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Nanoplastics (NPs) are widely distributed in the aquatic environment and have become a global concern as a new type of pollutant. Many researchers have studied the physiological effects of NPs on aquatic organisms, but relatively little is known about their effects on intestinal immune function in crustaceans. Therefore, we used NPs concentrations of 0, 5, 10, 20, 40 mg/L for 28 days of stress, evaluated the effects of NPs exposure on intestinal cell apoptosis, histopathological damage, and glutathione (GSH) metabolism of juvenile East Asian river prawns (Macrobrachium nipponense). As NPs concentration increased, the contents of total GSH and oxidized glutathione decreased gradually (P < 0.05), the concentration of GSH first increased and then decreased (P < 0.05), and the activities of lysozyme, acid phosphatase, phenoloxidase, and alkaline phosphatase first increased and then decreased (P < 0.05). Additionally, intestinal tissue structure was damaged, and the apoptosis rate significantly increased (P < 0.05). The expression of intestinal autophagy genes (CTL, ALF, Crustin, ATG8, and BCL-2) increased at first and then decreased, the expression levels of TNF and Wnt4 significantly decreased, and the expression of Beclin significantly increased with increasing NPs concentration. We also found that AP-1 and PTEN were highly expressed in the hepatopancreas and were involved in intestinal immune responses. Our results showed that exposure to NPs may induce apoptosis of intestinal tissue cells, induce autophagy, and inhibit GSH metabolism, thereby reducing intestinal immune function of M. nipponense. These findings provide a reference for healthy aquaculture and ecological risk assessment of prawns., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Polystyrene nanoplastics induce apoptosis, histopathological damage, and glutathione metabolism disorder in the intestine of juvenile East Asian river prawns (Macrobrachium nipponense)”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In many organ dysfunctions, arsenic and its compounds are well known to induce apoptosis by the mitochondria and death receptor apoptotic pathways in liver and airway. However, it is less reported that which signaling pathways contribute to excessive apoptosis of chicken immune organs, a major target of toxic metals biotransformation, which suffer from subchronic arsenism. In this study, we investigated whether the mitochondria or death receptor apoptotic pathways activated in the immune organs (spleen, thymus and bursa of Fabricius) of one-day-old male Hy-line chickens exposed to arsenic trioxide (As2O3), which were fed on diets supplemented with 0, 0.625, 1.25 and 2.5 mg/kg BW of As2O3 for 30, 60 and 90 days. We found that (1) Oxidative damage and inflammatory response were confirmed in the immune organs of chickens fed on As2O3 diet. (2) Subchronic arsenism induced typical apoptotic changes in ultrastructure. (3) TdT-mediated dUTP Nick-End Labeling (TUNEL) showed that the number of apoptotic cells significantly increased under subchronic arsenism. (4) As2O3-induced apoptosis of immune organs involved in mitochondrial pathway (decrease of B-cell lymphoma-2 (Bcl-2) and increase of protein 53 (p53), Bcl-2 Associated X Protein (Bax), caspase-9, caspase-3) and death receptor pathway (increase of factor associated suicide (Fas) and caspase-8). In conclusion, this work is the first to demonstrate that the activation of mitochondria and death receptor apoptosis pathways can lead to excessive apoptosis in immune organs of chickens, which suffer from subchronic arsenism, meanwhile, oxidative stress as well as subsequent inflammatory is a crucial driver of apoptosis.

Diphenyl phosphate (DPhP) is one of the frequently used derivatives of aryl phosphate esters and is used as a plasticizer in industrial production. Like other plasticizers, DPhP is not chemically bound and can easily escape into the environment, thereby affecting human health. DPhP has been associated with developmental toxicity, reproductive toxicity, neurodevelopmental toxicity, and interference with thyroid homeostasis. However, understanding of the underlying mechanism of DPhP on the reproductive toxicity of GC‐2spd(ts) cells remains limited. For the first time, we investigated the effect of DPhP on GC‐2spd(ts) cell apoptosis. By decreasing nuclear factor erythroid‐derived 2‐related factor (Nrf2)/p53 signaling, DPhP inhibited autophagy and promoted apoptosis. DPhP reduced total antioxidant capacity and nuclear Nrf2 and its downstream target gene expression. In addition, we investigated the protective effects of Curcumin (Cur) against DPhP toxicity. Cur attenuated the DPhP‐induced rise in p53 expression while increasing Nrf2 expression. Cur inhibited DPhP‐induced apoptosis in GC‐2spd(ts) cells by activating autophagy via Nrf2/p53 signaling. In conclusion, our study provides new insights into the reproductive toxicity hazards of DPhP and demonstrates that Cur is an important therapeutic agent for alleviating DPhP‐induced reproductive toxicity by regulating Nrf2/p53 signaling. [ABSTRACT FROM AUTHOR]

Abstract The regulation of interferon-α signaling pathways is essential to protect the host from infection with a broad range of viruses. However, information regarding antiviral response and the specific molecular mechanism of Columba livia interferon-α (CoIFN-α) has not been reported to date. In this study, we cloned a 723bp complete ORF of CoIFN-α gene. The specific antiviral activity of CoIFN-α in VSV (TCID 50 = 10−5.87/100 μL)-infected CEFs reached 5.5 × 105 U/mg. Moreover, our result indicated that the anti-VSV efficient of CoIFN-α might depend on the expression of NF-κB. CoIFN-α also showed high sensitivity to trypsin and relatively stable after acid, alkali or heat treatment. Moreover, CoIFN-α activated STAT/Jak signaling and autophagy to inhibit VSV-induced apoptosis. Although the expression of p53 was further increased, apoptosis was not involved in CoIFN-α against VSV. Notably, although STAT signaling was efficiently activated, knockdown p53 did inhibit the antiviral activity of the CoIFN-α via decreasing the expression of Mx1 but not weakened Jak phosphorylation. Moreover, VSV aggravated the apoptosis and the expression of cleaved Mdm2 in knockdown p53 under preincubated CoIFN-α. Taken together, p53 might as a highly interconnected regulator in IFN-α antiviral response and cleaved Mdm2 might as a dominant-negative regulator by competing with full length Mdm2 for p53 binding in virus infection. Overall, our research not only enriches CoIFN-α antiviral features but also helps explain that p53 enhance the CoIFN-α antiviral response against pigeon viral diseases. Highlights • The characterization and biological activity of Columba livia IFN-α were analyzed. • Columba livia IFN-α project protective effects on virus-induced apoptosis. • NF-κB is involved in the antiviral activity between CoIFN-α and ChIFN-α resisted VSV. • Knockdown p53 decrease the expression of Mx1 but not weakened Jak2 phosphorylation. • Cleaved Mdm2 might enhances the induction of p53 for innate cellular immunity. [ABSTRACT FROM AUTHOR]

Copper (Cu) is an essential trace element for organism of function properly. Overexposure to Cu causes chronic cardiac impairment. The aim of this study was to investigate the change of 28-trace element, inflammatory response, the possible mitochondrial dynamics and apoptosis under Cu exposure in the heart of chickens. Cupric sulfate (CuSO 4 ) (300 mg/kg) was administered in a basal diet to male Hy-line chickens (one-day-old) for 90 days. Results showed the concentrations of Cu in the Cu group were increased by 57.8%, 27.57% and 57.2% at 30, 60 and 90 days, respectively. The Cu supplement caused trace elements imbalance, including reduced concentrations of B, Al, Ni, Ba, Pb and increased Li, Na, Mg, Si, K, Ca, V, Mn, Fe, Co, Zn, As, Mo in the heart of chickens. Exposure to Cu induced the TUNEL positive nuclei, histopathological alterations and ultrastructural apoptotic features. Moreover, Cu exposure activated the NF-κB-mediated pro-inflammatory cytokines, decreased the mRNA levels of opa1, mfn1, mfn2, Bcl-2, increased the mRNA levels of drp1, Bax, caspase-3, caspase-9, P53, while not altered Fas and caspase-8 compared with the control group. Similarly, western blot results showed the same trend of mRNA. Correlation analysis indicated that mitochondrial fission and intrinsic apoptosis might function synergistic. Moreover, mitochondrial network seem to function as cytosolic sensors for the induction of NF-κB mediated inflammatory responses. In summary, we speculated that Cu-induced redistribution of trace elements contributed to inflammatory response and disrupted the mitochondrial network via fission and intrinsic apoptosis in the heart of chickens. [ABSTRACT FROM AUTHOR]

Synthetic phenolic antioxidants (SPAs) are an environmental concern due to their persistence nature and bioaccumulation. However, the hepatoxicity and mechanisms of SPAs in aquatic organisms remain poorly understood. In this study, grass carp were exposed to two representative SPAs (BHA and BHT) at environmentally relevant levels (0.1 μM) for 30 days. We observed that BHA and BHT exposure significantly increased the levels of serum aminotransferase (ALT) and aspartate aminotransferase (AST) in grass carp, accompanied by mild inflammatory cell infiltration and irregularity in the shape of hepatocytes. Dihydro ethylenediamine staining showed that BHA and BHT exposure resulted in elevated levels of superoxide levels, accompanied by increased antioxidant enzyme activities (T-AOC, SOD, CAT, GSH-PX) and MDA levels, which is suggestive of oxidative stress responses in the liver of grass carp. Besides, BHA and BHT could dock into the pocket of phosphatidylinositol 3-kinases (PI3K) and thereby inhibiting PI3K/mammalian target of rapamycin (mTOR)/protein kinase B (AKT) signaling cascades. Meanwhile, our results clarified that BHA and BHT could promote autophagosome production and increase the expression of key autophagy proteins, likely due to inhibition of PI3K/mTOR/AKT signaling pathway. Moreover, BHA and BHT could induce apoptotic process by upregulating the expression of Bax, Caspase3 and Caspase8 and downregulating Bcl2 expression. Notably, BHT exhibited more hepatoxicity on the indicators of the apoptosis and oxidative stress than BHA. In summary, our findings demonstrated that BHA and BHT exposure could induce liver damage induced via regulating ROS/PI3K-mediated autophagic hyperactivation, which is a crucial step in triggering hepatocyte death. This study provides novel insight into the potential mechanisms underlying liver damage caused by BHA and BHT in aquatic organisms, and offers a new theoretical basis for ecological risk assessment of SPAs. [Display omitted] • BHA and BHT could induce ROS burst in the liver of grass carp. • BHA and BHT could dock into the pocket of PI3K and promote autophagic hyperactivation. • BHA and BHT could inhibit PI3K/mTOR/AKT signaling cascades. • BHA and BHT could induces apoptotic cell death in liver of grass carp. • BHT exhibited more hepatoxicity than BHA in grass carp. [ABSTRACT FROM AUTHOR]

Nanoplastics (NaPs) has reported to accumulate in the testes and cause degeneration in the seminiferous tubules. Additionally, exogenous hydrogen sulfide (H 2 S) is proposed to enhance tolerance to oxidative stress. The current work aimed to investigate the mechanisms of NaPs-induced reproductive toxicity in vitro and probable reproductive protection by endogenous H 2 S. We firstly found that 80 nm fluorescent NaPs could enter into GC-2spd(ts) cells by fluorescent inverted microscope. In addition, we demonstrated that NaPs-induced could induce ROS-dependent mitochondrial apoptosis and autophagy in vitro. Our results showed that the H 2 S donor NaHS ameliorated NaPs-triggered mitochondrial apoptosis and autophagy in GC-2spd(ts) cells. Moreover, NaPs treatment did not change the interaction between nuclear factor erythroid-derived 2-related factor (Nrf2) and Kelch-like ECH associated protein 1 (Keap1), while inhibiting nuclear accumulation of Nrf2 protein was observed. Meanwhile, NaHS weakened this interaction, subsequently improving antioxidant ability via increasing the protein levels of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1). Further, in vitro experiments showed that NaPs-induced reproductive toxicity associated with reducing PGC-1α. Meanwhile, NaPs-induced higher expression PGC-1α was further enhanced by NaHS co-treatment. Together, this study highlight that exogenous H 2 S should be an essential therapeutic approach to alleviate NaPs-induced reproductive toxicity via regulating Nrf2/PGC-1α signal. [Display omitted] [ABSTRACT FROM AUTHOR]

As the most common heavy metal pollutant, hexavalent chromium [Cr(VI)] has caused serious environmental pollution and health damage. Although the toxic effect of Cr(VI) has been widely studied, and oxidative stress has been confirmed to be the main mechanism of its cytotoxicity, the toxicity of Cr(VI) to human immune system remains to be elucidated. Neutrophil extracellular traps (NETs) participate in the innate immune response, and the release of NETs is considered to be the most important part of the extracellular killing mechanism. We demonstrated in this study that Cr(VI) inhibited the formation of NETs in rat peripheral blood and induced neutrophils apoptosis by inhibiting the AMP-activated protein kinase (AMPK) signaling pathway. Cr(VI)-induced inhibition of NETs was accompanied by down-regulated myeloperoxidase (MPO)/Histones-3 (H3) protein expressions and decreased NETs-associated intracellular and extracellular DNA levels in the neutrophils. Metformin (Met), as an AMPK activator, triggered autophagy and thus alleviated the inhibitory effect of Cr(VI) on NETs. At the same time, Met can reduce the intracellular reactive oxygen species (ROS) level by activating the AMPK/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway, thus alleviating Cr(VI)-induced neutrophils apoptosis. In conclusion, this study elucidated the mechanism of Cr(VI)-induced neutrophils toxicity and the role of AMPK as a key regulatory signal, which could provide valuable experimental basis for the prevention and treatment of related diseases in Cr(VI)-exposed populations. [Display omitted] • Cr(VI) inhibits the formation of NETs via AMPK signaling pathway. • Cr(VI) promotes the apoptosis of neutrophils via AMPK signaling pathway. • Met alleviates the inhibitory effect of Cr(VI) on the formation of NETs. • Met reduces the intracellular ROS level by activating the AMPK/ Nrf2 pathway. • Met inhibits Cr(VI)-induced neutrophil apoptosis. [ABSTRACT FROM AUTHOR]

Improper treatment of a large amount of industrial waste makes hexavalent chromium [Cr(VI)] seriously pollute the atmosphere, soil and water, and enter the food chain, seriously affecting the health of workers and local residents. We previously proved that Clusterin (CLU) can inhibit the apoptosis of L02 hepatocytes induced by Cr(VI) through mitochondrial pathway, but the associated molecular mechanism has not been further studied. Mitochondrial biogenesis is an important step in mitochondrial damage repair, but the mechanism of mitochondrial biogenesis in Cr(VI)-induced liver toxicity is still unclear. We demonstrated in the present study that Cr(VI) triggered mitochondrial biogenesis dysfunction-associated apoptosis, and CLU delayed Cr(VI)-induced apoptosis by enhancing mitochondrial biogenesis. Signal transducer and activator of transcription 3 (STAT3) was down-regulated in Cr(VI)-induced apoptosis, and CLU may regulate STAT3 via protein kinase B (PKB/AKT) in Cr(VI)-exposed hepatocytes. We used the STAT3 inhibitor C188–9 and the AKT inhibitor Uprosertib to eliminate the anti-apoptotic effect of CLU, and found that CLU inhibited Cr(VI)-induced apoptosis by up-regulating AKT/STAT3 signal. Based on the fact that both AKT and STAT3 are closely related to mitochondrial biogenesis and mitochondrial pathway-associated apoptosis, this study is the first time to link CLU, STAT3, AKT and mitochondrial biogenesis function after Cr(VI) exposure, to further enrich the experimental basis of Cr(VI)-induced hepatotoxicity, clarify the molecular mechanism of CLU helping cells to escape apoptosis, and also suggest that new ways can be sought to prevent and treat Cr(VI)-induced hepatotoxicity by regulating mitochondrial biosynthesis. • Cr(VI) triggered mitochondrial biogenesis dysfunction-associated apoptosis. • CLU delayed Cr(VI)-induced apoptosis by enhancing mitochondrial biogenesis. • STAT3 was down-regulated in Cr(VI)-induced apoptosis. • CLU may regulate STAT3 via AKT in Cr(VI)-exposed hepatocytes. • CLU inhibited Cr(VI)-induced apoptosis by up-regulating AKT/STAT3 signal. [ABSTRACT FROM AUTHOR]

• Polystyrene microplastics (mic-PS) accumulated in the liver of mice. • Mic-PS induced inflammation, apoptosis and oxidative stress in mice. • NaHS ameliorated hepatic injury induced by mic-PS exposure. • NaHS reduced micro-Ps-induced hepatic ROS by facilitating nuclear accumulation of Nrf2. • Upregulation of HO-1 and NQO1 involved in positive effects of NaHS. Microplastics, which are new types of environmental pollutants, are recently receiving widespread attention worldwide. Hydrogen sulfide (H 2 S) as the third endogenous gaseous mediator had protective effects in multiple physiological and pathological conditions. However, the protective role of H 2 S in microplastics-induced hepatotoxocity remain unclear. In this study, our data showed that H 2 S significantly suppressed inflammation, apoptosis and oxidative stress induced by polystyrene microplastics (mic-PS) (20 mg/kg b.w.) in the liver. Strikingly, although mic-PS exposure increased the expression of nuclear factor-E2-related factor (Nrf2), it did not influence the levels of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQOl) in the L02 hepatocytes. Immunofluorescence assay showed that sodium hydrosulfide (NaHS) reduced micro-Ps-induced hepatic apoptosis by facilitating nuclear accumulation of Nrf2. Simultaneously, flow cytometry also showed that NaHS could prevent mic-PS-induced accumulation of reactive oxygen species (ROS) by increasing the expression of HO-1 and NQO1. Furthermore, inhibition of HO-1 could reverse the hepatic protective effects of NaHS during mic-PS exposure. Mechanistically, H 2 S elevating the HO-1 and NQO1 expression by facilitating nuclear accumulation of Nrf2, and consequently reducing mic-PS-induced hepatic apoptosis and inflammation. This study unveils the hepatotoxic effects of MPs and suggest NaHS have protective effects on mic-PS-induced liver damage. [ABSTRACT FROM AUTHOR]

Mercury (Hg) pollution poses global human health and environmental risks. However, still knowledge gaps exist on both exposures and health effects. Here, we combined transcriptome sequencing technique to further investigate the specific mechanisms of inorganic Hg toxicity in the kidney. Strikingly, transcriptomic analysis revealed that 4174 unigenes (including 2646 upregulated and 1528 downregulated unigenes) were differentially expressed under acute HgCl 2 (5 mg/kg) exposure in the kidney. Additionally, we observed that HgCl 2 selectively induced tumor necrosis factor superfamily (TNFSF) to participate in renal damage, which was consistent with the high-throughput sequencing data. The phenomenon is accompanied by NLRP3 inflammasome and NF-κB signal activation in the kidney. Simultaneously, ELISA results shown that TNF-α, IL-1β and IL-6 concentrations in the kidney were significant increased. KEGG enrichment analysis showed that peroxisome proliferators-activated receptors (PPAR) signaling pathway might be vital toxic mechanism of Hg in the kidney. Then, our data showed that PPARγ agonist (GW 1929) attenuated HgCl 2 (15 μg/ml)-induced apoptosis and NLRP3 inflammasome activation via decreasing translocation of NF-κB and increasing Bcl2 levels in vitro. Along with this, we demonstrated that PPARγ antagonists (GW9662) effectively aggravated HgCl 2 -induced nephrotoxicity. Overall, our results suggested that PPARγ signaling pathway is considered to be a protective mechanism to combat against HgCl 2 -triggered NLRP3 inflammasome activation and apoptosis. • Mercuric chloride (HgCl 2) selectively induced TNFSF to participate in renal damage. • PPARγ agonist alleviates HgCl 2 -induced apoptosis via enhancing Bcl2 expression. • PPARγ agonist attenuates HgCl 2 -induced inflammasome via negative regulating NLRP3. • PPARγ antagonists aggravated HgCl 2 -induced apoptosis and inflammasome. • Inhibition NF-κB translocation might decide the survive of HK2 cells in HgCl 2 exposure. [ABSTRACT FROM AUTHOR]