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BACKGROUND: Appropriate iron supplementation is essential for neonatal growth and development. However, there are few reports on the effects of iron overload on neonatal growth and immune homeostasis. Thus, the aim of this study was to investigate the effects of iron nutrition on neonatal growth and intestinal immunity by administering different levels of iron to neonatal pigs. RESULTS: We found that iron deficiency and iron overload resulted in slow growth in neonatal pigs. Iron deficiency and iron overload led to down-regulation of jejunum intestinal barrier and antioxidant marker genes, and promoted CD8+ T cell differentiation in jejunum and mesenteric lymph nodes (MLN) of pigs, disrupting intestinal health. Moreover, iron levels altered serum iron and tissue iron status leading to disturbances in redox state, affecting host innate and adaptive immunity. CONCLUSIONS: These findings emphasized the effect of iron nutrition on host health and elucidated the importance of iron in regulating redox state and immunity development. This study provided valuable insights into the regulation of redox state and immune function by iron metabolism in early life, thus contributing to the development of targeted interventions and nutritional strategies to optimize iron nutrition in neonates.
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Multiple beneficial effects have been attributed to green tea catechins (GTCs). However, the bioavailability of GTCs is generally low, with only a small portion directly absorbed in the small intestine. The majority of ingested GTCs reaches the large intestinal lumen, and are extensively degraded via biotransformation by gut microbiota, forming many low-molecular-weight metabolites such as phenyl-γ-valerolactones, phenolic acids, butyrate, and acetate. This process not only improves the overall bioavailability of GTC-derived metabolites but also enriches the biological activities of GTCs. Therefore, the intra- and inter-individual differences in human gut microbiota as well as the resulting biological contribution of microbial metabolites are crucial for the ultimate health benefits. In this review, the microbial degradation of major GTCs was characterized and an overview of the in vitro models used for GTC metabolism was summarized. The intra- and inter-individual differences of human gut microbiota composition and the resulting divergence in the metabolic patterns of GTCs were highlighted. Moreover, the potential beneficial effects of GTCs and their gut microbial metabolites were also discussed. Overall, the microbial metabolites of GTCs with higher bioavailability and bioactive potency are key factors for the observed beneficial effects of GTCs and green tea consumption.
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Disponibilidade Biológica , Catequina , Microbioma Gastrointestinal , Chá , Microbioma Gastrointestinal/fisiologia , Humanos , Chá/química , Catequina/metabolismoRESUMO
Metabolic disorders are highly prevalent in modern society. Exercise mimetics are defined as pharmacological compounds that can produce the beneficial effects of fitness. Recently, there has been increased interest in the role of eugenol and transient receptor potential vanilloid 1 (TRPV1) in improving metabolic health. The aim of this study was to investigate whether eugenol acts as an exercise mimetic by activating TRPV1. Here, we showed that eugenol improved endurance capacity, caused the conversion of fast-to-slow muscle fibers, and promoted white fat browning and lipolysis in mice. Mechanistically, eugenol promoted muscle fiber-type transformation by activating TRPV1-mediated CaN signaling pathway. Subsequently, we identified IL-15 as a myokine that is regulated by the CaN/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Moreover, we found that TRPV1-mediated CaN/NFATc1 signaling, activated by eugenol, controlled IL-15 levels in C2C12 myotubes. Our results suggest that eugenol may act as an exercise mimetic to improve metabolic health via activating the TRPV1-mediated CaN signaling pathway.
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Eugenol , Interleucina-15 , Fibras Musculares Esqueléticas , Fatores de Transcrição NFATC , Condicionamento Físico Animal , Canais de Cátion TRPV , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Animais , Interleucina-15/metabolismo , Eugenol/farmacologia , Eugenol/metabolismo , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , MiocinasRESUMO
The conversion of fast-twitch fibers into slow-twitch fibers within skeletal muscle plays a crucial role in improving physical stamina and safeguarding against metabolic disorders in individuals. Grape seed proanthocyanidin extract (GSPE) possesses numerous pharmacological and health advantages, effectively inhibiting the onset of chronic illnesses. However, there is a lack of research on the specific mechanisms by which GSPE influences muscle physiology and gut microbiota. This study aims to investigate the role of gut microbiota and their metabolites in GSPE regulation of skeletal muscle fiber type conversion. In this experiment, 54 male BALB/c mice were randomly divided into three groups: basal diet, basal diet supplemented with GSPE, and basal diet supplemented with GSPE and antibiotics. During the feeding period, glucose tolerance and forced swimming tests were performed. After euthanasia, samples of muscle and feces were collected for analysis. The results showed that GSPE increased the muscle mass and anti-fatigue capacity of the mice, as well as the expression of slow-twitch fibers. However, the beneficial effects of GSPE on skeletal muscle fibers disappeared after adding antibiotics to eliminate intestinal microorganisms, suggesting that GSPE may play a role by regulating intestinal microbial structure. In addition, GSPE increased the relative abundance of Blautia, Muribaculaceae, and Enterorhabdus, as well as butyrate production. Importantly, these gut microbes exhibited a significant positive correlation with the expression of slow-twitch muscle fibers. In conclusion, supplementation with GSPE can increase the levels of slow-twitch fibers by modulating the gut microbiota, consequently prolonging the duration of exercise before exhaustion. PRACTICAL APPLICATION: This research suggests that grape seed proanthocyanidin extract (GSPE) has potential applications in improving physical stamina and preventing metabolic disorders. By influencing the gut microbiota and increasing butyric acid production, GSPE contributes to the conversion of fast-twitch muscle fibers into slow-twitch fibers, thereby enhancing anti-fatigue capacity and exercise endurance. While further studies are needed, incorporating GSPE into dietary supplements or functional foods could support individuals seeking to optimize their exercise performance and overall metabolic health.
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Ácido Butírico , Microbioma Gastrointestinal , Extrato de Sementes de Uva , Camundongos Endogâmicos BALB C , Proantocianidinas , Animais , Proantocianidinas/farmacologia , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Extrato de Sementes de Uva/farmacologia , Camundongos , Ácido Butírico/metabolismo , Ácido Butírico/farmacologia , Ceco/microbiologia , Ceco/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares de Contração Lenta/efeitos dos fármacos , Fibras Musculares de Contração Lenta/metabolismo , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Rápida/metabolismo , Músculo Esquelético/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/classificaçãoRESUMO
Cytokine storms are associated with severe pathological damage and death in some diseases. Excessive activation of M1 macrophages and the subsequent secretion of pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, promoting the polarization of M2 macrophages to restore immune balance is a promising therapeutic strategy for treating cytokine storm syndrome (CSS). This study was aimed at investigating the potential protective effects of leucine on lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying mechanisms. CSS was induced by LPS administration in mice, which were concurrently administered leucine orally. In vitro, bone marrow derived macrophages (BMDMs) were polarized to M1 and M2 phenotypes with LPS and interleukin-4 (IL-4), respectively, and treated with leucine. Leucine decreased mortality in mice treated with lethal doses of LPS. Specifically, leucine decreased M1 polarization and promoted M2 polarization, thus diminishing pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies revealed that leucine-induced macrophage polarization through the mechanistic target of rapamycin complex 1 (mTORC1)/liver X receptor α (LXRα) pathway, which synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and subsequent M2 polarization. In summary, this study revealed that leucine ameliorates CSS in LPS mice by promoting M2 polarization through the mTORC1/LXRα/Arg1 signaling pathway. Our findings indicate that a fundamental link between metabolism and immunity contributes to the resolution of inflammation and the repair of damaged tissues.
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Síndrome da Liberação de Citocina , Interleucina-4 , Animais , Camundongos , Receptores X do Fígado , Leucina/farmacologia , Lipopolissacarídeos , Citocinas , Transdução de Sinais , Macrófagos , Alvo Mecanístico do Complexo 1 de RapamicinaRESUMO
BACKGROUND: Transmissible gastroenteritis virus (TGEV) is one of the main pathogens causing severe diarrhea of piglets. The pathogenesis of TGEV is closely related to intestinal inflammation. All-trans retinoic acid (ATRA) is the main active metabolite of vitamin A, which has immunomodulatory and anti-inflammatory properties. However, it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets. This study aimed to investigate the effects of ATRA on growth performance, diarrhea, intestinal inflammation and intestinal barrier integrity of TGEV-challenged piglets. METHODS: In a 19-d study, 32 weaned piglets were randomly divided into 4 treatments: Control group (basal diet), TGEV group (basal diet + TGEV challenge), TGEV + ATRA5 group (basal diet + 5 mg/d ATRA + TGEV challenge) and TGEV + ATRA15 group (basal diet + 15 mg/d ATRA + TGEV challenge). On d 14, piglets were orally administered TGEV or the sterile medium. RESULTS: Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV (P < 0.05). Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase (DAO) activity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV, and maintained intestinal barrier integrity (P < 0.05). Meanwhile, 5 mg/d ATRA feeding increased the sucrase activity and the expressions of nutrient transporter related genes (GLUT2 and SLC7A1) in jejunal mucosa of TGEV-challenged piglets (P < 0.05). Furthermore, 5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibiting the release of interleukin (IL)-1ß, IL-8 and tumor necrosis factor-α (TNF-α), and promoting the secretion of IL-10 and secretory immunoglobulin A (sIgA) (P < 0.05). Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes (TLR3, TLR4, RIG-I, MyD88, TRIF and MAVS) and the phosphorylation level of nuclear factor-κB-p65 (NF-κB p65), and up-regulated the inhibitor kappa B alpha (IκBα) protein level in jejunal mucosa of TGEV-challenged piglets (P < 0.05). CONCLUSIONS: ATRA alleviated TGEV-induced intestinal barrier damage by inhibiting inflammatory response, thus improving the growth performance and inhibiting diarrhea of piglets. The mechanism was associated with the inhibition of NF-κB signaling pathway mediated by TLR3, TLR4 and RIG-I.
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Rotaviruses (RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid (RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire (DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients (5 and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA (5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio (P < 0.05), enhancing intestinal stem cell signaling and promoting intestinal barrier functions. In addition, 15 mg/d RA supplementation significantly increased NRF2 and HO-1 protein expression (P < 0.05) and GSH content (P < 0.05), indicating that RA supplementation can enhance anti-oxidative signaling and redox homeostasis after RV challenge. Additionally, the research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.
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This experiment was conducted to explore the effects of dietary synbiotics (SYB) supplementation on growth performance, immune function, and intestinal barrier function in piglets challenged with porcine epidemic diarrhea virus (PEDV). Forty crossbred (Durocâ ×â Landraceâ ×â Yorkshire) weaned piglets (26â ±â 1 d old) with a mean body weight (BW) of 6.62â ±â 0.36 kg were randomly allotted to five groups: control (CON) I and CONII group, both fed basal diet; 0.1% SYB group, 0.2% SYB group, and 0.2% yeast culture (YC) group, fed basal diet supplemented with 0.1%, 0.2% SYB, and 0.2% YC, respectively. On day 22, all piglets were orally administrated with 40 mL PEDV (5.6â ×â 103 TCID50/mL) except piglets in CONI group, which were administrated with the same volume of sterile saline. The trial lasted for 26 d. Before PEDV challenge, dietary 0.1% SYB supplementation increased final BW, average daily gain (ADG), and decreased the ratio of feed to gain during 0 to 21 d (Pâ <â 0.05), as well as improved the apparent nutrient digestibility of dry matter (DM), organic matter (OM), crude protein, ether extract (EE), and gross energy (GE). At the same time, 0.2% YC also improved the apparent nutrient digestibility of DM, OM, EE, and GE (Pâ <â 0.05). PEDV challenge increased diarrhea rate and diarrhea indexes while decreased ADG (Pâ <â 0.05) from days 22 to 26, and induced systemic and intestinal mucosa innate immune and proinflammatory responses, destroyed intestinal barrier integrity. The decrease in average daily feed intake and ADG induced by PEDV challenge was suppressed by dietary SYB and YC supplementation, and 0.1% SYB had the best-alleviating effect. Dietary 0.1% SYB supplementation also increased serum interleukin (IL)-10, immunoglobulin M, complement component 4, and jejunal mucosal IL-4 levels, while decreased serum diamine oxidase activity compared with CONII group (Pâ <â 0.05). Furthermore, 0.1% SYB improved mRNA expressions of claudin-1, zonula occludens protein-1, mucin 2, interferon-γ, interferon regulatory factor-3, signal transducers and activators of transcription (Pâ <â 0.05), and protein expression of occludin, and downregulated mRNA expressions of toll-like receptor 3 and tumor necrosis factor-α (Pâ <â 0.05) in jejunal mucosa. Supplementing 0.2% SYB or 0.2% YC also had a positive effect on piglets, but the effect was not as good as 0.1% SYB. These results indicated that dietary 0.1% SYB supplementation improved growth performance under normal conditions, and alleviated the inflammatory response and the damage of intestinal barrier via improving innate immune function and decreasing PEDV genomic copies, showed optimal protective effects against PEDV infection.
Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea, vomiting, anorexia, and high mortality in piglets, which leads to serious economic losses in many pig-producing countries. Vaccination is commonly used for the prevention of PEDV infection. However, current vaccines are ineffective in preventing infections because of genetic variants of PEDV. Therefore, developing new and efficient strategies to reduce porcine epidemic diarrhea outbreaks for piglets is desirable. Synbiotics (SYB) refer to the biological mixture of probiotics and prebiotics, which combines the advantages of both. At present, the application of probiotics or prebiotics has been widely reported in piglets feeds, which improves growth performance, immune function, microbiota community, intestinal structure, and resistance to bacterial infection. However, there was little report on whether SYB can protect piglets against PEDV infection. Therefore, this study was conducted to investigate the effects of SYB on growth performance, intestinal barrier function, and immune function in PEDV-infected weaned piglets. Results indicated that dietary SYB supplementation improved growth performance, decreased the inflammatory response, and alleviated the damage of intestinal barrier by improving innate antiviral immunity and reducing PEDV genomic copies, ultimately offering optimal protective effects against PEDV infection.
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Gastroenteropatias , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Simbióticos , Animais , Suínos , Suplementos Nutricionais , Gastroenteropatias/veterinária , Diarreia/prevenção & controle , Diarreia/veterinária , Imunidade Inata , Nutrientes , RNA Mensageiro , Doenças dos Suínos/prevenção & controleRESUMO
Enterotoxigenic Escherichia coli (ETEC) is one of the major bacterial infections, causing substantial economic losses globally in the swine industry. This study aimed to investigate the impact of low Saccharomyces cerevisiae fermentation postbiotics (SCFP), high SCFP, essential oil (EO), or their combination on the growth performance and health of weanling pigs during ETEC infection. Forty-eight male weanling pigs were randomly allocated to five groups: 1) control group (CON-basal diet, nâ =â 16); 2) low SCFP group (LSC-basal dietâ +â 1.25 g/kg SCFP, nâ =â 8); 3) high SCFP group (HSC-basal dietâ +â 2 g/kg SCFP, nâ =â 8); 4) essential oil group (EO-basal dietâ +â 0.4 g/kg EO, nâ =â 8); 5) the SCFP and EO combination group (SE-basal dietâ +â 1.25 g/kg SCFPâ +â 0.4 g/kg EO, nâ =â 8). On day 15 of the trial, pigs in CON were divided into positive control (PC) and negative control (NC), and all pigs, except in NC, were challenged with ETEC. Under the normal condition, dietary LSC, HSC, EO, and EO all increased average daily gain (ADG) (Pâ <â 0.05), and decreased F:G ratio (Pâ <â 0.05) accompanied by decreased malondialdehyde (MDA) and increases in catalase (CAT), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) indicating enhanced anti-oxidative capacity, as well as decreased IL-2, IL-8, INF-γ, indicating mitigated systemic inflammation. During ETEC infection, all treatments alleviated ETEC-induced ADG reduction, diarrhea, damages in intestinal permeability and morphology, and down-regulation of tight junctions (Claudin1, ZO-1, and Occludin), while HSC and EO exhibited additional protections. All treatments increased CAT, T-SOD, and T-AOC, and decreased MDA in serum and jejunal mucosa at similar degrees (Pâ <â 0.05). Moreover, all treatments alleviated ETEC-induced inflammation as shown by decreased IL-6, TNF-α, INF-γ, and increased IL-4 and IL-10 in serum or jejunal mucosa (Pâ <â 0.05), and enhanced the immunity by increased serum IgG and mucosal sIgA (Pâ <â 0.05). HSC and SE further reduced mucosal INF-γ and TNF-α than LSC or EO aligning with their additional protection against diarrhea during ETEC infection. Additionally, the key gut bacteria (e.g., Terrisporobacter) related to the benefits of SCFP and EO were identified. In sum, all treatments enhanced growth performance and protected against ETEC-induced intestinal damage through the regulation of redox and immune homeostasis. HSP and SE offered extra protection during disease for their additional control of inflammation. Our study provided new insight into the use of feed additives in the context of animal health states.
Weanling pigs are vulnerable to a variety of stressors and pathogen infections. Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea and growth retardation in weanling pigs. The postbiotics, Saccharomyces cerevisiae fermentation postbiotics (SCFP), and essential oil (EO, mainly thymol, and cinnamaldehyde) were reported to exert health benefits in different sites of the intestine. However, whether SCFP and EO have dose and synergistic effects on weanling pigs, especially against ETEC infection, is incompletely understood. Our research has revealed that SCFP, EO, and their combination all enhanced the growth performance and intestinal barrier function, and reduced diarrhea of piglets, albeit to varying degrees, under both health conditions and ETEC infection. We further elucidated the disparity in the regulation of redox and immune homeostasis by SCFP, EO, and their combination contributing to their different action in distinct states. This has led to a reevaluation of the function of additives in the context of gut health and disease susceptibility.
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Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Óleos Voláteis , Doenças dos Suínos , Suínos , Masculino , Animais , Saccharomyces cerevisiae , Fator de Necrose Tumoral alfa , Óleos Voláteis/farmacologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Diarreia/microbiologia , Diarreia/veterinária , Dieta/veterinária , Inflamação/veterinária , Superóxido Dismutase , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/microbiologia , Ração Animal/análise , DesmameRESUMO
SCOPE: Endurance capacity is essential for endurance athletes' achievement and individuals' health. Nutritional supplements are a proven way to enhance endurance capacity. Previous studies have shown that ferulic acid (FA) enhances endurance capacity, but the underlying mechanism is unclear. The study is aimed to investigate the mechanism by which FA increases endurance capacity. METHODS AND RESULTS: Forty mice are divided into control and 0.5% FA-supplemented groups, and an exhaustive swimming test demonstrates increased endurance capacity with FA supplementation. This study investigates the underlying mechanism for this effect of FA. Firstly, RT-PCR and western blot analysis find that FA increases the transformation from fast to slow muscle fiber. Additionally, adenosine triphosphate concentration, metabolic enzyme activity, and mitochondrial DNA analysis find that FA increases mitochondrial biogenesis and activates nuclear factor erythroid 2-related factor (NRF)1 signaling pathway in muscle. Besides, through antioxidant capacity analysis, this study finds that FA activates NRF2 signaling pathway and improves the antioxidant capacity in muscle. Moreover, inhibiting NRF2 eliminates FA's effect on muscle fiber transformation in C2C12 cells. CONCLUSION: Our results suggest that FA increases endurance capacity by promoting skeletal muscle oxidative phenotype, mitochondrial function, and antioxidant capacity, which may be related to the NRF1 and NRF2 signaling pathways.
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Antioxidantes , Ácidos Cumáricos , Fator 2 Relacionado a NF-E2 , Humanos , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Músculo Esquelético/metabolismo , Mitocôndrias , Fenótipo , Estresse OxidativoRESUMO
Plant extracts are commonly used as feed additives to improve pork quality. However, due to their high cost, shortening the duration of supplement use can help reduce production costs. In this study, we aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on meat quality and muscle fiber characteristics of finishing pigs during the late stage of fattening, which was 30 days in our experimental design. The results indicated that short-term dietary supplementation of GSPE significantly reduced backfat thickness, but increased loin eye area and improved meat color and tenderness. Moreover, GSPE increased slow myosin heavy chain (MyHC) expression and malate dehydrogenase (MDH) activity, while decreasing fast MyHC expression and lactate dehydrogenase (LDH) activity in the Longissimus thoracis (LT) muscle. Additionally, GSPE increased the expression of Sirt1 and PGC-1α proteins in the LT muscle of finishing pigs and upregulated AMP-activated protein kinase α 1 (AMPKα1), AMPKα2, nuclear respiratory factor 1 (NRF1), and calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß) mRNA expression levels. These findings suggest that even during the late stage of fattening, GSPE treatment can regulate skeletal muscle fiber type transformation through the AMPK signaling pathway, thereby affecting the muscle quality of finishing pigs. Therefore, by incorporating GSPE into the diet of pigs during the late stage of fattening, producers can enhance pork quality while reducing production costs.
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Extrato de Sementes de Uva , Carne de Porco , Proantocianidinas , Carne Vermelha , Suínos , Animais , Fibras Musculares Esqueléticas/metabolismo , Extrato de Sementes de Uva/farmacologia , Suplementos Nutricionais , Músculo Esquelético/metabolismoRESUMO
The cell elimination strategy based on reactive oxygen species (ROS) is a promising method for tumor therapy. However, its efficacy is significantly limited by ROS deficiency caused by H2 O2 substrate deficiency and up-regulation of cellular antioxidant defense induced by high glutathione (GSH) content in tumor cells. To overcome these obstacles, a multifunctional self-cascaded nanocomposite: glucose oxidase (GOX) loaded NaYF4 :Yb/Er@Mn3 O4 (UC@Mn3 O4 , labeled as UCMn) is constructed. Only in tumor microenvironment, it can be specifically activated through a series of cascades to boost ROS production via a strategy of open source (H2 O2 self-supplying ability). The increased ROS can enhance lipid peroxidation and induce tumor cell apoptosis by activating the protein caspase. More importantly, the nanozyme can consume GSH to inhibit glutathione peroxidase 4 (GPX4) activity, which limits tumor cell resistance to oxidative damage and triggers the tumor cell ferroptosis. Therefore, this strategy is expected to overcome the resistance of tumor to oxidative damage and achieve efficient oxidative damage of tumor. Further, degradation of the Mn3 O4 layer induced by GSH and acidic environment can promote the fluorescence recovery of UC fluorescent nuclear for tumor imaging to complete efficient integration of diagnosis and treatment for tumor.
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Ferroptose , Nanocompostos , Neoplasias , Humanos , Glucose Oxidase , Espécies Reativas de Oxigênio , Apoptose , Imagem Óptica , Antioxidantes , Glutationa , Neoplasias/terapia , Linhagem Celular Tumoral , Microambiente Tumoral , Peróxido de HidrogênioRESUMO
In recent years, the impact of bile acids and their representative G protein-coupled bile acid receptor 1 Takeda-G-protein-receptor-5 (TGR5) signaling pathway on muscle function and metabolic health has gained considerable interest. Increasing the content of slow muscle fibers has been recognized as an effective strategy to improve metabolic health. Oleanolic acid (OA) is a naturally occurring triterpenoid compound derived from plants, which can activate TGR5. The aim of this study was to investigate the effect of OA and TGR5 on muscle fiber types and further explore the underlying TGR5-dependent mechanisms. In this study, mice were divided into three groups and dietary supplementation with 0, 50, or 100 mg/kg OA. In addition, C2C12 cells were treated with OA at concentrations of 0, 5, 10, and 20 µM. Our studies revealed that OA promoted the conversion of fast to slow muscle fibers. In addition, it was found that OA activated the TGR5-mediated calcineurin (CaN)/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Further mechanistic investigations demonstrated that inhibiting TGR5 and CaN abolished the effects of OA on muscle fiber types transformation. In conclusion, this study found that OA promotes the transformation of fast muscle fibers to slow muscle fibers through the TGR5-mediated CaN/NFATc1 signaling pathway.
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Calcineurina , Ácido Oleanólico , Transdução de Sinais , Animais , Camundongos , Calcineurina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMO
To explore the effects of fermented rapeseed meal (FRSM) on growth performance and intestinal health, a total of 30 growing pigs were randomly allotted to three treatments consisting of corn-soybean meal diet (CSD), rapeseed meal diet (RSD), and fermented rapeseed meal diet (FRSD). Results showed that compared with RSD, FRSD feeding increased the average daily gain and final body weight in pigs (P < 0.01). Compared with RSD feeding, FRSD feeding elevated the apparent digestibility of crude protein, acid detergent fiber, and ether extract in pigs (P < 0.01). Moreover, the FRSD group exhibited greater apparent ileal digestibility of His, Thr, Lys, and Ser than the RSD group (P < 0.01). The digestible energy, metabolic energy, and nitrogen utilization were higher in the FRSD and CSD groups than in the RSD group (P < 0.01). As compared to the RSD, FRSD feeding decreased the serum concentration of leptin but significantly increased the concentrations of immunoglobulin (Ig) A, IgG, ghrelin, and enzyme activities of amylase, lipase, and trypsin in the pancreas (P < 0.05). Interestingly, the villus height, the ratio of villus height to crypt depth, and the activities of brush border enzymes (e.g., maltase and sucrase) in the small intestine were higher in the CSD and FRSD groups than in the RSD group (P < 0.05). As compared to the RSD, the FRSD feeding not only increased the expression level of the occludin in the small intestinal epithelium (P < 0.05) but also elevated the expression levels of claudin-1, MUC1, and PepT1 genes in the duodenum, and elevated the expression levels of SGLT1 and CAT1 genes in the jejunum (P < 0.05). Importantly, FRSD feeding significantly decreased the abundance of Escherichia coli, but increased the abundance of Lactobacillus and the content of butyrate in the cecum and colon (P < 0.05). These results indicated that compared with rapeseed meal, fermented rapeseed meal exhibited a positive effect on improving the growth performance and intestinal health in growing pigs, and the results may also help develop novel protein sources for animal nutrition and the feed industry.
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The aim of this study was to investigate the effects of dietary fiber on the serum biochemistry, bile acid profile, and gut microbiota in piglets. Twenty-four pigs (initial body weight: 10.53 ± 1.23 kg) were randomly divided into three treatments with eight replicate pens of one pig per pen for 21 d. The dietary treatments consisted of the following: (1) a fiber-free diet (NS); (2) a fiber-free diet + 3% fructooligosaccharides (SI); (3) a fiber-free diet + 3% dietary fiber mixture (fructooligosaccharides, long-chain inulin, and microcrystalline cellulose at the ratio 1:1:1; MIX). The results showed that compared with the NS group, the 3% SI diet reduced the serum total cholesterol (TC) concentration of the piglets (p < 0.05). The metabolomics results showed that the 3% SI diet increased the level of taurohyocholic acid (THCA) and α-muricholic acid, and the 3% MIX diet increased the level of THCA and cholic acid (p < 0.05). The use of 3% SI or MIX decreased the glycodeoxycholic acid (GDCA) level in the bile of the piglets (p < 0.05). The correlation analysis shows that the GDCA was positively related to the TC. The 16S rRNA gene sequencing results showed that UCG-002 and Holdemanella were enriched in the SI group, while Bacteroides was enriched in the MIX group. The microbial function prediction indicated that SI supplementation tended to elevate the relative abundance of gut bacteria capable of expressing bile acid-metabolizing enzymes. To sum up, the regulatory effect of dietary fiber on lipid metabolism is related to bile acids in piglets. Compared with MIX, SI is more likely to regulate bile acids through the gut microbiota.
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This experiment was conducted to explore the effects of gut microbiota on neonatal diarrhea in a germ-free (GF) pig model. Twelve hysterectomy-derived GF piglets were housed in six sterile isolators. Among them, six piglets were treated as the GF group, and the other six piglets were orally introduced with healthy sow fecal suspension and regarded as the fecal microbiota transplantation (FMT) group. Another six piglets from natural birth were considered as the conventional (CV) group. The GF and FMT piglets were hand-fed with sterile milk powder for 21 days, and the CV piglets were suckled for the same days. Then, all piglets were fed with sterile feed for another 21 days. Results exhibited that the GF group's fecal score and moisture level were higher than those in the CV and FMT groups (p < 0.05). Meanwhile, the abundances of colonic AQP1 and AQP8 in the GF group were the greatest among these treatments (p < 0.05). However, FMT piglets had a lower fecal score in d 22-28 and d 29-35 than that in the CV piglets (p < 0.05). Collectively, the absence of gut microbiota may cause diarrhea in the piglet model, and transplantation of maternal fecal microbiota may reverse it.
Assuntos
Microbioma Gastrointestinal , Suínos , Animais , Feminino , Diarreia/terapia , Diarreia/veterinária , Transplante de Microbiota Fecal , FezesRESUMO
BACKGROUND: Iron plays a pivotal role in various physiological processes, including intestinal inflammation, ferroptosis, and the modulation of the gut microbiome. However, the way these factors interact with each other is unclear. METHODS: Mice models were fed with low, normal and high iron diets to assess their impacts on colitis, ferroptosis and gut microbiota. Untargeted fecal metabolomics analysis, 16S rRNA sequencing, histopathology analysis, real-time quantitative PCR and western blot were performed to analyze the differences in the intestinal inflammatory response and understanding its regulatory mechanisms between low, normal and high iron groups. RESULTS: The iron overload changed the serum iron, colon iron and fecal iron. In addition, the iron overload induced the colitis, induced the ferroptosis and altered the microbiome composition in the fecal of mice. By using untargeted fecal metabolomics analysis to screen of metabolites in the fecal, we found that different metabolomics profiles in the fecal samples between iron deficiency, normal iron and iron overload groups. The correlation analysis showed that both of iron deficiency and overload were closely related to Dubosiella. The relationship between microbial communities (e.g., Akkermansia, Alistipes, and Dubosiella) and colitis-related parameters was highly significant. Additionally, Alistipes and Bacteroides microbial communities displayed a close association with ferroptosis-related parameters. Iron overload reduced the concentration of metabolites, which exert the anti-inflammatory effects (e.g., (+)-.alpha.-tocopherol) in mice. The nucleotide metabolism, enzyme metabolism and metabolic diseases were decreased and the lipid metabolism was increased in iron deficiency and iron overload groups compared with normal iron group. CONCLUSION: Iron overload exacerbated colitis in mice by modulating ferroptosis and perturbing the gut microbiota. Iron overload-induced ferroptosis was associated with NRF2/GPX-4 signaling pathway. Specific microbial taxa and their associated metabolites were closely intertwined with both colitis and ferroptosis markers.
Assuntos
Colite , Ferroptose , Microbioma Gastrointestinal , Deficiências de Ferro , Sobrecarga de Ferro , Animais , Camundongos , RNA Ribossômico 16S , Colite/induzido quimicamente , Ferro , Bacteroidetes , Firmicutes , Camundongos Endogâmicos C57BLRESUMO
This study was to evaluate the effects of supplementing mixed dietary fibres (MDF) and essential oils blend (EOB) either alone or in combination on growth performance and intestinal barrier function in weaned piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Forty-two piglets (28 days old) were randomly allocated into six treatments in a 25-day experiment, and fed the basal diet (CON or ETEC) either with antibiotics (AT), MDF, EOB or MDF + EOB. On Day 22 of the experiment, pigs in CON and challenged groups (ETEC, AT, MDF, EOB and MDF + EOB) were orally administered sterile saline and ETEC containing 6 × 1010 CFU/kg body weight respectively. On Day 26, all pigs were euthanized to collect samples. Before ETEC challenge, piglets in MDF and EOB had lower diarrhoea incidence (p < 0.01) than others. After ETEC challenge, piglets in ETEC had lower average daily gain and higher diarrhoea incidence (p < 0.05) than those of CON. Furthermore, compared to CON, ETEC group increased the serum lipopolysaccharide concentration and diamine oxidase activity, and decreased mRNA levels of genes relating to barrier function (aquaporin 3, AQP3; mucin1, MUC1; zonula occludens-1, ZO-1; Occludin), and increased the concentration of cytokines (interleukin-1ß/4/6/10, IL-1ß/4/6/10) and secretory immunoglobulin A (sIgA) in jejunal mucosa (p < 0.05). However, these deleterious effects induced by ETEC were partly alleviated by MDF, EOB, MDF + EOB and AT. Additionally, compared to ETEC group, MDF increased Bifidobacterium abundance in cecal digesta and butyrate concentration in colonic digesta (p < 0.05). Also, EOB improved propionate concentration in cecal digesta, and MDF + EOB decreased IL-10 concentration in jejunal mucosa (p < 0.05) compared with ETEC. Conclusively, MDF and EOB either alone or in combination can improve growth performance and alleviate diarrhoea via improving intestinal barrier function of piglets after ETEC challenge, and all may serve as potential alternatives to AT for piglets.
Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Óleos Voláteis , Doenças dos Suínos , Animais , Suínos , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Óleos Voláteis/farmacologia , Diarreia/veterinária , Diarreia/microbiologia , Mucosa Intestinal , Antibacterianos/farmacologia , Doenças dos Suínos/microbiologiaRESUMO
BACKGROUND: Starch is a major component of carbohydrates and a major energy source for monogastric animals. Starch is composed of amylose and amylopectin and has different physiological functions due to its different structure. It has been shown that the energy supply efficiency of amylose is lower than that of amylopectin. However, there are few studies on the effect of starch structure on the available energy of pigs. The purpose of this study was to measure the effect of different structures of starch in the diet on the net energy (NE) of pigs using a comparative slaughter method and to establish a prediction equation to estimate the NE of starch with different structures. Fifty-six barrows (initial BW 10.18 ± 0.11 kg) were used, and they were housed and fed individually. Pigs were divided into 7 treatments, with 8 replicates for each treatment and 1 pig for each replicate. One of the treatments was randomly selected as the initial slaughter group (ISG). Pigs in the remaining treatments were assigned to 6 diets, fed with basic diet and semi-pure diets with amylose/amylopectin ratio (AR) of 3.09, 1.47, 0.25, 0.15 and 0.12, respectively. The experiment lasted for 28 d. RESULTS: Results showed that compared with the high amylose (AM) groups (AR 3.09 and 1.47), the high amylopectin (AP) group (AR 0.15) significantly increased the final BW, average daily weight gain and average daily feed intake of pigs (P < 0.05), but the F:G of the AM group was lower (P < 0.01). In addition, AR 0.15 and 0.12 groups have higher (P < 0.01) nutrient digestibility of dry matter, crude protein, gross energy and crude ash. Meanwhile, compared with other groups, AR 0.15 group has a higher (P < 0.05) NE intake and energy retention (RE). The regressive equation for predicting with starch structures was established as RE = 1,235.243 - 48.298AM/AP (R2 = 0.657, P = 0.05). CONCLUSIONS: In conclusion, NE intake and RE of pigs augmented with the increase of dietary amylopectin content, indicating that diets high in amylopectin were more conducive to promoting the growth of pigs in the late conservation period.
RESUMO
Grape seed proanthocyanidin extract (GSPE) plays a significant role in body health, including improving antioxidant capacity and maintaining lipid metabolism stability. However, whether dietary GSPE supplementation can improve lipid metabolism in finishing pigs remains unclear. Here 18 castrated male Duroc × Landrace × Yorkshire finishing pigs were randomly divided into three groups with six replicates and one pig per replicate. Pigs were fed a basal diet (control), a basal diet supplemented with 100 mg/kg GSPE, or a basal diet supplemented with 200 mg/kg GSPE for 30 days. Antioxidant analysis showed that dietary 200 mg/kg GSPE supplementation increased glutathione, total antioxidant capacity and glutathione peroxidase levels, and reduced malondialdehyde levels in serum, muscle and liver. Dietary 200 mg/kg GSPE supplementation also upregulated the mRNA and protein levels of nuclear-related factor 2 (Nrf2). Lipid metabolism analysis showed that dietary GSPE supplementation increased serum high-density lipoprotein cholesterol levels and reduced serum triglyceride and total cholesterol levels. Besides, GPSE upregulated the mRNA expression of lipolysis- and fatty acid oxidation-related genes downregulated the mRNA expression of lipogenesis-related genes, and activated the AMPK signal in finishing pigs. Together, we provided evidence that dietary GSPE supplementation improved the antioxidant capacity and lipid metabolism in finishing pigs.