Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have ...antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure.
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•ATO can induce autophagy and apoptosis by overproducing ROS in the kidney of ducks.•Cur might relieve excessive autophagy, apoptosis by regulating oxidative stress.•ATO exposure could induce dyslipidaemia in the kidneys of ducks.•Long-term Cur administration alleviates dyslipidaemia.
Exposure to copper (Cu) has been associated with metabolic disorders in animals and humans, but the underlying mechanism remains unclear. One-day-old broiler chickens, numbering a total of 192, were ...nourished with dietary intakes that contained varying concentrations of Cu, specifically 11, 110, 220, and 330 mg/kg of Cu, for a period extending over a duration of 7 wk. As a result of the study, Cu exposure resulted in vacuolization, fragmentation of mitochondria cristae, and the increase of autophagosomes in hepatocytes. Metabolomics analysis illustrated that Cu caused a total of 59 different metabolites in liver, predominantly associated with the glycerophospholipid metabolic pathway, leading to metabolic disruption. Moreover, high-Cu diet markedly reduced the levels of AMPKα1, p-AMPKα1, mTOR, and p-mTOR and enhanced the expression levels of the autophagy-related factors (Atg5, Dynein, Beclin1, and LC3-II). Overall, Cu exposure caused chicken liver injury and resulted in disturbed metabolic processes and mediated autophagy primarily through the AMPK-mTOR axis.
The Nuclear Pore Complex (NPC) represents a critical passage through the nuclear envelope for nuclear import and export that impacts nearly every cellular process at some level. Recent technological ...advances in the form of Auxin Inducible Degron (AID) strategies and Single-Point Edge-Excitation sub-Diffraction (SPEED) microscopy have enabled us to provide new insight into the distinct functions and roles of nuclear basket nucleoporins (Nups) upon nuclear docking and export for mRNAs. In this paper, we provide a review of our recent findings as well as an assessment of new techniques, updated models, and future perspectives in the studies of mRNA's nuclear export.
Arsenic (As) and copper (Cu) are two common contaminants in the environment. When organisms are exposed to As or/ and Cu in large quantities or for sustained periods, oxidative stress is induced, ...adversely affecting kidney function. However, the molecular mechanisms involved in As or/ and Cu-induced nephrotoxicity remain elusive. In this experiment, wild-type C57BL/6 and Nrf2-knockout mice (n = 24 each) were exposed to arsenic trioxide and copper chloride alone or in combination. Our research findings indicate that exposure to As or/ and Cu can activate the Nrf2 antioxidant pathway by upregulating the levels of Nrf2, HO-1, CAT, and downregulating the level of Keap1, thereby reducing As or/ and Cu-induced oxidative stress. Meanwhile, exposure induced kidney cell pyroptosis and apoptosis by promoting the expression of NLRP3 inflammasomes and Caspase-3, which peaked in mice co-treated with As and Cu. Subsequently, we investigated its role in As or/ and Cu-induced kidney injury by knocking out Nrf2. Our results show that after knocking out Nrf2, the expression of antioxidant factors CAT and HO-1 significantly decreased. Based on the low antioxidant capacity after Nrf2 knockout, the levels of NLRP3 inflammasome, GSDMD, and Caspase1 were significantly upregulated after exposure to As and Cu, indicating more severe cellular pyroptosis. In addition, the level of Caspase3-mediated apoptosis was also more severe. Taken together, there is crosstalk between Nrf2-mediated antioxidant capacity and apoptosis/ pyroptosis induced by exposure to As or/ and Cu. Depletion of Nrf2 alters its antioxidant capacity, ultimately leading to more severe apoptosis, pyroptosis, and nephrotoxicity.
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•Exposure to As and Cu could activate the Nrf2/ keap1 signaling pathway.•Exposure to As and Cu could induce apoptosis and pyroptosis in the kidneys.•Nrf2 knockout exacerbated As and Cu-induced oxidative damage in kidneys.•Nrf2 knockdown aggravated the apoptosis and pyroptosis induced by As and Cu.
Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium ...homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with As2O3 (4 mg/kg), SbCl3 (15 mg/kg) and co-treat with SbCl3 (15 mg/kg) and As2O3 (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca2+ release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca2+ uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway.
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Despite the fact that copper (Cu) is a vital micronutrient to maintain body function, high doses of Cu through environmental exposure damage various organs, especially the liver, which is the main ...metabolic organ. To investigate the influence of long-term Cu-induced toxicity on mitophagy and apoptosis in rat liver, 96 seven-month-old male Sprague-Dawley rats were fed TBCC for 24 weeks. The results revealed that exposure to high Cu concentrations could promote oxidative stress liver injury by increasing the hepatic function index (ALT, AST and ALP) and MDA content, while reducing the activity of antioxidant enzymes (T-SOD, GSH-Px and CAT) related to oxidative stress. Consistent with histopathological observations, proper dietary Cu (15–60 mg/kg) could improve antioxidant stress levels and induce a dose-dependent increase in the mRNA expression of mitophagy-related genes, whereas a high Cu concentration (120 mg/kg) could cause severe liver impairment and ultrastructural changes and a reduction in mitophagosomes, accompanied by downregulation of Atg5, Beclin1, Pink1, Parkin, NIX, P62 and LC3B. The expression of apoptosis-related genes (Bax, Bax/Bcl-2, Caspase3, Cytc and p53) and proteins (Caspase3 and p53) was upregulated with the addition of dietary Cu. The results demonstrated that an appropriate dose of TBCC could improve liver function by promoting mitophagy and Cu enzymes that play antioxidative roles, while the accumulation of excess Cu could induce liver lesions by enhancing apoptosis and inhibiting mitophagy pathways.
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•Long-term copper exposure induced oxidative damage and toxicity to rat liver by regulating mitophagy and apoptosis.•Copper exposure attenuated mitophagy through the p53-mediated apoptosis signaling pathway.•Mitophagy might be an adaptive stress response prior to apoptotic cell death.
Copper poses huge environmental and public health concerns due to its widespread and persistent use in the past several decades. Although it is well established that at higher levels copper causes ...nephrotoxicity, the exact mechanisms of its toxicity is not fully understood. Therefore, this experimental study for the first time investigates the potential molecular mechanisms including transcriptomics, metabolomics, serum biochemical, histopathological, cell apoptosis and autophagy in copper-induced renal toxicity in pigs. A total of 14 piglets were randomly assigned to two group (7 piglets per group) and treated with a standard diet (11 mg CuSO4 per kg of feed) and a high copper diet (250 mg CuSO4 per kg of feed). The results of serum biochemical tests and renal histopathology suggested that 250 mg/kg CuSO4 in the diet significantly increased serum creatinine (CREA) and induced renal tubular epithelial cell swelling. Results on transcriptomics and metabolomics showed alteration in 804 genes and 53 metabolites in kidneys of treated pigs, respectively. Combined analysis of transcriptomics and metabolomics indicated that different genes and metabolism pathways in kidneys of treated pigs were involved in glycerophospholipids metabolism and glycosphingolipid metabolism. Furthermore, copper induced mitochondrial apoptosis characterized by increased bax, bak, caspase 3, caspase 8 and caspase 9 expressions while decreased bcl-xl and bcl2/bax expression. Exposure to copper decreased the autophagic flux in terms of increased number of autophagosomes, beclin1 and LC3b/LC3a expression and p62 accumulation. These results indicated that the imbalance of glycosphingolipid metabolism, the impairment of autophagy and increase mitochondrial apoptosis play an important role in copper induced renal damage and are useful mechanisms to understand the mechanisms of copper nephrotoxicity.
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•Transcriptomics and metabolomics investigated nephrotoxicity induced by copper in pig.•Compound lipids metabolism was disrupted.•Copper induced mitochondrial apoptosis and decreased the autophagic flux.
Super-resolution imaging techniques have broken the diffraction-limited resolution of light microscopy. However, acquiring three-dimensional (3D) super-resolution information about structures and ...dynamic processes in live cells at high speed remains challenging. Recently, the development of high-speed single-point edge-excitation subdiffraction (SPEED) microscopy, along with its 2D-to-3D transformation algorithm, provides a practical and effective approach to achieving 3D subdiffraction-limit information in subcellular structures and organelles with rotational symmetry. One of the major benefits of SPEED microscopy is that it does not rely on complex optical components and can be implemented on a standard, inverted epifluorescence microscope, simplifying the process of sample preparation and the expertise requirement. SPEED microscopy is specifically designed to obtain 2D spatial locations of individual immobile or moving fluorescent molecules inside submicrometer biological channels or cavities at high spatiotemporal resolution. The collected data are then subjected to postlocalization 2D-to-3D transformation to obtain 3D super-resolution structural and dynamic information. In recent years, SPEED microscopy has provided significant insights into nucleocytoplasmic transport across the nuclear pore complex (NPC) and cytoplasm-cilium trafficking through the ciliary transition zone. This Review focuses on the applications of SPEED microscopy in studying the structure and function of nuclear pores.
Several studies have provided evidence about adverse pregnancy outcomes of nurses involved in occupational exposure. However, the pregnancy outcomes among nurses in middle-income countries are not ...well demonstrated. The main aim of this study is to present the prevalence and influencing factors of pregnancy outcomes among female nurses in China.
We included 2243 non-nurse health care workers, and 4230 nurses in this national cross-sectional study in China. Information on occupational exposures and pregnancy outcomes was collected using a face-to-face investigation. Odds ratios (ORs) were estimated through logistic regression.
The proportion of threatened abortion, spontaneous abortion, and stillbirth of female nurses was 2.6%, 7%, and 2.1%, respectively. We found an increased risk of threatened abortion among nurses with overtime work (OR = 1.719, 95% CI 1.158-2.550). The risk of threatened abortion and spontaneous abortion was elevated among nurses handling disinfectant (OR = 2.293 and 1.63, respectively). We found a nearly twofold increased risk of premature birth (OR = 2.169, 95% CI 1.36-3.459) among nurses handling anti-cancer drugs.
Our findings suggested that maternal occupational exposures might be associated with the risk of adverse pregnancy outcomes among female nurses in China. We recommend that policy-markers and hospital managers work together to reduce exposure to occupational hazards and improve pregnancy outcomes among female nurses.
The transient nature of RNA has rendered it one of the more difficult biological targets for imaging. This difficulty stems both from the physical properties of RNA as well as the temporal ...constraints associated therewith. These concerns are further complicated by the difficulty in imaging endogenous RNA within a cell that has been transfected with a target sequence. These concerns, combined with traditional concerns associated with super-resolution light microscopy has made the imaging of this critical target difficult. Recent advances have provided researchers the tools to image endogenous RNA in live cells at both the cellular and single-molecule level. Here, we review techniques used for labeling and imaging RNA with special emphases on various labeling methods and a virtual 3D super-resolution imaging technique.
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