Leu11Pro was identified in one isolated hypospadias patient and the in silico analysis predicted the mutation to be pathogenic. Three polymorphisms were identified, two in the non-coding region (c.-62G>C/rs632148 and c.281+15T>C/rs522638) and one in exon-1 (c.265C>G/p.Val89Leu/rs523349). Mutant alleles of these polymorphisms were significantly associated with syndromic hypospadias with odds ratios (OR) of 3.4, 3.13 and 2.54 respectively.CONCLUSION: This study suggests that SRD5A2 mutation is one of the causes of hypospadias in Indonesian population and rs632148, rs523349 and rs522638 polymorphisms are significantly associated with an increased risk of syndromic hypospadias.KEYWORDS: mutation, polymorphism, SRD5A2, syndromic hypospadias
Vegetables Spices Fermentation Extract Inhibit NAFLD Development by Attenuation of Steatosis through Suppression of C/EBPα and TNFα mRNA Expression Rachmawati, Ermin; Machdaniar, Maulidya; Kinasih, Larasati Sekar; Sargowo, Djanggan; Syarifuddin, Brillian Putra; Putri, Fayza Cinta Rahmadina; Ismail, Mahrus
The Indonesian Biomedical Journal Vol 16, No 2 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i2.2934

Abstract

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), characterized by inflammation and steatosis, is one of the metabolic problems that trigger serious complications. Statin is usually used for NAFLD therapy, however, statin intolerance and resistance reduce the effectiveness of NAFLD treatment. Therefore, this study was conducted to develop the phytopharmaca against NAFLD by elucidating the anti-inflammatory and steatosis suppression of vegetable spices fermentation extract (VSFE) in rabbits induced with high-fat diet (HFD).METHODS: Twenty New Zealand White rabbits were determined into 4 groups; which were groups receiving standard diet (SD), HFD, HFD and 100 mg/kgBW VSFE, as well as HFD and 200 mg/kgBW VSFE. mRNA expressions of tumor necrosis factor alpha (TNFα) and CCAAT/enhancer-binding protein alpha (C/EBPα) were evaluated. The TNFα concentration was quantified after protein and RNA isolation. Inflammation and steatosis were observed in liver hematoxylin-eosin-stained preparate using microscope.RESULTS: Macrophage cells and hepatic steatosis showed significant decrease in a drug dependent manner. An effective dose of 200 mg/kgBW decreased C/EBPα and TNFα expression to 0.45±0.32 and 0.72±0.29 (p=0.013 and p=0.002, compared to the HFD group), respectively. TNFα inflammatory cytokine concentrations also responded to the administration of 100 mg/kgBW and 200 mg/kgBW doses, with the value of 31.72±10.40 mg/dL and 48.35±7.15 mg/dL (p=0.009 and p=0.002, compared to the HFD group), respectively.CONCLUSION: VSFE might prevent NAFLD by inhibit steatosis and inflammation through suppression of C/EBPα expression and TNFα expression.KEYWORDS: C/EBPα, TNFα, fermentation, steatosis, NAFLD
Triglyceride-Glucose Index as A Crucial Marker for Polycystic Ovary Syndrome Women with Insulin Resistance Hestiantoro, Andon; Saraswati, Jaya; Prasetya, David Eka; Sandra, Ferry; Muharam, Raden; Pratama, Gita; Harzif, Achmad Kemal
The Indonesian Biomedical Journal Vol 16, No 1 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i1.2639

Abstract

BACKGROUND: Insulin resistance (IR) is considered as the main driver of polycystic ovary syndrome (PCOS) pathogenesis. In PCOS condition, IR is frequently related to glucose, anthropometric profile, lipid profile, and hormone profile parameters. However, not all PCOS phenotype show IR. Therefore, this study was conducted to determine the association the parameters mentioned above in PCOS subjects with and without IR.METHODS: Fifty PCOS women with IR and 26 PCOS women without IR were recruited. All subjects underwent physical examination for measurement of weight, waist circumference (WC), and body mass index (BMI). Ferriman Gallwey Score (FGS) was used to evaluate hirsutism. Blood sample was taken from each subject for measurement of fasting glucose, postprandial glucose, fasting insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, triglyceride (TG), sex hormone binding globulin (SHBG), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin. Homeostatic model assessment for IR (HOMA-IR), TG-glucose index (TyGI), and free testosterone index (FTI) were then calculated.RESULTS: From all the parameters examined, only fasting insulin (p<0.001), HOMA-IR (p<0.001), SHBG (p=0.012), TG (p<0.001), and TyGI (p=0.008) that show significant differences between PCOS subjects with and without IR. After multivariate analysis, TyGI was found to have strong association with IR occurrence in PCOS subjects (p=0.005) with an odd ratio of 5.26 (1.65–16.74).CONCLUSION: TyGI appears to have a significant association with the IR occurrence in PCOS subjects. Hence, it can be suggested that TyGI could be an important marker for PCOS women with IR.KEYWORDS: insulin resistance, lipid metabolism, polycystic ovary syndrome, triglyceride-glucose index

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