Ecotoxicology and Environmental Safety最新文献

In this study, we aimed to investigate the mechanism by which fluoride exposure causes bone damage and the relationship with the loss of dorsal longitudinal anastomotic vessel (DLAV) formation in zebrafish larvae to further understanding of skeletal fluorosis. We assessed the development of chondrogenesis, osteogenesis, and DLAV angiogenesis, and reactive oxygen species (ROS) in zebrafish larvae subjected to blank control group (Con), low-fluoride group (LF), and high-fluoride group (HF). Abnormal development of the cartilage area, bone mineralization accompanied with abnormal mRNA expression of osteoblast-related OC, ALP, and Runx2b genes and osteoclast-related OPG and RANKL genes, and abnormal DLAV angiogenesis and ROS levels in zebrafish larvae were affected to varying degrees with the increase of fluoride exposure. We concluded that exposure of zebrafish embryos to fluoride can affect bone development process of chondrogenesis and osteogenesis, and that bone damage might be related to the loss of DLAV angiogenesis.

The reproductive age is a crucial stage for women to bear offspring. However, reproductive-aged women are simultaneously exposed to various phthalates, which may pose a threat to their reproductive health. This study employed generalized linear regression and weighted quantile sum (WQS) regression to explore the associations between monoesters of phthalates (MPAEs) and sex hormones in 913 reproductive-aged women in the National Health and Nutrition Examination Survey. Key risk factors driving hormone disruption were identified based on the weights of the WQS models. Interaction models were used to unravel the synergistic or antagonistic effects between MPAEs. The potential toxicological targets of MPAEs interfering with sex hormone-binding globulin (SHBG) levels were revealed based on prior knowledge and molecular docking of hepatocyte nuclear factor 4α (HNF4α). Compared with the first quartile, mono-benzyl phthalate (MBZP) in the second quartile exhibited a decrease in total testosterone (TT) and TT/E2 (estradiol) ratio. Mono-2-ethyl-5-carboxypentyl phthalate (MECPP) in the fourth quartile showed a decrease in SHBG and TT/E2. Additionally, mono-(carboxyoctyl) phthalate and mono-(carboxynonyl) phthalate (MCNP) were negatively associated with SHBG. Each unit increase in the WQS index of MPAE mixtures was associated with 6.73 % lower SHBG levels (95 %CI: -12.80 %, -0.24 %) with mono-(3-carboxypropyl) phthalate, MCNP, MBZP, and MECPP identified as major risk factors. Interaction analyses revealed that the effects of high-risk MPAEs on SHBG were predominantly antagonistic. Molecular docking suggested that MPAEs might compete to bind tryptophan residues of HNF4α. This study provides key information to help develop the most effective phthalate interventions and improve the reproductive health of reproductive-aged women.

Objective: Light exposure is thought to be associated with blood pressure (BP). However, the existing evidence is inconsistent, and the underlying mechanisms remain unclear.

Methods: This cohort study enrolled over 300,000 participants from the UK Biobank. Information on the time spent in outdoor light during typical summer and winter days was collected using questionnaires. Cases of hypertension and hypotension were identified using the 10th edition of the International Classification of Diseases codes. Cox proportional hazards regression models were employed to estimate the lightBP associations, and restricted cubic splines were utilized to detect potential nonlinear associations. Subgroup analyses were conducted to identify effect modifiers, and causal mediation analyses were performed to explore potential mechanisms.

Results: Using summer light exposure as an illustration, after a median follow-up of 13.4 years, each additional hour of summer light exposure was found to be associated with an increased risk of hypertension (hazard ratio [HR] 1.011, 95 % confidence interval [CI] 1.0061.017, P-nonlinear=0.803) and a decreased risk of hypotension (0.988, 0.9770.998, P-nonlinear=0.109). The lightBP association was found to be stronger in females (P=0.022), those with short sleep durations (P=0.049), and those with a high genetic risk of hypertension (P<0.001). Potential mechanisms included increases in biological age (proportion mediated, 24.1 %, P<0.001), neutrophil count (5.4 %, P<0.001), body mass index (32.0 %, P<0.001), etc. CONCLUSIONS: Our study revealed a positive lightBP association. Potential mechanisms include inflammation, aging, and lifestyle changes. Further epidemiological and experimental investigations are necessary to validate these findings.

Background: Nicotine, a major component of tobacco, is implicated in the pathogenesis of periodontitis. However, the exact mechanisms through which nicotine exerts its harmful effects remain incompletely understood. This study investigates the impact of nicotine-induced mitochondrial fission on human periodontal ligament cells (hPDLCs).

Methods: A range of assays, including MTT, immunofluorescence staining, flow cytometry, and western blotting, were utilized to evaluate hPDLC viability, apoptosis, mitochondrial fission, and function.

Results: Nicotine decreases hPDLC viability in a dose-dependent manner, leading to apoptosis, an elevated BAX/BCL-2 ratio, and cellular injury. Furthermore, nicotine induces phosphorylation of Drp1 at Ser616, which facilitates mitochondrial fission, elevates mitochondrial ROS production, reduces mitochondrial membrane potential, and lowers ATP generation, resulting in mitochondrial dysfunction. Inhibition of Drp1 phosphorylation by Mdivi-1 significantly alleviates mitochondrial fission and dysfunction, reduces nicotine-induced apoptosis, and promotes osteogenic differentiation.

Conclusion: Nicotine activates c-Jun N-terminal kinase (JNK), and the inhibition of JNK activity with SP600125 effectively prevents nicotine-induced mitochondrial fission, enhances cell viability, and inhibits Drp1 phosphorylation.

Functional Apis mellifera honey bee colonies rely on collaborative brood care typically performed by nurse bees with well-developed hypopharyngeal glands (HPGs). Neonicotinoids, widely used insecticides, have been shown to negatively affect HPG development when worker bees were exposed to field-realistic concentrations either as brood or adults. To date, it is unknown whether timing of neonicotinoid exposure influences the severity of these observed negative effects on HPGs. To address this, we conducted a fully-crossed field experiment assessing potential effects of a neonicotinoid blend (clothianidin and thiamethoxam combined) on worker HPGs when exposed during different life stages. We found that neonicotinoid exposure during the brood stage, but not the adult stage, significantly influenced subsequent HPG development. Since HPG morphogenesis begins during the brood stage, neonicotinoid-induced stress possibly impaired this process, resulting in smaller glands once these individuals became adult nurses. Because HPG productivity is correlated to their size, smaller glands as a result of neonicotinoid exposure could negatively affect colony functionality.

Plasticizers are recognized as environmental pollutants that may be associated with a range of health concerns, including impacts on growth, development, and oncogenic risks. Previous research demonstrated that prolonged exposure to di-(2-ethylhexyl) phthalate and its metabolite mono-(2-ethylhexyl) phthalate contributes to chemotherapeutic drug resistance and stemness in colorectal cancer cells. Aloe vera, an herbaceous plant with a long-standing history in traditional medicine, has attracted considerable attention for its diverse pharmacological properties. This study aimed to investigate the therapeutic potential of polysaccharides extracted from Aloe vera, specifically focusing on their anticancer properties. We eluted polysaccharides from Aloe vera using water and ethanol, resulting in the fractions designated A50 and I50, respectively. We characterized their effects on cell viability, migration, invasion, stemness, and glycosylation of colorectal cancer cells exposed to phthalates. Comprehensive glycan analysis revealed that phthalate exposure induced alterations in glycosylation patterns in colorectal cancer cells. Treatment with A50 and I50 reversed these changes to varying degrees, indicating distinct regulatory roles of the two polysaccharide fractions in colorectal cancer cells subjected to phthalate exposure. A50 exhibited a dose-dependent reduction in cell viability induced by phthalates, whereas I50 demonstrated no such effect. Notably, I50 displayed a notable inhibitory effect on migration, invasion, and stemness induced by phthalates when compared with A50. The differing polysaccharide structures of A50 and I50 may account for their divergent effects on the malignancy of colorectal cancer cells. These findings underscore the potential of Aloe vera polysaccharides in anticancer therapy and highlight the necessity for further investigation into their clinical applications.

Humans are constantly exposed to low doses of various metals and organic compounds in electronic waste (e-waste) recycling areas. Although these substances individually have been identified as environmental carcinogens that influence the onset and progression of tumors, their combined effect on human cancers has not been sufficiently investigated. For this reason, the goal of the current analysis is to evaluate the possible molecular mechanisms between exposure to a mixture of As, Cd, Cr, Hg, Pb, Sb, DBDE, DBDPE, and TBBPA from e-waste and the onset and progression of common human cancers via in silico toxicogenomic tools. The CTD, GeneMANIA, ToppGene Suite portal, and TIMER2 online server were utilized as the primary data-mining tools. Eleven genes that were linked to different types of cancer were found to be shared by most of the substances under investigation. Notably, co-expression (58.91 %) was the most common interaction among these genes. The examined mixture's primary molecular route linked to human cancers was found to be the interleukin 4 and interleukin 13 signaling pathway, which was further connected to the macrophage infiltration. These results underline the critical need for the future research that focus on examining the 11 particular genes as well as the mechanism involving IL4/IL13-mediated macrophage infiltration, to address this environmental health hazard and the development of targeted tumor prevention and control policies for populations exposed to the toxic substance from e-waste recycling process.

Ferroptosis emerges as one of the pivotal types of cell death during fine particulate matter (PM2.5)-induced lung injury. The recently discovered cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), triggers the activation of the downstream adaptor protein STING by synthesizing cyclic GMP-AMP, playing vital roles in innate immunity and cell death. Nonetheless, the specific function of cGAS in lung injury caused by PM2.5 remains to be elucidated. The present study aimed to explore the involvement of cGAS in the pathogenesis of PM2.5-induced lung injury and its potential mechanisms. The expression levels of cGAS in lung tissues and different types of cells isolated from murine lungs were detected. We generated a PM2.5-induced lung injury model with cGAS conditional knockout mice in type II alveolar epithelial (AT2) cells and investigated the roles of cGAS in ferroptosis in PM2.5-treated AT2 cells. The results demonstrated that PM2.5 could upregulate the expression of cGAS in lung tissues and AT2 cells. cGAS deficiency in AT2 cells not only improved pulmonary function, including lung compliance and oxygen saturation, but also relieved lung pathological injury in mice. In terms of mechanism, the absence of cGAS in AT2 cells notably reduced lipid peroxidation and ferroptosis in lungs exposed to PM2.5, achieved by increasing the protein level of ferritin. Meanwhile, cGAS deficiency also blocked the interaction between NCOA4 and ferritin, thus decreasing ferritinophagy. Additionally, periillaldehyde, one of the cGAS inhibitors, could protect against PM2.5-induced inflammation, oxidative stress, and edema in lung tissues by downregulating cGAS. Overall, cGAS promotes ferroptosis in PM2.5-induced lung injury by enhancing NCOA4-mediated ferritinophagy and shows promise as a therapeutic option for diseases associated with PM2.5 exposure.