The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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CAPN10 SNP-19 is Associated with Susceptibility of Type 2 Diabetes Mellitus: A Javanese Case-control Study
Get PDFBACKGROUND: The health data of Central Java, Indonesia showed that diabetes mellitus (DM) was the second most increasing non-communicable disease in the province. More than 20 genes have been reported to be associated with DM. Calpain-10 (CAPN10) polymorphism has been reported to be associated with Type 2 Diabetes Mellitus (T2DM). However, the association between CAPN10 single nucleotide polymorphism (SNP)-19 and T2DM among Javanese ethnics has never been reported. Therefore, this study was conducted to investigate the association.METHODS: After fasting for 8 hours, blood samples were drawn from veins of 107 T2DM and 107 non diabetic subjects. A half of the drawn blood was collected for identification of CAPN10 SNP-19, and another half for measuring triglycerides and fasting blood glucose (FBG). Identification of CAPN10 SNP-19 was performed with polymerase chain reaction (PCR) method, while measurement of triglycerides and FBG with colorimetric enzymatic method.RESULTS: The number of T2DM Javanese subjects with 2R/3R and 3R/3R CAPN10 SNP-19 genotypes was significantly higher than the number of T2DM Javanese subjects with 2R/2R genotype (p=0.002). When each number of 2R/3R and 3R/3R T2DM subjects was compared with the number of 2R/2R T2DM subjects, the number of 2R/3R T2DM subjects was significantly higher than the number of 2R/2R T2DM subjects (p=0.000).CONCLUSION: Javanese subjects with 2R/3R and 3R/3R CAPN10 SNP19 genotypes might have susceptibility of T2DM.KEYWORDS: Calpain-10, CAPN10, polymorphism, type 2 diabetes mellitus, triglycerides, fasting blood glucos
Lactobacillus plantarum IS-20506 Probiotic Restores Galectin-4 and Myosin-1a Expressions in Duodenum, Jejunum and Ileum of Lipopolysaccharide-induced Rats
Get PDFBACKGROUND: Galectin-4 and Myosin-1a are important proteins for normal intestinal brush border structure and composition. Damage of these proteins by inflammation may alter digestion, absorption and barrier function. Probiotic has been widely known in maintaining gut health. However, the molecular mechanism of Lactobacillus plantarum IS-2056 probiotic in repairing intestinal brush border is not well defined. Therefore, current study was conducted by investigating the Galectin-4 and Myosin-1a expressions in a rodent model.METHODS: Male Wistar rats were induced with/without lipopolysaccharide (LPS) and treated with/without L. plantarum IS-2056 probiotic. On the seventh day, duodenum, jejunum, and ileum were collected and analyzed with western blot and immunohistochemistry for Galectin-4 and Myosin-1a expressions.RESULTS: Rats administrated with L. plantarum IS-2056 probiotic showed significant increase of Galectin-4 and Myosin-1a expressions in duodenum, jejunum, and ileum compared to the control group (p<0.05). While in control group, Galectin-4 level tended to increase in more distal of intestinal segment and Myosin-1a level tended to decrease in more distal intestinal segment.CONCLUSION: L. plantarum IS-20506 probiotic may facilitate the repairment of damaged intestinal brush border as demonstrated by significant restoration of Galectin-4 and Myosin-1a expressions in duodenum, jejunum, and ileum of LPS-induced rats.KEYWORDS: Lactobacillus plantarum, IS-20506, probiotic, galectin-4, myosin-1a, duodenum, jejunum, ileu
Current Progress in Adipose Tissue Biology: Implications in Obesity and Its Comorbidities
Get PDFBACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function.CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige.SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic diseas
Role of HIF-1, Siah-1 and SKN-1 in Inducing Adiposity for Caenorhabditis elegans under Hypoxic Conditions
Get PDFBACKGROUND: Hypoxia has been shown to be able to induce adiposity. However, the mechanism and factors involved in this effect still remains unclear. Hence, we sought to investigate the role of oxygensensitive factors regarding hypoxia-induced adiposity in nematode Caenorhabditis elegans.METHODS: The C. elegans were grown on nematode growth medium (NGM) agar plates seeded with Escherichia coli OP50 at 20°C. The ratio of width/body length was measured using the morphometry analysis. Fat accumulation was examined using Sudan Black methods. Protein levels of sterol binding protein (SBP)-1 were assessed by immunoblotting. Lifespan assay was performed at 20°C and was monitored every two days.RESULTS: The results showed that of all mutant used, only hif-1 mutant which did not experience an increase in the ratio of width/body length (p>0.05) and fat accumulation (p>0.05), indicating that hypoxia-inducible factors (HIF)-1 plays an important role in the pathogenesis of hypoxia-induced adiposity. Both siah-1 and skn-1 mutants experienced SBP-1 protein elevation (p0.05) further supporting that HIF-1 acts as an upstream regulator fromSBP-1.CONCLUSION: In general, the results of this study provide evidences of the involvement of the transcription factor HIF-1 in inducing adiposity under the hypoxic conditions. However, we did not find the involvement of seven in absentia homolog-1 (Siah-1) and skinhead-1 (SKN-1).KEYWORDS: hypoxia, adiposity, fat, HIF-1, Siah-1, SKN-1, C. elegan
Circulating Plasma miRNA-21 as a Superior Biomarker Compared to CA 15-3: Assessment in Healthy Age Matched Subjects and Different Stage of Breast Cancer Patients
Get PDFBACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breast cancer group was elevated 4.92 folds compared to control group (p=0.001), 4.43 and 0.90, respectively. There was no significant difference of CA 15-3 level between controls and all stages of breast cancer group. CA 15-3 cut-off value was 15.05 m/mL (p=0.016) with 59.2% sensitivity and 62.5% specificity. Meanwhile, there was a significant difference of miRNA-21 expression between controls and most stages of breast cancer group. Circulating miRNA-21 expression cut-off value was 2.07 (p=0.000) with 91.8% sensitivity and 87.5% specificity.CONCLUSION: Circulating miRNA-21 expression and CA 15-3 levels were significantly increased in breast cancer group compared to control group. The miRNA-21 expression increased consistently with breast cancer stage progression. miRNA-21 could serve as superior biomarker compared to CA 15-3.KEYWORDS: biomarker, breast cancer, circulating plasma, liquid biopsy, miRNA-2
Nutrigenetics, Nutrigenomics and Precision Nutrition
Get PDFBACKGROUND: Since our conception to death, we were permanently exposed to nutrition. Indeed, food intake is the key of the environmental factor that modulates our gene. Nutrigenomics focus on how common dietary chemicals altering an individual’s genetic makeup including genome, proteome, and metabolome. While nutrigenetics refer to how the genetic variation gives different responses to nutrients.CONTENT: Nutrigenomics applied the high-throughput genomic-related tools to find out the influence of nutrients on the genes’ expression. While nutrigenetics (nutritional genetics) focus on the heterogenous response of gene variants to nutrients and dietary factors. Application nutrigenomics and nutrigenetics, integrated with system biology result in a precision nutrition as a relevant precise personal dietary change recommendation, thus will increase the motivation and sustain to whom the intervention is being delivered.SUMMARY: Individual diet recommendation is not simple. Many factors and tools should be involved adequately. The application of integrated -omics approaches, together with nutrigenomic and nutrigenetics for novel biomarker discovering and precision nutrition tailoring were expected to develop a healthier lifestyle and behavior.KEYWORDS: nutrigenetics, nutrigenomics, precision nutrition, metabolomics, system biolog
Positivity Rate of Pyrosequencing to Diagnose Drug-Resistant Tuberculosis Directly from Sputum with Different Bacterial Load
Get PDFBACKGROUND: Molecular techniques, which detect mutations associated with drug resistance tuberculosis (TB), are promising technologies for rapid diagnosis and monitoring of drug-resistant TB. Pyrosequencing is a potential rapid and robust molecular technique to detect drug resistance but its performance in clinical samples is less investigated. This study aimed to determine the positivity rate of pyrosequencing to diagnose drug-resistant TB directly from sputum samples with different grades of sputum smear microscopy results.METHODS: Thirty-five sputum specimens from drug-resistant TB suspects were submitted for acid-fast bacilli (AFB) microscopy. All specimens were cultured using microscopic observation drug susceptibility (MODS) culture. Pyrosequencing was performed to DNA extracted from sputum of culture-positive patients.RESULTS: MODS culture was positive in 19/35 subjects (54.29%) samples; 16 smear-positive and three smear-negative. Using pyrosequencing, Mycobacterium tuberculosis was identified in all culture-positive samples, including smear-negative samples. A complete resistance profile for 16 (82.35%) samples could be generated. Pyrosequencing failed to show results for eis or gyrA promoter in three samples. Nine of 19 patients were multidrug resistant-TB (MDR-TB), 1/19 was rifampicin-resistance TB (RR-TB), and 4/19 were pre-extensively drug-resistant TB (pre-XDR-TB). Two novel mutations in rpoB and rrs (associated with rifampicin and aminoglycoside, respectively) were found in this study.CONCLUSION: The results of this study demonstrates high positivity rates of pyrosequencing to detect drug-resistant TB directly from sputum samples with different grades of smear microscopy, as the surrogate of bacterial load. The assay can be used as a first prediction test of drug resistance prior to confirmation by phenotypic tests.KEYWORDS: drug-resistant tuberculosis, pyrosequencing, direct sputu
Differentiation of Low-Grade and High-Grade Glioma Using the Combination of Conventional Magnetic Resonance Imaging and Apparent Diffusion Coefficient Value
Get PDFBACKGROUND: The conventional magnetic resonance imaging (cMRI) and apparent diffusion coefficient (ADC) may have a role in predicting tumor grade for gliomas and may in turn assist in identifying tumor biopsy sites. In this study, we aimed to determine the added value of a joint approach of diffusion-weighted imaging (DWI) and cMRI to determine of low grade and high-grade glioma, compare to cMRI alone.METHODS: Data were collected from 56 glioma patients, who underwent examinations and received treatment at Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia, from the period of 2015–2018. Inclusion criteria was patients who underwent cMRI with a DWIADC sequence and patient that were diagnosed with glioma according to the histopathological results. Pathology reports of the imaging results were reviewed independently. A receiver operator curve (ROC) analysis assessed the predictive potential of cMRI and ADC values for low-grade and high-grade gliomas.RESULTS: Fifty-six subjects met the inclusion criteria. The combination of MRI and ADC values increased sensitivity (to 90%) and negative predictive value (to 92.9%), and also improved the negative likelihood ratio (to 0.14). However, the combination of MRI and ADC values had the highest area under the curve (78.6%) and sensitivity (78.6%), which was similar to the separated examination.CONCLUSION: The combination of ADC value and conventional MRI increases sensitivity in differentiating low-grade and high-grade glioma compared to separated examination.KEYWORDS: glioma, conventional MRI, ADC valu
Survivin and Telomerase as Radiotherapeutic Response Predictors of Subjects with Stage IIIB Cervical Squamous Cell Carcinoma
Get PDFBACKGROUND: Cervical cancer is one of the most prevalent cancers in women. Even with similar clinicopathologic features, radiotherapy outcomes are still vary among patients. This research was conducted to measure radiotherapy responses on cervical cancer patients by using Survivin, Telomerase and Cytochrome C.METHODS: Subjects who matched the criteria were selected and requested to fill questionnaires. Subjects were then evaluated with magnetic resonance imaging (MRI) pre- and post-3D conformal radiotherapy. Histopathological study was conducted using resected tumors to determine the differentiation type. Enzyme-linked Immunosorbent Assays for detection of Survivin, Telomerase and Cytochrome C was performed using the resected tumors as well.RESULTS: There were 76 patients in this study. Mean ofage was 50 and diameter of tumor size was 5.35 cm. Mean levels of Survivin, Telomerase and Cytochrome C were 632.82 pg/mL, 5.59 pg/mL and 204.75 ng/mL, respectively. There were significant correlations between radiotherapy response and Survivin (p=0.041) or Telomerase (p=0.022). Subjects with lower Survivin level (<932 pg/mL) had higher 1-year survival rate (63%) than subjects with higher Survivin level (50%). Similar results were obtained for subjects with lower Telomerase level (<5.75 pg/mL), who had higher 1-year survival rate (60%) than subjects with higher Telomerase level (43%).CONCLUSION: Since radiotherapy response is significantly correlated with Survivin and Telomerase levels and subjects with lower Survivin or Telomerase level have higher 1-year survival rate, it can be suggested that Survivin and Telomerase could be potential predictors of radiotherapeutic response for subjects with stage IIIB cervical squamous cell carcinoma.KEYWORDS: cervical cancer, radiotherapy Survivin, Telomerase, Cytochrome
Correlation of Maternal Serum Hepcidin, Soluble Transferrin Receptor (sTfR) and Cholecalciferol with Third Trimester Anemia: Findings from A Nested Case-control Study on A Pregnancy Cohort
Get PDFBACKGROUND: Cholecalciferol, hepcidin, and soluble transferrin receptor (sTfR) interaction play an essential role in iron hemostasis. Anemia in pregnancy contributes to morbidity and mortality both for the mother and baby. In this study, we assessed the correlation between hepcidin, sTfR and cholecalciferol in third trimester maternal anemia. We aimed to find the cut-off for hepcidin and sTfR.METHODS: A case-control study involving 56 pregnant women in each anemia and healthy group was nested on a previous larger cohort study in Indonesia. Serum hepcidin, sTfR and cholecalciferol level were measured by enzyme-linked immunosorbent assay (ELISA) method.RESULTS: Serum hepcidin and sTfR level were significantly higher in case group, while serum cholecalciferol level has no difference between the two groups. New cut-off points were found for hepcidin (2234.45 ng/mL). Low level of hepcidin (OR=5.32) and high level of sTfR (OR=8.28) increase the risk of anemia. High level of sTfR (adjusted OR=4.725; CI 95%=1.730-12.904; p=0.02) was the most important factor contributes to anemia, followed by the low level of hepcidin (adjusted OR=3.677; CI 95%=1.363-9917; p=0.01).CONCLUSION: The high level of sTfR is the most important factor related to anemia in the third trimester, followed by the low level of hepcidin. Low cholecalciferol level tends to favor the incident of anemia. The new cut-off point of third trimester sTfR and third trimester hepcidin were established in this study and may be useful for risk assessment and treatment monitoring for anemia in pregnancy.KEYWORDS: anemia, cholecalciferol, hepcidin, pregnancy, soluble transferrin recepto