Decreased Expression of Peroxisome Proliferator-activated Receptor α Gene as an Indicator of Metabolic Disorders in Stunting Toddler

BACKGROUND: Stunting in children increases the risk of degenerative diseases in adulthood, including dyslipidemia, obesity, type 2 diabetes mellitus, and cardiovascular disease. This is based on the result of metabolic changes that may be caused by chronic malnutrition and experienced by stunting children. Stunting in children is associated with metabolic disorders that are based on impaired fat oxidation, a trigger factor for obesity in adulthood. The peroxisome proliferator-activated receptor (PPAR) α gene is a transcriptional factor that regulates fat, carbohydrate, and amino acid metabolism whose genetic variants are linked to the development of dyslipidemia and cardiovascular disease. AIM: The study assessed the effect of metabolic changes in stunting toddler on PPARα gene expression. MATERIALS AND METHODS: An analytical-observational laboratory was done using 41 blood samples, coming from 23 stunting toddlers, and 18 not-stunting toddlers. In all research subjects, anthropometric measurements and examination of PPARα gene mRNA expression were carried out. Analysis of PPARα gene mRNA expression using one-step quantitative reverse transcriptase-polymerase chain reaction using specific primers, as a comparison of gene expression using the GAPDH gene. The relative expression of the PPARα mRNA gene was analyzed using the LIVAK formula. RESULTS: The study obtained a mean of ΔCT in stunting toddlers of 5.81, whereas in stunting toddlers at 5.082. Analysis with LIVAK 2 ^ - formula (ΔCT stunting -ΔCT not stunting) obtained PPARα mRNA gene expression of 0.6. CONCLUSION: We conclude that there is a decrease in PPARα gene expression in stunting toddlers

Exercise Intensity Alter Insulin Receptor Gene Expression in Diabetic Type - 2 Rat Model

AIM: To analyse the differential expression of the insulin receptor (IR) gene between moderate continuous and severe continuous training in the T2DM rat model. METHODS: This was an experimental study. Healthy male Wistar was used in this study, which divided into sedentary, moderate continuous training, and severe continuous training. Treated groups were assigned to run on the treadmill three times a week for eight weeks consequently. RESULTS: The result shown that expression of mRNA IR gene in treated groups decline compared to control. There was a difference mRNA IR gene expression after eight weeks of exercise between MCT and control, SCT and control so are MCT and SCT. IR expression on skeletal muscle in treated groups was different compared with control. The distribution of IR on skeletal muscles in treatment groups was significantly increased compared control, but there was no significant difference distribution between MCT and SCT. HOMA-IR post-test in SCT was lower than MCT but FBG post-test lower in MCT than SCT. CONCLUSION: The intensity of exercise makes a difference in IR gene expression between moderate continuous training and severe continuous training after eight weeks of assigned exercise in T2DM rat models

Durian Consumption Effect on the Plasma Malondialdehyde Level as Biomarker of Stress Oxidative in Rats

Background: Excessive consumption of durian (Durio zibethinus Murray) in Indonesia is often connected with its effect on health. This study aims to understand the effect of durian consumption to malondialdehyde (MDA) in plasma as oxidative stress biomarker.Methods: The study used an experimental research design on animal models, in the Biochemistry and Molecular Biology Department, Faculty of Medicine, Universitas Indonesia, July–August 2012. Thirty two Sprague-Dawley rats were used, divided into four groups: control, treatment week 1, 2, and 3. Each treatment group was given 20 gram durian fruit diluted with water until 20 ml volume per oral, divided into two doses (10 ml each) with 4 hours interlude between doses for 1 week, 2 weeks, and 3 weeks. All groups got normal diet and water ad libitum. Plasma MDA level was measured by TBARS method, then analyzed using Kurskal-Wallis and Mann-Whitney tests.Results: Seventeen samples were successfully decapitated (5 for control; 6 for week 1; 3 for week 2; 3 for week 3). Average plasma MDA level for control treatment week 1, 2 and 3 groups were 0.707 nmol/ml, 0.432 nmol/ml, 0.312 nmol/ml, and 0.746 nmol/ml respectively. Data was significant (p<0.05) with p=0.02. Compared with control group, a significant increase occurred in week 1 and 2 groups with p=0.028 and p=0.025 respectively.Conclusions: Results of durian consumption show MDA level significantly decreases in week 1 and 2. However, MDA level dramatically increases exceeding control group level in week 3. [AMJ.2016;3(1):22–8] DOI: 10.15850/amj.v3n1.69

ROLE OF SDF-1 AND CELECOXIB IN INCREASING QUANTITY OF NEURAL STEM CELL IN THE LESION ZONE AND OUTCOME OF SPONTANEOUS INTRACEREBRAL HEMORRHAGE

Objective: We studied the effect of stromal derived factor-1 (SDF-1) and celecoxib for increasing the amount of neural stem cells in the lesion zone and clinical outcomes of spontaneous intracerebral hemorrhage.Methods: Twenty-eight rats, strain Wistar, divided into four groups: control, treated with celecoxib, SDF-1, and the combination of celecoxib+SDF-1. The neural stem cells identified by immunohistochemistry procedures with Nestin as primary antibodies and the levels of proliferation were assessed by Ki-67 as primary antibodies. The clinical outcomes were examined by Bederson scale. Results: This study revealed the combination treatment group had the highest histoscores of Nestin and highest of Ki-67 histoscores for SDF-1 group. The amount of neural stem cells in the lesion zone of treatments groups was higher than controls (p&lt;0.005), but similar between treated groups (P&gt;0.05). The proliferation levels were higher in SDF-1 group (P&lt;0.05), and the clinical outcomes back to normal were highest in combination therapeutic groups, even though not different when compared to another group (p&gt;0.05).Conclusion: The results suggest celecoxib, SDF-1, and the combination of celecoxib+SDF-1 can increase neural stem cells in spontaneous intracerebral hemorrhage, and SDF-1 increased proliferation levels. The clinical outcomes were not significantly different between rats, regardless of the fact that almost all of rats in the combination group were back to normal.Keywords: Neuroinflammation, Cyclooxygenase-2, Bederson Scal

Distribution of VDR Gene Polymorphisms Bsm-I rs1544410 and Apa-I rs7975232 among HIV/AIDS Patients from West Java

Vitamin D receptor, encoded by VDR gene, mediates vitamin D functions by not only regulating calcium metabolism and homeostasis but also in regulating immune response. Polymorphisms in VDR gene may increase the progression of human immunodeficiency virus (HIV) infection into acquired immunodeficiency syndrome (AIDS). This study aimed to explore the distribution of VDR polymorphisms among HIV sero-positive patients in West Java. A cross-sectional study was performed, recruiting 96 patients infected with HIV and VDR polymorphisms were analyzed. The genotype distributions of Bsm-I among HIV-infected patients were 2.2%, 18.5%, and 79.3% for BB, Bb, and bb, respectively whereas the distributions of Apa-I were 54.4%, 38.9%, and 6.7% for AA, Aa and aa, respectively. The frequency of VDR polymorphisms in Bsm-I among HIV-infected patients in West Java were considered high for b allele (88.6%), and in contrast for A allele in Apa-I that was 73.91%. Further studies involving healthy controls are needed to explore the VDR polymorphisms distribution in general population. Moreover, a cohort study, albeit challenging, is needed to further assess the association between VDR polymorphisms and the progression of HIV infection.Distribusi Polimorfisme gen VDR Bsm-I rs1544410 dan Apa-I rs7975232 pada Pasien HIV/AIDS di Jawa BaratReseptor vitamin D yang dikode oleh gen VDR mempunyai peranan penting terhadap fungsi vitamin D, tidak hanya dalam regulasi metabolisme dan keseimbangan kalsium namun juga berperan dalam meregulasi respon imun. Polimorfisme pada gen VDR ditengarai dapat meningkatkan progresivitas infeksi human immunodeficiency virus (HIV) menjadi acquired immunodeficiency syndrome (AIDS). Penelitian ini bertujuan mengetahui distribusi polimorfisme gen VDR pada pasien HIV di Jawa Barat. Penelitian ini melibatkan 96 pasien HIV dan dilakukan analisis polimorfisme gen VDR. Distribusi genotip Bsm-I pada pasien HIV di Jawa Barat adalah 2,2%, 18,5%, dan 79,3% untuk BB, Bb, dan bb, secara beurutan; sedangkan pada Apa-I adalah 54,4%, 38,9%, dan 6,7% untuk AA, Aa, dan aa. Frekuensi polimorfisme pada Bsm-I pada pasien HIV di Jawa Barat tergolong tinggi pada alel b (88,6%) dan berbanding terbalik pada dan Apa-I dengan alel A yaitu 73,91%. Penelitian lebih lanjut yang melibatkan individu kontrol diperlukan untuk mengetahui distribusi polimorfisme gen VDR pada populasi umum. Selain itu, studi kohort pada pasien HIV/AIDS diperlukan untuk menilai hubungan antara polimorfisme gen VDR terhadap progresivitas infeksi HIV

Durian Consumption Effect on the Plasma Malondialdehyde Level as Biomarker of Stress Oxidative in Rats

Background: Excessive consumption of durian (Durio zibethinus Murray) in Indonesia is often connected with its effect on health. This study aims to understand the effect of durian consumption to malondialdehyde (MDA) in plasma as oxidative stress biomarker.Methods: The study used an experimental research design on animal models, in the Biochemistry and Molecular Biology Department, Faculty of Medicine, Universitas Indonesia, July–August 2012. Thirty two Sprague-Dawley rats were used, divided into four groups: control, treatment week 1, 2, and 3. Each treatment group was given 20 gram durian fruit diluted with water until 20 ml volume per oral, divided into two doses (10 ml each) with 4 hours interlude between doses for 1 week, 2 weeks, and 3 weeks. All groups got normal diet and water ad libitum. Plasma MDA level was measured by TBARS method, then analyzed using Kurskal-Wallis and Mann-Whitney tests.Results: Seventeen samples were successfully decapitated (5 for control; 6 for week 1; 3 for week 2; 3 for week 3). Average plasma MDA level for control treatment week 1, 2 and 3 groups were 0.707 nmol/ml, 0.432 nmol/ml, 0.312 nmol/ml, and 0.746 nmol/ml respectively. Data was significant (p<0.05) with p=0.02. Compared with control group, a significant increase occurred in week 1 and 2 groups with p=0.028 and p=0.025 respectively.Conclusions: Results of durian consumption show MDA level significantly decreases in week 1 and 2. However, MDA level dramatically increases exceeding control group level in week 3. [AMJ.2016;3(1):22–8] DOI: 10.15850/amj.v3n1.69

Frequency of MTHFR GENE C677T Polymorphism for Non-Syndromic Autism Spectrum Disorder Patients

Background: The folate metabolism is a pathway that may involve in the non-syndromic Autism Spectrum Disorder (ASD). Methylenetetrahydrofolate reductase enzyme has a key role in folate metabolism. The C677T polymorphism of MTHFR gene could reduce the effectiveness of the enzyme.Objectives: To evaluate the frequency of MTHFR geneC677T polymorphism for non-syndromic ASD patients.Method: Thirty-four DNA samples were taken from each group. PCR mixture was consisted of 1µL DNA, 2.5µL PCR buffer, 0.5µL dNTP, 1.5µL MgCL2, 0.125µLTaqenzyme, 0.5µLofforwardandreverseprimerandaquabidesttoreach a volume of 25 µL. The PCR profiles were initiation 95ºC for 5 min, denaturation 94ºC for 1min, annealing 55ºCfor 45 seconds, and elongation 72ºC for30 seconds. The cycles were done in 35 times an dfinal elongation was at 72ºC for 5min. The PCR product was 198bp, and then digested by the Hinfl enzyme for 16hours at 37°C, and visualized using2%agarosegeland then electrophoresed for 30 minutes at 100 volts.Result: Non-syndromic ASD samples showed none had homozygote mutant type (677TT), 3 (8.8%) samples had heterozygote (677CT)and 31 (91.2%) samples had wild type (677CC). Meanwhile, normal control showed only 1 (2.9%)sample had homozygote mutant type(677TT), 9 (26.5%) samples had heterozygote (677CT)and 24 (70.6%) samples had  wild type (677CC).Conclusion: The frequency of MTHFR geneC677T polymorphism in patients with non-syndromic ASD and controls are not significantly different

The Role of Transforming Growth Factor-Beta, Fibroblast Growth Factor, Platelet-derived Growth Factor, Epidermal Growth Factor, Insulin-like Growth Factor, Vascular Endothelial Growth Factor, and Sonic Hedgehog in the Non-syndromic cleft lip with or without cleft palate development: A Scoping Review

Non-syndromic cleft lip with or without cleft palate (NSCLP) birth defect, it imposes an enormous stress on society and requires nutrition, dental, speech, behavioural, and surgical therapies. The NSCLP multifactorial aetiology, including the environment and genetic factors. The environment and genetic factors affect the cellular mechanism, cell proliferation, cell differentiation, and cell migration and signalling pathways. Genetic growth factors including Transforming Growth Factor-Beta (TGF-β), Fibroblast Growth factors (FGFs), Platelet-derived Growth factors (PDGFs), Epidermal Growth factor (EGF), Insulin-like growth factors (IGF), Vascular Endothelial Growth factor (VEGF), Sonic Hedgehog (SHH). The study aims to understand the role of the growth factors “TGF-β, FGFs, PDGFs, EGF, IGF, VEGF, and SHH” in NSCLP development. Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards were followed when performing this scoping review. The 942 articles were extracted, and the following inclusion and exclusive criteria 43 articles were eligible for review. Twenty-seven studies identify 26 genes and 25 single-nucleotide polymorphisms (SNPs)/variants of the growth factors that are a significant risk for NSCLP development. In conclusion, the analysis of diverse populations and growth factors including TGF-β, FGFs, PDGFs, EGF, IGF, VEGF, and SHH were associated with NSCLP. The growth factors were involved in the cellular mechanism, cell proliferation, cell differentiation cell migration and signalling pathways that lead to the pathogenesis of NSCLP

Natural resistance-associated macrophage protein 1 gene polymorphisms in thalassemia patients with tuberculosis infection

that needs regular blood transfusions leading to accumulation of iron in the cells. This iron overload level in macrophage might cause intracellular bacteria, particularly Mycobacterium tuberculosis (MTB) to multiply. Polymorphisms in natural resistance-associated macrophage protein 1 (NRAMP1), a metal transporter across the phagosome membrane, play important role in regulating iron, which is also needed by MTB. Increased iron in thalassemia patients may have an increased potential risk for TB. Objective To compare natural resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms (INT4, D543N, and 3’UTR) in thalassemia patients with and without tuberculosis (TB) infection. Methods A cross-sectional measurement of NRAMP1 genetic polymorphisms was performed in pediatric thalassemia patients with TB (n=40) and without TB (n=50). Iron status including serum iron, total iron-binding capacity (TIBC), and ferritin, was compared between the two groups. The NRAMP1 genetic polymorphisms were analysed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Allelic and genotypic distributions of each polymorphism were assessed for possible associations with TB infection. Results Mean serum iron and TIBC in thalassemia patients with TB were higher compared to thalassemia patients without TB (mean serum: 166.26 vs. 134.92 μmol/L, respectively; P=0.026) and (mean TIBC: 236.78 vs. 195.84 μmol/L, respectively; P=0.029). In thalassemia patients with TB, we observed significantly higher frequency of the C allele in INT4 (10% vs. 2%, respectively; OR=5.44; 95%CI 1.1 to 26.4; P=0.02) and the TGTG deletion allele (78.8% vs. 51%, respectively; OR=3.56; 95%CI 1.83 to 6.9; P=0.0002) in 3’UTR polymorphisms than in thalassemia patients without TB. There were no significant  differences in distributions of the A allele between TB and non-TB groups (16.3% vs. 15%, respectively; P=0.84) or the GA genotype (32.5% vs. 30%, respectively; P=0.79) in D543N. Conclusion The NRAMP1 polymorphisms are known to be associated with major gene susceptibility to TB, and in our thalassemia patients this association is even more pronounced

Distribution of rs1801279 and rs1799930 Polymorphisms in NAT2 Gene among Population in Kupang, Nusa Tenggara Timur, Indonesia

BACKGROUND: N-acetyltransferase-2 (NAT2) enzyme, encoded by NAT2 gene, plays a key role in metabolism of anti-tuberculosis (TB) drug isoniazid. Polymorphisms in NAT2 gene may result in different responses to TB therapy. Since TB prevalence in the eastern part of Indonesia is high, the aim of this study is to explore the distribution of NAT2 gene polymorphisms among population from Kupang, Nusa Tenggara Timur.METHODS: A total of 234 respondents were included from Kupang in 2012. Polymorphisms of NAT2 gene were examined using mass screening platform and the genotypes distribution were presented in percentage. To confirm NAT2 gene polymorphisms, polymerase chain reaction (PCR)-sequencing was performed in a subset of population.RESULTS: The polymorphisms of NAT2 gene showed that the distribution of rs1801279 for GG genotype was 100%; whereas the genotype distribution of rs1799930 for GG, GA and AA was 57%, 35.1% and 7.9%, respectively. In a subset of individuals (n13), acetylator status was well determined by PCR-sequencing, resulting in individual with wild type fast acetylator (NAT2*4; n4), intermediate (NAT2*4/*5 or NAT2*4/*6 or NAT2*4/*7; n7) and poor acetylators (NAT2*6/*6 or NAT2*7/*7; n2).CONCLUSION: The amino acid change in rs1799930 result in intermediate and poor acetylator status in Kupang population. This may lead to suboptimal response of TB therapy. Assessing acetylator status before TB therapy is important and may serve as personalized INH therapy.KEYWORDS: NAT2 gene, polymorphism, acetylator status, Kupan