Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women.

Recently, there has been a noticeable increase in disorders of the female reproductive system, accompanied by a rise in adverse pregnancy outcomes. This trend is increasingly being linked to environmental pollution, particularly through the lens of Endocrine Disrupting Chemicals (EDCs). These external agents disrupt natural processes of hormones, including synthesis, metabolism, secretion, transport, binding, as well as elimination. These disruptions can significantly impair human reproductive functions. A wealth of animal studies and epidemiological research indicates that exposure to toxic environmental factors can interfere with the endocrine system's normal functioning, resulting in negative reproductive outcomes. However, the mechanisms of these adverse effects are largely unknown. This work reviews the reproductive toxicity of five major environmental EDCs-Bisphenol A (BPA), Phthalates (PAEs), Triclocarban Triclosan and Disinfection Byproducts (DBPs)-to lay a foundational theoretical basis for further toxicological study of EDCs. Additionally, it aims to spark advancements in the prevention and treatment of female reproductive toxicity caused by these chemicals.

Dexmedetomidine improves DM-induced oxidative stress injury to protect liver function through Nrf2 pathway.

OBJECTIVE: Diabetes mellitus-induced oxidative stress (OS) causes liver injury. Intraoperative pumping of dexmedetomidine (DEX) effectively reduced the postoperative OS response in patients with type 2 diabetes mellitus (T2DM) and had a certain protective effect on liver function. However, the mechanisms of the protective effect on the liver remained unclear. In this study, we investigated the antagonistic effects and the possible mechanism of DEX on T2DM-induced liver injury in the mouse model and Palmitic acid (Pal)-induced injury in hepatocellular carcinoma cells (HepG2). METHODS: Seven wt/wt mice served as Control group, and 28 db/db mice were randomly divided into four groups using a random number table method: Model group (n=7), D25 group (n=7), D50 group (n=7) and D75 group (n=7). Different concentrations of DEX were injected intraperitoneally in the D25 group, D50 group and D75 group, while the Control group and the Model group were intraperitoneally injected with the same amount of normal saline for 3 weeks. In the cell intervention experiments, HepG2 cell line was used. The control group (Con group), the palmitic acid group (Pal group) and the DEX treatment group (Pal + Dex group) were set up. The test results were compared among mice groups and cell groups, respectively. RESULTS: DEX alleviated the increase of alanine aminotransferase, triglyceride, total cholesterol and aspartate aminotransferase contents induced by high fat or T2DM. DEX reversed the decrease of nuclear factor E2 related factor 2 (Nrf2) in the nuclear translocation and the lower transcriptional activity of Nrf2 to inhibit the expression of heme oxygenase-1, NADPH quinone oxidoreductase-1 and superoxide dismutase 2 and reduced the activity of superoxide dismutase to increase reactive oxygen species content induced by high fat or T2DM. CONCLUSION: By attenuating the high-fat or T2DM-induced Nrf2 pathway impairment, DEX can reduce OS injury and inhibit the disorder of lipid anabolism and protect liver function. This study provides a theoretical basis for the protection of liver function by DEX in clinical T2DM patients.

Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC-type diffuse large B-cell lymphoma: a network meta-analysis of 20 RCTs.

Because of lacking of head-to-head comparison among polatuzumab (Pola) vedotin and other novel agents for untreated diffuse large B-cell lymphoma (DLBCL), the optimal option remains undefined. We searched twelve relevant published reports, covering 8376 subjects. Interestingly, the PFS benefit with Pola-R-CHP over other regimens was found prominently in those B-cell-like type (ABC-type) patients. For those ABC-type patients, the PFS advantage with Pola-R-CHP was statistically significant, when compared to R-CHOP+Bort (HR: 0.52, P=0.02), R-CHOP+Ibru (HR: 0.43, P=0.001), R-CHOP+Lena (HR: 0.51, P=0.009), G-CHOP (HR: 0.46, P=0.008), and R-CHOP (HR: 0.40, P<0.001). Meanwhile, for those germinal center B-cell-like (GCB) type patients, no PFS advantage with Pola-R-CHP was found when compared to R-CHOP+Bort (HR: 1.18, P=0.46), R-CHOP+Lena (HR: 1.21, P=0.45), G-CHOP (HR: 1.39, P=0.14), R-CHOP-14 (HR: 0.94, P=0.82), and R-CHOP (HR: 1.00, P=1). The PFS advantage with Pola-R-CHP over other regimens might be confined to those patients of ABC-type DLBCL.

lncRNA-Z38 promotes occurrence and progression of gastric cancer though regulating TGF-β signaling pathway / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨lncRNA-Z38对胃癌细胞恶性生物学行为的影响及其可能的调控机制。方法：构建lncRNA-Z38稳定过表达的胃癌细胞系（AGS、MKN74细胞），通过细胞成球实验检测过表达lncRNA-Z38对胃癌细胞肿瘤特征的影响。对过表达lncRNA-Z38的AGS细胞及对照细胞进行高通量测序，对差异表达基因进行KEGG富集分析，筛选出可能参与调控胃癌发生发展的信号通路，采用WB等技术验证lncRNA-Z38通过调控该信号通路参与提高胃癌细胞的干性。结果：成功构建lncRNA-Z38过表达细胞株，细胞成球实验提示lncRNA-Z38过表达细胞的成球能力显著高于对照细胞（P<0.05）。通过测序筛选出lncRNA-Z38过表达胃癌细胞中的1 999个差异表达基因，其中上调基因1 238个、下调基因761个；经KEGG富集分析得到其中变化最显著的通路为TGF-β信号通路（P<0.05）。WB实验结果提示，lncRNA-Z38高表达胃癌细胞中TGF-β信号通路组成基因编码蛋白ID3、BMP6显著上调（均P<0.05）、GDF-5、WNT8B显著下调（P<0.05）。结论：在胃癌中高度表达的lncRNA-Z38通过调控TGF-β信号通路提高胃癌细胞的干性。