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Bisphenol A (BPA) is an endocrine-disrupting toxicant commonly used in the plastics industry, as a result, it is present in large quantities in the environment. Therefore, current study was designed to assess BPA induced neurotoxicity and molecular fate within common carp (Cyprinus carpio), largely used edible fish. Following 6 weeks exposure to BPA 1/5th of 96 h LC 50 (1.31 mg/L), brain exhibited oxidative damage, which was evidenced by compromised antioxidant system (CAT, SOD, GSH) and increased level of biomacromolecule peroxidation (MDA and 8-OHDG). Functional damage to the brain observed in the form of blood-brain barrier disruption (decreased tight junction gene expression) and nerve conduction impairment (reduced acetylcholinesterase activity). Mechanistically, apoptotic cell death indicated by characteristic alteration in key biomarkers (bcl-2, caspase, and p53-related gene family). Whereas, coadministration of powdered PP (pomegranate peel) (8 %) with BPA effectively mitigated the BPA toxicity, as evidenced by the restoration of the above-mentioned bioindicators. Thereby, BPA-induced neurotoxicity could be potentially detoxified by applying PP dietary enrichment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The widespread application of herbicides raises concerns about their impact on non-target aquatic organisms. This study aimed to evaluate the toxicity of a commercially available herbicide formulation containing Bromoxynil+MCPA (2-Methyl-4-chlorophenoxyacetic acid) on Cirrhinus mrigala (economically significant fish). A total of 210 juvenile fish were subjected to a triplicate experimental setup, with 70 fish allocated to each replicate, exposed to seven different concentrations of herbicide: 0 mg/L, 0.133 mg/L, 0.266 mg/L, 0.4 mg/L, 0.5 mg/L, 0.66 mg/L, and 0.8 mg/L, respectively, for a duration of 96 h. The median lethal concentration (LC50) was determined to be 0.4 mg/L. Significant hematological alterations were observed, including decreases in RBC counts, hemoglobin, hematocrit, and lymphocyte counts, along with an increase in erythrocyte indices. Biochemical analysis revealed elevated levels of neutrophils, WBCs, bilirubin, urea, creatinine, ALT, AST, ALP, and glucose in treated groups. Morphological abnormalities in erythrocytes and histopathological changes in gills, liver, and kidneys were noted. Pathological alterations in gills, liver and kidneys including epithelial cell uplifting, lamellar fusion, hepatolysis, and renal tubule degeneration were observed. Oxidative stress biomarkers such as TBARS (Thiobarbituric Acid Reactive Substance), ROS (Reactive Oxygen Species), and POD (Peroxides) activity increased, while antioxidant enzymatic activities decreased as toxicant doses increased from low to high concentrations. The study reveals that Bromoxynil+MCPA significantly disrupts physiological and hematobiochemical parameters in Cirrhinus mrigala, which highlights the substantial aquatic risks. In conclusion, the herbicide formulation induced significant alterations in various fish biomarkers, emphasizing their pivotal role in assessing the environmental impact of toxicity. This multi-biomarker approach offers valuable insights regarding the toxicological effects, thereby contributing substantially to the comprehensive evaluation of environmental hazards., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Infectious bronchitis virus (IBV) is prevalent in Pakistan causing enormous economic losses. To date no clear data are available on circulating genotypes and phylogeographic spread of the virus. Hence current study assessed these parameters for all available IBV Pakistani isolates, based on the 9 new sequences, with respect to other Asian and non-Asian countries. Results indicated that all Pakistani isolates belonged to genotype I (GI), with more than half of them (16/27) belonging to the GI-24 lineage, against which no vaccine is available. Three possible introduction events of the GI-13 IBV lineage into Pakistan, based on the estimated IBV population using isolates from this study, were observed possibly from Afghanistan, China, and/or Egypt. These events were further analyzed on the S1 amino acid level which showed unique alterations (S250H, T270K, and Q298S) in 1 isolate (IBV4, GI-13) when compared to GI-1 lineage. Both GI-1 and GI-13 Pakistani strains showed close homology with homologous vaccine strains that are used in Pakistan. For GI-24 strains, none of the used vaccines showed substantial homology, necessitating the need for further exploration of this lineage and vaccine design. In addition, our findings highlight the importance of genomic surveillance to support phylogeographical studies on IBV in genotyping and molecular epidemiology., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A brain tumor is a dynamic system in which cells develop rapidly and abnormally, as is the case with most cancers. Cancer develops in the brain or inside the skull when aberrant and odd cells proliferate in the brain. By depriving the healthy cells of leisure, nutrition, and oxygen, these aberrant cells eventually cause the healthy cells to perish. This article investigated the development of glioma cells in treating brain tumors. Mathematically, reaction-diffusion models have been developed for brain glioma growth to quantify the diffusion and proliferation of the tumor cells within brain tissues. This study presents the formulation the two-stage successive over-relaxation (TSSOR) algorithm based on the finite difference approximation for solving the treated brain glioma model to predict glioma cells in treating the brain tumor. Also, the performance of TSSOR method is compared to the Gauss-Seidel (GS) and two-stage Gauss-Seidel (TSGS) methods in terms of the number of iterations, the amount of time it takes to process the data, and the rate at which glioma cells grow the fastest. The implementation of the TSSOR, TSGS, and GS methods predicts the growth of tumor cells under the treatment protocol. The results show that the number of glioma cells decreased initially and then increased gradually by the next day. The computational complexity analysis is also used and concludes that the TSSOR method is faster compared to the TSGS and GS methods. According to the results of the treated glioma development model, the TSSOR approach reduced the number of iterations by between 8.0 and 71.95%. In terms of computational time, the TSSOR approach is around 1.18-76.34% faster than the TSGS and GS methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The influence of ethnicity on outcome of simultaneous pancreas-kidney transplantation (SPK) is poorly defined. After excluding technical failures, we retrospectively reviewed 96 consecutive SPKs (63 Caucasians [C], 33 African-Americans [AA]). All patients received antibody induction, tacrolimus, mycophenolate mofetil, and steroids. One-, 3-, and 5-year actuarial patient survival was similar between C (98%, 95%, 87%) and AA (90%, 90%, 81%), p=NS. One-, 3-, and 5-year kidney graft survival was similar between C (98%, 86%, 81%) and AA (85%, 85%, 78%), p =NS. One-, 3-, and 5-year pancreas graft survival was significantly worse in AA (71%, 68%, 46%) than in C (90%, 85%, 81%), p = 0.008. The cumulative incidence of kidney and pancreas acute rejection (AR) was higher in AA compared with C. Distribution of kidney and pancreas rejection grade was similar between C and AA. AA experienced more pancreas graft losses from early death with functioning graft, AR, and late chronic rejection. The higher incidence of AR and resistance to currently employed induction, maintenance, and antirejection immunosuppression therapies in AA may account for their inferior pancreas graft survival. More aggressive immunosuppression strategies may improve pancreas graft survival in AA but may be associated with increased morbidity and mortality. Further study is warranted.

Objectives: To study the incidence of p53 oncoprotein overexpression and its relationship to tumour grade, stage and clinical prognosis in a cohort of local Malaysian patients., Methods: All cases of transitional cell carcinoma (TCC) of the bladder diagnosed and treated at the University of Malaya Medical Centre from January 1995 to December 2000 were retrieved from the hospital records. Sections from paraffin-embedded tissues were retrieved and stained for p53 oncoprotein using immunohistochemistry techniques. P53 oncoprotein results were analyzed in relation to tumour grade, stage and clinical prognosis. Fisher's exact test was used to evaluate the relationship between categorical variables and the Kaplan-Meier procedure was used to assess survival outcomes. The Cox regression model was used for multivariate analysis., Results: A total of 64 cases were studied. The mean follow-up period was 23.7 months. The number of p53 positive cases was significantly higher in high-grade (G3) (p = 0.006) and muscle-invasive tumours ( summation operator T2, p = 0.035). The status of p53 expression had no significant association with recurrence-free (p = 0.594) or overall survival (p = 0.955). In multivariate analysis, a multiplicity of tumours at presentation (p = 0.004) and a history of cigarette smoking (p = 0.016) were independent predictors of recurrence. Tumour stage (p = 0.024) was the single independent predictor for poor overall survival., Conclusions: Overexpression of p53 is associated with TCC of higher grade and tumour stage. It had no significant impact on prognosis in this cohort of TCC cases.

Nitric oxide (NO) has been implicated in the local regulation of bone metabolism. However, the contribution made by specific NO synthase (NOS) enzymes is unclear. Here we show that endothelial NOS gene knockout mice (eNOS-/-) have marked abnormalities in bone formation. Histomorphometric analysis of eNOS-/- femurs showed bone volume and bone formation rate was reduced by up to 45% (P: < 0.01) and 52% (P: < 0.01), respectively. These abnormalities were prevalent in young (6 to 9 weeks old) adults but by 12 to 18 weeks bone phenotype was restored toward wild-type. Dual energy X-ray absorptiometry analysis confirmed the age-related bone abnormalities revealing significant reductions in femoral (P: < 0.05) and spinal bone mineral densities (P: < 0.01) at 8 weeks that were normalized at 12 weeks. Reduction in bone formation and volume was not related to increased osteoclast numbers or activity but rather to dysfunctional osteoblasts. Osteoblast numbers and mineralizing activity were reduced in eNOS-/- mice. In vitro, osteoblasts from calvarial explants showed retarded proliferation and differentiation (alkaline phosphatase activity and mineral deposition) that could be restored by exogenous administration of a NO donor. These cells were also unresponsive to 17ss-estradiol and had an attenuated chemotactic response to transforming growth factor-beta. In conclusion, eNOS is involved in the postnatal regulation of bone mass and lack of eNOS gene results in reduced bone formation and volume and this is related to impaired osteoblast function.

Oestradiol can stimulate osteoblast activity. Osteoblast function is thought to be regulated by nitric oxide (NO). We hypothesised that the effect of 17beta-oestradiol (17beta-E(2)) on osteoblast activity is mediated by NO. This hypothesis was tested using osteoblasts isolated from human trabecular bone, calvariae of rats, endothelial NO synthase (eNOS) gene-deficient mice, and their wild-type counterparts. Our results show that 17beta-E(2) dose-dependently stimulated proliferation and differentiation of primary human, rat and wild-typeosteoblasts. The presence of N(G)-monomethyl-l-arginine (10(-3) M), an inhibitor of NOS activity, blocked the 17beta-E(2)-(10(-7) M)-induced increases in thymidine incorporation (P < 0.01), alkaline phosphatase activity (P < 0.01) and bone nodule formation (P < 0.01) of wild-type, human and rat osteoblasts, respectively. Moreover, 17beta-E(2) did not induce a response in eNOS gene-deficient osteoblasts. 17beta-E(2) also increased total eNOS enzyme expression in rat osteoblasts. These findings indicate 17beta-E(2) modulates osteoblast function by NO-dependent mechanisms mediated via the eNOS isoform., (Copyright 2000 Academic Press.)