Chlorantraniliprole induces mitophagy, ferroptosis, and cytokine homeostasis imbalance in grass carp (Ctenopharyngodon idella) hepatocytes via the mtROS-mitochondrial fission/fusion axis.

Chlorantraniliprole (CAP) is a bis-amide pesticide used for pest control mainly in agricultural production activities and rice-fish co-culture systems. CAP residues cause liver damage in non-target organism freshwater fish. However, it is unclear whether CAP-exposure-induced liver injury in fish is associated with mitochondrial dysfunction-mediated mitophagy, ferroptosis, and cytokines. Therefore, we established grass carp hepatocyte models exposed to different concentrations of CAP (20, 40, and 80 µM) in vitro. MitoSOX probe, JC-1 staining, immunofluorescence double staining, Fe2+ staining, lipid peroxidation staining, qRT-PCR, and Western blot were used to verify the physiological regulatory mechanism of CAP induced liver injury. In the present study, the CAP-treated groups exhibited down-regulation of antioxidant-related enzyme activities and accumulation of peroxides. CAP treatment induced an increase in mitochondrial reactive oxygen species (mtROS) levels and altered expression of mitochondrial fission/fusion (Drp1, Fis1, Mfn1, Mfn2, and Opa1) genes in grass carp hepatocytes. In addition, mitophagy (Parkin, Pink1, p62, LC3II/I, and Beclin-1), ferroptosis (GPX4, COX2, ACSL4, FTH, and NCOA4), and cytokine (IFN-γ, IL-18, IL-17, IL-6, IL-10, IL-1ß, IL-2, and TNF-α)-related gene expression was significantly altered. Collectively, these findings suggest that CAP exposure drives mitophagy activation, ferroptosis occurrence, and cytokine homeostasis imbalance in grass carp hepatocytes by triggering mitochondrial dysfunction mediated by the mtROS-mitochondrial fission/fusion axis. This study partly explained the physiological regulation mechanism of grass carp hepatocyte injury induced by insecticide CAP from the physiological and biochemical point of view and provided a basis for evaluating the safety of CAP environmental residues to non-target organisms.

Exploring the impact of stress on the electronic structure and optical properties of graphdiyne nanoribbons for advanced optoelectronic applications.

Graphdiyne (GDY), a two-dimensional carbon material with sp- and sp2-hybridization, is recognized for its unique electronic properties and well-dispersed porosity. Its versatility has led to its use in a variety of applications. The precise control of this material's properties is paramount for its effective utilization in nano-optical devices. One effective method of regulation, which circumvents the need for additional disturbances, involves the application of external stress. This technique provides a direct means of eliciting changes in the electronic characteristics of the material. For instance, when subjected to uniaxial stress, electron transfer occurs at the triple bond. This results in an armchair-edged graphdiyne nanoribbon (A(3)-GDYNR) with a planar width of 2.07 nm, which exhibits a subtle plasmon effect at 500 nm. Conversely, a zigzag-edged graphdiyne nanoribbon (Z(3)-GDYNR) with a planar width of 2.86 nm demonstrates a pronounced plasmon effect within the 250-1200 nm range. This finding suggests that the zigzag nanoribbon surpasses the armchair nanoribbon in terms of its plasmon effect. First principles calculations and ab initio molecular dynamics further confirmed that under applied stress Z(3)-GDYNR exhibits less deformation than A(3)-GDYNR, indicating superior stability. This work provides the necessary theoretical basis for understanding graphene nanoribbons (GDYNRs).

New Insights into Decabromodiphenyl Ether-Induced Splenic Injury in Chickens: Involvement of ROS-Mediated Endoplasmic Reticulum Stress Pathway Triggering Autophagy and Apoptosis.

Decabromodiphenyl ether (BDE-209) is a widely used brominated flame retardant that can easily detach from materials and enter into feed and foodstuffs, posing a serious risk to human and animal health and food safety of animal origin. However, the immunotoxic effects of BDE-209 on the avian spleen and the exact mechanism of the toxicity remain unknown. Therefore, we established an experimental model of BDE-209-exposed chickens and a positive control model of cyclophosphamide-induced immunosuppression in vivo and treated MDCC-MSB-1 cells and chicken splenic primary lymphocytes with BDE-209 in vitro. The results showed that BDE-209 treatment caused morphological and structural abnormalities in the chicken spleens. Mechanistically, indicators related to oxidative stress, endoplasmic reticulum stress (ERS), autophagy, and apoptosis were significantly altered by BDE-209 exposure in both the spleen and lymphocytes, but the use of the N-acetylcysteine or the 4-phenylbutyric acid significantly reversed these changes. In addition, BDE-209 exposure decreased the spleen antimicrobial peptide and immunoglobulin gene expression. In conclusion, the present research revealed that BDE-209 exposure enhanced lymphocyte autophagy and apoptosis in chicken spleen via the ROS-mediated ERS pathway. This signaling cascade regulatory relationship not only opens up a new avenue for studying BDE-209 immunotoxicity but also provides important insights into preventing BDE-209 hazards to animal health.

Graphyne and graphdiyne nanoribbons: from their structures and properties to potential applications.

Graphyne (GY) and graphdiyne (GDY) have properties including unique sp- and sp2-hybrid carbon atomic structures, natural non-zero band gaps, and highly conjugated π electrons. GY and GDY have good application prospects in many fields, including catalysis, solar cells, sensors, and modulators. Under the influence of the boundary effect and quantum size effect, quasi-one-dimensional graphyne nanoribbons (GYNRs) and graphdiyne nanoribbons (GDYNRs) show novel physical properties. The various structures available give GYNRs and GDYNRs greater band structure and electronic properties, and their excellent physical and chemical properties differ from those of two-dimensional GY and GDY. However, the development of GYNRs and GDYNRs still faces problems, including issues with accurate synthesis, advanced structural characterization, the structure-performance correlation of materials, and potential applications. In this review, the structures and physical properties of quasi-one-dimensional GYNRs and GDYNRs are reviewed, their advantages and disadvantages are summarized, and their potential applications are highlighted. This review provides a meaningful basis and research foundation for the design and development of high-performance materials and devices based on GYNRs and GDYNRs in the field of energy.

Perfluorooctane sulfonate causes pyroptosis and lipid metabolism disorders through ROS-mediated NLRP3 inflammasome activation in grass carp hepatocyte.

The surfactant perfluorooctane sulfonate (PFOS) is widely produced worldwide. It is a persistent organic pollutant in the aquatic environment and poses a serious threat to aquatic organisms, as PFOS exposure can cause liver injury in a wide range of organisms. However, it is unclear whether PFOS exposure-induced hepatocellular injury in fish is associated with ROS-mediated activation of NLRP3 inflammasome. In this study, various PFOS concentrations were applied to L8824 cells, a cell line of grass carp hepatocytes. The detrimental impacts of PFOS on oxidative stress, pyroptosis, lipid metabolism, and the discharge of inflammatory factors were examined. MCC950 and N-acetylcysteine were employed to hinder the PFOS-stimulated activation of the NLRP3 inflammasome and the excessive generation of reactive oxygen species in L8824 cells, respectively. This study demonstrated that treatment with PFOS resulted in oxidative stress and activation of NLRP3 inflammasome in L8824 cells. This led to increased expression levels of indicators related to pyroptosis, accompanied by the upregulation of pro-inflammatory cytokine expression as well as downregulation of anti-inflammatory factors. In addition, following PFOS exposure, the expression levels of genes related to lipid synthesis were upregulated and lipid catabolism-related genes were downregulated. Surprisingly, both N-acetylcysteine and MCC950 interventions significantly reduced PFOS-induced L8824 cell pyroptosis and lipid metabolism disorders. In conclusion, this research demonstrated that PFOS drives NLRP3 inflammasome activation through oxidative stress induced by reactive oxygen species overload. This in turn leads to pyroptosis and lipid metabolism disorders.

The mechanism of cadmium exposure-induced lymph node necroptosis and inflammation in piglets: Activation of CYP450 through VDR / CREB1 pathway.

Cadmium (Cd) is toxic non-essential heavy metal that precipitates adverse health effects in humans and animals, but the effect of Cd on lymph node toxicity of piglets is still unclear. In order to explore the possible molecular mechanism of Cd toxicity to lymph nodes of piglets, ten 6-week-old male weaned piglets were randomly divided into two groups, C group and Cd group. Group C was fed with basal diet, while group Cd was fed with basal diet supplemented with CdCl2 (20 mg/kg) for 40 days, the pigs were euthanized and the mesenteric, inguinal and submandibular lymph nodes (MLN, ILN, SLN) were collected. The results indicated that Cd could induce the inflammatory cell infiltration, microvascular hemorrhage, microthrombosis and cell necrosis in MLN, ILN and SLN of piglets, induced Cytochrome P450 proteins (CYP1A1、CYP2E1、CYP2A1 and CYP3A2) mRNA levels and the protein levels of Vitamin D receptor (VDR) and cAMP response element binding protein 1 (CREB1). In addition, Cd exposure upregulated the mRNA and protein levels of dynamin-related protein 1 (DRP1), receptor-interacting protein kinase 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), and increased tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), interleukin-2 (IL-2), interleukin-4 (IL-4), cyclooxygenase 2 (COX-2) protein levels, and the damage degree of three kinds of lymph nodes was similar after Cd exposure. In general, these results manifest that Cd exposure regulates VDR/CREB1 pathway, activates CYP450s, induces necroptosis of lymph nodes, and leads to inflammation.

Role of Txnrd3 in NiCl2-induced kidney cell apoptosis in mice: Potential therapeutic effect of melatonin.

Nickel (Ni) exposure is a significant risk factor for kidney dysfunction and oxidative stress injury in humans. Thioredoxin reductase 3 (Txnrd3), an important enzyme in animals, plays a role in maintaining cellular homeostasis and regulating oxidative stress. However, its protective effect against kidney injury has been determined. Melatonin (Mel) has antioxidant and anti-apoptotic effects and therefore may be a preventive and therapeutic agent for kidney injury. Our study aimed to investigate the roles of Mel and Txnrd3 in the treatment of nickel-induced renal injury. We divided 80 wild-type mice and 80 Txnrd3 -/- mice (C57BL/6 N) into a control group treated with saline, Ni group treated with 10 mg/kg NiCl2, Mel group treated with 2 mg/kg Mel, and Ni + Mel group given NiCl2 and Mel for 21 days. Histopathological and ultrastructural observation of the kidney showed that nuclei were wrinkled and mitochondrial cristae were broken in the Ni group, and these changes were significantly attenuated by Mel treatment. Mitochondrial and nuclear damage improved significantly in the Ni + Mel and Txnrd3-/- Ni + Mel groups. Furthermore, NiCl2 exposure decreased T-AOC, SOD, and GSH activities in the kidney. The decreases in antioxidant enzyme activity were attenuated by Mel, and these improvements were abolished by Txnrd3 knockout. NiCl2-induced increases in the mRNA and protein levels of apoptosis factors (Bax, Cyt-c, caspase-3, and caspase-9) were attenuated by Mel treatment, and Txnrd3 knockout abolished the repressive effect of Mel on apoptosis genes. Overall, we concluded that Mel improves oxidative stress and apoptosis induced by NiCl2 by regulating Txnrd3 expression in the kidney. Our results provide evidence for the role of Mel in NiCl2-induced kidney injury and identify Txnrd3 as a potential therapeutic target for renal injury.

Txnrd3 knockout enhancement of lung injury induced by Ni exposure via the VEGF-VEGFR-2 axis and alleviation of this effect by melatonin.

Ni exposure leads to respiratory diseases in mice. Txnrd3 has been shown to have a protective effect on the body, but there is a paucity of empirical research focusing specifically on lung tissue. Melatonin possesses potent antioxidant, anti-inflammatory, and anti-fibrotic effects. By regulating inflammation-related factors, melatonin can activate the VEGF signaling pathway, ultimately alleviating lung injuries caused by Ni exposure. One hundred and sixty 8-week-old C57BL/6N mice, that were wild-type or Txnrd3-/- mice and 25-30 g in weight, were randomly divided into eight groups, including the NC group, Ni group, melatonin-treated group, and Ni plus melatonin group. Ni (10 mg/kg) was gavaged, and melatonin (2 mg/kg) was administered for 21 days. Inflammatory cells were found in the bronchioles of Txnrd3-/- mice under Ni exposure. Ultrastructural examination revealed that the homozygous-Ni group had a high amount of collagen fibers. The antioxidant capacity studies also revealed that mice lungs underwent oxidative stress. The results of qRT-PCR and WB showed that Ni induced an inflammatory response, which was also aggravated in Txnrd3-/- mice. Melatonin can effectively reduce the above symptoms. In conclusion, Ni causes lung injury by activating the VEGF-VEGFR-2 pathway and Txnrd3 knockout aggravates injury after Ni exposure.

New insights into Microalgal astaxanthin's effect on Lambda-cyhalothrin-induced lymphocytes immunotoxicity in Cyprinus carpio: Involving miRNA-194-5p-FoxO1-mediated-mitophagy and pyroptosis.

Lambda-cyhalothrin (LC), a pyrethroid insecticide widely used in agriculture, causes immunotoxicity to aquatic organisms in the aquatic environment. Microalgal astaxanthin (MA) is a natural carotenoid that enhances viability of a variety of fish. To investigate the immunotoxicity of LC and the improvement effect of MA in lymphocytes (Cyprinus carpio), lymphocytes were treated with LC (80 M) and/or MA (50 M) for 24 h. Firstly, CCK8 combined with PI staining results showed that MA significantly attenuated the LC-induced lymphocyte death rate. Secondly, LC exposure resulted in excessively damaged mitochondrial and mtROS, diminished mitochondrial membrane potential and ATP content, which could be improved by MA. Thirdly, MA upregulated the levels of mitophagy-related regulatory factors (Beclin1, LC3, ATG5, Tom20 and Lamp2) induced by LC. Importantly, MA decreased the levels of pyroptosis-related genes treated with LC, including NLRP3, Cas-4, GSDMD and active Cas-1. Further study indicated that LC treatment caused excessive miRNA-194-5p and reduced levels of FoxO1, PINK1 and Parkin, which was inhibited by MA treatment. Overall, we concluded that MA could enhance damaged mitochondrial elimination by promoting the miRNA-194-5p-FoxO1-PINK1/Parkin-mitophagy in lymphocytes, which reduced mtROS accumulation and alleviated pyroptosis. It offers insights into the importance of MA application in aquaculture as well as the defense of farmed fish against agrobiological hazards in fish under LC.

Micro-algal astaxanthin improves lambda-cyhalothrin-induced necroptosis and inflammatory responses via the ROS-mediated NF-κB signaling in lymphocytes of carp (Cyprinus carpio L.).

Lambda-cyhalothrin (LCY) is a widely used toxic pesticide that causes harmful effects on the immune organs of fish and aquatic species. Micro-algal astaxanthin (MAA), a heme pigment found in haematococcus pluvialis, has been shown to benefit antioxidants and immunity in aquaculture. To investigate how MAA protects carp lymphocytes from LCY-induced immunotoxicity, a model of fish lymphocytes treated with LCY and/or MAA was established. Lymphocytes from carp (Cyprinus carpio L.) were given LCY (80 µM) and/or MAA (50 µM) as a treatment for a period of 24 h. Firstly, LCY exposure resulted in excessive ROS and malondialdehyde production and reduces antioxidant enzymes (SOD and CAT), indicating a reduced capacity of the antioxidant system. Secondly, the results of flow cytometry and AO/EB labeling proved that lymphocytes treated with LCY have a larger ratio of necroptosis. In addition, LCY upregulated the levels of necroptosis-related regulatory factors (RIP1, RIP3 and MLKL) via the ROS-mediated NF-κB signaling pathway in lymphocytes. Thirdly, LCY treatment caused increased secretion of inflammatory genes (IL-6, INF-γ, IL-4, IL-1ß and TNF-α), leading to immune dysfunction in lymphocytes. Surprisingly, LCY-induced immunotoxicity was inhibited by MAA treatment, indicating that it effectively attenuated the LCY-induced changes described above. Overall, we concluded that MAA treatment could ameliorate LCY-induced necroptosis and immune dysfunction by inhibiting the ROS-mediated NF-κB signaling in lymphocytes. It provides insights into the protection of farmed fish from agrobiological threats in fish under LCY and the value of MAA applications in aquaculture.

miR-210/NF-κB axis: A new direction for regulating cadmium-induced pig artery inflammatory injury.

Cadmium (Cd) is a toxic metal pollutant that still exists in the environment. The microRNA (miRNA) is a type of noncoding RNA that plays an important role in gene posttranscriptional regulation and disease development. Although the toxic effects of Cd have been extensively studied, studies on the mechanism of Cd from the perspective of miRNA are still limited. So, we established a Cd-exposure pig model, which confirmed that Cd exposure would cause pig artery damage. The miR-210 with the most reduced expression and the nuclear factor kappa B (NF-κB) that had a targeting relationship with miR-210 were screened. The effect of miR-210/NF-κB on the artery damage induced by Cd exposure was investigated by acridine orange/ethidium bromide staining, reactive oxygen species (ROS) staining, quantitative PCR, and western blotting. The results showed that miR-210 inhibitor, pcDNA-NF-κB could induce ROS overproduction in pig hip artery endothelial cells, thus inducing Th1/Th2 imbalance and necroptosis, leading to increased inflammation, while small interfering RNA-NF-κB played a mitigating role. In conclusion, Cd can induce artery necroptosis and Th1/Th2 imbalance by regulating the miR-210/NF-κB axis, so as to lead to artery inflammatory damage. In this study, we explored the way in which Cd exposure causes artery damage in pig, providing a new perspective on the regulatory damage of miR-210/NF-κB axis.

Evaluating the effect of electroconvulsive therapy (ECT) on post-traumatic stress disorder (PTSD): A systematic review and meta-analysis of five studies.

ECT has been proposed as a potential treatment for PTSD. There is a small number of clinical studies to date, but no quantitative review of the efficacy has been conducted. We performed a systematic review and meta-analysis to evaluate the effect of ECT in reducing PTSD symptoms. We followed the PICO and the PRISMA guidelines and searched PubMed, MEDLINE (Ovid), EMBASE (Ovid), Web of Science, and the Cochrane Central Register of Controlled Trials (PROSPERO No: CRD42022356780). A random effects model meta-analysis was conducted with the pooled standard mean difference, applying Hedge's adjustment for small sample sizes. Five within-subject studies met the inclusion criteria, containing 110 patients with PTSD symptoms receiving ECT (mean age 44.13 ± 15.35; 43.4% female). ECT had a small but significant pooled effect on reducing PTSD symptoms (Hedges' g = -0.374), reducing intrusion (Hedges' g = -0.330), avoidance (Hedges' g = -0.215) and hyperarousal (Hedges' g = -0.171) symptoms. Limitations include the small number of studies and subjects and the heterogeneity of study designs. These results provide preliminary quantitative support for the use of ECT in the treatment of PTSD.

Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart. / 硒蛋白Mæ•²é™¤åœ¨è¤ªé»‘ç´ æ‹®æŠ—é•è¯±å¯¼çš„å°é¼ å¿ƒè„ç»†èƒžå‡‹äº¡å’Œå† è´¨ç½‘åº”æ¿€ä¸­çš„ä½œç”¨.

The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl2) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl2 was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl2 in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.

N-acetyl-L-cysteine alleviated the oxidative stress-induced inflammation and necroptosis caused by excessive NiCl2 in primary spleen lymphocytes.

Introduction: Nickel (Ni) is widely used in industrial manufacturing and daily life due to its excellent physical and chemical properties. However, Ni has the potential to harm animals' immune system, and spleen is a typical immune organ. Therefore, it is crucial to understand the mechanism of NiCl2 damage to the spleen. The purpose of this study is to investigate the effects of different concentrations of NiCl2 exposure and intervening with strong antioxidants on spleen lymphocytes to better understand the damage mechanism of Ni on spleen lymphocytes. Methods: In this experiment, mice spleen lymphocytes were used as the research object. We first measured the degree of oxidative stress, inflammation, and necroptosis caused by different NiCl2 concentrations. Subsequently, we added the powerful antioxidant N-acetyl-L-cysteine (NAC) and used hydrogen peroxide (H2O2) as the positive control in subsequent experiments. Results: Our findings demonstrated that NiCl2 could cause spleen lymphocytes to produce a large number of reactive oxygen species (ROS), which reduced the mRNA level of antioxidant enzyme-related genes, the changes in GSH-PX, SOD, T-AOC, and MDA, the same to the mitochondrial membrane potential. ROS caused the body to produce an inflammatory response, which was manifested by tumor necrosis factor (TNF-α) in an immunofluorescence experiment, and the mRNA level of related inflammatory genes significantly increased. In the case of caspase 8 inhibition, TNF-α could cause the occurrence of necroptosis mediated by RIP1, RIP3, and MLKL. AO/EB revealed that spleen lymphocytes exposed to NiCl2 had significant necroptosis, and the mRNA and protein levels of RIP1, RIP3, and MLKL increased significantly. Moreover, the findings demonstrated that NAC acted as an antioxidant to reduce oxidative stress, inflammation, and necroptosis caused by NiCl2 exposure. Discussion: Our findings showed that NiCl2 could cause oxidative stress, inflammation, and necroptosis in mice spleen lymphocytes, which could be mitigated in part by NAC. The study provides a point of reference for understanding the toxicological effect of NiCl2. The study suggests that NAC may be useful in reducing the toxicological effect of NiCl2 on the immune system. The research may contribute to the development of effective measures to prevent and mitigate the toxicological effects of NiCl2 on the immune system.

Polystyrene-microplastics and DEHP co-exposure induced DNA damage, cell cycle arrest and necroptosis of ovarian granulosa cells in mice by promoting ROS production.

The joint pollution of microplastics (MPs) and di-(2-ethylhexyl) phthalic acid (DEHP) often occurs, and consequently poses a serious threat to human and animal health, which has attracted widespread attention. However, the damage to the female mammalian ovary caused by the single exposure and co-exposure of MPs and DEHP and its specific mechanisms are not clear. Here, we established mouse models of single and co-exposures to polystyrene-microplastics (PS-MPs) and DEHP. The results showed that exposed to 100 mg/L PS-MPs and 200 mg/kg DEHP for 35 days destroyed the ovarian granulosa cell layer of mice, leading to follicular fragmentation and atresia. We cultured ovary granulosa cells in vitro to perform further mechanism studies and found that PS-MPs and DEHP had synergistic effects. Both of them promoted the excessive production of ROS and induced oxidative stress by triggering the CNR1/CRBN/YY1/CYP2E1 signaling axis, which in turn caused DNA oxidative damage. Additionally, we provided compelling evidence that oxidative stress mediated-hippo signaling pathway played a critical role in PS-MPs and DEHP caused ovary damage, resulting in ovarian granulosa cell cycle arrest and necroptosis. Using oxidative stress inhibitor AM251 or DAS could reverse these changes markedly and alleviate the reproductive toxicity caused by PS-MPs and DEHP, effectively. Overall, these results demonstrated that co-exposure of PS-MPs and DEHP adversely affected the integrity of ovary granulosa cell layer, resulting in DNA oxidative damage, cell cycle arrest and increased necroptosis of mouse ovarian granulosa cells by inducing oxidative stress. Our study shed new light on the co-exposure toxicity of PS-MPs and DEHP, provided novel insights for the reproductive toxicity of PS-MPs combined exposure with DEHP in female animals from a new free radical generation pathway perspective.

The role of selenoprotein M in nickel-induced pyroptosis in mice spleen tissue via oxidative stress.

Nickel (Ni) is a heavy metal element and a pollutant that threatens the organism's health. Melatonin (Mel) is an antioxidant substance that can be secreted by the organism and has a protective effect against heavy metals. Selenoprotein M (SelM) is a selenoprotein widely distributed of the body, and its role is to protect these tissues from oxidative damage. To study the mechanism of Ni, Mel, and SelM in mouse spleen, 80 SelM+/+ wild-type and 80 SelM-/- homozygous mice were divided into 8 groups with 20 mice in each group. The Ni group was intragastric at a concentration of 10 mg/kg, while the Mel group was intragastric at 2 mg/kg. Mice were injected with 0.1 mL/10 g body weight for 21 days. Histopathological and ultrastructural observations showed the changes in Ni, such as the destruction of white and red pulp and the appearance of pyroptosomes. SelM knockout showed more severe injury, while Mel could effectively interfere with Ni-induced spleen toxicity. The results of antioxidant capacity determination showed that Ni could cause oxidative stress in the spleen, and Mel could also effectively reduce oxidative stress. Finally, Ni exposure increased the expression levels of the pyroptotic genes, including apoptosis-associated speck protein (ASC), absent in melanoma-2 (AIM2), NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), Caspase-1, interleukin- (IL-) 18, and IL-1ß (p < 0.05). Loss of SelM significantly increased these (p < 0.05), while Mel decreased the alleviated impact of Ni. In conclusion, the loss of SelM aggravated Ni-induced pyroptosis of the spleen via activating oxidative stress, which was alleviated by Mel, but the effect of Mel was not obvious in the absence of SelM, which reflected the important role of SelM in Ni-induced pyroptosis.

Decreased thioredoxin reductase 3 expression promotes nickel-induced damage to cardiac tissue via activating oxidative stress-induced apoptosis and inflammation.

Thioredoxin reductase 3 (Txnrd3) plays a crucial role in antioxidant and anti-cancer activities, and sperm maturation. The damage of heavy metals, including Nickel (Ni), is the most prominent harm in social development, and hampering Txnrd3 might exacerbate Ni-induced cardiac damage. In this study, a total of 160 8-week-old C57BL/N male mice with 25-30 g weight of Txnrd3+/+ wild-type and Txnrd3-/- homozygote-type were randomly divided into eight groups. The mice in the control and Ni groups were gavaged with distilled water and a freshly prepared 10 mg/kg NiCl2 solution. Melatonin (Mel) groups were administered at a concentration of 2 mg/kg for 21 days at the mice's 0.1 ml/10 g body weight. Ni exposure up-regulated the messenger RNA (mRNA) levels of mitochondrial apoptosis (caspase-3, caspase-9, cytochrome c, p53, and BAX), autophagy (LC3, ATG 1, ATG 7, and Beclin-1), and inflammation (TNF-α, COX 2, IL-1ß, IL-2, IL-6, and IL-7)-related markers, but down-regulated the mRNA levels of BCL-2, p62 and mTOR (p < .05). Ni exposure decreased the expression of BCL-2 and p62 protein but increased the expression levels of caspase-3, caspase-9, cytochrome c, p53, BAX, ATG 7, Beclin-1, TNF-α, COX 2, IL-1ß and IL-2 protein (p < .05). Ni increased the contents of glutathione disulfide (GSSG) and malondialdehyde (MDA) and decreased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) (p < .05). Decreased Txnrd3 expression significantly exacerbated changes compared to the Ni exposure (p < .05). Mel significantly attenuated these changes, but the effect decreased when Txnrd3 was inhibited (p < .05). In conclusion, decreased Txnrd3 expression promoted Ni-induced mitochondrial apoptosis and inflammation via oxidative stress and aggravated heart damage in mice. Decreased Txnrd3 expression significantly reduced the protective effect of Mel to Ni exposure.

Atrazine exposure induces necroptosis through the P450/ROS pathway and causes inflammation in the gill of common carp (Cyprinus carpioL.).

Atrazine (ATR) is used worldwide and has been confirmed be hazardous materials that harmful to the health of organisms. Since ATR was more persistent in the water, the specific damage caused by ATR to aquatic organisms should be concern. The role of P450/ROS has been proposed in many pathomechanisms. To explore whether P450/ROS mediated necroptosis and promote inflammatory response caused by ATR exposure, 120 common carp (Cyprinus carpio L.) were randomly divided into four groups which were exposed to 0 µg/L, 4 µg/L, 40 µg/L and 400 µg/L ATR respectively. The residual levels of ATR and its metabolites increased, signs of necrosis and inflammation were found in the gills of the ATR-treatment groups. The levels of ROS and cytochrome P450 content were increased, and P450 enzymes were activated. The expression levels of the core components of necroptosis (RIPK1, RIPK3 and MLKL) increased. Moreover, gene expression of inflammatory factors (TNF-α, NF-κB, iNOS, COX-2, IL-1ß and PTGE) increased significantly in the ATR-spiked group. Our results suggested that ATR exposure triggered necroptosis through the P450/ROS pathway and causes inflammation of common carp gill. This study provides valuable clue about the mechanism by which ATR causes injury to common carp gill.