F-53B mediated ROS affects uterine development in rats during puberty by inducing apoptosis.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.

Polystyrene microplastics disturb maternal glucose homeostasis and induce adverse pregnancy outcomes.

Pregnant women are a special group that is sensitive to adverse external stimuli, causing metabolic abnormalities and adverse pregnancy outcomes. Microplastics (MPs), an environmental pollutant widely used in various fields, can induce a variety of toxic responses in mammals. Recent studies verified an association between MPs and metabolic disorders. Our research built a gestational mouse model in which polystyrene microplastics (PS-MPs) of 1 µm size were consumed at concentrations of 0.1, 1, and 10 mg/L during pregnancy. Results indicated that PS-MPs induced placental malfunction and fetal growth retardation. Significant glucose disorders, decreased liver function, hepatic inflammation, and oxidative stress were also observed after PS-MPs exposure. The hepatic SIRT1/IRS1/PI3K pathway was inhibited in the 10 mg/L PS-MPs exposure group. Our study found that PS-MPs activated inflammatory response and oxidative stress by increasing hepatic lipopolysaccharide (LPS) that inhibited the hepatic SIRT1/IRS1/PI3K pathway, ultimately leading to insulin resistance, glucose metabolism disorders, and adverse pregnancy outcomes. This study provides a basis for preventing environment-related gestational diabetes and concomitant adverse pregnancy outcomes.

Associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan: A cross-sectional study in U.S. women.

Female reproductive timing and lifespan, with a close relation to long-term health outcomes, have been altered in U.S. women over the past decades. However, epidemiologic evidence of the potential causes was lacking. On the basis of 1981 naturally postmenopausal women from the National Health and Nutrition Examination Survey 1999-2020, this study aimed to investigate the associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan. Multivariate generalized linear regression and addictive models were used for single metal exposure analysis, and weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed for mixed exposures. In the fully adjusted model, higher urinary antimony concentration was associated with earlier age at menarche of 0.137 years, while higher concentrations of cadmium, cesium, lead, antimony, and thallium were associated with delayed age at menopause of 0.396-0.687 years. Additionally, urinary barium, cesium, lead, antimony, and thallium levels were associated with longer reproductive lifespan ranging between 0.277 and 0.713 years. Both WQS and BKMR models showed significantly positive associations of metal mixtures with age at menopause (ß: 0.667, 95 % CI: 0.120-1.213) and reproductive lifespan (ß: 0.686, 95 % CI: 0.092-1.280), with cadmium and lead identified as principal contributors. In conclusion, heavy metal exposures were associated with reproductive timing and lifespan of U.S. women, highlighting the need for further prevention and intervention strategies.

Combined exposure of nano-titanium dioxide and polystyrene nanoplastics exacerbate oxidative stress-induced liver injury in mice by regulating the Keap-1/Nrf2/ARE pathway.

It is well known that polystyrene nanoplastics (PS-NaP) and nano-titanium dioxide (TiO2 NPs) are frequently co-appeared in daily life and can cause liver injury when they accumulate in the liver. Nonetheless, the combined toxicological impacts and potential molecular mechanisms of PS-NaP and TiO2 NPs in the hepatic system have not been revealed. Thus, we conducted experiments on C57BL/6 mice exposed to PS-NaP or/and TiO2 NPs for 4 weeks. The findings suggested that PS-NaP and TiO2 NPs co-exposed significantly altered the hepatic function parameters, levels of antioxidant-related enzymes and genes expression of Keap-1/Nrf2/ARE signaling pathway, as well as significantly increased the hepatic Ti contents, aggravated hepatic pathological and oxidative stress (OS) damage compared with individual exposure to PS-NaP or TiO2 NPs. Using N-Acetyl-L-cysteine (NAC), an OS inhibitor, we further demonstrated that OS played a pivotal role in coexposure-induced liver injury. NAC reduced the levels of OS in mice, which mitigated co-exposure-induced liver injury. Taken together, we proposed that PS-NaP and TiO2 NPs co-exposed activated the Keap-1, then inhibited the recognition of Nrf2 and ARE, consequently exacerbated liver injury. These findings shed light on the co-toxicity and potential mechanism of nanoplastics and nanoparticles, which informed the risk assessment of human exposure to environmental pollutants.

Synthesis, applications, toxicity and toxicity mechanisms of silver nanoparticles: A review.

Silver nanoparticles (AgNPs) have become one of the most popular objects of study for the past few decades. The ability to design AgNPs through different synthetic methods according to the application area and desired features is their advantage in many applications. Green synthesis of silver nanoparticles has become one of the most potential synthesis methods. Because of their strong antibacterial activity, AgNPs have been used in a wide range of applications, such as food packaging and medical products and devices. With the increasing application of AgNPs, it is becoming necessary for a better understanding of the toxicity of AgNPs and their potential mechanism of toxicity. In the review, we first describe the synthetic methods of AgNPs. The application of AgNPs in the field is then briefly described. The toxicity of AgNPs and their potential toxicity mechanisms are discussed.

TiO2 NPs induce the reproductive toxicity in mice with gestational diabetes mellitus through the effects on the endoplasmic reticulum stress signaling pathway.

The effect of one of the most widely studied nanomaterials at present, TiO2 nanoparticles (NPs), on pregnancy-related diseases is not clear. In this study, the adverse effects of TiO2 NPs on mice with gestational diabetes mellitus (GDM) and their possible mechanism were investigated. GDM mice were orally administered 0, 10, 50 and 250 mg/kg TiO2 NPs for 14 days. GDM reduced the weight of pregnant mice, destroyed the placental structure and caused abnormal fetal development. After exposure to increasing doses of TiO2 NPs, blood glucose levels increased significantly and body weight further decreased in GDM mice. The accumulation of the Ti content was detected in the placenta and fetus, which may further damage the placental structure in GDM mice, thereby exacerbating abnormal fetal development. In addition, the MDA and SOD activities were obviously increased, and the expression of genes associated with endoplasmic reticulum stress (ERS) (PERK, eIF2α, AFT4, IRE1α, and XBP1s) and apoptosis (CHOP, JNK, Bax/Bcl-2, Caspase-12, Caspase-9, and Caspase-3) were also obviously increased in the placenta, which reflected the possible activation of apoptosis. It could be speculated that the reproductive toxicity of TiO2 NPs in GDM mice triggered oxidative stress that subsequently activated ERS pathways to induce cell apoptosis.

Restraining the TiO2 nanoparticles-induced intestinal inflammation mediated by gut microbiota in juvenile rats via ingestion of Lactobacillus rhamnosus GG.

Human were given a lot of opportunities to ingest TiO2 NPs in the environment. Children have low, sensitive intestinal tolerance, and they could be exposed to higher levels of TiO2 NPs than adults. Few studies have been conducted on the interaction between TiO2 NPs and juvenile intestine phase models. Thus, in this work, weaning rats were orally exposed to TiO2 NPs for 7 and 14 days. Results indicate that Ti accumulated in the intestine, liver, and feces. Inflammatory infiltration damage was observed in the colonic epithelial tissue, and gut microbiota fluctuated with a decreased abundance of Lactobacilli in feces. Oral supplementation with Lactobacillus rhamnosus GG (LGG) lessened TiO2 NPs-induced colonic inflammatory injury, which might due to downregulation of nuclear factor kappa-B (NF-κB). Meanwhile, LGG maintained normal intestinal microbiome homeostasis, thereby improving TiO2 NPs-induced colon injury in juvenile rats. Moreover, fecal microbiota transplant (FMT) experiment indicated possible TiO2 NPs-induced intestinal microbiota disorder led to colonic inflammation. Our works suggested the urgent need for additional studies on the risk safety assessment, mechanism, and prevention of juvenile health damage from exposure to TiO2 NPs.

Adolescent F-53B exposure induces ovarian toxicity in rats: Autophagy-apoptosis interplay.

As a substitute for perfluorooctane sulfonates, F-53B has permeated into the environment and can reach the human body through the food chain. Adolescent individuals are in a critical stage of development and may be more sensitive to the impacts of F-53B. In the present study, we modeled the exposure of adolescent female rats by allowing them free access to F-53B at concentrations of 0 mg/L, 0.125 mg/L, and 6.25 mg/L in drinking water, aiming to simulate the exposure in the adolescent population. Using the ovary as the focal point, we investigated the impact of developmental exposure to F-53B on female reproduction. The results indicated that F-53B induced reproductive toxicity in adolescent female rats, including ovarian lesions, follicular dysplasia and hormonal disorders. In-depth investigations revealed that F-53B induced ovarian oxidative stress, triggering autophagy within the ovaries, and the autophagy exhibited the interplay with apoptosis in turn, collectively leading to significant ovarian toxicity. Our findings provided deeper insights into the roles of the autophagy-apoptosis interplay in ovarian toxicity, and offered a new perspective on the developmental toxicity inflicted by adolescent F-53B exposure.

Exploration of Lactiplantibacillus plantarum P101 ameliorated the alcohol-induced testicular dysfunction based on metabolome analysis.

The decline in male sperm quality caused by multiple factors has become a widespread concern. Alcohol excessive consumption is one of the factors that induce testicular dysfunction. Testicular dysfunction caused by alcohol abuse is related to oxidative stress and inflammation. Probiotics can ameliorate alcohol-induced testicular dysfunction. However, the specific mechanism is not explicit. This study aimed to elucidate the underlying mechanism by which Lactiplantibacillus plantarum P101 ameliorates the alcohol-induced testicular dysfunction. The model of alcohol-induced testicular dysfunction in C57B/6 male mice was established according to the National Institute on Alcohol Abuse and Alcoholism, and Lactiplantibacillus plantarum P101 supplementation was orally administered to mice during the experiment. The results showed that Lactiplantibacillus plantarum P101 promoted androgen production, reduced testis inflammation, and improved testis antioxidant capacity, thereby improving sperm quality and sperm motility and ultimately ameliorating alcohol-induced testicular disorder. Three key metabolite pathways and six key metabolites were identified by metabolome analysis.

Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.

Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.

Overexpression of interleukin-10 in engineered macrophages protects endothelial cells against LPS-induced injury in vitro.

Endothelial dysfunction is a primary pathophysiological change in sepsis. Macrophages are known to interact with vascular endothelial cells during the development of sepsis. Recently, drug delivery based on engineered macrophages was reported as an alternative approach for the management of diseases. Interleukin-10 (IL10) is a well-known anti-inflammatory cytokine, which reduces inflammation and inhibits dysfunction of endothelial cells caused by sepsis. It is currently poorly understood whether genetically modified macrophages with overexpression of IL10 are able to restore endothelial integrity and function at the cellular level. In this study, we used lentiviral vectors to construct RAW264.7 macrophages engineered to overexpress IL10 (IL10-eM) and investigated the effects of the IL10-eM supernatant on LPS-induced endothelial dysfunction using a noncontact coculture system. We found that cotreatment with IL10-eM supernatant significantly attenuates the effects of LPS-induced dysfunction of endothelial cells, including endothelial inflammatory response, endothelial permeability, and apoptosis. In addition, we discovered that LPS-induced downregulation of VE-cadherin and high production of reactive oxygen species were significantly attenuated upon IL10-eM exposure. Furthermore, upregulation of IL6, TNFα, and Bax was decreased after treatment of cells with IL10-eM supernatant. These results demonstrated that supernatant from engineered macrophages genetically modified with IL10 can effectively protect endothelial cells against LPS-induced dysfunction in vitro, suggesting that exosomes from such engineered macrophages may have therapeutic effects against sepsis.

Protective Effect of Lactobacillus rhamnosus GG on TiO2 Nanoparticles-Induced Oxidative Stress Damage in the Liver of Young Rats.

The potential toxicity of titanium dioxide nanoparticles (TiO2 NPs) to mammals has become a widespread concern. Young individuals exposed to TiO2 NPs have a higher risk than adults. In this study, the protective effects of Lactobacillus rhamnosus GG (LGG) on liver toxicity in young rats induced by TiO2 NPs were explored. Results show that the four-week-old rats that underwent LGG after the oral intake of TiO2 NPs could prevent weight loss, reduce hematological indicators (WBC and NEUT) and serum biochemical indicators (AST, ALT, AST/ALT, and ALP). Moreover, it alleviated the pathological damage of the liver (as indicated by the disordered hepatocytes, more eosinophilic, ballooning degeneration, and accompany with blood cells), but it did not reduce the Ti contents in the liver. In addition, RT-qPCR results indicated that LGG restored the expression of anti-oxidative stress-related genes, such as SOD1, SOD2, CAT, HO-1, GSH, GCLC, and GCLM in the liver. In summary, the hepatotoxicity of TiO2 NPs in young rats is closely related to oxidative stress, and the antioxidant effect of LGG might protect the harmful effects caused by TiO2 NPs.