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INDONESIA
The Indonesian Biomedical Journal
ISSN : -     EISSN : -     DOI : -
Core Subject : Health, Science,
Arjuna Subject : -
Articles 621 Documents
Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats Rachmi Fauziah Rahayu; Adi Prayitno; Bambang Purwanto; Widiastuti Soewondo; Ida Nurwati; Eti Poncorini Pamungkasari; Paramasari Dirgahayu
The Indonesian Biomedical Journal Vol 16, No 6 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i6.3360

Abstract

BACKGROUND: Diabetes, which causes various complications, involves pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B p65 (NF-κB p65), interleukin-6 (IL-6), cluster of differentiation 4 (CD4), and matrix metalloproteinase-9 (MMP-9). Magnesium has demonstrated anti-diabetic properties, but its anti-inflammatory effects in preventing cardiovascular complications remain unclear. This study aimed to evaluate the anti-inflammatory effects of magnesium citrate, alone and in combination with metformin, by measuring TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression in diabetic model rats.METHODS: Thirty male Wistar rats were divided into five groups: normal control, diabetes control, metformin (treated with 9 mg/200 g/day metformin), magnesium citrate (treated with 3.6 mg/200 g/day magnesium citrate), and combination therapy (treated with 4.5 mg/200 g/day metformin + 1.8 mg/200 g/day magnesium citrate). Diabetes was induced in all groups except the normal control group using streptozotocin (STZ) and nicotinamide (NA). TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression levels were measured using enzyme-linked immunosorbent assay (ELISA).RESULTS: Significant differences in TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression levels were observed across all groups (p<0.001). The combination therapy group demonstrated the most significant reduction in all parameters compared to the diabetic control group (p<0.001) and other therapy groups. Both metformin and magnesium citrate monotherapies showed moderate reductions in cytokine levels but were less effective than combination therapy.CONCLUSION: Combination therapy with metformin and magnesium citrate exhibited the most potent anti-inflammatory effects, significantly reducing TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expressions in diabetic Wistar rats. This combination has potential as a therapeutic approach for managing diabetes and its complications.KEYWORDS: diabetes mellitus, inflammation, cytokines, metformin, magnesium citrate
Expression of Plasma miRNA-133a is Significantly Lower in Acute Coronary Syndrome (ACS) than in Healthy/Non-ACS Subjects Rachmawati, Ermin; Sargowo, Djanggan; Saputra, Indra Wahyu; Riskiyah, Riskiyah; Handirosiyanto, Ikhwan; Hakim, Arief Rachman; Ismail, Mahrus; Tarsadi, Tarsadi; Maulana, Syafiq; Ahdi, Iwal Reza; Puspitasari, Alvina; Wardhani, Syanindita Puspa
The Indonesian Biomedical Journal Vol 16, No 5 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i5.3243

Abstract

BACKGROUND: The current biomarker diagnostic modality for acute coronary syndrome (ACS), cardiac troponin, has several limitations. Emerging studies showed that micro-RNA (miR)-133a was released from infarcted heart to circulation, yet the diagnostic value of miR-133a in ACS demonstrated a conflicting result. Therefore, this study was conducted to investigate the potency of plasma miR-133a as a biomarker candidate of ACS.METHODS: This was a case-controlled study, involving ACS and control subjects. The sociodemographic and clinical characteristics were assessed through medical records. A final of 39 ACS and 31 control subjects (consist of healthy and non-ACS subjects) passed the selection procedure by demonstrating a high purity of RNA. miR-133a from ACS and control subjects were detected by quantitative polymerase chain reaction (qPCR). Expression of miR-133a was evaluated for sensitivity and specificity as an ACS biomarker diagnostic using the receiver operating characteristic (ROC) curve.RESULTS: Plasma miR-133a expression was stably found in ACS subjects. The plasma miR-133a level was lower in ACS than in control subjects. miR-133a effectively distinguished ACS subjects from healthy subjects (AUC=0.911) and exhibited high diagnostic performance, with a sensitivity of 87.1% and specificity of 100% at a cut-off value of 44.035. In an extended model including both control subjects (healthy and non-ACS with comorbid conditions), miR-133a maintained diagnostic significance (AUC=0.874), showing sensitivity of 76.9% and specificity of 100% at a cut-off value of 11.69.CONCLUSION: Plasma miR-133a is significantly lower and effectively distinguishes ACS patients from both healthy individuals and non-ACS individuals with comorbid, with a cut-off value of 11.69. Therefore, plasma miR-133a is suggested to be a good candidate for diagnostic biomarkers of ACS.KEYWORDS: circulating miRNA, miRNA-133a, acute coronary syndrome, diagnostic biomarker
Inhibition of Neurogenesis and Induction of Glial Scar Formation by Neuroinflammation Following Ischemic Stroke: Evaluation of BDNF, GFAP, HMGB1 and TNF-α Expressions Aris Widayati; Fedik Abdul Rantam; Abdulloh Machin; Wibi Riawan
The Indonesian Biomedical Journal Vol 17, No 1 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i1.3439

Abstract

BACKGROUND: Ischemic stroke remains as a major health problem and one important process in Ischemic Stroke is neuroinflammation which has a principal role to maintain the balance of neurogenesis and neurodegeneration process in the brain. Neuroinflammation can lead to glial scar and inhibit neurogenesis processes which is needed for recovery neuron function. This study was conducted to observe the role of high mobility group box 1 (HMGB1) and tumor necrosis factor-α (TNF-α) as neuroinflammation markers to glial fibrillary acidic protein (GFAP) as glial scar marker and to brain-derived neurotrophic factor (BDNF) as neurogenesis marker in brain tissue following ischemic stroke.METHODS: Fifteen male Wistar rats were randomized to three groups; sham group, rats receiving occlusion and terminated 180 minutes later (group A), and rats receiving occlusion and terminated after 7 days (group B). Expressions of BDNF and BDNF mRNA were examined using immunohistochemistry (IHC) and Reverse Transcription Polymerase Chain Reaction (RT-PCR), respectively. While GFAP, HMGB1, TNF-α were assessed using IHC.RESULTS: Expression of BDNF was found lower in group A and group B than in sham group (5.20±1.924, 5.00±1.581, and 7.80±1.304, respectively; p=0.032). Expression of BNDF mRNA was found lower in group A and B than in sham group as well. While expression of GFAP was found higher in group A and B than in sham group (9.60±1.517, 11.40±2.074, and 5.20±1.48, respectively; p=0.000). Higher level of HMGB1 and TNF-α expressions were also found to in group A and group B than in sham group (9.3±1.528, 11.67±1.528, and 2.00±1.000, respectively; p=0.000 for HMGB1 and 6.33±1.155, 9.33±1.528, and 3.00±1.000, respectively; p=0.002 for TNF-α).CONCLUSION: The presence of low BDNF levels and high levels of GFAP, HMGB1 and TNF-α markers, possibly reflects inhibition of the neurogenesis process by neuroinflammation, and induced glial scar formation in ischemic stroke conditions after than 180 hours until 7 days. KEYWORDS: ischemic stroke, BDNF, GFAP, TNF-α, HMGB1
Roles of Mesenchymal Stem Cell-derived Extracellular Vesicles in Cancer: Development and Target Therapy Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya
The Indonesian Biomedical Journal Vol 17, No 1 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i1.3408

Abstract

Extracellular vesicles (EVs) are membrane structures that enclose proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs derived from mesenchymal stem cells (MSCs) can either stimulate or inhibit tumor growth in various malignancies through paracrine signaling. Tumor-associated MSCs (TA-MSCs), often described as "wounds that never heal," actively participate in the development, propagation, and metastasis of tumors, impacting the immunological state of the tumor microenvironment. For instance, TA-MSCs can alter immune cell recruitment and cytokine production, leading to a pro-tumorigenic environment. Consequently, both the tumor and its microenvironment undergo functional alterations, the cargo of exosomes is modified, and an abnormal tumor-associated MSC phenotype is acquired. MSC-EVs contain exosome microRNA with both tumor-inhibitory and tumor-supportive effects. For example, MSC-EVs have been shown to deliver tumor-suppressive microRNAs that inhibit cancer cell proliferation and induce apoptosis. This review outlines the criteria for the modification, isolation, and characterization of exosomes, as well as their application in cancer, providing insights for clinical use. By understanding these mechanisms, we can better harness MSC-EVs for therapeutic purposes.Keywords: mesenchymal stem cell, extracellular vesicle, exosome, cancer therapy, drug delivery
Lactococcus lactis D4 Restores Gut Microbiota Balance in Azoxymethane and Dextran Sulfate Sodium-induced Colorectal Cancer Rat Model Suswita, Rini; Rivai, Muhammad Iqbal; Iqbal, Muhammad; Irwan, Irwan; Suchitra, Avit
The Indonesian Biomedical Journal Vol 16, No 6 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i6.3311

Abstract

BACKGROUND: Gut microbiota plays a crucial role in the initiation and progression of colorectal cancer (CRC), with various bacterial species including Lactococcus lactis implicated in this process. However, there is a lack of studies reporting the specific effects of L. lactis on microbiota balance in the context of CRC, especially strain D4. Therefore, this study was conducted to evaluate the effect of L. lactis D4 administration on gut microbiota balance in a rat model of CRC.METHODS: This experimental study involved Sprague Dawley rats that were separated into untreated control (CO group), CRC-induced (CA group), and L. lactis D4-treated CRC-induced (LLD group). The CRC induction was performed by giving azoxymethane (AOM) and dextran sulfate sodium (DDS). Gut microbiota profile was analyzed using next generation sequencing (NGS), and microbial community dynamics were assessed through alpha and beta diversity metrics.RESULTS: L. lactis D4 restored gut microbiota balance by regulating Firmicutes/Bacteroidota ratio, and changing the microbiota composition by increasing the number of bacteria from the phylum Actinobacteria and decreasing bacteria from the phylum Bacteroidota and Proteobacteria. Alpha diversity was reduced in the LLD group, suggesting a decreased bacterial diversity post-treatment, but more closely aligned with the CO group than the CA group. Beta diversity analysis showed that the microbial composition of the treated group was similar to the CO group, while the CA group exhibited a distinct microbiota profile, characterized by higher abundance of pathogenic bacteria and reducing beneficial microbial species.CONCLUSION: L. lactis D4 administration effectively modulates gut microbiota in CRC model, enhancing the presence of beneficial bacteria from the Firmicutes and Bacteroidota phylum while suppressing pathogenic species from the Proteobacteria phylum.KEYWORDS: colorectal cancer, gut microbiota, next generation sequencing, Lactococcus lactis D4 
Adiponectin and Endothelin-1 are Correlated with the Development of Normal-tension Glaucoma in Metabolic Syndrome Patients Prayitnaningsih, Seskoati; Oktarina, Virna Dwi; Nusanti, Syntia; Diarsvitri, Wienta; Rif'ati, Lutfah; Siswanto, Bambang Budi; Santoso, Anwar
The Indonesian Biomedical Journal Vol 16, No 5 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i5.3196

Abstract

BACKGROUND: Glaucoma can lead to irreversible blindness, but normotension glaucoma (NTG) often shows no early symptoms. However, to date, there is limited knowledge regarding the potential parameters for early detection. Therefore, in this study, various metabolic parameters and biomarkers which may contribute to NTG in metabolic syndrome (MetS) patients were evaluated.METHODS: A retrospective cross-sectional study was conducted in the National Cardiac Center Harapan Kita Hospital. Mets were confirmed following the IDF criteria. NTG was determined based on normal intraocular pressure (IOP) with a mean defect (MD) of the visual field, thinning of the retinal nerve fiber layer (RNFL), and enlargement of cup disc ratio (CDR) by ocular coherence tomography (OCT). Metabolic parameters results of waist circumference (WC), body weight, body height, body mass index (BMI), blood pressures, HbA1c, fasting blood glucose (FBG), lipid profiles; and biomarkers including thiobarbituric acid reactive substance (TBARS) and ferric reducing antioxidant power (FRAP), leptin, adiponectin, high-sensitivity C-reactive protein (hs-CRP), and endothelin-1 (ET-1) were analyzed. Statistical analysis was performed using comparative and correlative tests.RESULTS: From 29 subjects, 19 subjects (65.5%) were included in the NTG group and 10 subjects (34.5%) were included in the non-NTG group. In the NTG group, we found significant correlation between MD with systolic blood pressure (p=0.035); CDR with ET-1 (p=0.049); and CDR with adiponectin (p=0.010). The non-NTG group had a significant correlation between MD with BMI (p=0.043); CDR with LDL (p=0.042); and CDR with TG (p=0.031).CONCLUSION: There are correlation between adiponectin and ET-1 with NTG in MetS patients. Therefore, they might be considered as potential early detectors for NTG in MetS patients.KEYWORDS: normal tension glaucoma, metabolic syndrome, biomarker, endothelin-1, adiponectin
Granule Nanoparticle Citrus sinensis (L.) Osbeck Peel Lowers Blood Glucose Levels and HbA1C in Alloxan-induced Diabetes Rats Maya Sari Mutia; Yelvreza Rastiani Sipayung; Dwi Elmiam; Widya Yanti Sihotang; Juliana Lina
The Indonesian Biomedical Journal Vol 17, No 1 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i1.3334

Abstract

BACKGROUND: The peel of Citrus sinensis (L.) Osbeck (sunkist orange) peels, which are often seen as waste, actually contains valuable properties such as antioxidants, hypoglycemic, nephroprotective, and anti-inflammatories. The potential effects of C. sinensis peel on diabetes have been discussed but not clear yet. Therefore, this study was performed to evaluate the effects of Granule Nanoparticle Sunkist Peel (GNSP) extracts as an antidiabetic agent in alloxan-induced diabetic rats.METHODS: The nanoparticle suspension was prepared by mixing a formulation of 0.2% chitosan and 0.1% sodium tripolyphosphate. The characteristics of nanoparticles were measured by flow time, tap index and angle of repose. Rats were induced with alloxan injection to create diabetes rat models. Rats were divided into five groups; normal control group, diabetic controls, and diabetic rats receiving either 50, 100, or 200 mg/kg/day GNSP. After 28 days of diabetes induction, rats were euthanized, and blood as well as tissue samples were collected. Blood glucose levels, HbA1c, and histopathology of the liver, kidneys, and pancreas were then assessed.RESULTS: The particle size of the synthesized material was 92.3 nm, which confirmed the nature of nanoparticle. The characteristics of the granule nanoparticle were also in accordance with the standards for drugs suitable for consumption. The administration of GNSP in dose dependent manner significantly decrease blood glucose levels and HbA1C to normal levels compared to control group (p<0.05). Histopathological analysis indicated recovery in pancreas, liver, and kidney tissues following GNSP administration.CONCLUSION: GNSP administration lowers blood glucose levels and HbA1C, as well as improved histopathological condition of pancreas, liver, and kidney in diabetic rats. These findings suggest the potential of utilizing GNSP as a potent antidiabetic agent.KEYWORDS: Citrus Sinensis (L.) Osbeck, histopathology, hyperglycemia, nano medicine, and type 2 diabetes mellitus
Snail Expression is Positively Correlated with Depth of Invasion in Colorectal Carcinoma Miskad, Upik Anderiani; Akil, Fardah; Cangara, Muhammad Husni; Dahlan, Haslindah; Hutasoit, Gina Andyka; Ilyasa, Muhammad Riza
The Indonesian Biomedical Journal Vol 16, No 6 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i6.3392

Abstract

BACKGROUND: Colorectal carcinoma ranks as the second deadliest and third most prevalent cancer globally. The depth of tumor invasion and the presence of tumor-infiltrating lymphocytes (TILs) are linked to survival rates in this disease. Meanwhile, Snail expression is positively correlated with tumor grade, recurrence, metastasis and poor prognosis in various tumors. However, not many studies discuss the correlation of Snail expression with invasion depth and TILs in Indonesia. Therefore, this study was conducted to investigate the correlation between Snail expression and both the depth of invasion and TIL scoring in colorectal carcinoma.METHODS: A cross-sectional study was conducted to evaluate 70 paraffin-embedded blocks of colorectal carcinoma patients. Snail expression was measured with immunohistochemistry using Snail rabbit polyclonal antibody. Stromal TILs were assessed on a single full-face hematoxylin and eosin (H&E) slide, and classified into high, intermediate, and low TILs.RESULTS: The results showed that the most invasion was to the muscularis propria (42.9%) and the least invasion was to the submucosa (4.3%). In scoring TILs, the most samples with intermediate TILs (58.6%) and the least samples with low TILs (4.3%). The analysis employing a Spearman Rank coefficient shows significant positive correlation between the expression of Snail with depth of invasion (r=0.273; p=0.022) but there was no significant correlation with TILs scoring (p=0.892).CONCLUSION: Even though, there is no significant correlation between Snail expression with TILs, there is, however, a significant positive correlation between Snail expression with depth of invasion in colorectal carcinoma. Therefore, Snail expression might be potentially used as a prognostic factor in colorectal carcinoma.KEYWORDS: Colorectal, carcinoma, Snail, depth of invasion and TILs
Stenochlaena palustris Ethanol Extract Decreases Viability and Induces G1-Phase Cell Cycle Arrest in HSC-3 Tongue Cancer Cells via p21 and p27 Sandra, Ferry; Ranggaini, Dewi; Halim, Johni; Taramalinda, Elizabeth Yuliani; Scania, Alifah Evi; Roeslan, Boedi Oetomo; Lee, Kyung Hoon
The Indonesian Biomedical Journal Vol 16, No 5 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i5.3308

Abstract

BACKGROUND: Oral squamous cell carcinoma (OSCC) of the tongue is an aggressive cancer with a poor prognosis due to its resistance to standard treatments. Stenochlaena palustris, a medicinal fern containing bioactive compounds, has shown potential anticancer properties. However, there is a lack of studies addressing the effects of S. palustris ethanol extract (SPEE) on tongue cancer. This study examined the effects of SPEE on the cell viability and cell cycle of human squamous cell carcinoma (HSC)-3 tongue cancer cells.METHODS: SPEE was prepared with the maceration method. HSC-3 cells were treated with SPEE at concentrations of 100, 500, and 1000 µg/mL for 24 and 48 hours. Cell viability was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis was performed using flow cytometer. Immunoblotting was used to measure amount of cell cycle regulators, protein 21 (p21) and protein 27 (p27).RESULTS: SPEE treatment led to a significant decrease in HSC-3 viable cells in a concentration- and time-dependent manner, with the most pronounced effect at higher concentration and prolonged treatment time. There was a slightly increase in the percentage of cells in the Sub-G1 phase in SPEE-treated group, meanwhile there was a significant increase in the percentage of cells in the G1-phase. Increased amount of p21 and p27 were observed in SPEE-treated group.CONCLUSION: SPEE significantly inhibited HSC-3 cell proliferation in a concentration- and time-dependent manner, primarily by inducing G1-phase cell cycle arrest through the upregulation of p21 and p27. Taken together, SPEE could be a potential anti-cancer agent for tongue cancer cell. KEYWORDS: Stenochlaena palustris, tongue cancer, cytotoxic, cell cycle arrest, HSC-3 cells, p21, p27
Transcriptional Regulation of CYP2D6 by Nrf2 and Its Implications in Breast Cancer Therapy: Bioinformatics and Experimental Evidence Ferbian Milas Siswanto; Maria Dara Novi Handayani; Lonah Lonah; Rita Dewi; Zita Arieselia; Linawati Hananta; Putu Suwarastra Andarisuta
The Indonesian Biomedical Journal Vol 17, No 1 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i1.3194

Abstract

BACKGROUND: Tamoxifen (TAM) resistance in patient with breast cancer is the leading cause of mortality among women globally. Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of TAM, and recently NF-E2-related factor 2 (Nrf2) has recently been found as its regulator. However, the impact of Nrf2-mediated CYP2D6 regulation in the context of breast cancer and TAM resistance are currently unknown. Therefore, this study was conducted to examine the role of CYP2D6 and Nrf2 in breast cancer prognosis. MEDTHODS: The roles of CYP2D6 and Nrf2 were investigated in the T47D breast cancer cell line and T47D-derived TAM-resistant cells by examining the gene expression, cell viability, and transcriptional regulation by quantitative reverse transcription polymerase chain reaction (qRT-PCR), MTT, and reporter gene assay, respectively. Additionally, comprehensive in silico analysis of the transcriptomic and clinical data from The Cancer Genome Atlas database were performed to uncover the prognostic role of CYP2D6 and its regulator in breast cancer patients. RESULTS: CYP2D6 mRNA was low and Nrf2 protein was high in TAM-resistant T47D cells compared to parental cells. Nrf2 knockdown upregulated CYP2D6 mRNA levels and enhanced the cytotoxicity of TAM. Similarly, in silico analysis revealed that low CYP2D6 mRNA and high Nrf2 protein were related to a lower probability of survival. The rs1238662089 within the identified Nrf2-binding site was found to greatly affect CYP2D6 expression levels, indicating its role as predictor for better prognosis. CONCLUSION: This study revealed for the first time that Nrf2 regulates CYP2D6expression in breast cancer and is involved in TAM sensitivity; thus, plays a role in breast cancer patient prognosis.KEYWORDS: breast cancer, CYP2D6, Nrf2, pharmacoepigenetics, SNPs