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The gut microbial compositions are easily affected by the environmental chemicals like arsenic (As) leading to dysbiosis. The dysbiosis of gut microbiome has associated with numerous diseases; among which cancer is one of the major diseases. The meticulous mechanism underlying As- altered gut microbiome, Nucleotide domine containing protein 2 (NOD2) and how altered gut microbiome disturbs the intestinal homeostasis to regulate colon cancer markers remains unclear. For this, one hundred twenty 8-week old age male mice were divided into two exposure periods (3 and 6 months), and each exposure group animals were further divided into four groups as control (received only distilled H 2 O), low (0.15 mg As 2 O 3 /L), medium (1.5 mg As 2 O 3 /L) and high (15 mg As 2 O 3 /L) dose (each group containing 15 mice) administrated for 3 and 6 months. The results showed that As exposure highly altered gut microbiome with a significant depletion in NOD2 in contrast to control groups. Moreover, the dendritic cells (CD11a, CD103, CX3CR1) and macrophages (F4/80) were significantly increased by As exposure. Interestingly, increased trend of inflammatory cytokines (TNF-α, IFN-γ, IL-17) and depleted anti-inflammatory cytokines (IL-10) was observed in As exposed mice. Furthermore, the colon cancer markers β-catenin has increased while APC was arrested by As both in 3 and 6 months treated animals. Many studies reported that As altered gut microbial compositions, in this study, our results suggested that altered gut microbiome indirectly regulates colon cancer marker through immune system destruction mediated by inflammatory cytokines., Competing Interests: Declaration of competing interest The authors declare that they have no financial conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Despite the knowledge of AS-induced reprotoxicity, the literature concerning arsenic trioxide (As 2 O 3 )-induced oxidative stress and consequent intracellular events, like autophagy process, in the hypothalamic-pituitary- gonadal (HPG) axis of F1- pubertal male mice is sparse to date. Hence, we made an attempt to study the reproductive toxicities and the underlying mechanisms induced by As 2 O 3 in the HPG axis of pubertal F1- male mice in correlation with oxidative stress-induced autophagy. Parental mice were challenged with As 2 O 3 (0, 0.2, 2, and 20 ppm) from five weeks before mating, and continued till puberty age for the male pups. It was recorded that higher As 2 O 3 doses (2 and 20 ppm) were a potent inducer of oxidative stress and autophagy in the HPG axis. Concomitant with a decrease on mean body weight, total antioxidant capacity, and stereology indices, an increase in the number of MDC-labeled autophagic vacuoles, and MDA/GSH ratio in HPG axis of pubertal F1- male mice which were exposed to higher As 2 O 3 doses was observed. Meanwhile, concomitant with a dose-dependent increment in the gene expression of ATG3, ATG5, Beclin, as well as protein expression of P62, ATG12, and Beclin in HPG axis tissues; a dose-dependent decrease in PI3K and mTOR gene expression was recorded in the HPG tissues of pubertal F 1 -males. Altogether, our observations suggest that higher doses of As 2 O 3 have detrimental effects on the functionality of HPG axis in pubertal male mice offspring by increasing MDA/GSH ratio and autophagic cell death-related genes and proteins, as well as by reducing total antioxidant capacity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) is widely used in the production of epoxy resins and polycarbonate plastics. Under harsh situations, these plastics likely desorb BPA, which then can seep into the environment. Various concentrations of BPA have been detected in most biological fluid. However, there is paucity of information on the detrimental effects of BPA and its subsequent cellular events in chronic kidney disease (CKD). Hence, in this in vitro study, we aimed to investigate the effects of BPA on renal epithelial cell activation, apoptosis, and DNA damage. Rhesus monkey embryo renal epithelial Marc-145 cells were exposed to 0, 10 -1 , 10 -2 , 10 -3 , 10 -4 , 10 -5 , and 10 -6  M of BPA. Alterations in intracellular apoptosis, oxidative stress, and DNA damage were evaluated. The results showed that BPA decreased cell viability, superoxide dismutase (SOD) activity and glutathione (GSH) level, with concomitant increases in apoptosis related indices, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS) generation, thiobarbituric acid reactive substances (TBARS) content, and the rate of comet Marc-145 cells with a dose-dependent manner. The data indicated that increased oxidative stress, apoptosis and DNA damage in epithelial Marc-145 cells might play a pivotal role in the mechanism of BPA-induced nephrotoxicity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The mechanism of GSTO1, as a high-risk factor for neurological damage, in sodium fluoride (NaF)-induced learning and memory impairment remained still unclear. Hence, in this study, we used the siRNA-GSTO1 HT22 model to explore the effect of NaF and siRNA-GSTO1 on the viability, and proliferation rate of HT22 cells, as well as the mRNA and protein expression levels of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), neural cell adhesion molecule (NCAM), stem cell factor (SCF) and brain-derived neurotrophic factor (BDNF). The results of MTT showed that 10 -3 , 10 -4 , and 10 -5  moL/L sodium fluoride (NaF) exposure could significantly promote the proliferation of HT22 cells at 24 h, 36 h, and 48 h, respectively. In addition, our results showed that exposure to 10 -3 , 10 -4 , and 10 -5  moL/l NaF increased GSTO1 mRNA and protein expression, but decreased CREB and BDNF expression levels in a dose and time-dependent manner. The mRNA and protein expressions of GSTO1, CREB and BDNF were significantly decreased in the siRNA-GSTO1 and NaF + siRNA-GSTO1 group (P < 0.05). We have shown that various NaF doses affected the learning and memory ability by down-regulation the expressions of CREB, BDNF, NCAM and SCF. In summary, we concluded that GSTO1 plays a mediator role in NaF-induced neurological damage., (Copyright © 2019 Elsevier Ltd. All rights reserved.)