Journal of Biochemical and Molecular Toxicology

The endocrine disruptor hexavalent chromium [Cr(VI)] is a proven reproductive toxicant. We recently demonstrated that prenatal Cr(VI) exposure causes testicular resistance to gonadotropins, resulting in hypergonadotropic hypoandrogenism in F1 rats. However, the mechanism driving hypergonadotropism in F1 rats exposed to Cr(VI) prenatally remains an enigma. Therefore, we hypothesized that 'Prenatal Cr(VI) exposure may disrupt steroid hormones-mediated negative feedback regulation of the hypothalamic GnRH, and its receptor in the pituitary of F1 rats, leading to hypergonadotropism...

The study investigated the potential association of the low-density lipoprotein (LDL) genome with endometrial cancer progression based on the Gene Expression Omnibus data set and The Cancer Genome Atlas data set. Differential and weighted gene coexpression network analysis was performed on endometrial cancer transcriptome datasets GSE9750 and GSE106191. The protein-protein interaction network was built using LDL-receptor proteins and the top 50 tumor-associated genes. Low-density lipoprotein-related receptors 5/6 (LRP5/6) in endometrial cancer tissues were correlated with oncogenes, cell cycle-related genes, and immunological checkpoints using Spearman correlation...

Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism in NSCLC progression need to be further explored. The expression levels of circ_0000735, miR-345-5p and A disintegrin and metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing and transwell assays were utilized to detect cell proliferation and metastasis. The protein levels of metastasis markers, exosome markers and ADAM19 were determined using western blot...

Although cyclophosphamide (CP) has been approved as an anticancer drug, its toxic effect on most organs, especially the testis, has been established. Piperine (PIP) is an alkaloid that has antioxidant, antiapoptotic, and anti-inflammatory activities. This study was investigated the protective effects of PIP on CP-induced testicular toxicity in the mice. In this experimental study, 48 adult male BALB/c mice (30-35 g) were divided into six groups (n = 8), receiving normal saline (C), 5 mg/kg of PIP (PIP5), 10 mg/kg of PIP (PIP10), 200 mg/kg of CP, 200 mg/kg of CP + PIP5, and 200 mg/kg of CP + PIP10...

To analyze the expression profile of fatty acid metabolism (FAM)-related genes, identify a prognostic signature, and evaluate its clinical value for gastric cancer (GC) patients. The mRNA expression profiles of 493 FAM-related genes were obtained from TCGA database. Differentially expressed genes (DEGs) between cancer and non-cancer samples were identified, and their relationships with overall survival (OS) of GC patients were evaluated. A prognostic signature of FAM-related genes was identified by the LASSO regression model, and its predictive performance was tested by an independent external cohort...

In women, breast cancer (BC) accounts for 7%-10% of all cancer cases and is one of the most common cancers. To identify a new method for treating BC, the role of CD93 and its underlying mechanism were explored. MDA-MB-231 cells were used in this study and transfected with si-CD93, si-MMRN2, oe-CD93, si-integrin β1, or oe-SP2 lentivirus. After MDA-MB-231 cells were transfected with si-NC or si-CD93, they were injected into nude mice by subcutaneous injection at a dose of 5 × 106 /mouse to construct a BC animal model...

This article describes how methylcobalamin (MeCbl) restores nerve myelination in a moderate- grade hepatic encephalopathy (MoHE) model of ammonia neurotoxicity. The comparative profiles of myelin basic protein (MBP), homocysteine (Hcy) and methionine synthase (MS: a MeCbl- dependent enzyme) activity versus nerve myelination status were studied in the hippocampus of the control, the MoHE (developed by administering 100 mg/kg bw thioacetamide i.p. for 10 days) and the MoHE rats treated with MeCbl (500 µg/kg BW i...

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in newborns, which severely influences the health of infants and lacks effective clinical treatment strategies. The pathogenesis of BPD is correlated to enhanced inflammation and activated oxidative stress (OS). The application of antioxidants and anti-inflammatory treatment could be hot spots for BPD treatment. Nesfatin-1, a peptide with a suppressive property against inflammation, was tested herein for its potential therapeutic value in BPD...

Chronic liver injury due to various etiological factors results in excess secretion and accumulation of extracellular matrix proteins, leading to scarring of liver tissue and ultimately to hepatic fibrosis. If left untreated, fibrosis might progress to cirrhosis and even hepatocellular carcinoma. Thymoquinone (TQ), an active compound of Nigella sativa, has been reported to exhibit antioxidant, anti-inflammatory and anticancer activities. Therefore, the effect of TQ against thioacetamide (TAA)-induced liver fibrosis was assessed in rats...

Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti-inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation-induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty-two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group...

Sustained liver injuries predominantly promote oxidative stress and inflammation that lead to the progression of chronic liver disease (CLD), including fibrosis, cirrhosis, and hepatocellular carcinoma. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects. Currently, there is no definitive treatment option available for CLD. Therefore, we investigated the hepatoprotective effect of boldine against carbon tetrachloride (CCl4 )-induced chronic liver injury in rats...

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death...

The cytotoxic activity, EGFR/VEGFR2 target inhibition, apoptotic activity, RT-PCR gene expression, in vivo employing a solid-Ehrlich carcinoma model, and in silico investigations for highlighting the binding affinity of eight quinoxaline derivatives were tested for anticancer activities. The results showed that compound 8 (N-allyl quinoxaline) had potent cytotoxicity against A594 and MCF-7 cancer cells with IC50 values of 0.86 and 1.06 µM, respectively, with noncytotoxic activity against WISH and MCF-10A cells having IC50 values more than 100 µM...

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay...

Normoxic inactivation of prolyl hydroxylase-2 (PHD-2) in tumour microenvironment paves the way for cancer cells to thrive under the influence of HIF-1α and NF-κB. Henceforth, the present study is aimed to identify small molecule activators of PHD-2. A virtual screening was conducted on a library consisting of 265,242 chemical compounds, with the objective of identifying molecules that exhibit structural similarities to the furan chalcone scaffold. Further, PHD-2 activation potential of screened compound was determined using in vitro 2-oxoglutarate assay...

Cellular senescence and iron accumulation were separately observed in diabetic nephropathy (DN). Limited evidence supports that iron was significantly accumulated in senescent cells. We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN. Renal cells were treated with high glucose (HG, 35 mM) for 10 or 15 days, and DN mice were induced by high-fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, β-galactosidase staining, 5-ethynyl-2-deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN...

The intricate pathogenesis of the hepatitis B virus (HBV) and its progression to hepatocellular carcinoma (HCC) have not yet been fully elucidated. H19 is one of the earliest imprinted long noncoding RNAs (lncRNAs) associated with liver pathobiology. This study investigated the association of H19 single nucleotide polymorphisms (SNPs) rs2839698 C/T and rs217727 C/T with HBV and HBV-related HCC and their correlation with H19 expression level. A total of 230 subjects were enrolled in this study including 100 HBV-infected patients, 30 HBV-related HCC patients, and 100 apparently healthy controls...

Claudin-6 (CLDN6) has been extensively studied in different tumors to date. However, in the case of nonsmall cell lung cancer (NSCLC), CLDN6 has a largely unknown role and molecular mechanism. We detected the expression of CLDN6 in NSCLC tissues and cells using reverse transcription-quantitative polymerase chain reaction (PCR) and western blot assays. A gain-of-function experiment was performed to evaluate the biological effects of CLDN6 on NSCLC cell behaviors. Methylation-specific PCR was utilized to detect the DNA methylation of CLDN6 gene promoter region...

Adhesion G protein-coupled receptor G4 (ADGRG4) is a G protein-coupled receptor (GPCR) that belongs to the adhesion family. Participation of ADGRG4 in cell adhesion and migration, signaling pathway activation, influence on angiogenesis, and modulation of immune responses are some of the possible ways through which it may contribute to oncogenesis. Conducting extensive omics studies poses budgetary challenges to small labs in peripheral areas, primarily due to restricted research funding and resource limitations...

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN...