Non-alcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury that is closely related to obesity, insulin resistance, type 2 diabetes, atherosclerosis, and metabolic syndrome. The pathological features are diffuse hepatic vesicular steatosis, including non-alcoholic steatohepatitis, liver fibrosis, and even liver cancer. A variety of pathological outcomes cause serious harm to human health. At present, an increasing number of researchers are investigating the pathogenesis of NAFLD from the perspective of changes in the function of the intestinal barrier. The physical, chemical, immunological, and microbiological barriers in the intestinal tract constitute the complete intestinal barrier, which plays an important defensive role against the invasion of harmful substances from the intestines. Protecting the function of the intestinal barrier is a new way to treat NAFLD and its related diseases. In this perspective, we summarized the current knowledge of the role of the intestinal barrier in NAFLD.

Intravenous immunoglobulin (IVIg) is increasingly used in the treatment of autoimmune and inflammatory diseases, including vasculitides and Kawasaki disease. However, the outcome of IVIg interaction with endothelial cells of the vascular bed is not clear as yet. We have investigated the effect of IVIg on the in vitro activation of human endothelial cells, as assessed by cell proliferation and reverse transcription-polymerase chain reaction-detected expression of mRNA coding for adhesion molecules (intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1), chemokines (monocyte chemoattractant protein-1, macrophage colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor), and proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6). IVIg inhibited proliferation of endothelial cells in a time-dependent manner. This effect was dependent on both Fc and F(ab')2 fragments of the immunoglobulin molecule and was fully reversible. Tumor necrosis factor-alpha and interleukin-1beta also inhibited thymidine incorporation, but to a lesser degree. IVIg had no effect on basal levels of mRNA coding for the adhesion molecules, chemokines, and proinflammatory cytokines. IVIg fully down-regulated the expression induced by tumor necrosis factor-alpha or interleukin-1beta of mRNA coding for these molecules. Thus, blockade of cellular proliferation and of cytokine-induced expression of adhesion molecules, chemokines, and cytokines may explain the therapeutic effect of IVIg in vascular and inflammatory disorders.

LYC against H2O2-induced oxidative damage in bMEC at least partly depended on activation of the NFE2L2 signaling pathway.

Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using 1H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows.

Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is closely related to lipid metabolism homeostasis and inflammation. Perilipin 1 (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above physiological function. The aim of this study is to investigate the role of PLIN1 in lipid metabolism regulation and inflammatory factor synthesis in cow adipocytes. The results showed that PLIN1 overexpression upregulated the expression of fatty acid and triglyceride (TAG) synthesis molecule sterol regulator element-binding protein-1c (SREBP-1c) and its target genes, diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation of the NF-κB inflammatory pathway and decreased the expression and content of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of the NF-κB inflammatory pathway in cow adipocytes. In ketotic cows, the expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-κB pathway, and downstream inflammatory cytokines were overinduced in adipose tissue. Taken together, these results indicate that PLIN1 can maintain lipid metabolism homeostasis and inhibit the NF-κB inflammatory pathway in adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat mobilization, NF-κB pathway, and inflammatory cytokine synthesis in ketotic cows.

Motoneurons of Onuf's nucleus innervate the pelvic striated muscles, which play a crucial role in erection, ejaculation, and urinary continence. Serotonergic descending projections from the brain are involved in the modulation of Onuf's motoneuron activity. However, conflicting results regarding the effects of spinal serotonin (5-HT) on pelvi-perineal functions have been reported. They may be partly accounted for by the multiplicity of neuronal targets and receptor subtypes on which 5-HT is acting. In order to provide comparative data regarding 5-HT receptor expression in various groups of Onuf's motoneurons, we used retrograde tracing techniques from different pelvic muscles combined with immunocytochemistry of 5-HT2A and 5-HT5A receptors in male and female rats. In males, 5-HT2A receptor immunolabeling was very dense in motoneurons innervating the ischiocavernosus muscle. By contrast, in female rats, 5-HT2A receptor expression in Onuf's nucleus was very weak. In both genders, 5-HT5A receptor immunoreactivity was found in motoneurons innervating the external urethral sphincter. In males, a moderate or low 5-HT5A immunolabeling was observed in motoneurons innervating the bulbospongiosus and ischiocavernosus muscles, respectively. These data show a preferential localization of 5-HT2A and 5-HT5A receptors to motoneurons controlling the striated muscles located at the penile crus and sphincter muscles, respectively, suggesting a specific serotoninergic control on different pelvic functions. In addition, the subcellular distribution of receptors suggests a different mode of action of 5-HT, paracrine at 5-HT2A receptors and synaptic at 5-HT5A receptors. This might have implications for pharmacological research targeting different pelvic functions e.g., micturition and ejaculation.

BackgroundAstragalus membranaceus (Fisch.) Bunge is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The purpose of the study was to investigate the curative effects of the decoction obtained from Astragalus membranaceus root in intestinal mucosal injury induced by LPS in mice. An LPS-induced intestinal mucosal injury mice model was applied in the study.MethodsThe mice were post-treated with Astragalus membranaceus decoction (AMD) for 4 days after 3 days LPS induction. ELISA kit was used to detect the content of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4,IL-6 and IL-8 in the serum of each group mice. The morphological changes in intestinal mucosa at the end of the experiments were observed. Both VH (villus height) and CD (crypt depth) were measured using H&E-stained sections.ResultsThere were significant differences in IL-1β, IL-4,IL-6, IL-8 and TNF-α levels in AMD-treated group on the 7th day compared to the controls group. The VH was lower in duodenum, jejunum and the ileum in LPS-treated mice compared to the control animals. Similarly, there was also decrease in V/C. Compared to the control mice, for AMD-treated mice, VH and CD had no significantly differences.ConclusionsAstragalus membranaceus reduced intestinal mucosal damage and promoted tissue repair by inhibiting the expression of inflammatory cytokine.

Exogenous molecules derived from catabolic states (e.g., fatty acids, β-hydroxybutyrate) during periods of stress such as the periparturient period or pathogen challenges [e.g., lipopolysaccharide (LPS)] can trigger an inflammatory response in tissues such as the liver and the mammary gland. Butyrate is one of the major short-chain fatty acids produced in the rumen, and work with non-ruminants has demonstrated that it can alter inflammatory processes. The primary objective of this study was to explore the preventive effect of sodium butyrate (SB) on LPS-induced inflammation in bovine mammary epithelial cells along with underlying molecular mechanisms. Immortalized bovine mammary epithelial cells (MAC-T) were treated with SB (0.1, 0.25, 0.5, 1, 2, or 5 mM) or with the histone deacetylase inhibitor trichostatin A (TSA; 6.25, 12.5, 25, or 50 nM) for 18 h, followed by a challenge with 1 µg/mL LPS for an additional 6 h. Pretreatment with SB prevented increase in apoptosis of LPS-challenged MAC-T cells in a dose-dependent manner. The LPS treatment upregulated mRNA abundance of tumor necrosis factor α (TNFA), interleukin-6 (IL6), and interleukin-1B (IL1B), whereas inhibition of histone deacetylase with TSA dampened this effect. More importantly, SB had clear dose-dependent effects on the inflammatory response by preventing upregulation of TNFA, IL6, and IL1B. Furthermore, pretreatment with TSA or SB attenuated the downregulation of histone H3 acetylation protein abundance induced by LPS. The greater ratio of p-IκB α/IκB α and p-p65/p65 protein abundance and the increase in nuclear localization of NF-κB p65 protein in response to LPS were attenuated by pretreatment with SB. Overall, the data indicated that exogenous SB alleviates mammary cell pro-inflammatory responses partly through post-translational mechanisms that diminish NF-κB signaling. Thus, the cytoprotective effect of SB against an inflammatory challenge might represent a preventive tool to help the mammary gland against pathogens such as those causing mastitis.