NaYF4 :Yb/Er@Mn3 O4 @GOX Nanocomposite for Upconversion Fluorescence Imaging and Synergistic Cascade Cancer Therapy by Apoptosis and Ferroptosis.

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.

Prebiotic inulin as a treatment of obesity related nonalcoholic fatty liver disease through gut microbiota: a critical review.

The microbial-derived products, including short chain fatty acids, lipopolysaccharide and secondary bile acids, have been shown to participate in the regulation of hepatic lipid metabolism. Previous studies have demonstrated that prebiotics, such as oligosaccharide and inulin, have abilities to change the concentration of microbial-derived products through modulating the microbial community structure, thus controlling body weight and alleviating hepatic fat accumulation. However, recent evidence indicates that there are individual differences in host response upon inulin treatment due to the differences in host microbial composition before dietary intervention. Probably it is because of the multiple relationships among bacterial species (e.g., competition and mutualism), which play key roles in the degradation of inulin and the regulation of microbial structure. Thereby, analyzing the composition and function of initial gut microbiota is essential for improving the efficacy of prebiotics supplementation. Furthermore, considering that different structures of polysaccharides can be used by different microorganisms, the chemical structure of processed inulin should be tested before using prebiotic inulin to treat obesity related nonalcoholic fatty liver disease.

Dietary grape seed proanthocyanidin extract supplementation improves antioxidant capacity and lipid metabolism in finishing pigs.

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.

Comparison of maternal and neonatal gut microbial community and function in a porcine model.

Our knowledge of the difference in maternal and neonatal gut microbiota composition is not fully understood. Using the Bama miniature pig model, the bacterial community in the feces from sows and piglets was analyzed on an IonS5TMXL platform targeting the single-end reads strategy. Results revealed that the maternal and neonatal bacteria profile in the pig model was distinct. Compared with the piglets, sows had higher proportions of bacteria in Spirochetes, Clostridiales, and Spirochaetales (p < 0.10) and had a lower abundance of bacteria in Tyzzerella (p < 0.05) and Alistipes (p < 0.10). Meanwhile, the proportions of bacteria in Oscillibacter and the index of Chao1, Shannon, and observed_species increased in the sows compared with those in the piglets (p < 0.05). Moreover, the abundance of bacteria associated with the human disease was higher (p < 0.05) and the population of bacteria associated with cellular processes was lower (p < 0.05) in the piglets compared with those in the sows. Collectively, the diversity and beneficial bacteria populations in the sow fecal microbiota exhibit more than those in the piglets. This study indicates that maternal fecal microbiota may be a beneficial source of transplanted bacteria to promote healthy function in neonates.

Gut microbiota absence and transplantation affect diarrhea: an investigation in the germ-free piglet model.

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.

Dietary ferulic acid supplementation improves antioxidant capacity and lipid metabolism in liver of piglets with intrauterine growth retardation.

Intrauterine growth retardation (IUGR) can result in early liver oxidative damage and abnormal lipid metabolism in neonatal piglets. Ferulic acid (FA), a phenolic compound widely found in plants, has many biological functions, such as anti-inflammation and anti-oxidation. Thus, we explored the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in newborn piglets with IUGR. In the study, 24 7-day-old piglets were divided into three groups: normal birth weight (NBW), IUGR, and IUGR + FA. The NBW and IUGR groups were fed formula milk as a basal diet, while the IUGR + FA group was fed a basal diet supplemented with 100 mg/kg FA. The trial lasted 21 days. The results showed that IUGR decreased absolute liver weight, increased transaminase activity, reduced antioxidant capacity, and disrupted lipid metabolism in piglets. Dietary FA supplementation enhanced absolute liver weight, reduced serum MDA level and ROS concentrations in serum and liver, markedly increased serum and liver GSH-PX and T-SOD activities, decreased serum HDL-C and LDL-C and liver NEFA, and increased TG content and HL activity in the liver. The mRNA expression related to the Nrf2-Keap1 signaling pathway and lipid metabolism in liver were affected by IUGR. Supplementing FA improved the antioxidant capacity of liver by down-regulating Keap1 and up-regulating the mRNA expression of SOD1 and CAT, and regulated lipid metabolism by increasing the mRNA expression level of Fasn, Pparα, LPL, and CD36. In conclusion, the study suggests that FA supplementation can improve antioxidant capacity and alleviate lipid metabolism disorders in IUGR piglets.

Eugenol promotes appetite through TRP channels mediated-CaMKK2/AMPK signaling pathway.

Eugenol is a major component of clove oil. A recent study found that inhalation of eugenol promoted the appetite of mice. However, whether oral ingestion of eugenol promoted appetite is unclear and its mechanism await study. Here, mice were divided into four treatments (n = 20) and fed a basal diet supplemented with 0%, 0.005%, 0.01% and 0.02% eugenol for 4 weeks. In addition, mice (n = 7) were injected intraperitoneally with 3 mg/kg body weight eugenol. Our data showed that feeding mice with 0.01% and 0.02% eugenol promoted their appetite. In addition, the short-term intraperitoneal injection of eugenol enhanced the feed intake in mice within 1 h. Further studies found that dietary eugenol increased orexigenic factors expression and decreased anorexigenic factors expression in mice. We then carried out N38 cell experiments to explore the transient receptor potential (TRP) channels-dependent mechanism of eugenol in promoting appetite. We found that eugenol activated the TRP channels mediated-CaMKK2/AMPK signaling pathway in the hypothalamus and N38 cells. Besides, the inhibition of TRPV1 and AMPK eliminated the upregulation of eugenol on the agouti-related protein level in N38 cells. In conclusion, the study suggested that eugenol promotes appetite through TRPV1 mediated-CaMKK2/AMPK signaling pathway.

Ultrasound-assisted extraction of tamarind xyloglucan: an effective approach to reduce the viscosity and improve the α-amylase inhibition of xyloglucan.

BACKGROUND: Water extraction (WE) is the classical extraction method for tamarind xyloglucan (XyG), but its low yield, high viscosity and poor dispersion in aqueous solution are not conducive to the industrial applications. To promote the industrial application of tamarind XyG, an ultrasonic-assisted extraction (UAE) method for extracting low-viscosity XyG from tamarind kernel powder was proposed. RESULTS: The yield of UAE-XyG was higher (502.33 ± 0.036 g kg-1 ) than that of WE-XyG (163.43 ± 0.085 g kg-1 ). UAE reduced the molecular weight, monosaccharide content and apparent viscosity of XyG. The hypoglycemic experiment in vitro showed that UAE-XyG had a stronger inhibitory effect on α-amylase activity than WE-XyG, but its glucose dialysis retardation index was lower. CONCLUSION: In sum, UAE is a type of extraction method that could effectively improve the yield of XyG and reduce its viscosity to expand its application without reducing its physiological activity. UAE exhibits an excellent potential in the extraction of XyG. © 2022 Society of Chemical Industry.

Effects of dietary l-theanine supplementation on pork quality and muscle fiber type transformation in finishing pigs.

BACKGROUND: This experiment aimed to investigate effects of dietary l-theanine supplementation on pork quality and muscle fiber type transformation in finishing pigs. In a 30-day experiment, 18 healthy Duroc × Landrace × Yorkshire (DLY) pigs with an average body weight of 86.03 ± 0.83 kg were randomly divided into three groups (a basal diet or a basal diet supplemented with 500 and 1000 ppm l-theanine, respectively), with six duplicates and one pig per replicate. RESULTS: The results showed that dietary 1000 ppm l-theanine supplementation significantly reduced (P < 0.05) b*24 h and drip loss. Dietary 1000 ppm l-theanine supplementation significantly increased (P < 0.05) slow myosin heavy chain (MyHC) protein expression and the percentage of slow-twitch fibers, as well as significantly decreased (P < 0.05) fast MyHC protein expression and the percentage of fast-twitch fibers, accompanied by an increase in succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) activities and a decrease in lactate dehydrogenase (LDH) activity. In addition, the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway was activated by l-theanine. CONCLUSION: Together, this study demonstrated for the first time that dietary supplementation of 1000 ppm l-theanine can improve pork color and drip loss and promote muscle fiber type transformation from fast-twitch to slow-twitch in finishing pigs. © 2022 Society of Chemical Industry.

Effects of mixed fibres and essential oils blend on growth performance and intestinal barrier function of piglets challenged with enterotoxigenic Escherichia coli K88.

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.

Dietary supplementation of fructo-oligosaccharides alleviates enterotoxigenic E. coli-induced disruption of intestinal epithelium in a weaned piglet model.

Diarrhoea caused by pathogens such as enterotoxigenic E. coli (ETEC) is a serious threat to the health of young animals and human infants. Here, we investigated the protective effect of fructo-oligosaccharides (FOS) on the intestinal epithelium with ETEC challenge in a weaned piglet model. Twenty-four weaned piglets were randomly divided into three groups: (1) non-ETEC-challenged control (CON); (2) ETEC-challenged control (ECON); and (3) ETEC challenge + 2·5 g/kg FOS (EFOS). On day 19, the CON pigs were orally infused with sterile culture, while the ECON and EFOS pigs were orally infused with active ETEC (2·5 × 109 colony-forming units). On day 21, pigs were slaughtered to collect venous blood and small intestine. Result showed that the pre-treatment of FOS improved the antioxidant capacity and the integrity of intestinal barrier in the ETEC-challenged pigs without affecting their growth performance. Specifically, compared with ECON pigs, the level of GSH peroxidase and catalase in the plasma and intestinal mucosa of EFOS pigs was increased (P < 0·05), and the intestinal barrier marked by zonula occluden-1 and plasmatic diamine oxidase was also improved in EFOS pigs. A lower level (P < 0·05) of inflammatory cytokines in the intestinal mucosa of EFOS pigs might be involved in the inhibition of TLR4/MYD88/NF-κB pathway. The apoptosis of jejunal cells in EFOS pigs was also lower than that in ECON pigs (P < 0·05). Our findings provide convincing evidence of possible prebiotic and protective effect of FOS on the maintenance of intestinal epithelial function under the attack of pathogens.

ß-defensin 118 attenuates inflammation and injury of intestinal epithelial cells upon enterotoxigenic Escherichia coli challenge.

BACKGROUND: Antimicrobial peptides including various defensins have been attracting considerable research interest worldwide, as they have potential to substitute for antibiotics. Moreover, AMPs also have immunomodulatory activity. In this study, we explored the role and its potential mechanisms of ß-defensin 118 (DEFB118) in alleviating inflammation and injury of IPEC-J2 cells (porcine jejunum epithelial cell line) upon the enterotoxigenic Escherichia coli (ETEC) challenge. RESULTS: The porcine jejunum epithelial cell line (IPEC-J2) pretreated with or without DEFB118 (25 µg/mL) were challenged by ETEC (1×106 CFU) or culture medium. We showed that DEFB118 pretreatment significantly increased the cell viability (P<0.05) and decreased the expressions of inflammatory cytokines such as the interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in IPEC-J2 cells exposure to ETEC (P<0.05). Interestingly, DEFB118 pretreatment significantly elevated the abundance of the major tight-junction protein zonula occludens-1 (ZO-1), but decreased the number of apoptotic cells upon ETEC challenge (P<0.05). The expression of caspase 3, caspase 8, and caspase 9 were downregulated by DEFB118 in the IPEC-J2 cells exposure to ETEC (P<0.05). Importantly, DEFB118 suppressed two critical inflammation-associated signaling proteins, nuclear factor-kappa-B inhibitor alpha (IκB-α) and nuclear factor-kappaB (NF-κB) in the ETEC-challenged IPEC-J2 cells. CONCLUSIONS: DEFB118 can alleviate ETEC-induced inflammation in IPEC-J2 cells through inhibition of the NF-κB signaling pathway, resulting in reduced secretion of inflammatory cytokines and decreased cell apoptosis. Therefore, DEFB118 can act as a novel anti-inflammatory agent.

Dietary ferulic acid supplementation improves intestinal antioxidant capacity and intestinal barrier function in weaned piglets.

This study was conducted to explore the effects of dietary ferulic acid (FA) supplementation on intestinal antioxidant capacity and intestinal barrier function in weaned piglets. Eighteen 21-day-old castrated male DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.05% FA, and 0.45% FA groups, respectively. The experiment lasted for 5 weeks. The results showed that dietary 0.05 and 0.45% FA supplementation significantly increased catalase activity (p < 0.001), the protein levels of nuclear factor E2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (p < 0.05), and the mRNA levels of superoxide dismutase 1, glutathione reductase and Nrf2 (p < 0.05) in jejunum when compared with the control group. Dietary 0.05% FA supplementation also increased the mRNA level of glutathione S-transferase (p < 0.05) in jejunum. Meanwhile, Dietary 0.05 and 0.45% FA supplementation significantly increased the protein expression of zonula occludens 1 (ZO-1) (p < 0.05), and dietary supplementation of 0.05% FA increased the mRNA levels of ZO-1, zonula occludens 2, mucin 1, mucin 2, occluding, and claudin-1 (p < 0.05) in jejunum. Together, our data suggest that dietary 0.05% FA supplementation improves the intestinal antioxidant capacity and intestinal barrier function of weaned piglets.

Effects of slaughter age on carcass traits and meat quality of crossbred (Duroc × Landrace × Yorkshire) finishing pigs.

Thirty castrated Duroc × Landrace × Yorkshire (DLY) pigs were randomly divided into three groups and slaughtered at 180, 210, and 240 days of age, respectively. Here, we found that the live weight, carcass weight, carcass length, dressing percentage, eye muscle area, backfat deposit, muscle yellowness b* value, drip loss, and cooking loss increased significantly, and the muscle pH 45 min value decreased dramatically as the slaughter age of DLY pigs extended. Moreover, increasing the slaughter age of DLY pigs could obtain higher n-3 polyunsaturated fatty acid (PUFA) percentage, crude protein, essential amino acids (EAA) contents and EAA/NEAA level, and lower n-6/n-3 PUFA level and antioxidant capacity. Together, this study suggests that the older slaughter age improves the carcass traits and nutritional value of pork, but leads to a significant decrease in pork sensory quality in DLY finishing pigs.

Resveratrol regulates muscle fiber type gene expression through AMPK signaling pathway and miR-22-3p in porcine myotubes.

This study aimed to investigate the effect and underlying mechanisms of resveratrol on porcine muscle fiber type gene expression in porcine myotubes. Here, results showed that resveratrol treatment significantly promoted slow myosin heavy chain (MyHC) and inhibited fast MyHC in porcine myotubes. The phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and the downstream factors of AMPK signaling, such as Sirtuin1 (Sirt1) and peroxlsome proliferator-activated receptor-γ coactlvator-1α (PGC-1α), were also increased by resveratrol, suggesting that resveratrol could activate the AMPK signaling pathway. Interestingly, resveratrol inhibited the expression of miR-22-3p in porcine myotubes. Furthermore, AMPK inhibitor compound C and miR-22-3p mimic effectively eliminated the effects of resveratrol on slow MyHC and fast MyHC expressions in porcine myotubes. Taken together, our findings indicate that resveratrol regulates muscle fiber type gene expression through the AMPK signaling pathway and miR-22-3p in porcine myotubes.

Procyanidin B2 induces porcine skeletal slow-twitch myofiber gene expression by AMP-activated protein kinase signaling pathway.

In this study, our aim is to investigate the effect of dimer procyanidin B2 [epicatechin-(4ß-8)-epicatechin] (PB2) on porcine skeletal myofiber gene expression in vitro. Our data showed PB2 promoted the protein expression of slow myosin heavy chain (MyHC) in porcine myotubes, concomitant with the increases in mRNA levels of MyHC I, MyHC IIa and Tnni1. We also found PB2 activated AMPK signaling in porcine myotubes. NRF1 and CaMKKß that are two important upstream factors of AMPK, and Sirt1 and PGC-1α that are two major downstream factors of AMPK, were also up-regulated by PB2. The mechanism study showed the effect of PB2 on slow-twitch myofiber gene expression was abolished by AMPK inhibitor compound C or by AMPKα1 siRNA. Together, we found PB2 induced porcine skeletal slow-twitch myofiber gene expression by AMPK signaling pathway.

Effects of dietary lycopene supplementation on intestinal morphology, antioxidant capability and inflammatory response in finishing pigs.

In this study, eighteen healthy Duroc × Landrace × Yorkshire barrows with initial body weight of 63.89 ± 1.15 kg were randomly allotted to three treatments and fed a basal diet or a basal diet supplemented with 100 mg/kg and 200 mg/kg lycopene, respectively. Data showed that villus height to crypt depth ratio increased with 200 mg/kg lycopene (p < 0.05) in the jejunum. In duodenum, the malondialdehyde content was decreased (p < 0.05) in 100 and 200 mg/kg lycopene groups. Furthermore, in the jejunum, dietary 100 and 200 mg/kg lycopene supplementation increased (p < 0.05) catalase activity. In the duodenum, interleukin-1ß (IL-1ß), nuclear factor-κB and tumor necrosis factor-α contents were decreased (p < 0.05) in 200 mg/kg lycopene group. In the jejunum, IL-1ß content was reduced (p < 0.05) and IL-1ß mRNA expression was down-regulated (p = 0.046) in 200 mg/kg lycopene group. Additionally, claudin-1 mRNA and protein levels in 200 mg/kg group were also increased (p < 0.05). These results indicated that dietary lycopene supplementation could maintain intestinal health, which was associated with improving intestinal morphology, enhancing tight junction function, inhibiting inflammatory response, and elevating antioxidant capacity in finishing pigs.

Effect of dietary dihydromyricetin supplementation on lipid metabolism, antioxidant capacity and skeletal muscle fiber type transformation in mice.

This study aimed to investigate the effect of dietary dihydromyricetin (DHM) supplementation on lipid metabolism, antioxidant capacity and muscle fiber type transformation. Twenty-four male Kunming mice were randomly allotted to either control (basal diet) or DHM diets (supplemented with 300 mg/kg DHM). Our data showed that DHM administration decreased the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) contents, and increased the catalase (CAT), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities in serum. In the liver, DHM decreased the TG and malondialdehyde (MDA) levels and increased the T-SOD and GSH-Px activities. For the tibialis anterior (TA) muscle, DHM increased the total antioxidant capacity (T-AOC) level and T-SOD activities. Western blotting and real-time quantitative PCR analysis showed that DHM increased the protein and mRNA levels of MyHC I and MyHC IIa and decreased the protein and mRNA levels of MyHC IIb in TA muscle, which may be achieved by activating the AMP-activated protein kinase (AMPK) signal. The mRNA levels of several regulatory factors related to mitochondrial function were up-regulated by DHM. In conclusion, dietary 300 mg/kg DHM supplementation improved lipid metabolism and antioxidant capacity and promoted the transformation of muscle fiber type from glycolysis to oxidation in mice.

Effects of dietary dihydromyricetin supplementation on intestinal barrier and humoral immunity in growing-finishing pigs.

In this study, we investigated the effect of dietary dihydromyricetin (DHM) supplementation on intestinal barrier and humoral immunity in growing-finishing pigs. The data showed that dietary DHM supplementation improved jejunal barrier function by upregulating the protein expressions of Occludin and Claudin-1 and the mRNA levels of MUC1 and MUC2. Dietary DHM supplementation increased the amylase, lipase, sucrase and maltase activities and the mRNA expression of nutrient transporter (SGLT1, GLUT2, PepT1) in the jejunum mucosa. Dietary DHM supplementation significantly reduced the E. coli population in the cecum and colon and increased the Lactobacillus population in the cecum. In addition, dietary DHM supplementation increased the contents of butyric acid and valeric acid in cecum and colon. In serum, dietary DHM supplementation reduced interleukin-1ß (IL-1ß) content and increased interleukin-10 (IL-10), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) contents (p < 0.05). In addition, compared with the control group, dietary DHM supplementation improved secretory immunoglobulin A (sIgA) and interleukin-10 (IL-10) contents and down-regulated TNF-α protein expression in jejunum mucosa (p < 0.05). Together, this study demonstrated that dietary DHM supplementation improved intestinal barrier function, digestion and absorption capacity and immune function in growing-finishing pigs.

1,25-Dihydroxyvitamin D3 Negatively Regulates the Inflammatory Response to Porcine Epidemic Diarrhea Virus Infection by Inhibiting NF-κB and JAK/STAT Signaling Pathway in IPEC-J2 Porcine Epithelial Cells.

Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea and vomiting in piglets. The pathogenesis of PEDV infection is related to intestinal inflammation. It is known that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent anti-inflammatory activity, but it is unknown whether 1,25(OH)2D3 can inhibit the PEDV-induced inflammatory response and the underlying mechanism. We used transcriptome analysis, gene and protein expression, RNA interference and overexpression, and other techniques to study the anti-inflammatory effects of 1,25(OH)2D3 on PEDV infection in IPEC-J2 cells. The results showed that interleukin 19 (IL-19) and C-C motif chemokine ligand 20 (CCL20) gene expression were enhanced with the increase in PEDV infection time in IPEC-J2 cells. Interestingly, 1,25(OH)2D3 supplementation obviously inhibited IL-19 and CCL20 expression induced by PEDV. Meanwhile, we also found that 1,25(OH)2D3 reduced p-NF-κB, p-STAT1, and p-STAT3 protein levels induced by PEDV at 24 h post-infection. IκBα and SOCS3, NF-κB, and STAT inhibitor respectively, were increased by 1,25(OH)2D3 supplementation upon PEDV infection. In addition, 1,25(OH)2D3 supplementation inhibited ISG15 and MxA expression induced by PEDV. Although 1,25(OH)2D3 suppressed the JAK/STAT signal pathway and antiviral gene expression, it had no significant effects on PEDV replication and IFN-α-induced antiviral effects. In addition, when the vitamin D receptor (VDR) was silenced by siRNA, the anti-inflammatory effect of 1,25(OH)2D3 was inhibited. Meanwhile, the overexpression of VDR significantly downregulated IL-19 and CCL20 expression induced by PEDV infection. Together, our results provide powerful evidence that 1,25(OH)2D3 could alleviate PEDV-induced inflammation by regulating the NF-κB and JAK/STAT signaling pathways through VDR. These results suggest that vitamin D could contribute to inhibiting intestinal inflammation and alleviating intestinal damage in PEDV-infected piglets, which offers new approaches for the development of nutritional strategies to prevent PEDV infection in piglets.