As a widely existing traditional Chinese medicine component, TP (triptolide) has serious reproductive toxicity which causes severe damage to the reproductive system and limits its application prospect. TP and MET (metformin) have shown great potential in combined with each other in anticancer and anti-inflammatory. Whether metformin can resist the reproductive toxicity caused by triptolide, the effects of MET on TP-induced reproductive capacity has not been reported. In this study, metformin was used to investigate the therapeutic effect on reproductive toxicity induced by TP in rat. The results showed that metformin had significant therapeutic effects on oxidative stress damage, destruction of the blood-testosterone barrier and apoptosis. And it proved that its therapeutic effect is mainly to restore the structural and functional stability of testis through antioxidant stress. It will provide guidance for the treatment of reproductive toxicity caused by TP and the adjuvant detoxification of TP application.Severe haze events, especially with high concentration of fine particulate matter (PM2.5), are frequent in China, which have gained increasing attention among public. The purpose of our study was explored the toxic effects and potential damage mechanisms about PM2.5 acute exposure. Here, the diverse dosages of PM2.5 were used to treat SD rats and human bronchial epithelial cell (BEAS-2B) for 24 h, and then the bioassays were performed at the end of exposure. The results show that acute exposure to diverse dosages of PM2.5 could trigger the inflammatory response and apoptosis. The severely oxidative stress may contribute to the apoptosis. Also, the activation of Nrf2-ARE pathway was an important compensatory process of antioxidant damage during the early stage of acute exposure to PM2.5. Furthermore, the HO-1 was suppression by siRNA that promoted cell apoptosis triggered by PM2.5. In other words, enhancing the expression of HO-1 may mitigate the cell apoptosis caused by acute exposure to PM2.5. In summary, our findings present the first time that prevent or mitigate the damage triggered by PM2.5 through antioxidant approaches was a promising strategy.Inorganic arsenic compounds are environmental toxicants that are widely distributed in air, water, and food. B-cell lymphoma 2 (BCL-2) is an oncogene having anti-apoptotic function. In this study, we clarify that BCL-2, as a pro-apoptotic factor, participates in As2O3-induced apoptosis in BEAS-2B cells. Specifically, As2O3 stimulated the expression of BCL-2 mRNA and protein in a dose-dependent manner which was highly accumulated in the nucleus of BEAS-2B cell together with chromatin condensation and DNA fragmentation during apoptosis. Mechanistically, the process described above is mediated through the NF-κB and p38 MAPK signaling pathways, which can be abated by corresponding inhibitors, such as BAY11-7082 and SB203580, respectively. Additionally, BAY11-7082, actinomycin D, and cycloheximide have inhibitory effects on As2O3-induced expression of BCL-2 mRNA and protein, and restore the cell viability of BEAS-2B cells. Suppression of BCL-2 protein activation by ABT-199 also restored viability of BEAS-2B cell in As2O3-induced apoptosis. Furthermore, As2O3 increased the level of BCL-2 phosphorylation. These results suggest that in BEAS-2B cells, As2O3-induced apoptosis is mainly dominated by BCL-2 upregulation, nuclear localization and phosphorylation. The study presented here provides a novel insight into the molecular mechanism of BCL-2-induced apoptosis.The natural co-occurrence of multiple mycotoxins has been reported in cereals and cereal products worldwide. Even though the dietary exposure to mycotoxins constitutes a serious human health, most reports are limited to the toxic effect of individual mycotoxins. The purpose of the present study was to assess the combined toxic effects of zearalenone (ZEN) and fumonisin B1 (FB1) and the potential interaction of their mixture on zebrafish (Danio rerio) embryos. Our results showed that ZEN possessed the higher toxicity to embryonic zebrafish (7-day LC50 value of 0.78 mg a.i. L-1) compared with FB1 (7-day LC50 value of 227.7 mg a.i. L-1). The combination of ZEN and FB1 exerted an additive effect on zebrafish embryos. Meanwhile, the activities of antioxidant CAT, caspase-3, and detoxification enzyme CYP450, as well as the expressions of six genes (Mn-sod, cas9, bax, cc-chem, ERα, and crh) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were prominently altered in the mixture exposure compared with the corresponding single treatment group of ZEN or FB1. Taken together, the regulatory standards of mycotoxins in food and feed should be updated based on the mixture effects of mycotoxins, and there is an increased need on effective detoxification methods for controlling and reducing the toxicity of multiple mycotoxins in animal feed and throughout the food supply chain.Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z' > 0.7). The screening resulted in the identification of two novel noscapine derivatives as inhibitors of MDA cell growth with IC50 values of 5 µM and 1.5 µM, respectively. Both hit molecules have a five-fold and seventeen-fold higher potency, compared with that of lead compound noscapine (IC50 26 µM). The identified active derivatives retain the tubulin-binding ability of noscapine. Further testing of both hit molecules, alongside the natural product against additional cancer cell lines (HepG2, HeLa and PC3 cells) confirmed our initial findings. https://www.selleckchem.com/products/hsp990-nvp-hsp990.html Both molecules have improved anti-proliferative properties when compared to the initial natural product, noscapine.