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BACKGROUND: Flaxseed has been widely used in animal diets to increase the omega-3 polyunsaturated fatty acid content in animal products and promote overall animal health, but little known about its effects on the productive performance and the mictobita of gut of laying duck. METHODS AND RESULTS: Jinding duck, a Chinese indigenous breed, was used in the study. The corn-soybean basal diet supplemented with 0, 2%, 3% 4% and 5% flaxseed were provided to Control, 2% Fla, 3% Fla, 4% Fla and 5% Fla groups for 53 days, respectively. Compared with Control group, groups fed with flaxseed diets showed higher egg production, egg mass, ovary weight and more preovulatory follicles. The Docosahexaenoic Acid content of egg was extremely significantly elevated by flaxseed diets (P < 0.01), and the albumen height and haugh unit were elevated, especially in 4% Fla and/or 5% Fla group (P < 0.05). Groups 4% Fla and 5% Fla had highest ileal villus height, jejunal and ileal crypt depth. Moreover, Flaxseed diets significantly increased the levels of IgG and IgM in all Fla groups (P < 0.01), while increased IgA levels except for in 3% Fla group (P < 0.05). The results of 16s rDNA sequencing showed that flaxseed diet altered the microbial composition of gut and reduced the diversity and evenness of gut microbial communities except for 5% Fla. The correlation analysis identified Blautia, Butyricicoccus and Subdoligranulum positively associated with egg production. Genera Fourinierella, Fusobacterium and Intestinimonas positively associated with ovary weight, haught unit and album height. And Mucispirillum positively associated with haugh unit and album height. CONCLUSION: This study has suggested that flaxseed play a positive role in productive performance, the overall or intestinal health of laying ducks.
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Ração Animal , Patos , Linho , Microbioma Gastrointestinal , Animais , Feminino , Dieta , Suplementos Nutricionais , RNA Ribossômico 16S/genéticaRESUMO
T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1â¯mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160â¯nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.
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Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25â¯mg/kg and 5â¯mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells.
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Public participation is crucial to improving the performance of water governance systems, especially in a governance model dominated by a top-down hierarchical structure. Public concerns, as a vital form of public participation, have been acknowledged as an essential component in contributing to water governance. However, few studies explore the varying effects of diverse public concerns in leading to different water governance outcomes. This study addresses this gap by exploring the direct and indirect effects of water-related public concerns on water pollution control and governments' pollution mitigating actions, using citizens' water-related posts crawled from China's social media. Results show that public water-related concerns contribute to water governance both through its direct effects on reducing water pollution and indirect effects by promoting policy actions. Specifically, the concerns related to water pollution hazards, water pollution monitoring, prevention products, and water pollution control measures have more positive impacts on water pollution reduction compared to other types of concern. Meanwhile, public concerns demonstrate stronger effects in triggering economic-related and infrastructure-related water pollution mitigation actions. This study provides nuanced insights to understand the role of public participation in improving water governance, the findings of which are insightful to enhance accountability of water governance systems through a bottom-up approach.
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Enhanced biological phosphorus removal (EBPR) is an economical and sustainable process for phosphorus removal from wastewater. Despite the widespread application of EBPR for low-strength domestic wastewater treatment, limited investigations have been conducted to apply EBPR to the high-strength wastewaters, particularly, the integration of EBPR and the short-cut nitrogen removal process in the one-stage system remains challenging. Herein, we reported a novel proof-of-concept demonstration of integrating EBPR and nitritation (oxidation of ammonium to nitrite) in a one-stage sequencing batch reactor to achieve simultaneous high-strength phosphorus and short-cut nitrogen removal. Excellent EBPR performance of effluent 0.8 ± 1.0 mg P/L and >99% removal efficiency was achieved fed with synthetic high-strength phosphorus wastewater. Long-term sludge acclimation proved that the dominant polyphosphate accumulating organisms (PAOs), Candidatus Accumulibacter, could evolve to a specific subtype that can tolerate the nitrite inhibition as revealed by operational taxonomic unit (OTU)-based oligotyping analysis. The EBPR kinetic and stoichiometric evaluations combined with the amplicon sequencing proved that the Candidatus Competibacter, as the dominant glycogen accumulating organisms (GAOs), could well coexist with PAOs (15.3-24.9% and 14.2-33.1%, respectively) and did not deteriorate the EBPR performance. The nitrification activity assessment, amplicon sequencing, and functional-based gene marker quantification verified that the unexpected nitrite accumulation (10.7-21.0 mg N/L) in the high-strength EBPR system was likely caused by the nitritation process, in which the nitrite-oxidizing bacteria (NOB) were successfully out-selected (<0.1% relative abundance). We hypothesized that the introduction of the anaerobic phase with high VFA concentrations could be the potential selection force for achieving nitritation based on the literature review and our preliminary batch tests. This study sheds light on developing a new feasible technical route for integrating EBPR with short-cut nitrogen removal for efficient high-strength wastewater treatment.
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Desnitrificação , Águas Residuárias , Nitritos , Esgotos , Nitrogênio , FósforoRESUMO
The aim of this study was to evaluate the effects of anti-stress agents on the growth performance and immune function of broilers under immune stress conditions induced by vaccination. A total of 128, 1-day-old Arbor Acres broilers were randomly divided into four groups. Group normal control (NC) was the control group. Group vaccination control (VC), T 0.5%, and T 1% were the treatment groups, which were nasally vaccinated with two doses of the Newcastle disease virus (NDV) vaccine. The chicks in groups T 0.5% and T 1% were fed conventional diets containing 0.5% and 1% anti-stress agents. Thereafter, these broilers were slaughtered on 1, 7, 14, and 21 days post-vaccination. The results indicated that anti-stress agents could significantly reduce serum adrenocorticotropic hormone (ACTH) (P < 0.01) and cortisol (CORT) (P < 0.05) levels, and improve the growth performance (P < 0.05) and immune function of broilers (P < 0.05); However, the levels of malondialdehyde (MDA) (P < 0.05) were decreased, and the decreased total antioxidant capacity (T-AOC) (P < 0.01) levels mediated by vaccination were markedly improved. In addition, anti-stress agents could attenuate apoptosis in spleen lymphocytes (P < 0.01) by upregulating the ratio of Bcl-2 to BAX (P < 0.01) and downregulating the expression of caspase-3 and -9 (P < 0.01), which might be attributed to the inhibition of the enzymatic activities of caspase-3 and -9 (P < 0.05). In conclusion, anti-stress agents may improve growth performance and immune function in broilers under immune-stress conditions.RESEARCH HIGHLIGHTS Investigation of effects and mechanism of immune stress induced by vaccination.Beneficial effect of anti-stress agents on growth performance, immune function, oxidative stress, and regulation of lymphocyte apoptosis.Demonstration of the effects of apoptosis on immune function in the organism.
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Antioxidantes , Galinhas , Animais , Caspase 3/metabolismo , Antioxidantes/metabolismo , Dieta/veterinária , Vacinação/veterinária , Imunidade , Ração Animal/análise , Suplementos NutricionaisRESUMO
Sludge stabilization was affected by solid content during autothermal thermophilic aerobic digestion (ATAD). Thermal hydrolysis pretreatment (THP) could alleviate the issues of high viscosity, slow solubilization and low ATAD efficiency caused by increased solid content. The influence of THP on the stabilization of sludge with different solid contents (5.24%-17.14%) during ATAD was investigated in this study. The results demonstrated that stabilization was achieved with volatile solid (VS) removal of 39.0%-40.4% after 7-9 days of ATAD for sludge with solid content of 5.24%-17.14%. The solubilization of sludge with different solid contents reached 40.1%-45.0% after THP. The rheological analysis indicated that the apparent viscosity of sludge was obviously reduced after THP at different solid contents. The increase in fluorescence intensity of fulvic acid-like organics, soluble microbial by-products and humic acid-like organics in the supernatant after THP and the decrease in fluorescence intensity of soluble microbial by-products after ATAD were detected by excitation emission matrix (EEM). The molecular weight (MW) distribution in the supernatant elucidated that the proportion of 50 kDa < MW < 100 kDa increased to 16%-34% after THP and the proportion of 10 kDa < MW < 50 kDa decreased to 8%-24% after ATAD. High throughput sequencing showed that the dominant bacterial genera shifted from Acinetobacter, Defluviicoccus and Norank_f__norank_o__PeM15 to Sphaerobacter and Bacillus during ATAD. This work revealed that solid content of 13%-17% was appropriate for efficient ATAD and rapid stabilization under THP.
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Esgotos , Eliminação de Resíduos Líquidos , Esgotos/microbiologia , Hidrólise , Eliminação de Resíduos Líquidos/métodos , Reatores Biológicos/microbiologia , DigestãoRESUMO
Medium-low temperature pyrolysis is an effective method of retaining active components in sludge char. However, we found that incomplete cracking reactions resulted in residues of microplastics (MPs) remaining in the char; moreover, high levels of environmentally persistent free radicals (EPFRs) were detected in these MPs. Here, we investigated the temperature-dependent variations in the char-volatile products derived from sludge and MPs under different pyrolysis scenarios using multiple in situ probe coupling techniques and electron paramagnetic resonance spectroscopy, thereby identifying the sources of EPFRs and elucidating the corresponding formation-conversion mechanisms. The temperature was the key factor in the formation of EPFRs; in particular, in the 350-450 °C range, the abundance of EPFRs increased exponentially. Reactive EPFR readily formed in MPs with conjugated aromatic-ring structures (polyethylene terephthalate and polystyrene) at a temperature above 350 °C; EPFR concentrations were 5-17 times higher than those found in other types of polymers, and these radicals exhibited half-lives of more than 90 days. The EPFR formation mechanism could be summarized as solid-solid/solid-gas interfacial interactions between the polymers and the intermediate products from sludge pyrolysis (at 160-350 °C) and the homolytic cleavage-proton transfer occurring in the polymers themselves under the dual action of thermal induction and acid sites (at 350-450 °C). Based on the understanding of the evolution of EPFRs, temperature regulation and sludge components conditioning may be effective approaches to inhibit the formation of EPFRs in MPs, constituting reliable strategies to diminish the environmental risk associated with the byproducts of sludge pyrolysis.
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Pirólise , Esgotos , Esgotos/química , Microplásticos , Plásticos , Temperatura , Radicais Livres/química , PolímerosRESUMO
Citrinin, a secondary metabolite, can pose serious risks to the environment and organisms, but its hepatotoxic mechanisms are still unclear. Histopathological and ultrastructural results showed that citrinin-induced liver injury in Kunming mice, and the mechanism of citrinin-induced hepatotoxicity was studied in L02 cells. Firstly, citrinin mades L02 cell cycle arrest in G2/M phase by inhibition of cyclin B1, cyclin D1, cyclin-dependent kinases 2 (CDK2), and CDK4 expression. Secondly, citrinin inhibits proliferation and promotes apoptosis of L02 cells via disruption of mitochondria membrane potential, increase Bax/Bcl-2 ration, activation of caspase-3, 9, and enhance lactate dehydrogenase (LDH) release. Then, citrinin inhibits superoxide dismutase (SOD) activity and increases the accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS), resulting oxidative damage in L02 cells; upregulates the protein expression of binding immunoglobulin protein (Bip), C/EBP homologous protein (CHOP), PKR-like ER kinase (PERK) and activating transcription factor6 (ATF6), inducing ER stress in L02 cells; increases the phosphorylation of AMP-activated protein kinase (AMPK) and decreases the content of adenosine-triphosphate (ATP), activating AMPK pathway in L02 cells. Eventually, pretreatment with NAC, an ROS inhibitor, alleviates citrinin-induced cell cycle G2/M arrest and apoptosis by inhibiting ROS-mediated ER stress; pretreatment with 4-PBA, an ER stress inhibitor, reversed ER stress and p-AMPK; pretreatment with dorsomorphin, an AMPK inhibitor, decreases citrinin-induced cell cycle G2/M arrest and apoptosis. In summary, citrinin induces cell cycle arrest and apoptosis to aggravate liver injury by activating ROS-ER stress-AMPK signaling pathway.
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Doença Hepática Induzida por Substâncias e Drogas , Citrinina , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citrinina/metabolismo , Citrinina/toxicidade , Estresse do Retículo Endoplasmático , Pontos de Checagem da Fase G2 do Ciclo Celular , Camundongos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin, which mainly contaminates grains and has estrogen-like effects on the reproductive system. Betulinic acid (BA), a natural lupane-type pentacyclic triterpene, has anti-oxidative and anti-inflammatory properties. This study aimed to investigate whether BA alleviates ZEA-induced testicular damage and explore the possible mechanism. Here, BA ameliorated testicular damage by mitigating the disordered arrangement of seminiferous tubules, the exfoliation of lumen cells, and the increase of cell apoptosis caused by ZEA. Meanwhile, BA alleviated ZEA-triggered testicular damage by restoring hormone levels and sperm motility, and reconstructing the blood-testis-barrier. Moreover, BA alleviated ZEA-exposed testicular oxidative stress by activating Nrf2 pathway. Furthermore, BA moderated ZEA-evoked testicular inflammation by inhibiting p38/ERK MAPK pathway. Overall, our results revealed that BA has a therapeutic protective effect on ZEA-induced testicular injury and oxidative stress via p38/ERK MAPK inhibition and Nrf2-mediated antioxidant defense activation, which provides a viable alternative to alleviate ZEA-induced male reproductive toxicology.
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Sistema de Sinalização das MAP Quinases , Fator 2 Relacionado a NF-E2 , Triterpenos Pentacíclicos , Testículo , Zearalenona , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Zearalenona/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Ácido BetulínicoRESUMO
T-2 toxin is a highly toxic trichothecene that can induce toxic effects in a variety of organs and tissues, but the pathogenesis of its nephrotoxicity has not been elucidated. In this study, we assessed the involvement of protein kinase RNA-like ER kinase (PERK)-mediated endoplasmic reticulum (ER) stress and apoptosis in PK-15 cells cultured at different concentrations of T-2 toxin. Cell viability, antioxidant capacity, intracellular calcium (Ca2+) content, apoptotic rate, levels of ER stress, and apoptosis-related proteins were studied. T-2 toxin inhibited cell proliferation; increased the apoptosis rate; and was accompanied by increased cleaved caspase-3 expression, altered intracellular oxidative stress marker levels, and intracellular Ca2+ overloading. The ER stress inhibitor 4-phenylbutyrate (4-PBA) and PERK selective inhibitor GSK2606414 prevented the decrease of cell activity and apoptosis caused by T-2 toxin. The altered expression of glucose regulatory protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12 proved that ER stress was involved in cell injury triggered by T-2 toxin. T-2 toxin activated the phosphorylation of PERK and the alpha subunit of eukaryotic initiation factor 2 (eIF2α) and upregulated the activating transcription factor 4 (ATF4), thereby triggering ER stress via the GRP78/PERK/CHOP signaling pathway. This study provides a new perspective for understanding the nephrotoxicity of T-2 toxin.
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Fator 4 Ativador da Transcrição/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Fator de Iniciação 2 em Eucariotos/metabolismo , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Toxina T-2/toxicidade , eIF-2 Quinase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 12/metabolismo , Linhagem Celular , Chaperona BiP do Retículo Endoplasmático/metabolismo , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Rim/enzimologia , Rim/patologia , Nefropatias/enzimologia , Nefropatias/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Sus scrofa , Fator de Transcrição CHOP/metabolismoRESUMO
Betulinic acid (BA), a pentacyclic triterpenoid, has been associated with several biological effects, such as antioxidant, anti-inflammatory and antiviral activities. Previous studies have demonstrated that BA has the ability to alleviate intestinal mucosal damage, however, the potential mechanism associated with the effect has not been reported. This study aimed to investigate the possible protective mechanism of BA against cyclophosphamide (CYP)-induced intestinal mucosal damage. Here, we found that BA pretreatment prevented intestinal mucosal barrier dysfuction from CYP-challenged mice by repairing the intestinal physical, chemical, and immune barriers. Moreover, BA treatment suppressed the CYP-induced oxidative stress by activating the nuclear factor erythroid 2 [NF-E2]-related factor (Nrf2) pathway blocked reactive oxygen species (ROS) accumulation. In addition, BA inhibited CYP-triggered intestinal inflammation through down-regulating the nuclear transcription factor kappa B (NF-κB)/mitogen-activating protein kinase (MAPK) pathways. Furthermore, BA pretreatment reduced intestinal apoptosis by blocking ROS-activated mitochondrial apoptotic pathway. Overall, the current study demonstrated the protective effect of BA against CYP-caused intestinal mucosal damage by regulating the Nrf2 and NF-κB/MAPK signalling pathways, which may provide new therapeutic targets to attenuate intestinal impairment and maintain intestinal health.
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Fator 2 Relacionado a NF-E2 , Triterpenos , Animais , Ciclofosfamida/toxicidade , Mucosa Intestinal/metabolismo , Camundongos , Mitógenos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Triterpenos Pentacíclicos , Triterpenos/metabolismo , Triterpenos/farmacologia , Ácido BetulínicoRESUMO
Ganoderma lucidum polysaccharide (GLP) extracted from Ganoderma lucidum (Leyss. ex Fr.) Karst, a traditional Chinese medicine, is a biologically active substance reported to possess anti-oxidative, anti-apoptotic, and neurological protection. However, it is unknown whether GLP have any protective effect against high-fat constituents-induced epithelial cell injury. The aim of this study was to investigate the protection and molecular mechanism of GLP on injury induced by palmitic acid (PA) in the intestinal porcine epithelial cell line (IPEC-J2). First, we tested whether the treatment of GLP attenuate PA-induced IPEC-J2 cell death. GLP markedly blocked PA-caused cytotoxicity and apoptosis in IPEC-J2 cells. Moreover, GLP recovered the decreased mitochondrial function and inhibited activation of caspase-dependent apoptotic pathway. Interestingly, PA promoted cell apoptosis and autophagy through stimulation of phosphorylation of mitogen-activated protein kinases (MAPKs), AMP-activated protein kinase (AMPK), and inhibition of phosphorylation of Akt and mammalian target of rapamycin (mTOR), which was reversed by GLP. Taken together, this study revealed a protective effect of GLP against PA-evoked IPEC-J2 cell death through anti-apoptotic and anti-autophagic properties.
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Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Basidiomycota/química , Polissacarídeos Fúngicos/farmacologia , Mucosa Intestinal/metabolismo , Ácido Palmítico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Suínos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Medicinal herbal plants have been commonly used for intervention in different diseases and improvement of health worldwide. Koumine, an alkaloid monomer found abundantly in Gelsemium plants, can be effectively used as an antioxidant. The purpose of this study was to evaluate the potential protective effect of koumine against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in porcine intestinal epithelial cell line (IPEC-J2 cells). MTT assays showed that koumine significantly increased cell viability in H2O2-mediated IPEC-J2 cells. Preincubation with koumine ameliorated H2O2-medicated apoptosis by decreasing reactive oxygen species (ROS) production, and efficiently suppressed the lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production. Moreover, a loss of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) activities was restored to normal level in H2O2-induced IPEC-J2 cells upon koumine exposure. Furthermore, pretreatment with koumine suppressed H2O2-mediated loss of mitochondrial membrane potential, caspase-9 and caspase-3 activation, decrease of Bcl-2 expression and elevation of Bax expressions. Collectively, the results of this study indicated that koumine possesses the cytoprotective effects in IPEC-J2 cells during exposure to H2O2 by suppressing production of ROS, inhibiting the caspase-3 activity and influencing the expression of Bax and Bcl-2. Koumine could potentially serve as a protective effect against H2O2-induced apoptosis.
Assuntos
Antioxidantes/farmacologia , Gelsemium/química , Peróxido de Hidrogênio/farmacologia , Alcaloides Indólicos/farmacologia , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Alcaloides Indólicos/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , SuínosRESUMO
Although mTOR (the mammalian target of rapamycin) can regulate intracellular free Ca2+concentration in normal cultured podocytes, it remains elusive as to how mTORC2/AKT-mediated Ca2+participates in the process of T-2 toxin-induced apoptosis. The potential signaling responsible for intracellular Ca2+ concentration changes was investigated using immunoblot assays in an in vitro model of TM3 cell injury induced by T-2 toxin. Changes in Ca2+ were assessed using the Ca2+-sensitive fluorescent indictor dye Fura 2-AM. The cytotoxicity of TM3 cells was assessed with an MTT bioassay, and apoptosis was measured using Annexin V-FITC staining. Following T-2 toxin treatment, the growth of cells, phospho-mTORSer2481, phospho-mTORSer2448, and phospho-AktSer473 were significantly decreased in a time-dependent manner, whereas Ca2+ and apoptosis were increased. T-2 toxin-induced apoptosis was prevented by BAPTA-AM (a Ca2+chelator) and MHY1485 (an mTOR activator), and the application of mTOR activator MHY1485 also prevented the increase of intracellular free Ca2+concentration in TM3 cells. Our results strongly suggest that T-2 toxin exposure induces apoptosis in TM3 cells by inhibiting mTORC2/AKT to promote Ca2+ production.
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Apoptose , Cálcio/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Toxina T-2/toxicidade , Animais , Linhagem Celular , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , CamundongosRESUMO
Medicinal herbal plants have been commonly used for intervention of different diseases and health enhancement worldwide. Koumine, an alkaloid monomer found abundantly in Gelsemium plants, can be effectively used as an anti-inflammatory medication. In this study, the mechanisms associated with the preventative effect of koumine on lipopolysaccharide (LPS)-mediated inflammation in RAW264.7 macrophages were investigated. Koumine induced a decrease in the level of inducible nitric oxide synthase (iNOS) protein, concomitant reduction in the production of nitric oxide (NO) and reduction of the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1ß. Furthermore, koumine decreased the phosphorylation of p65 and inhibited nuclear factor κ Bα (IκBα) proteins, resulting in lower production of nuclear factor (NF)-κB transactivation. Koumine also induced a decrease in the phosphorylation of extracellular-signal-regulated kinases (ERK) and p38 in RAW264 cells. In conclusion, these findings reveal that koumine decreases the productions of pro-inflammatory mediators though the suppression of p38 and ERK MAPK phosphorylation and the inhibition of NF-κB activation in RAW264.7 cells.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Alcaloides Indólicos/farmacologia , Sistema de Sinalização das MAP Quinases , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Linhagem Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Koumine is a kind of alkaloid extracted from Gelsemium elegans (G. elegans). Benth, which has shown promise as an anti-tumor, anxiolytic, and analgesic agent. In our present study, the effect of koumine on lipopolysaccharide (LPS)-mediated RAW 264.7 cell apoptosis was evaluated. MTT assays showed that koumine obviously increased cell viability in LPS-mediated RAW 264.7 macrophages. Preincubation with koumine ameliorated LPS-medicated apoptosis by decreasing reactive oxygen species (ROS) production, which resulted in a significant decrease in the levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS). In addition, koumine-pretreated RAW 264.7 macrophages exhibited reduction of LPS-induced levels of TNF-α, IL-1ß, and IL-6 mRNA. Furthermore, pretreatment with koumine suppressed LPS-mediated p53 activation, loss of mitochondrial membrane potential, caspase-3 activation, decrease of Bcl-2 expression, and elevation of Bax and caspase-3 expressions, suggesting that koumine might act directly on RAW 264.7 cells to inhibit LPS-induced apoptosis. It seems as though the mechanism that koumine possesses is the anti-apoptotic effect mediated by suppressing production of ROS, activation of p53, and mitochondrial apoptotic pathways in RAW 264 cells. Koumine could potentially serve as a protective effect against LPS-induced apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Lipopolissacarídeos/toxicidade , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Monocinas/biossíntese , Óxido Nítrico/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Células RAW 264.7RESUMO
Dynamic computation has emerged as a promising strategy to improve the inference efficiency of deep networks. It allows selective activation of various computing units, such as layers or convolution channels, or adaptive allocation of computation to highly informative spatial regions in image features, thus significantly reducing unnecessary computations conditioned on each input sample. However, the practical efficiency of dynamic models does not always correspond to theoretical outcomes. This discrepancy stems from three key challenges: 1) The absence of a unified formulation for various dynamic inference paradigms, owing to the fragmented research landscape; 2) The undue emphasis on algorithm design while neglecting scheduling strategies, which are critical for optimizing computational performance and resource utilization in CUDA-enabled GPU settings; and 3) The cumbersome process of evaluating practical latency, as most existing libraries are tailored for static operators. To address these issues, we introduce Latency-Aware Unified Dynamic Networks (LAUDNet), a comprehensive framework that amalgamates three cornerstone dynamic paradigms-spatially-adaptive computation, dynamic layer skipping, and dynamic channel skipping-under a unified formulation. To reconcile theoretical and practical efficiency, LAUDNet integrates algorithmic design with scheduling optimization, assisted by a latency predictor that accurately and efficiently gauges the inference latency of dynamic operators. This latency predictor harmonizes considerations of algorithms, scheduling strategies, and hardware attributes. We empirically validate various dynamic paradigms within the LAUDNet framework across a range of vision tasks, including image classification, object detection, and instance segmentation. Our experiments confirm that LAUDNet effectively narrows the gap between theoretical and real-world efficiency. For example, LAUDNet can reduce the practical latency of its static counterpart, ResNet-101, by over 50% on hardware platforms such as V100, RTX3090, and TX2 GPUs. Furthermore, LAUDNet surpasses competing methods in the trade-off between accuracy and efficiency. Code is available at: https://www.github.com/LeapLabTHU/LAUDNet.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Viola yedoensis Makino (VYM) is a traditional Chinese herbal medicine widely distributed in China. It has many pharmacological effects such as anti-inflammatory, immune regulation and anti-oxidation. However, the protective effect of VYM on the spleen and thymus of broilers induced by heat stress has rarely been reported. AIM OF THE STUDY: We established a heat stress model of broilers to explore the protective effect of VYM on spleen and thymus of broilers. MATERIALS AND METHODS: In this experiment, a heat stress model was made by adjusting the feeding temperature of broilers. The protective effect of VYM on the spleen and thymus of heat-stressed broilers were evaluated by detecting immune organ coefficient, histological observation, Enzyme-Linked Immunosorbent Assay, production of antioxidant enzymes and peroxides, TUNEL Staining, Quantitative Real-time PCR. RESULTS: In this study, 60 healthy male AA broilers were divided into 6 groups: Control, 4.5% VYM, HS, HS + 0.5% VYM, HS + 1.5% VYM, HS + 4.5% VYM. After 42 days of feeding, serum, spleen and thymus were collected for detection and analysis. The study revealed that heat stress can lead to pathological damage in the spleen and thymus of broilers, reduce the content of immunoglobulin and newcastle disease (ND), infectious bursal disease (IBD) antibody levels, increase the expression of inflammatory factors IL-1ß, INF-γ, heat shock 70 kDa protein (HSP70), heat shock 90 kDa protein (HSP90). Heat stress inhibits the activity of antioxidant enzymes CAT and SOD, promotes the production of MDA, and then lead to oxidative damage of the spleen and thymus. In addition, apoptotic cells and the ratio of Bax/Bcl-2 was increased. However, the addition of VYM to the feed can alleviate the adverse effects of heat stress on the spleen and thymus of broilers. CONCLUSIONS: This study showed that the addition of VYM to the diet could inhibit oxidative stress and apoptosis, and reduce the inflammatory damage of heat stress on the spleen and thymus of broilers. This study provides a basis for further exploring the regulatory role of VYM in heat stress-induced immune imbalance in broilers. In addition, this study also provides a theoretical basis for the development of VYM as a feed additive with immunomodulatory effects.
Assuntos
Baço , Viola , Masculino , Animais , Galinhas , Antioxidantes/farmacologia , Estresse Oxidativo , Apoptose , Inflamação , Proteínas de Choque Térmico , Resposta ao Choque TérmicoRESUMO
T-2 toxin, an unavoidable contaminant in animal feeds, can induce oxidative stress and damage immune organs. Melatonin (MT), a natural and potent antioxidant, has shown promise as a detoxifier for various mycotoxins. However, the detoxifying effect of MT on T-2 toxin has not been previously reported. In order to investigate the protective effect of MT added to diets on the immune system of T-2 toxin-exposed piglets, twenty piglets weaned at 28d of age were randomly divided into control, T-2 toxin (1 mg/kg), MT (5 mg/kg), and T-2 toxin (1 mg/kg) + MT (5 mg/kg) groups(n = 5 per group). Our results demonstrated that MT mitigated T-2 toxin-induced histoarchitectural alterations in the spleen and thymus, such as hemorrhage, decreased white pulp size in the spleen, and medullary cell sparing in the thymus. Further research revealed that MT promoted the expression of Nrf2 and increased the activities of antioxidant enzymes CAT and SOD, while reducing the production of the lipid peroxidation product MDA. Moreover, MT inhibited the NF-κB signaling pathway, regulated the expression of downstream cytokines IL-1ß, IL-6, TNF-α, and TGF-ß1. MT also suppressed the activation of caspase-3 while down-regulating the ratio of Bax/Bcl-2 to reduce apoptosis. Additionally, MT ameliorated the T-2 toxin-induced disorders of immune cells and immune molecules in the blood. In conclusion, our findings suggest that MT may effectively protect the immune system of piglets against T-2 toxin-induced damage by inhibiting oxidative stress, inflammatory response, and apoptosis in the spleen and thymus. Therefore, MT holds the potential as an antidote for T-2 toxin poisoning.