Nickel induces epithelial-mesenchymal transition in pulmonary fibrosis in mice via activation of the oxidative stress-mediated TGF-ß1/Smad signaling pathway.

Nickel (Ni) is recognized as a carcinogenic metal, and its widespread use has led to severe environmental and health problems. Although the lung is among the main organs affected by Ni, the precise mechanisms behind this effect remain poorly understood. This study aimed to elucidate the physiological mechanisms underlying Ni-induced pulmonary fibrosis (PF), using various techniques including histopathological detection, biochemical analysis, immunohistochemistry, western blotting, and quantitative real-time PCR. Mice were treated with nickel chloride (NiCl2), which induced PF (detected by Masson staining), up-regulation of α-smooth muscle actin (α-SMA), and collagen-1 mRNA and protein expression. NiCl2 was found to induce PF by: activation of the epithelial-mesenchymal transition (EMT) and the transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway; up-regulation of protein and mRNA expression of TGF-ß1, p-Smad2, p-Smad3, vimentin, and N-cadherin; and down-regulation of protein and mRNA expression of E-cadherin. In addition, NiCl2 treatment increased malondialdehyde content while inhibiting antioxidant activity, as indicated by decreased catalase, total antioxidant capacity, and superoxide dismutase activities, and glutathione content. Co-treatment with the effective antioxidant and free radical scavenger N-acetyl cysteine (NAC) plus NiCl2 was used to study the effects of oxidative stress in NiCl2-induced PF. The addition of NAC significantly mitigated NiCl2-induced PF, and reversed activation of the TGF-ß1/Smad signaling pathway and EMT. NiCl2-induced PF was therefore shown to be due to EMT activation via the TGF-ß1/Smad signaling pathway, mediated by oxidative stress.

Improvement in ovarian function following fecal microbiota transplantation from high-laying rate breeders.

The underlying mechanism between the gut microbiota and reproductive function is not yet well-known. This study was conducted to investigate the effect of the administration of fecal microbiota transplantation (FMT) from highly laying rate donors on the cecal microbiota, intestinal health and ovarian function in broiler breeders. A total of 60 broiler breeders (53 wk of age) were selected by their laying rate [high (HP, 90.67 ± 0.69%; n = 10) and low (LP, 70.23 ± 0.87%; n = 20)]. The LP breeders were then be transplanted with fecal microbiota from HP hens (FMTHP; n = 10) or the same dosage of PBS (FMTCON; n = 10) for 28 d. The results revealed that FMT from HP donors increased egg-laying rate and serum hormone levels [17ß-estradiol (E2), anti-Müller hormone], also decreased proinflammatory cytokine levels (interleukin-6, interleukin-8, tumor necrosis factor-α) of LP breeders (P < 0.05). The FMTHP group breeders had higher villus height, villus height/crypt depth ratio, and upregulated mRNA expression of jejunum barrier-related gene (ZO-2 and mucin-2) and estrogen, follicle-stimulating hormone (FSH) and anti-Müller hormone (AMH) receptor genes (ESR1, ESR2, FSHR, AMHR) (P < 0.05) than FMTCON group. FMT from HP donors led to higher mRNA expression of Bcl2 and sirtuin1 (SIRT1), while it downregulated the proapoptotic genes (Bax, caspase-3, caspase-8, and caspase-9) mRNA expressions in ovary compared with the FMTCON breeders (P < 0.05), and this pattern was also observed in HP donors. Also, HP breeder had higher observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group, while FMTHP can increase observed_species and alpha-diversity indexes (Chao1 and ACE) than FMTCON group (P < 0.05). The bacteria enrichment of Firmicutes (phylum), Bacteroidetes (phylum), Lactobacillus (genus), Enterococcus (genus), and Bacteroides (genus) were increased by FMTHP treatment. The genera Butyricicoccus, Enterococcus, and Lactobacillus were positively correlated with egg-laying rate. Therefore, cecal microbiomes of breeders with high egg-laying performance have more diverse activities, which may be related to the metabolism and health of the host; and FMT from high-yield donors can increase the hormone secretion, intestinal health, and ovarian function to improve egg-laying performance and the SIRT1-related apoptosis and cytokine signaling pathway were involved in this process.

Effects of Dietary Fat Sources during Late Gestation on Colostrum Quality and Mammary Gland Inflammation in Lipopolysaccharide-Challenged Sows.

This study aimed to investigate the effects of maternal lipopolysaccharide (LPS) challenge and dietary fat sources on colostrum quality and inflammatory response in sows. Sixty Landrace × Yorkshire sows were randomly assigned to three dietary treatments supplemented with 3% soybean oil (SO), 3% coconut oil (CO) or 3% fish oil (FO), respectively, from Day 90 of gestation until parturition. On Day 112 of gestation, half the sows from each dietary treatment were challenged with LPS (10 µg/kg BW) or saline. The results showed that maternal LPS challenge decreased colostrum yield and dry matter content. A similar pattern of changes was observed for body weight gain and colostrum intake in piglets from LPS-challenged sows. Maternal LPS challenge increased the levels of tumor necrosis factor α (TNFα), interleukin 1ß (IL1ß) and IL6 in colostum, and the mRNA abundance of IL6, IL1ß and TNFα and the phosphorylation level of p65 in mammary glands. However, the responses of these variables to LPS treatment were lower in sows fed a FO diet. In conclusion, maternal immune challenge reduced the growth performance of piglets by decreasing colostrum yield and intake by piglets, and dietary supplementation with FO in sows attenuates the LPS-induced inflammatory response in mammary glands.

Reduced meal frequency alleviates high-fat diet-induced lipid accumulation and inflammation in adipose tissue of pigs under the circumstance of fixed feed allowance.

PURPOSE: The present study was conducted to determine whether reduced meal frequency (MF) could restore high-fat diet (HFD)-modified phenotypes and microbiota under the condition of fixed feed allowance. METHODS: A total of 32 barrows with initial weight of 61.6 ± 0.8 kg were assigned to two diets [control diet (CON) versus HFD] and two meal frequencies [12 equal meals/day (M12) versus 2 equal meals/day (M2)], the trial lasted 8 weeks. The lipid metabolism and inflammatory response in adipose tissue as well as the profiles of intestinal microbiota and bacterial-derived metabolites were determined. RESULTS: M2 versus M12 feeding regimen decreased perirenal fat weight and serum triglyceride and liposaccharide (LPS) concentrations in HFD-fed pigs (P < 0.05). Reduced MF down-regulated mRNA expression of lipoprotein lipase, CD36 molecule, interleukin 1 beta, tumor necrosis factor alpha, toll-like receptor 4, myeloid differentiation factor 88 (MYD88), and nuclear factor kappa beta 1 as well as protein expression of MYD88 in perirenal fat of HFD-fed pigs (P < 0.05). M2 feeding regimen increased abundance of Prevotella and decreased abundance of Bacteroides in colonic content of HFD-fed pigs (P < 0.05). No difference in short-chain fatty acids (SCFAs) profile in colonic content was observed among four groups (P > 0.05). CONCLUSION: Our results suggested that M2 versus M12 feeding regimen ameliorated HFD-induced fat deposition and inflammatory response by decreasing fatty acid uptake and deactivating LPS/TLR4 signaling pathway in adipose tissue and restoring microbiota composition in distal intestine, without affecting SCFAs profile in distal luminal content.