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Heat stress as a result of global warming has harmful consequences for livestock and is thus becoming an urgent issue for animal husbandry worldwide. Ruminants, growing pigs, and poultry are very susceptible to heat stress because of their fast growth, rapid metabolism, high production levels, and sensitivity to temperature. Heat stress compromises the efficiency of animal husbandry by affecting performance, gastrointestinal health, reproductive physiology, and causing cell damage. Selenium (Se) is an essential nutritional trace element for livestock production, which acts as a structural component in at least 25 selenoproteins (SELs); it is involved in thyroid hormone synthesis, and plays a key role in the antioxidant defense system. Dietary Se supplementation has been confirmed to support gastrointestinal health, production performance, and reproductive physiology under conditions of heat stress. The underlying mechanisms include the regulation of nutrient digestibility influenced by gastrointestinal microorganisms, antioxidant status, and immunocompetence. Moreover, heat stress damage to the gastrointestinal and mammary barrier is closely related to cell physiological functions, such as the fluidity and stability of cellular membranes, and the inhibition of receptors as well as transmembrane transport protein function. Se also plays an important role in inhibiting cell apoptosis and reducing cell inflammatory response induced by heat stress. This review highlights the progress of research regarding the dietary supplementation of Se in the mitigation of heat stress, addressing its mechanism and explaining the effect of Se on cell damage caused by heat stress, in order to provide a theoretical reference for the use of Se to mitigate heat stress in livestock., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Xie, Li, Wang, Wang, Cao and Yang.)

Atherosclerosis (AS) is a chronic metabolic disease in arterial walls, characterized by lipid deposition and persistent aseptic inflammation. AS is regarded as the basis of a variety of cardiovascular and cerebrovascular diseases. It is widely acknowledged that macrophages would become foam cells after internalizing lipoprotein particles, which is an initial factor in atherogenesis. Here, we showed the influences of Bruton's tyrosine kinase (BTK) in macrophage-mediated AS and how BTK regulates the inflammatory responses of macrophages in AS. Our bioinformatic results suggested that BTK was a potential hub gene, which is closely related to oxidative stress, ER stress, and inflammation in macrophage-induced AS. Moreover, we found that BTK knockdown could restrain ox-LDL-induced NK- κ B signaling activation in macrophages and repressed M1 polarization. The mechanistic studies revealed that oxidative stress, mitochondrial injury, and ER stress in macrophages were also suppressed by BTK knockdown. Furthermore, we found that sh-BTK adenovirus injection could alleviate the severity of AS in ApoE -/- mice induced by a high-fat diet in vivo. Our study suggested that BTK promoted ox-LDL-induced ER stress, oxidative stress, and inflammatory responses in macrophages, and it may be a potential therapeutic target in AS., Competing Interests: No conflicts of interest need to be declared by the authors., (Copyright © 2021 Junxiong Qiu et al.)

Withaferin A (WFA), a withanolide derived from medicinal plant Withania somnifera, possesses anti-tumorigenic and immunomodulatory activities against various cancer cells. However, the role of WFA in myocardial ischemia reperfusion (MI/R) injury remains unclear. In the present study, we determined whether WFA may regulate cardiac ischemia reperfusion injury and elucidate the underlying mechanisms. We demonstrated that WFA enhanced H9c2 cells survival ability against simulated ischemia/reperfusion (SI/R) or hydrogen peroxide (H 2 O 2 )-induced cell apoptosis. In addition, the enhanced oxidative stress induced by SI/R was inhibited by WFA. Among the multiple antioxidant molecules determined, antioxidants SOD2, SOD3, Prdx-1 was obviously upregulated by WFA. When Akt inhibitor IV was administrated, WFA's suppression effect on oxidative stress was obviously abolished. Additional experiments demonstrated that WFA successfully inhibited H 2 O 2 induced upregulation of SOD2, SOD3, and Prdx-1, ameliorated cardiomyocyte caspase-3 activity via an Akt dependent manner. Collectively, these results support the therapeutic potential of WFA against cardiac ischemia reperfusion injury and highlight the application of WFA in cardiovascular diseases holding great promise for the future., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND: Without timely and effective interventions or treatments, radiation-induced liver damage (RILD) can lead to serious consequences for the patients and their families. OBJECTIVE: To investigate the protective effect of intermittent hypobaric hypoxia preconditioning (IHHP) in RILD. METHODS: Male adult SD rats were randomly divided into 8 groups including one control group, one only irradiation group and other experimental groups. Blood routine tests and liver function tests were all assessed with abdominal venous blood. Moreover, hematoxylin eosin (HE) staining and immunohistochemistry assay were used to detect the histopathological changes and expressions of transforming growth factor- β 1 (TGF- β 1), tumor necrosis factor α (TNF- α) and hypoxia-inducible factor 1 α (HIF-1 α) in radiated liver sections. RESULTS: Blood routing tests showed that RBC, WBC and Hb were all significantly increased while the differences of these results between different groups with same simulated altitude were approximate. However, liver function in the IHHP plus irradiation at 4000 m group was significantly decreased (P < 0.05) compared to only irradiation groups, and the manifestation of HE and lower positive expression of TNF- α showed improved histopathological changes in the liver section. Furthermore, no significant difference of HIF-1 α expression between any two groups treated with IHHP was observed. CONCLUSION: IHHP at the altitude of 4000 m group could alleviate the radioactive liver damage by downregulating TNF- α and less strong positive expression of TGF- β 1. Furthermore, patients exposed to radiation might benefit from this treatment to prevent or reduce the RILD. [ABSTRACT FROM AUTHOR]

Mastitis (inflammation of the mammary gland) commonly occurs in dairy cattle during the periparturient period (transition period), in which dairy cattle experience physiological and hormonal changes and severe negative energy balance, followed by oxidative stress. To maintain successful lactation and combat negative energy balance (NEB), excessive fat mobilization occurs, leading to overproduction of reactive oxygen species (ROS). Excessive fat mobilization also increases the concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyric acid (BHB) during the periparturient period. In addition, the excessive utilization of oxygen by cellular respiration in the mammary causes abnormal production of oxidative stress (OS). OS impairs the immunity and anti-inflammatory efficiency of periparturient dairy cattle, increasing their susceptibility to mastitis. To alleviate oxidative stress and subsequent mastitis, antioxidants are supplemented to dairy cattle from an external source. Extensive studies have been conducted on the supplementation of selenium (Se) and vitamins E and B9 to mitigate mastitis during the transition period in dairy cattle. Altogether, in the current review, we discuss the research development on bovine mastitis and its major causes, with special emphasis on oxidative stress during the transition period. Moreover, we discuss the antioxidant, immunoregulatory, and anti-inflammatory properties of Se and vitamins E and B9 and their role in the control of bovine mastitis in periparturient dairy cattle. [ABSTRACT FROM AUTHOR]

The clinical treatment of ulcerative colitis (UC) faces great challenges due to lifetime medication. In this study, Gingerol oil was extracted and purified by the process easily scale-up and cost effective, with productivity 2.72 ± 0.38% (w /w, versus crude drugs). The quality control of gingerol oil was fully established by HPLC fingerprint with 4 common peaks identified as 6-gingerol, 8-gingerol, 6-shogaol and 10-gingerol. The similarities of 6 batches of gingerol oil are within 0.931–0.999. The protective effects of gingerol oil are equivalent to or even stronger than that of 6-gingerol on inflammation and oxidative stress of HT-29 cells induced by lipopolysaccharide and H 2 O 2 , as well as on UC in mice caused by dextran sulfate sodium salt (DSS). Our research conclusions coincide well with the holistic view of Traditional Chinese Medicine and network pharmacology. The absorption kinetics of gingerol oil were conducted using the in situ intestinal perfusion in rats and comparable absorption were achieved in the jejunum, ileum and colon segments within 2 h. Thus, gingerol oil colon targeting pellets were prepared by extrusion-spherization technique. The cumulative dissolution behaviors and mechanisms were observed and analyzed by fitting to dissolution model. Our studies provided reliable theoretical and experimental support for the gingerol oil as reliable therapeutic choice of UC. [Display omitted] [ABSTRACT FROM AUTHOR]

Fluoride is an important trace element in the living body. A suitable amount of fluoride has a beneficial effect on the body, but disproportionate fluoride entering the body will affect various organs and systems, especially the liver, kidneys, nervous system, endocrine system, reproductive system, bone, and intestinal system. In recent years, with the rapid development of agriculture and industry, fluoride pollution has become one of the important factors of environmental pollution, and fluoride pollution in any form is becoming a serious problem. Although countries around the world have made great breakthroughs in controlling fluoride pollution, however fluorosis still exists. A large amount of fluoride accumulated in animals will not only produce the toxic effects, but it also causes cell damage and affect the normal physiological activities of the body. There is no systematic description of the damage mechanism of fluoride. Therefore, the study on the toxicity mechanism of fluoride is still in progress. This review summarizes the existing information of several molecular mechanisms of the fluoride toxicity comprehensively, aiming to clarify the toxic mechanism of fluoride on various body systems. We have also summerized the pathological changes of those organ systems after fluoride poisoning in order to provide some ideas and solutions to the reader for the prevention and control of modern fluoride pollution. ①After fluoride enters the body, it induces the production of caspase-12,caspase-9,caspase-3, caspase-7 through different ways, causes cell apoptosis and induces body damage. ②After fluoride enters the body, it induces the production of autophagy markers U1K1, Atg13, LC3 and Beclin1 through mTOR signaling pathway, resulting in autophagy.③ After fluoride enters the body, it affects the antioxidant system of various organs, inhibits the activity of antioxidant enzymes, increases reactive oxygen species and the occurrence of oxidative stress.④Fluoride promotes the degradation of IκBβ, activate NF-κB pathway, increase the content of proinflammatory cytokines TNF- α, IL-6 and IL-1 β, and induce inflammation. [Display omitted] • Fluoride exposure induces mitochondrial dysfunction. • Fluoride exposure mediates organs injury both in apoptosis and autophagy. • Fluoride exposure induces inflammatory reaction. • Fluoride exposure facilitates changes in intestinal microbial abundance. [ABSTRACT FROM AUTHOR]

Heat stress affects granulosa cells and the ovarian follicular microenvironment, ultimately resulting in poor oocyte developmental competence. This study aims to investigate the metabo-lomics response of bovine granulosa cells (bGCs) to in vitro acute heat stress of 43 °C. Heat stress triggers oxidative stress-mediated apoptosis in cultured bGCs. Heat-stressed bGCs exhibited a time-dependent recovery of proliferation potential by 48 h. A total of 119 metabolites were identified through LC–MS/MS-based metabolomics of the spent culture media, out of which, 37 metabolites were determined as differentially involved in metabolic pathways related to bioenergetics support mechanisms and the physical adaptations of bGCs. Multiple analyses of metabolome data identified choline, citric acid, 3-hydroxy-3-methylglutaric acid, glutamine, and glycocyamine as being upregulated, while galactosamine, AICAR, ciliatine, 16-hydroxyhexadecanoic acid, lysine, succinic acid, uridine, xanthine, and uraconic acid were the important downregulated metabolites in acute heat stress. These differential metabolites were implicated in various important metabolic pathways directed towards bioenergetics support mechanisms including glycerophospholipid metabolism, the citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolism, and serine, threonine, and tyrosine metabolism. Our study presents important metabolites and metabolic pathways involved in the adaptation of bGCs to acute heat stress in vitro. [ABSTRACT FROM AUTHOR]

In humans, oxidative stress and antioxidant defenses are the sum of a complicated network of enzymatic and non-enzymatic processes. Depending on the stage and severity of diseases, a patient's antioxidant armamentarium may increase as an appropriate response to an oxidant challenge, whereas others may decrease as an indication of unbalanced consumption. In some cases, the formation of reactive oxygen species is a requisite and healthy event. In fact, free radicals can affect intracellular signal transduction and gene regulation, resulting in cytokine production essential to the inflammatory process. In many other cases, especially liver diseases, excessive oxidative stress undoubtedly contributes to the progression and pathological findings of disease and serves as a prognostic indicator. Reactive oxygen species are highly reactive molecules that are naturally generated in small amounts through metabolism and could damage cellular molecules such as lipids, proteins or DNA. Oxidative stress plays a major role in many liver diseases. In this review, we summarize the biological character of free radicals and some antioxidants, and the related methods of analysis. Then, we discusses the association of oxidative stress to many types of liver diseases. [ABSTRACT FROM AUTHOR]

Adiponectin (APN) has traditionally been viewed as an adipocyte-specific endocrine molecule with cardioprotective effects. Recent studies suggest that APN is also expressed in cardiomyocytes. However, biological significances of this locally produced APN remain completely unknown. The aim of this study was to investigate the pathological and pharmacological significance of cardiac-derived APN in cardiomyocyte pathology. Adult cardiomyocytes from wild-type littermates (WT) or gene-deficient mice were pretreated with vehicle (V) or rosiglitazone (RSG) for 6 h followed by simulated ischemia-reperfusion (STIR, 3 h/12 h). Compared with WT cardiomyocytes, myocytes from APN knockout (APN-KO) mice sustained greater STIR injury, evidenced by greater oxidative/nitrative stress, caspase-3 activity, and lactate dehydrogenase (LDH) release (P < 0.05). Myocytes from adiponectin receptor 1 knockdown (AdipoR1-KD) or AdipoR1-KD/AdipoR2-KO mice had slightly increased STIR injury, but the difference was not statistically significant. RSG significantly (P < 0.01) increased APN mRNA and protein expression, upregulated AdipoRTI AdipoR2 expression, reduced STIR-induced apoptosis, and decreased LDH release in WT cardiomyocytes. However, the anti-oxidativel anti-nitrative and cell protective effects of RSG were completely lost in APN-KO cardiomyocytes (P> 0.05 vs. vehicle group), although a comparable degree of AdipoRl/AdipoR2 upregulation was observed. The upregulatory effect of RSG on APN mRNA and protein expression was significantly potentiated in AdipoRl-KD/AdipoR2-KO cardiomyocytes. However, the cellular protective effects of RSG were significantly blunted, although not completely lost, in these cells. These results demonstrated that cardiomyocyte APN is biologically active in protecting cells against ST/R injury. Moreover, this locally produced APN achieves its protective effect primarily through paracrine/autocrine activation of APN receptors. [ABSTRACT FROM AUTHOR]

Adiponectin (APN) exerts its metabolic regulation largely through AMP-dependent protein kinase (AMPK). However, the role of AMPK in APN's antiapoptotic effect in ischemic-reperfused (I/R) adult cardiomyocytes remains incompletely understood. The present study was designed to determine the involvement of AMPK in the antiapoptotic signaling of APN. Cardiomyocytes from adult male mice overexpressing a dominant-negative α2-subunit of AMPK (AMPK-DN) or wild-type (WT) littermates were subjected to simulated hR (SI/R) and pretreated with 2 μg/ml globular domain of APN (gAPN) or vehicle. SI/R-induced cardiomyocyte apoptosis was modestly increased in AMPK-DN cardiomyocytes (P < 0.05). Treatment with gAPN significantly reduced SI/R-induced apoptosis in WT cardiomyocytes as well as in AMPK-DN cardiomyocytes, indicating that the antiapoptotic effect of gAPN is partially AMPK independent. Furthermore, gAPN-induced endothelial nitric oxide synthase (eNOS) phosphorylation was significantly reduced in AMPK-DN cardiomyocytes, suggesting that the APN-eNOS signaling axis is impaired in AMPK-DN cardiomyocytes. Additional experiments demonstrated that treatment of AMPK-DN cardiomyocytes with gAPN reduced SI/R-induced NADPH oxidase overexpression, decreased superoxide generation, and blocked peroxynitrite formation to the same extent as that observed in WT cardiomyocytes. Collectively, our present study demonstrated that although the metabolic and eNOS activation effect of APN is largely mediated by AMPK, the superoxide-suppressing effect of APN is not mediated by AMPK, and this AMPK-independent antioxidant property of APN increased nitric oxide bioavailability and exerted significant antiapoptotic effect. [ABSTRACT FROM AUTHOR]

Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood. Dysregulation of miRNAs plays a significant role in disease development. However, whether hypoadiponectinemia alters cardiac miRNA profile, contributing to diabetic heart injury, remains unclear. Methods and Results: Wild-type (WT) and APN knockout (APN-KO) mice were subjected to MI/R. A cardiac microRNA profile was determined. Among 23 miRNAs increased in APN-KO mice following MI/R, miR-449b was most significantly upregulated (3.98-fold over WT mice). Administrating miR-449b mimic increased apoptosis, enlarged infarct size, and impaired cardiac function in WT mice. In contrast, anti-miR-449b decreased apoptosis, reduced infarct size, and improved cardiac function in APN-KO mice. Bioinformatic analysis predicted 73 miR-449b targeting genes, and GO analysis revealed oxidative stress as the top pathway regulated by these genes. Venn analysis followed by luciferase assay identified Nrf-1 and Ucp3 as the two most important miR-449b targets. In vivo administration of anti-miR-449b in APN-KO mice attenuated MI/R-stimulated superoxide overproduction. In vitro experiments demonstrated that high glucose/high lipid and simulated ischemia/reperfusion upregulated miR-449b and inhibited Nrf-1 and Ucp3 expression. These pathological effects were attenuated by anti-miR-449b or Nrf-1 overexpression. In a final attempt to validate our finding in a clinically relevant model, high-fat diet (HFD)-induced diabetic mice were subjected to MI/R and treated with anti-miR-449b or APN. Diabetes significantly increased miR-449b expression and downregulated Nrf-1 and Ucp3 expression. Administration of anti-miR-449b or APN preserved cardiac Nrf-1 expression, reduced cardiac oxidative stress, decreased apoptosis and infarct size, and improved cardiac function. Conclusion: We demonstrated for the first time that hypoadiponectinemia upregulates miR-449b and suppresses Nrf-1/Ucp3 expression, promoting oxidative stress and exacerbating MI/R injury in this population. Dysregulated APN/miR-449b/oxidative stress pathway is a potential therapeutic target against diabetic MI/R injury. [Display omitted] [ABSTRACT FROM AUTHOR]