Throughout time, there has always been a trend connecting stress and tangible damage to one's physical well-being. However, there's a lack of research that elucidates the physical and molecular traits Show more
Throughout time, there has always been a trend connecting stress and tangible damage to one's physical well-being. However, there's a lack of research that elucidates the physical and molecular traits of this stress on organ integrity. Chronic stress disrupts homeostasis, causing oxidative stress, mitochondrial dysfunction, inflammatory markers, and histological damage. In this study, a repeated forced-swim stress was used to induce stress in the C57BL/6 mice model, and its effects on the brain and liver were analyzed at behavioral, biochemical, histological, and genetic marker levels. Behavioral analysis showed reduced mobility duration in experimental mice. This was further supplemented by histopathological data, which revealed mild brain deterioration and moderate liver damage. Biochemical analysis revealed upregulated levels of aminotransferase and alkaline phosphatase (ALP) and decreased levels of mean corpuscular hemoglobin, pointing toward the existence of liver dysfunctionality due to stress. Moreover, we reported the gene expression analysis of stress biomarkers (Bdnf, Fkbp5, Npy, Comt, Ppm1f, Adra2b, and Slc6a4), with a particular focus on Fkbp5, which is associated with depression and cognitive impairment. Similarly, we also studied the expressions of Crp, Cyp2e1, and Irs-2 to gauge liver damage. Results revealed significantly upregulated expression of Npy, Fkbp5, and Ppm1f in stressed mice. Our study identifies that chronic stress shows physical and molecular realizations. Additionally, this offers further incentive to look closely at Fkbp5, Npy, and Ppm1f under similar conditions and highlights their possible roles as markers of stress-induced damage. Show less
Ventricular septal defects (VSDs) are one of the leading causes of death due to cardiac anomalies during the first months of life. The prevalence of VSD in neonates is reported up to 4%. Despite the r Show more
Ventricular septal defects (VSDs) are one of the leading causes of death due to cardiac anomalies during the first months of life. The prevalence of VSD in neonates is reported up to 4%. Despite the remarkable progress in medication, treatment and surgical procedure for VSDs, the genetic etiology of VSDs is still in infancy because of the complex genetic and environmental interactions. Three hundred fifty subjects (200 VSD children and 150 healthy controls) were recruited from different pediatric cardiac units. Pediatric clinical and demographic data were collected. A total of six variants, rs1017 (ISL1), rs7240256 (NFATc1), rs36208048 (VEGF), variant of HEY2, rs11067075 (TBX5) and rs1801133 (MTHFR) genes were genotyped by tetra-ARMS PCR and PCR-RFLP methods. The results showed that in cases, the rs1017 (g.16138A > T) variant in the ISL1 gene has an allele frequency of 0.42 and 0.58 respectively for the T and A alleles, and 0.75 and 0.25 respectively in the controls. The frequencies of the AA, TA and TT genotypes were, 52%, 11% and 37% in cases versus 21%, 8% and 71% respectively in the controls. For the NFATc1 variant rs7240256, minor allele frequency (MAF) was 0.43 in cases while 0.23 in controls. For the variant in the VEGF gene, genotype frequencies were 0% (A), 32% (CA) and 68% (CC) in cases and 0.0%, 33% and 67% respectively in controls. The allele frequency of C and A were 0.84 and 0.16 in cases and 0.83 and 0.17 respectively in controls. The TBX5 polymorphism rs11067075 (g.51682G > T) had an allelic frequency of 0.44 and 0.56 respectively for T and G alleles in cases, versus 0.26 and 0.74 in the controls. We did not detect the presence of the HEY2 gene variant (g.126117350A > C) in our pediatric cohort. For the rs1801133 (g.14783C > T) variant in the MTHFR gene, the genotype frequencies were 25% (CC), 62% (CT) and 13% (TT) in cases, versus 88%, 10% and 2% in controls. The ISL1, NFATc1, TBX5 and MTHFR variants were found to be in association with VSD in the Pakistani pediatric cohort whilst the VEGF and HEY2 variants were completely absent in our cohort. We propose that a wider programme of genetic screening of the Pakistani population for genetic markers in heart development genes would be helpful in reducing the risk of VSDs. Show less
To explore the association of rs662799 variants of Apolipoprotein A5 gene with metabolic syndrome in Pakistani population. The case-control study was conducted at Pakistan Institute of Medical Science Show more
To explore the association of rs662799 variants of Apolipoprotein A5 gene with metabolic syndrome in Pakistani population. The case-control study was conducted at Pakistan Institute of Medical Sciences, Islamabad, Pakistan from 2014 to2016, and comprised subjects enrolled from the out-patient clinics. Groups were formed on the basis of preliminary screening for risk factors like obesity, insulin resistance, hypertension, dyslipidemia and fasting blood glucose levels. Met S was diagnosed based on the international diabetes federation criteria. Blood samples were collected for biochemical testing and deoxyribonucleic acid extraction. Genotyping of rs662799 was performed a the Genome Research Centre of the University of Hong Kong using Sequenom Mass ARRAY, iPLEX Gold technology. Data was analysed using SPSS 16and Plink software. :There were 712 subjects in two groups of 356(50%) each. The overall mean age was 41.59}7.18 years. There was a significant association of risk allele C of rs662799 with metabolic syndrome (p=0.002). The risk showed strong association with dyslipidaemia (p=0.03) and obesity (p=0.01) which are risk phenotypes of metabolic syndrome in age- and gender-adjusted model. The association of risk allele C of genetic variant rs662799 of Apolipoprotein A5 gene with dyslipidaemia and obesity may lead to the development of metabolic syndrome in the Pakistan adult population. Show less
Chromium (Cr) is one of the most important environmental pollutants which are released into the environment due to their wide usage in numerous industries. The excess of Cr (VI) can induce hepatotoxic Show more
Chromium (Cr) is one of the most important environmental pollutants which are released into the environment due to their wide usage in numerous industries. The excess of Cr (VI) can induce hepatotoxicity, while the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is unclear. We demonstrated the induction of chromium poisoning model in chickens to identify the differentially expressed genes (DEGs), and their functions were analyzed under different physiological and pathological conditions. Histopathological examination and transcriptome data for chromium-poisoned livers and control livers were annotated with Illumina® HiSeq 2000. The histopathological examination in chromium poisoning groups showed diapedesis, hemolysis, degeneration, nucleus pycnosis, and central phlebectasia in the liver. A total of 334 genes were upregulated and 509 genes were downregulated. The most strongly upregulated genes were HKDC1, DDX4, ACACA, FDFT1, CYYR1, PPP1R3C, and SLC16A14, while the most downregulated genes were MYBPC3, CCKAR, PCK1, and CPT1A. A Gene Ontology (GO) term with the highest enrichment of DEGs is small molecule metabolic process. In cell component domain, the term with the highest enrichment is extracellular matrix. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that glucose metabolism, lipid metabolism, and protein metabolism were the most important metabolic pathways in the liver. The current study first time provides important clues and evidence for identifying the differentially expressed genes in livers due to Cr (VI)-induced liver injury in chickens. Show less