The Indonesian Biomedical Journal

76-92

Authors: Anna Meiliana, Andi Wijaya

BACKGROUND: Less than a decade ago the prospect for reprogramming the human somatic cell looked bleak at best. It seemed that the only methods at our disposal for the generation of human isogenic pluripotent cells would have to involve somatic cell nuclear transfer (SCNT). Shinya Yamanaka in August 2006 in his publication (Cell) promised to change everything by showing that it was apparently very simple to revert the phenotype of a differentiated cell to a pluripotent one by overexpressing four transcription factors in murine fibroblasts. CONTENT: Mouse and human somatic cells can be genetically reprogrammed into induced pluripotent stem cells (iPSCs) by the expression of a defined set of factors (Oct4, Sox2, c-Myc, and Klf4, as well as Nanog and LIN28). iPSCs could be generated from mouse and human fibroblasts as well as from mouse liver, stomach, pancreatic, neural stem cells, and keratinocytes. Similarity of iPSCs and embryonic stem cells (ESCs) has been demonstrated in their morphology, global expression profiles, epigenetic status, as well as in vitro and in vivo differentiation potential for both mouse and human cells. Many techniques for human iPSCs (hiPSCs) derivation have been developed in recent years, utilizing different starting cell types, vector delivery systems, and culture conditions. A refined or perfected combination of these techniques might prove to be the key to generating clinically applicable hiPSCs. SUMMARY: iPSCs are a revolutionary tool for generating in vitro models of human diseases and may help us to understand the molecular basis of epigenetic reprogramming. Progress of the last four years has been truly amazing, almost verging on science fiction, but if we can learn to produce such cells cheaply and easily, and control their differentiation, our efforts to understand and fight disease will become more accessible, controllable and tailored. Ability to safely and efficiently derive hiPSCs may be of decisive importance to the future of regenerative medicine.

110-5

Authors: Lies Gantini, Syakib Bakri, Andi Wijaya, Anwar Santoso

BACKGROUND: Hypertension and obesity are proinflammatory conditions. Vascular remodeling is one of the pathomechanisms reflecting increased cardiovascular (CV) risks and represented as ratio of MMP-9 and sVEGFR-2 concentration. There is no association confirmed between inflammation and remodeling yet. This study was conducted to investigate the correlation between inflammation and vascular remodeling-repairing balances in hypertensive obese subjects. METHODS: This was a cross–sectional study recruited 34 hypertensive obese subjects and 10 hypertensive non obese subjects. They had no antihypertensive medications, neither diabetics nor renal disease and nor acute inflammation detected. Inflammation was assessed as increased hsCRP concentration. Vascular remodeling and repairing were consecutively represented by ratio of MMP-9 and sVEGFR-2. RESULTS: Concentration of hsCRP and MMP-9 were significantly higher in hypertensive obese group than non obese group (2.094±1.90 vs. 0.714±0.40 mg/L; p=0.029; 363.43±143.64 vs. 261.15±61.13 ng/mL, p=0.035, respectively), nonetheless no significant differences of sVEGFR-2 concentration (9.77±2.30 vs. 9.76±1.38 pg/mL, p=0.980) found in both groups. Ratio of MMP-9/sVEGFR-2 was significantly higher in hypertensive obese group than those in non-obese group (38.67±16 vs. 27.22±10, p=0.038). Likewise, they had more subjects with ratio of MMP-9/sVEGFR-2 ≥31.53. This figure is considered as cut-off point of vascular remodeling versus repairing. CONCLUSION: In hypertensive obese subjects, inflammation was activated and vascular remodeling more dominant than repairing process. Inflammation was associated with increased remodeling-repairing balances.

122-6

Authors: Meiriza Djohari, Mansyur Arif, Burhanuddin Bahar

BACKGROUND: Several researches reported that inflammatory and immunological mechanism such as autoantibody to β2-glycoprotein I (anti β2GPI) appear as related factors in initiation and progress of atherosclerosis lesion in patient with autoimmune disease. Antibody to β2GPI titers are correlated with atherosclerosis and in vitro studies showed that they enhance oxidized low density lipoprotein (ox-LDL) uptake by macrophages. Immunization with auto-antigen β2GPI elicits an immune response to influence lesion progression that mostly happens in autoimmune subjects. The metabolic syndrome (MetS) is combination of several metabolic disorders such as obesity, dyslipidemia, Diabetes Mellitus (DM) and conditions due to inflammation and stress oxidative. The Correlation between inflammatory markers such as High sensitivity C-Reactive Protein (hsCRP) and anti-β2GPI antibody in MetS needs to be further investigated. METHODS: This was an observational study with cross sectional design on subject with MetS as determined by the International Diabetes Federation (IDF) 2005’s criteria. RESULTS:There was a positive and significant correlation between hsCRP and anti-β2GPI antibody in MetS group (r=0.406; p≤0.05) as compared to non-MetS group. We found that there was elevated level of anti-β2GPI antibody in hsCRP of 3-10 mg/L. CONCLUSIONS: Anti-β2GPI antibody may be elevated in subjects with MetS who have low grade of inflammation as shown by hsCRP.

133-7

Authors: Widya Kurniawati, Marsetio Donosepoetro, Andi Wijaya

BACKGROUND: Central obesity is known as the cause of many metabolic disorders called Metabolic Syndrome. Accumulation of adipocytes in central obesity increases production of cytokines proinflammation. Free fatty acid increases in obesity that drives atherogenic dyslipidemia and insulin resistance. IDF 2005 states that waist circumference (WC) is regarded as the simple criteria of obesity. Energy imbalance lasting for a long period is a determinant factor for obesity, e.g. when energy intake is greater than energy expenditure. The brain and gastrointestinal tract work together to maintain this system. Ghrelin and Obestatin are two gut hormones that work in different ways to keep the energy balance. Ghrelin increases appetite but Obestatin decreases it. The two hormones play an important role in maintaining the dynamic equilibrium of energy balance. This study was aimed to determine correlation of Ghrelin and Obestatin with WC in central obese men. METHODS: This was a cross sectional study involving 53 central obese men. Based on IDF 2005 central obesity is most easily measured by waist circumference using the guidelines ethnic group (not country of residence) specific. We used South Asia ethnic which including Chinese, Malay and Asian Indian population as criteria for this study, that was WC >90 cm, aged 20-60 years. Subjects who had smoking habit, any infectious disease, and ACS were excluded from the study. No restriction was applied on the kind of meals the subjects were having or activities they were doing. The correlation of waist circumference with ghrelin and obestatin was assessed with a significance level of 95% (α=0,05). RESULTS: Patient's age was 40.9623±7.9080 year, waist circumferences was 102.1981±10.2696 cm, weight was 85.8679±16.5475 kg, height was 168.8066±6.3535 cm, BMI was 29.9723±2.4937 kg/m2. Concentration of Ghrelin were 0.70-13.72 ng/mL, and Obestatin 16.66-148.84 pg/mL. Pearson correlation showed that Ghrelin (r=-0.1114, p=0.4271) and Obestatin (r=-0.1781, p=0.2020) had no significant correlation with WC. But in patients WC ≥120 cm had significant negative correlation with Obestatin (r=-0.375, p=0.049). CONCLUSIONS: There was no significant correlation of Ghrelin and Obestatin with WC in obese men. However, there was a negative correlation tendency found in patients with greater WC (≥102 cm).