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Ethnopharmacological Relevance: The root of Polygonum cuspidatum Sieb. et Zucc (PC), known as 'Huzhang' in the Chinese Pharmacopoeia, has been traditionally employed for its anti-inflammatory, antiviral, antimicrobial, and other biological activities. Polydatin (PD) and its aglycone, resveratrol (RES), are key pharmacologically active components responsible for exerting anti-inflammatory and antioxidant effects. However, its specific targets and action mechanisms remain unclear., Aim of the Study: The equilibrium of the KEAP1-NRF2 system serves as the primary protective response to oxidative and electrophilic stresses within the body, particularly in cases of acute lung injury caused by pathogenic microbial infection. In this study, the precise mechanisms by which RES alleviates oxidative stress damage in conjunction with NRF2 activators are discussed., Materials and Methods: The active components from PC were screened to evaluate their potential to inhibit reactive oxygen species (ROS) and activate antioxidant activity dependent on antioxidant response elements (ARE). RES was evaluated for its potential to alleviate the oxidative stress caused by pathogenic microbial infection. Functional probes were designed to study the RES distribution and identify its targets. A lipopolysaccharide (LPS)-induced oxidative injury model was used to evaluate the effects of RES on the KEAP1-NRF2/ARE pathway in RAW 264.7 cells. The interaction between RES and NRF2 was elucidated using drug-affinity responsive target stability (DARTS), cellular thermal shift assays (CETSA), co-immunoprecipitation (Co-IP), and microscale thermophoresis (MST) techniques. The key binding sites were predicted using molecular docking and validated in NRF2-knockdownand reconstructed cells. Finally, protective effects against pulmonary stress were verified in a mouse model of pathogenic infection., Results: The accumulation of RES in lung macrophages disrupted the binding between KEAP1 and NRF2, thereby preventing the ubiquitination degradation of NRF2 through its interaction with Ile28 on the NRF2-DLG motif. The activation of NRF2 resulted in the upregulation of nuclear transcription, enhances the expression of antioxidant genes dependent on ARE, suppresses ROS generation, and ameliorates oxidative damage both in vivo and in vitro., Conclusion: These findings shed light on the potential of RES to mitigate oxidative stress damage caused by pathogenic microorganism-induced lung infections and facilitate the discovery of novel small molecule modulators targeting the KEAP1-NRF2 DLG motif interaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrogen sulfide (H 2 S), an important gaseous messenger, is known to have neuroprotective effects in many neurological disorders. This study examined the neuroprotective effects and the associated mechanisms of H 2 S in the model Sprague-Dawley (SD) rats with spinal cord injury (SCI). We found that H 2 S showed neuroprotective effects in SCI model rats, improved the symptoms of neurological impairment, reduced the secretion of inflammatory factors, nerve cell apoptosis, and endoplasmic reticulum (ER), and oxidative stresses. Moreover, these effects were produced by activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) protein. Our results suggest that H 2 S supplementation could be a potential therapeutic strategy to promote SCI recovery.

Heme homeostasis is of vital importance to many biological processes associated with cell redox activity. However, the role of heme in the doxorubicin (DOX)-induced cardiotoxicity is still not clear. The aim of the present study was to test the hypothesis that heme is related to the DOX-induced oxidative stress and inhibition of heme expression may protect H9c2 cardiomyocytes against DOX-induced cardiotoxicity. For the evaluation of heme changing under doxorubicin treatment, H9c2 cells were treated with 0.5, 1, 2, and 4 mg/mL doxorubicin respectively. H9c2 cells were divided into 5 groups: Control group (cells were cultured without intervention), DOX group (cells were treated with 2 mg/mL doxorubicin for 6 h), Heme depletion+DOX group (cells were cultured with heme-depleted serum media, 0.5 mM succinylacetone and 2 mg/mL doxorubicin), Heme group (cells were treated with 30 μM heme), and Heme depletion+DOX+Heme group. Apoptotic cells were detected by flow cytometry with Annexin V-FITC/PI. The intracellular oxidant levels were measured by DCFH-DA fluorescence. The levels of heme were detected by ELISA. Doxorubicin significantly increased intracellular heme level from 5013 ± 187 ng/mL to the highest level of 11,720 ± 107 ng/mL, as well as the intracellular oxidants and cell apoptosis rate elevated by the increase of doxorubicin concentration. Heme depletion can significantly suppress the DOX-induced apoptosis from 39.8 ± 0.5% to 20.8 ± 0.5% (p < 0.001). Re-supplemented with exogenous heme partially but significantly restored the DOX-induced apoptosis. Heme plays an important role in doxorubicin toxicity-induced cardiomyocyte injury. By appropriate reduction in the accumulation of free heme in cardiomyocytes, doxorubicin-induced cardiotoxicity may be alleviated.

The aim of this study was to investigate the protective effect of sulforaphane (SFN) on 1‑methyl‑4‑phenyl pyridine ion (MPP+)‑induced cytotoxicity and to investigate its possible mechanisms., Methods: PC12 cell toxicity induced by MPP+ served as a cell model of Parkinson's diseases. The cell culture + experiments were divided into four groups based on the different treatments, namely, vehicle control, SFN, MPP+ and SFN pretreatment plus MPP+. Cell viability and apoptosis were examined by MTT assay and flow cytometry, respectively. Expressions of nuclear factor erythroid 2‑related factor 2 (Nrf2), heme oxygenase 1 (HO‑1) and nicotinamide quinone oxidoreductase 1 (NQO1) were detected using western blotting., Results: MPP+ reduced the survival rate of PC12 cells in a dose‑ and time‑dependent manner. After 24‑h treatment with 500 µmol/l MPP+, the survival rate of PC12 cells decreased to 58.2±0.03% of that in the control groups. Under the same conditions MPP+ resulted in significant apoptosis of PC12 cells (apoptosis rate: 30.4±0.6%). However, SFN pretreatment significantly attenuated the cell damage induced by MPP+. Furthermore, it was demonstrated that SFN reversed the reduction of Nrf2, HO‑1 and NQO1 expression induced by MPP+., Conclusion: SFN may protect PC12 cells from MPP+‑induced damage via activating the Nrf2‑ARE (antioxidant responsive element) pathway.

Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2-/- mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2-/- mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.

New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 μL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca 2+ and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells. DNA damage and nuclear fragmentation assays also revealed apoptosis of C. albicans cells. In summary, by means of fluorescent microscopy, flow cytometer analysis, and Western blot, our data uncovered that PAE exerts its antifungal activity through Ca 2+ and oxidative stress-mediated apoptosis mechanisms. This study deciphered the mode of action of PAE, which will be useful in the design of improved antifungal therapies.

The objective of this study was to investigate the effects of organic iodine (3,5-diiodotyrosine, DIT) and inorganic iodine (potassium iodine, KI) on thyroid function and oxidative stress in iodine-excess Wistar rats. Seventy-two Wistar rats were randomly divided into eight groups: normal control (NC), thyroid tablet-induced hyperthyroidism model (HM), low DIT (L-DIT), medium DIT (M-DIT), high DIT (H-DIT), low KI (L-KI), medium KI (M-KI), and high KI (H-KI). All rats were fed ad libitum for 30 days. Morphological changes in the thyroid, absolute and relative weights of the thyroid, thyroid function markers free triiodothyronine (FT3) and free thyroxine (FT4), urinary iodine level, and oxidative stress indicators were measured. Compared to the HM groups, the FT3 and FT4 levels decreased in the L-DIT groups; the thyroid weight and thyroid weight/body weight values decreased markedly in the L-DIT and M-DIT groups; serum superoxide dismutase/malondialdehyde increased markedly; glutathione peroxidase activity increased markedly in the L-DIT groups; and malondialdehyde levels decreased significantly in the M-DIT groups. However, the FT3 and FT4 levels decreased and glutathione peroxidase levels increased significantly in the DIT groups compared to their corresponding KI groups. Additionally, urinary iodine levels increased significantly in both DIT and KI groups, while the highest urinary iodine excretion was showed in the DIT groups among groups. When the addition of iodine with the same doses in iodine-excess rats, although neither DIT nor KI normalized iodine levels in the iodine-excess rats, the DIT did less damage than did KI to thyroid follicular cells. Therefore, DIT rather than KI had a protective effect by balancing the antioxidant system when exposed to supraphysiological iodine. These suggest that DIT may be used as a new alternative iodized salt in the universal salt iodization to avoid the potential damage of surplus KI.

Toxicity due to overexposure to manganese (Mn) is becoming increasingly prevalent. Mn-induced neurodegenerative toxicity has been demonstrated, but little is known concerning the adverse effects of the element on the liver. Under physiological conditions, manganese primarily exists as divalent manganese (Mn(2+)) and trivalent manganese (Mn(3+)). The present study was designed to evaluate and compare the effects of Mn(2+) and Mn(3+) on oxidative hepatic damage, membrane fluidity and histopathological changes in rats. Rats exposed to Mn(2+) or Mn(3+) (2.0mg Mn/kg body weight) showed significant inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as well as decreased levels of glutathione (GSH) and increased levels of malondialdehyde (MDA) in liver tissues. We also showed a significant inhibition of SOD activity and increased MDA levels in hepatocyte nuclei. We also observed reduced Na(+),K(+)-ATPase activity, increased MDA levels and decreased plasma membrane fluidity, which was accompanied by an increase of fluorescence anisotropy (r) values, in hepatic plasma membranes. In addition, Mn(2+) and Mn(3+) both caused histopathological changes, such as mononuclear cell infiltration, congestion, enlargement of the veins and sinusoids, hepatocellular damage, necrotic changes, mitochondrial hyperplasia, swelling and vacuolization, as determined by light and electron microscopy. Taken together, these data suggest that both Mn(2+) and Mn(3+) inhibit the normal physiological functioning of the liver. Under the experimental conditions used, the adverse effects of Mn(2+) were more severe than those of Mn(3+)., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

The aim of this study was to investigate the contents of lanthanum (La), cerium (Ce), and neodymium (Nd) that accumulate in nuclei and mitochondria isolated from the liver and their corresponding potential oxidative damage effects on nuclei and mitochondria. Five-week-old male imprinting control region (ICR) mice were exposed to chlorides of La, Ce, or Nd by oral gavage with one of three doses: 10, 20, or 40 mg/kgBW/day for 6 weeks. The concentrations of administered elements in hepatocyte nuclei and mitochondria were determined with inductively coupled plasma-mass (ICP-MS) spectrometry. The accumulation of La, Ce, and Nd in hepatocyte nuclei and mitochondria gradually increased in a dose-dependent manner with exposure to the elements, although the concentrations of La, Ce, and Nd in hepatocyte mitochondria were lower than those in their counterpart nuclei. In hepatocyte nuclei, superoxide dismutase (SOD) and catalase (CAT) activities decreased, whereas glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) levels increased. In hepatocyte mitochondria, SOD, CAT, and GPx activities and GSH levels were significantly decreased, and MDA levels were significantly increased. These results suggest that La, Ce, and Nd presumably enter hepatocytes and mainly accumulate in the nuclei and induce oxidative damage in hepatic nuclei and mitochondria., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Toxoplasma gondii is one of the most widespread apicomplexans and can cause serious infections in humans and animals. Its antioxidant system plays an important role in defending against oxidant stress imposed by the host. Some genes encoding the antioxidant enzymes of T. gondii have been identified; however, critical genes that function in response to reactive oxygen species (ROS) stress are still poorly understood. Here, we performed genome-wide CRISPR/Cas9 loss-of-function screening in the T. gondii RH strain to identify potential genes contributing to the ROS stress response. Under hydrogen peroxide treatment, 30 single guide RNAs targeting high-confidence genes were identified, including some known important antioxidant genes such as catalase and peroxiredoxin PRX3. In addition, several previously uncharacterized genes were identified, among which five hypothetical protein-coding genes, namely, HP1 – HP5 , were selected for further functional characterization. Targeted deletion of HP1 in T. gondii RH led to significant sensitivity to H2O2, suggesting that HP1 is critical for oxidative stress management. Furthermore, loss of HP1 led to decreased antioxidant capacity, invasion efficiency, and proliferation in vitro. In vivo results also revealed that the survival time of mice infected with the HP1 -KO strain was significantly prolonged relative to that of mice infected with the wild-type strain. Altogether, these findings demonstrate that the CRISPR/Cas9 system can be used to identify potential genes critical for oxidative stress management. Furthermore, HP1 may confer protection against oxidative damage and contributes to T. gondii virulence in mice. [ABSTRACT FROM AUTHOR]

Alfalfa (Medicago sativa L.) is an important forage, and salinity is a major stress factor on its yield. In this study, we show that osmotic stress retards alfalfa seedling growth, while ionic/oxidative stress reduces its seed germination. Ethylene treatment can recover the germination rate of alfalfa seeds under salt stress, while ethylene inhibitor silver thiosulfate exacerbates salt effects. ETH reduces the accumulation of MDA and H2O2 and increases POD activity. ETH and ACC improve the salt tolerance of alfalfa by increasing proline content under salt stress. In contrast, STS inhibits alfalfa seed germination by reducing POD activity. NaCl treatment reduces chlorophyll content in alfalfa leaves, while ETH and ACC can increase the chlorophyll content and promote seedling growth. ETH promotes the growth of alfalfa in saline condition by reducing the expression of MsACO and MsERF8 genes, while increases its germination rate by upregulating MsERF11 gene. Silencing of MsETR2 , a putative ethylene receptor gene in alfalfa, abolishes ethylene triggered tolerance to salt stress. In summary, we show that ethylene improves salt tolerance in alfalfa via MsETR2 dependent manner, and we also analyze the regulatory mechanism of ethylene during germination of alfalfa seeds under salt stress. [ABSTRACT FROM AUTHOR]

Glutathione peroxidases (GPxs) belong to a family of enzymes that is important in organisms; these enzymes promote hydrogen peroxide metabolism and protect cell membrane structure and function from oxidative damage. Based on the establishment and development of the theory of the pathological roles of free radicals, the role of GPxs has gradually attracted researchers' attention, and the involvement of GPxs in the occurrence and development of malignant tumors has been shown. On the other hand, the incidence of breast cancer in increasing, and breast cancer has become the leading cause of cancer-related death in females worldwide; breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. Therefore, this article focused on the molecular mechanism and function of GPxs in the occurrence and development of breast cancer to understand their role in breast cancer and to provide a new theoretical basis for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is the most toxic mycotoxin contaminant, which is widely present in crops and poses a major safety hazard to animal and human health. To alleviate the cytotoxic effects of AFB1 on the intestine, we tested the protective effects of porcine β-defensin-2 (pBD-2). Results demonstrated that pBD-2 inhibited oxidative stress induced by AFB1 via decreasing the levels of ROS and enhancing the expression of antioxidant factors SOD-2 and NQO-1. In addition, pBD-2 attenuated AFB1-induced intestinal porcine epithelial cell line-J2 (IPEC-J2) injury through blocking mitochondria-mediated apoptosis. In vivo, pBD-2 treatment restored the intestinal mucosal structure and reduced the expression levels of apoptosis factors caspase-3 and Bax/Bcl-2. In conclusion, these results indicated that pBD-2 can alleviate AFB1-induced intestinal mucosal injury by inhibiting oxidative stress and mitochondria-mediated apoptosis. This study provides an effective strategy in developing pBD-2 as green feed additive to prevent AFB1 damage to animals. • Effects of pBD-2 on AFB1-induced intestinal mucosal injury were evaluated. • pBD-2 inhibited oxidative stress on AFB1-induced intestinal mucosal injury. • pBD-2 inhibited apoptosis on AFB1-induced intestinal mucosal injury. • pBD-2 can restore AFB1-induced intestinal mucosal structural damage. [ABSTRACT FROM AUTHOR]

Highlights from the article: (C) Statistical graph of Nrf2 and GAPDH protein in the different groups. (H, I) Statistical graph of NF- B, I B, and GAPDH protein in the different groups. (C) Statistical graph of Nrf2 and GAPDH protein in the different groups.

Traumatic brain injury (TBI) is among the leading causes of irreversible neurological damage and death worldwide. The aim of the present study was to investigate whether edaravone (EDA) had a neuroprotective effect on TBI as well as to identify the potential mechanism. Results demonstrated that EDA suppressed inflammatory and oxidative responses in mice following TBI. This was evidenced by a reduction in glutathione peroxidase, interleukin 6, tumor necrosis factor-α and hydrogen peroxide levels, in addition to an increase in hemeoxygenase-1, quinone oxidoreductase 1 and superoxide dismutase levels, thereby mitigating neurofunctional deficits, cell apoptosis and structural damage. EDA prevented the transfer of NF-κB protein from the cytoplasm to the nucleus, whilst promoting the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) protein in mice following TBI. These results indicated that EDA exerted neuroprotective effects, including impeding neurofunctional deficits, cell apoptosis and structural damage, in mice with TBI, potentially via suppression of NF-κB-mediated inflammatory activation and promotion of the Nrf2 antioxidant pathway. [ABSTRACT FROM AUTHOR]

Severe acute pancreatitis (SAP) is a digestive system disease that is associated with a range of complications including intestinal dysfunction. In this study, we determined that the chalcone compound, isoliquiritigenin (ISL), reduces pancreatic and intestinal injury in a mouse model of SAP. These effects were achieved by suppressing oxidative stress and the inflammatory responses to SAP. This was evidenced by a reduction in histological score, and malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and cleaved-caspase-3 (c-caspase-3) protein along with an increase in Nrf2, hemeoxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and superoxide dismutase (SOD). We then used Nrf2-/- mice to test the protective effect of Nrf2 during ISL treatment of SAP. Our results indicated that Nrf2-/- mice had greater pancreatic injury and intestinal dysfunction than wild-type mice. They also had reduced adherens junctions (P120-catenin) and tight junctions (occludin), and increased activated nuclear factor-κB (NF-κB) protein. In Nrf2-/- mice, ISL was less effective at these functions than in the WT mice. In conclusion, this study demonstrated that ISL exerts its protective effects against oxidative stress and inflammatory injury after SAP via regulation of the Nrf2/NF-κB pathway. It also showed that the efficacy of ISL in repairing the intestinal barrier damage caused by SAP is closely related to the Nrf2 protein. Our findings demonstrated that Nrf2 is an important protective factor against SAP-induced injuries in the pancreas and intestines. [ABSTRACT FROM AUTHOR]

The contamination of food with Aspergillus flavus and subsequent aflatoxins is one of the most serious safety problems in the world. In this study of nerol (NEL)’s antifungal mechanism of action, we observed morphological and physiological changes in Aspergillus flavus. We found that NEL resulted in elevated levels of reactive oxygen species (ROS) and calcium ions (Ca2+). On ROS assays, compared with the controls, the proportion of fluorescent cells treated with concentrations of 0.25, 0.5, 1, and 2 μL/mL NEL increased to 8.4 ± 1.07%, 10.2 ± 1.72%, 13.4 ± 0.50%, and 26.2 ± 4.21%, respectively. Increased mitochondrial dysfunction and oxidative stress induced by the interactions between Ca2+ and ROS subsequently activate the release of cytochrome c and caspase activity. Characteristic changes of apoptosis were also observed via various detection methods, including phosphatidylserine externalization, nuclear condensation, and DNA fragmentation. Meanwhile, we found that the expression of CaMKs increased significantly in NEL-treated cells. In conclusion, our findings indicate that NEL has great potential as an eco-friendly antifungal agent for food preservation. [ABSTRACT FROM AUTHOR]

The present work constructs a meso-structure finite element model to characterize the effect of thermo-oxidative ageing on compressive behaviors of 3-D carbon fiber/epoxy braided composites. Nanoindentation tests were carried out to investigate the thermo-oxidation effect on localized property of aged resin. Based on the experimental results obtained from both macro-compression tests and nanoindentation tests, two different models referred to as ‘homogeneous model’ and ‘multilayer model’ were proposed, respectively. Both of the two models gave satisfactory predictions. We found that the post-curing stiffening and thermal degradation of matrix are the main ageing mechanisms at lower temperatures (below glass-transition temperature). At higher temperatures above the glass-transition point, interfacial damage also contributes a lot to the property degradation of the composite. The combination of matrix ageing and interfacial weakening leads to a significant reduction in compressive behaviors of the 3-D braided composite. We also found that the presence of oxidized layer has little effect on the compressive properties of aged braided composites. Simulation results have confirmed that ageing mechanism strongly depends on the ageing conditions. [ABSTRACT FROM AUTHOR]

Mitophagy has distinct functions, which can lead to either protection or damage of tissues. Though current evidence indicated that NaF triggers mitophagy, the role and regulation of mitophagy in sodium fluoride (NaF)-induced liver injury still remain unclear. Therefore, we exployed the cell and mouse models and confirmed that NaF treatment activates mitophagy. Knocking down PTEN-induced putative kinase protein 1 (PINK1) expression attenuated mitophagy and increased the degree of mitochondrial impairment, oxidative stress, and apoptosis in NaF-treated HepG2 cells. In vivo experiments indicated that PINK1 deficiency weakened NaF-induced mitophagy. Moreover, PINK1-deficient mices aggravated NaF-induced hepatic mitochondrial injury, oxidative stress, and inflammation in livers, evidenced by the increased number of abnormal mitochondria, decreased adenosine triphosphate (ATP) and glutathione (GSH) levels, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) content, enhanced hepatic macrophage infiltration and inflammatory cytokine levels. Notably, NaF exposure activated Nrf2 signaling both in vitro and in vivo. Nrf2 siRNA transfection blocked the upregulation of PINK1 expression and the induction of mitophagy in NaF-treated HepG2 cells. Also, ML385 (Nrf2 inhibitor) partially blocked the upregulation of PINK1 expression caused by NaF in mice livers. To sum up, the present study provided the demonstration that Nrf2/PINK1-mediated mitophagy activation offers a hepatoprotective effect by inhibiting NaF-induced mitochondrial dysfunction, oxidative stress, and inflammation. [Display omitted] • NaF-induced mitophagy activation is regulated by PINK1/Parkin signaling. • Mitophagy induction alleviates NaF-induced mitochondrial impairment. • Mitophagy inhibition aggravates NaF-induced oxidative stress and apoptosis. • Mitophagy induction ameliorates inflammation caused by NaF. • Nrf2 triggers PINK1 expression under NaF stimulation. [ABSTRACT FROM AUTHOR]

The frequent occurrence of cyanobacterial blooms (CYBs) caused by toxic Microcystis aeruginosa poses a great threat to aquatic organisms. Although freshwater benthic bivalves have proven to be capable of uptake high levels of microcystins (MCs) due to their filter-feeding habits, there is a paucity of information concerning their systemic resistance mechanisms to MCs. In this study, the resistance mechanisms in Corbicula fluminea (O. F. Müller, 1774) in response to the exposure of toxic M. aeruginosa were explored through transcriptional analysis combined with histopathological and biochemical phenotypic analysis. Toxic M. aeruginosa exposure caused dose-dependent histological damage in the hepatopancreas. The conjugation reaction catalyzed by glutathione S-transferases was vulnerable to being activated by high concentrations of M. aeruginosa (10 ×105 cells mL−1). Additionally, reactive oxygen species scavenging processes mediated by superoxide dismutase and catalase were active in the initial stage of toxic M. aeruginosa exposure. The results of the integrated biomarker response index suggested that the biotransformation and antioxidant defense system in C. fluminea could be continuously activated after acute exposure to the high concentration of toxic M. aeruginosa. The eggNOG and GO analysis of the differentially expressed genes (DEGs) indicated that DEGs were significantly enriched in transporter activity, oxidant detoxification and response to oxidative stress categories, which were consistent with the alterations of biochemical indices. Besides, DEGs were significantly annotated in a few KEGG pathways involved in biotransformation (oxidation, cooxidation and conjugation) and immunoreaction (lysosome and phagosome responses), which could be responsible for the tolerance of C. fluminea to toxic M. aeruginosa. These findings improve our understanding of potential resistance mechanisms of freshwater bivalves to MCs. [Display omitted] • Toxic M. aeruginosa exposure caused dose-dependent histological damage in the hepatopancreas. • Conjugation reaction and antioxidation were coordinated in C. fluminea in response to toxic M. aeruginosa exposure. • Biotransformation and immunoreaction were pathways enriched after toxic M. aeruginosa exposure. [ABSTRACT FROM AUTHOR]

Abstract: Toxicity due to overexposure to manganese (Mn) is becoming increasingly prevalent. Mn-induced neurodegenerative toxicity has been demonstrated, but little is known concerning the adverse effects of the element on the liver. Under physiological conditions, manganese primarily exists as divalent manganese (Mn2+) and trivalent manganese (Mn3+). The present study was designed to evaluate and compare the effects of Mn2+ and Mn3+ on oxidative hepatic damage, membrane fluidity and histopathological changes in rats. Rats exposed to Mn2+ or Mn3+ (2.0mg Mn/kg body weight) showed significant inhibition of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as well as decreased levels of glutathione (GSH) and increased levels of malondialdehyde (MDA) in liver tissues. We also showed a significant inhibition of SOD activity and increased MDA levels in hepatocyte nuclei. We also observed reduced Na+,K+-ATPase activity, increased MDA levels and decreased plasma membrane fluidity, which was accompanied by an increase of fluorescence anisotropy (r) values, in hepatic plasma membranes. In addition, Mn2+ and Mn3+ both caused histopathological changes, such as mononuclear cell infiltration, congestion, enlargement of the veins and sinusoids, hepatocellular damage, necrotic changes, mitochondrial hyperplasia, swelling and vacuolization, as determined by light and electron microscopy. Taken together, these data suggest that both Mn2+ and Mn3+ inhibit the normal physiological functioning of the liver. Under the experimental conditions used, the adverse effects of Mn2+ were more severe than those of Mn3+. [Copyright &y& Elsevier]

The original version of this article unfortunately contained a mistake. The Fluorescence Immunoassays text written in Materials and Methods section and Fig. 1i, j is incorrect. In Fig. 1j, the images corresponding to Sham and TBI + ILG are incorrect. In Fig. 1i the figure caption "TBI + EDA" are incorrect. The corrected text and Fig. 1i, j are given below. [ABSTRACT FROM AUTHOR]

Keywords: alfalfa; salinity; ethylene; MsETR2; seed germination; seedling growth EN alfalfa salinity ethylene MsETR2 seed germination seedling growth N.PAG N.PAG 1 01/13/21 20210108 NES 210108 Author contribution for Lingqi Kong was incorrectly written as SP ** sp B Lingqi Kong SP 3 sp ** b . Alfalfa, salinity, ethylene, MsETR2, seed germination, seedling growth. [Extracted from the article]

Plant-derived dietary lectins have been reported to be involved in the pathogenesis of several inflammatory diseases, including hepatitis, inflammatory bowel disease, diabetes, and celiac disease. In this present study, we aimed to assess whether green tea polyphenols (GTPs) exerts protective effects against plant lectins-induced liver inflammation and immunological reaction in mice. The C57BL/6 mice received intragastric GTPs (200 mg/kg b.w.) once per day for 7 consecutive days prior to plant lectins stimulation (50 mg/kg b.w., intraperitoneally). GTPs supplementation alleviated the histopathological changes of liver and the disorder of serum biochemical parameters in plant lectins-challenged mice. GTPs supplementation also alleviated plant lectins-induced oxidative stress and liver inflammation, decreasing protein contents and gene expression levels of pro-inflammatory cytokines in the plasma and hepatic tissue and increasing antioxidant capacity in the liver. GTPs decreased the protein expression levels of myeloperoxidase, F4/80 and neutrophil, as determined by immunohistochemical analysis, and T lymphocytes (CD4 and CD8) contents as determined by immunofluorescence analysis, in the liver. Moreover, we found that GTPs inhibited Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome expression and increased nuclear factor erythroid 2-related factor 2 (Nrf2) pathways in the liver tissues of plant lectins-challenged mice. Taken together, these results show that GTPs alleviates hepatic inflammatory damage and immunological reaction after plant lectins challenge, and GTPs (or green tea intake) supplements can be beneficial for people exposed to plant lectins. • GTPs ameliorated plant lectins-induced inflammation and increasing antioxidant capacity in the liver. • GTPs alleviated the histopathological changes in plant lectins-challenged mice. • GTPs decreased the expression of MPO, F4/80, neutrophil and T lymphocytes in plant lectins-challenged mice. • GTPs inhibited NLRP3 inflammasome activation and increased Nrf2 pathway in the liver. [ABSTRACT FROM AUTHOR]

A correction to the article "Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans,"

[Display omitted] • Aqueous extract (AE) of butterfly pea petals has mainly flavonoids (anthocyanins). • AE ameliorated the oxidative stress and inflammation mediators in obese mice. • AE reduced plasma leptin, free fatty acid, LDL, and hepatic MDA contents. • AE reduced total cholesterol and ameliorated insulin resistance in obese mice. • AE exert hypolipidemic/anti-inflammatory effects by promoting reverse cholesterol transport. This study examined the chemical compounds and bioactivity of the aqueous extract of Clitoria ternatea blue petals and investigated its beneficial effects in vivo on a mouse model of obesity and metabolic syndrome. The extract mainly contained flavonoids, and nine compounds were tentatively identified. Male C57BL/6J mice were either fed a standard diet (SD) or a high-fat, high-fructose diet (HFFD) for 16 weeks, and HFFD-fed animals were treated with 0.25%, 0.5%, and 2% (w/w) of the aqueous extract in drinking water. The aqueous extract ameliorated oxidative stress and inflammation mediators. Furthermore, the aqueous extract reduced plasma leptin, free fatty acid, low-density lipoprotein cholesterol levels and hepatic malondialdehyde content. The aqueous extract significantly reduced total cholesterol and ameliorated insulin resistance. The results demonstrated that the aqueous extract of C. ternatea blue petals contains bioactive anthocyanins that exert substantial hypolipidemic and anti-inflammatory effects by promoting reverse cholesterol transport in HFFD-fed mice. [ABSTRACT FROM AUTHOR]

• Notoginsenoside R1 (NGR1) reduces nasopharyngeal carcinoma (NPC) cell growth and invasion. • NGR1 induces apoptosis and oxidative stress of NPC cells. • NGR1 alleviates LPS-induced inflammation in NPC cells. • NGR1 regulates the growth and oxidative stress of NPC cells through the TRAF6/NF-κB pathway. • NGR1 represses NPC proliferation in vivo. Nasopharyngeal carcinoma (NPC) is a malignant tumor with high incidence. Notoginsenoside R1 (NGR1) is the main active compound of total Panax notoginseng saponin, and has multiple anti-tumor effects. This study aimed to investigate the effect and mechanism of NGR1 in NPC. NPC cells were treated with different doses of NGR1. The NGR1 function in NPC was evaluated using Cell Counting Kit-8, Transwell, Western blot, flow cytometry, immunofluorescence assay, and quantitative real-time PCR. Meanwhile, the NGR1 mechanism in NPC was assessed by rescue experiments. Furthermore, the NGR1 function in vivo was determined by constructing an NPC xenotransplantation model, TUNEL, and immunohistochemistry assays. NGR1 repressed NPC cell growth and invasion but facilitated NPC cell apoptosis and oxidative stress. Also, NGR1 alleviated inflammation in NPC cells. Mechanistically, NGR1 restrained NPC cell growth and induced oxidative stress in NPC cells, while these effects were abolished after lipopolysaccharide (an activator of the TRAF6/NF-κB pathway) treatment, implying that NGR1 reduced NPC cell growth and induced oxidative stress in NPC cells by the inactivation of TRAF6/NF-κB axis. Moreover, in vivo studies further proved the palliative effect of NGR1 on NPC. NGR1 inhibited NPC cell growth and induced oxidative stress in NPC cells by inactivating TRAF6/NF-κB axis. [ABSTRACT FROM AUTHOR]