Objective(s): Bisphenol A (BPA) that is a monomer of plastic products may possibly interfere with epigenetics and be involved in onset and progression of several diseases. This study was aimed to detect the epigenetic effects of in utero BPA exposure in mice offspring. Materials and Methods: All experiments were performed according to the national guidelines for laboratory animals and after ethical approval. Thirty adult BALB/c female mice were divided into 3 equal groups, G1 (controls), G2 (ethanol 0.10 m1/100m1 of PBS so that final concentration would be 0.01%) vehicle control and G3 (BPA 10 mg/kg). Chemicals were given twice a week throughout the pregnancy. Once delivered at term, female offspring were observed for body weight, behavior and movements. Blood glucose, serum insulin, cholesterol and high-density lipoprotein cholesterol (HDLc) were measured at 5 and 15 months postnatal. Animals were sacrificed at 15 months and pancreas, kidney, adipose tissue and uterine tissue were taken and stained with either Hematoxylin and eosin (H & E) or immunostaining and examined under light microscope. Results: Offspring of group G3 revealed abnormal changes of body weight, behavior and movements. Blood glucose, serum insulin, cholesterol and HDLc were high in group G3 offspring compared to controls. H & E staining showed changes in the parenchyma of pancreas, kidneys and uterus, which were confirmed by staining with anti- islet-1, kidney-specific (Ksp) cadherin, and anti- MLH antibody.Conclusion: In utero exposure of BPA exerts diabetogenic and atherogenic effects with less parenchymal tissue in endocrine pancreas, kidney and uterus.

Glaucoma is a neurodegenerative ophthalmic disorder and is considered among the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG) is the most common type of glaucoma that affects after 30 years of life, progressing slowly, and manifests as decreased visual acuity leading to blindness if not treated. POAG is genetically heterogeneous, inherited most commonly in autosomal dominant mode. Several genes have been reported for POAG with myocilin (Myoc) being most common. The present study has been conducted to screen 25 POAG families with 2 or more affected members for their association with Myoc and CYP1B1 (the most common gene in primary congenital glaucoma). After approval from Institutional Ethical Review Committee (ERC), 25 POAG families were enrolled from the southern province (Sindh) of Pakistan. Written informed consent was obtained from all participating individuals and diagnosis was confirmed by consultant ophthalmologists using various instruments and means. Venous blood was obtained from affected individuals and their normal family members for DNA extraction and subsequent analysis. All samples were initially screened for the Myoc gene followed by CYP1B1. Screening for Myoc revealed one previously reported variant c.144G>T in POAG-06 whereas screening for CYP1B1 in all 25 families showed a novel variant c.649G>A in POAG-02. The pathogenicity of the novel variant was confirmed using various bioinformatics tools. This is the first report of any POAG family found associated with a novel variant in CYP1B1 from the southern province of Pakistan whereas one family found associated with a reported variant in Myoc. The remaining 23 POAG families did not found to be associated with either Myoc or CYP1B1 indicating genetic heterogeneity of the population in this part of the world.

Background: Organophosphates (OPs) are one of the pesticides causing toxicity to humans and animals. OPs toxicity involve many organs such as liver, kidney, nervous system and immune system. Liver fibrosis is a wound healing response in which there is increased production and deposition of extracellular matrix (ECM), due to prolonged injury to liver by viral hepatitis, alcohol consumption, metabolic diseases and toxins (pesticides). Angiotensin receptor blockers (ARBs) are potential therapeutic agents for liver fibrosis. Objectives: To determine the effects of ARBs on Chlorpyrifos(CPF) induced liver fibrosis. Methods: 40 adult male albino wistar rats were used in the study. Rats were grouped as control group (A1), positive control group (A2) and experimental groups (B, C and D). Group A2 was treated with carbon tetrachloride (CCL4) to induce liver fibrosis, with 2 ml/kg of 50% solution of CCL4 by oral gavage two times per week for eight weeks, group B was treated with 1ml/bw/day CPF intraperitoneally for eight weeks. Group C was treated with 1ml/bw/day CPF intraperitoneally for eight weeks and then ARBs orally (30mg/kg/day) for 8 weeks. Group D was simultaneously treated with CPF and ARBs for 8 weeks with same doses as for group C. At the end of experiment blood was collected by cardiac puncture for liver function test and rats were sacrificed to collect liver samples. Pathological changes in liver were examined using H&E and Masson’s trichrome staining. Real time PCR was used to detect alpha smooth muscle actin (α-SMA), transforming growth factor beta 1(TGF- β1) and Collagen-I(coll-I) mRNA expression. Results: CPF caused liver injury evidenced by raised liver enzymes and bilirubin with histological changes and increased expression of genes. ARBs decreases liver enzymes, CPF induced histological changes and decreases the expression of α-SMA, TGF- β1 and Coll-I. Conclusion: The present study suggests that ARBs prevent fibrogenesis and may serve as a promising therapeutic agent to reduce CPF induced liver fibrosis.

Preeclampsia is one of hypertensive disorders in pregnancy that occurs after the 20th weeks of pregnancy along with proteinuria. It threatens maternal and child health and has worldwide prevalence of about 3–8%. This cross-sectional study included 90 cases among them 45 women were diagnosed with preeclampsia and 45 normal pregnant women was carried out from December 2021 to November 2022 at department of anatomy in collaboration with department of gyneacology and obstetric, Liaquat University of Medical and Health Sciences, Jamshoro after getting ethical approval. Placental histological changes were matched for betatrophin levels. Their age, gravidity, gestational age, socioeconomic status, and mode of delivery were recorded. The mean betatrophin level in control 1.66 ± 0.10 and in pre-eclampsia 1.71± 0.06. Plasma betatrophin levels were found significant in PE than in control groups (p<0.008). Placental morphological and morphometric parameters were significant in PE than control group. All gross and microscopic parameters of placenta were altered in preeclampsia along with plasma elevated levels of betatrophin. These findings may bring out betatrophin as a new marker to predict, prevent, and treat pre-eclampsia.