Proteomic-miRNA Biomics Profile Reveals 2D Cultures of Human iPSC-Derived Neural Progenitor Cells More Sensitive than 3D Spheroid System Against the Experimental Exposure to Arsenic.

The iPSC-derived 3D models are considered to be a connective link between 2D culture and in vivo studies. However, the sensitivity of such 3D models is yet to be established. We assessed the sensitivity of the hiPSC-derived 3D spheroids against 2D cultures of neural progenitor cells. The sub-toxic dose of Sodium Arsenite (SA) was used to investigate the alterations in miRNA-proteins in both systems. Though SA exposure induced significant alterations in the proteins in both 2D and 3D systems, these proteins were uncommon except for 20 proteins. The number and magnitude of altered proteins were higher in the 2D system compared to 3D. The association of dysregulated miRNAs with the target proteins showed their involvement primarily in mitochondrial bioenergetics, oxidative and ER stress, transcription and translation mechanism, cytostructure, etc., in both culture systems. Further, the impact of dysregulated miRNAs and associated proteins on these functions and ultrastructural changes was compared in both culture systems. The ultrastructural studies revealed a similar pattern of mitochondrial damage, while the cellular bioenergetics studies confirm a significantly higher energy failure in the 2D system than to 3D. Such a higher magnitude of changes could be correlated with a higher amount of internalization of SA in 2D cultures than in 3D spheroids. Our findings demonstrate that a 2D culture system seems better responsive than a 3D spheroid system against SA exposure.

Pattern of dyslipidemia and evaluation of non-HDL cholesterol as a marker of risk factor for cardiovascular disease in type 2 diabetes mellitus.

People with type 2 Diabetes have an elevated risk for developing cardiovascular disease (CVD) for which dyslipidemia is the major contributor. Diabetic patients have characteristic pattern of dyslipidemia with decreased level of high density lipoprotein cholesterol (HDL-C) and elevated triglycerides (TG) level. However, in diabetes mellitus, low density lipoprotein cholesterol (LDL-C) which is used as one of the markers for the risk of CVD, is underestimated so in such cases the levels of non-High density lipoprotein cholesterol (non-HDL-C) can be a stronger predictor of CVD as it strongly correlates with atherogenic lipoproteins. Therefore, an attempt has been made to evaluate the level of non-HDL-C as a newer marker for the risk of cardiovascular disease and to find out the pattern of dyslipidemia in diabetes mellitus. The present study comprised of 82 type 2 Diabetic cases and 81 non-diabetic controls. Among the diabetics, the majority of the subjects (61.0%) were HDL-C dyslipidemic. However, among the controls, the maximum numbers of individuals (40.7%) were TG dyslipidemic. Diabetics have significantly elevated ratio of total cholesterol to high density lipoprotein cholesterol (TC/HDL-C) and the significant increased levels of non-high density lipoprotein cholesterol (non-HDL-C) compared to controls which can be used as markers of dyslipidemia and can also be used to predict the risk of cardiovascular disease in type 2 Diabetes Mellitus.

Serum lipid profile in patients with thyroid disorders in central Nepal.

Thyroid dysfunction is a major public health problem among Nepalese population. Hence the study is aimed to find out the prevalence of thyroid dysfunction and to investigate the effect of it in serum lipids. Serum fT3, fT4, TSH, total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides (TG) were measured using standardized assays. Overall thyroid dysfunction was detected in 25.7% of the study population with the higher prevalence among females. The distribution of overt hypothyroidism, subclinical hypothyroidism, overt hyperthyroidism and subclinical hyperthyroidism were 3.7%, 14.1%, 3.3% and 4.6% respectively. There was a positive association between hypothyroidism and TC>200, LDL>130 and TG>200mg/dl; 48.4% of hypothyroid patient had hypercholesterolemia and 32.3% had hypertriglyceridemia. The mean TC, LDL and TG levels were increased progressively with the increase in the serum TSH. It was noteworthy in this study that even a slight increase in serum TSH (between 6.2-10 mIU/L) showed significant increase in serum lipid level. However there was no association among patients with hyperthyroidism and control group.

Assessment of kidney stone and prevalence of its chemical compositions.

Kidney stone analysis is the test done on the stone which cause problems when they block the flow of urine through or out of the kidneys. The stones cause severe pain and are also associated with morbidity and renal damage. There is also no clear understanding on the relative metabolic composition of renal calculi. Hence, the study is aimed to find out the chemical composition of it which can guide treatment and give information that may prevent more stones from forming. The study was carried out on the stones that had been sent to the department of Biochemistry (n = 99; M = 61; F = 38; Mean age: 33.6 +/- 14.4 years) Approximately 98.9% of stones were composed of oxalate, 95.9% of Calcium, 85.8% of phosphate, 62.6% of Urate, 46.4% of Ammonium and very few percentages of Carbonate.

Oxidative stress in benign prostate hyperplasia.

Benign Prostate Hyperplasia (BPH) is the common health problem in ageing male. Free radicals and reactive oxygen species (ROS) are produced more with advancement of age leads to oxidative stress. This study aims to assess Malondialdehyde (MDA), the marker of lipid peroxidation and vitaminic antioxidants e.g. alpha-Tocopherol (Toc) and Ascorbate (Asc) status in plasma of BPH patients. This is a case control study conducted in Department of Biochemistry in collaboration with Dept of Surgery, BPKIHS. Forty eight (n = 48) confirmed patients of BPH and forty six (n = 46) healthy age matched controls were enrolled. Plasma MDA, Asc and alpha-Toc were estimated. Plasma MDA level showed 4.81 +/- 1.87 nmol/ml in BPH patients compared to 3.69 +/- 1.56 nmol/ml in healthy controls (p < 0.001). There were significant decrease in plasma alpha-Toc and Asc level which were 0.85 +/- 0.12 mg/dl and 0.93 +/- 0.13 mg/dl in BPH patients compared to 1.37 +/- 0.31 mg/dl and 1.44 +/- 0.38 mg/dl in healthy controls respectively. Inverse correlation of plasma MDA with a- Toc (r = -0.09) and Asc (r = -0.51) was found in BPH patients. There was mild elevation of PSA in BPH patients compared with control but was not statistically significant. Thus, our study showed the evidence of association of oxidative stress in BPH patients.

Oxidative stress in patients with benign prostate hyperplasia.

Benign Prostate Hyperplasia (BPH) is a common health problem in aging male. Free radicals and Reactive Oxygen Species (ROS) are produced in overwhelming quantity with advancement of age. When in oxidative stress, these reactive species cause extensive damage to various organ in the body, may be associated with pathogenesis of BPH also. This study aimed at assessing Malondialdehyde (MDA), the marker of lipid peroxidation and anti-oxidants e.g. alpha-Tocopherol and Ascorbate status in plasma in BPH patients. Forty eight (n=48) cases of BPH and forty six (n = 46) healthy age matched controls were enrolled. Plasma MDA level showed 4.81+/-1.87 nmol/ml in cases compared to 3.69+/-1.56 nmol/ml in healthy controls (p<0.001). There were significant decrease in plasma alpha-Tocopherol and ascorbate level which were 0.85+/-0.12 mg/dl and 0.93 +/- 0.13 mg/dl in cases compared to 1.37+/-0.31 mg/dl and 1.44+/-0.38 mg/dl in healthy controls respectively. Inverse correlation of plasma MDA with alpha-Tocopherol (r = -0.09, p>0.05) and Ascorbate (r =-0.51, p=0.008) was found in BPH patients. There was mild elevation of PSA in BPH patients compared with control but was not statistically significant. Thus, our study showed the evidence of association of oxidative stress in BPH patients.