Protective effect of amygdalin on epithelial-mesenchymal transformation in experimental chronic obstructive pulmonary disease mice.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory pulmonary disease characterized by continuous, progressive limitation of airflow. Airway remodelling, which is correlated with epithelial-mesenchymal transitions (EMTs), is a typical pathophysiological change of COPD. Amygdalin, an active ingredient in the traditional Chinese medicine bitter almond with extensive pharmacological effects, was shown to inhibit tissue fibrosis in recent studies. In this study, a human bronchial epithelial cell line (BEAS-2B) and mice were exposed to cigarette smoke, and EMT levels were investigated after treatment with different concentrations of amygdalin. Morphology was assessed by immunohistochemical staining. Evaluation of the expression of TGF-ß1, smad2/3, and p-smad2/3 in lung tissue was conducted out via ELISA, Western blot, and real-time PCR. The results showed that E-cadherin expression was significantly increased, whereas vimentin, TGF-ß1, and phosphorylated smad2/3 (p-smad2/3) expression was markedly decreased in the amygdalin-treated groups compared with the model group. Therefore, our study demonstrated a protective role of amygdalin in the murine EMT process after COPD.

Inhibitory Effect of Methotrexate on Rheumatoid Arthritis Inflammation and Comprehensive Metabolomics Analysis Using Ultra-Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry (UPLC-Q/TOF-MS).

Rheumatoid arthritis (RA) is a common autoimmune disease. The inflammation in joint tissue and system endanger the human health seriously. Methotrexate have exhibited a satisfactory therapeutic effect in clinical practice. The aim of this research was to establish the pharmacological mechanism of methotrexate on RA therapy. Collagen induced arthritic rats were used to identify how methotrexate alleviates inflammation in vivo. Lipopolysaccharide-induced inflammatory proliferation in macrophages was also be detected in vitro. The activation level of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nucleotide binding domain and leucine-rich repeat pyrin 3 domain (NLRP3)/Caspase-1 and related cytokines were examined by real-time PCR and western blotting or quantified with the enzyme-linked immunosorbent assay. Comprehensive metabolomics analysis was performed to identify the alteration of metabolites. Results showed that treating with methotrexate could alleviate the inflammatory condition, downregulate the activation of NF-κB and NLRP3/Caspase-1 inflammatory pathways and reduce the level of related cytokines. Docking interaction between methotrexate and caspase-1 was visualized as six H-bonds indicating a potential inhibitory effect. Metabolomics analysis reported three perturbed metabolic inflammation related pathways including arachidonic acid, linoleic acid and sphingolipid metabolism. These findings indicated that methotrexate could inhibit the onset of inflammation in joint tissue by suppressing the activation of NF-κB and NLRP3/Caspase-1 pathways and regulating the inflammation related metabolic networks.

Obesity-Related Asthma: Immune Regulation and Potential Targeted Therapies.

Obesity, one of the most severe public health problems of the 21st century, is a common metabolic syndrome due to excess body fat. The incidence and severity of obesity-related asthma have undergone a dramatic increase. Because obesity-related asthma is poorly controlled using conventional therapies, alternative and complementary therapies are urgently needed. Lipid metabolism may be abnormal in obesity-related asthma, and immune modulation therapies need to be investigated. Herein, we describe the immune regulators of lipid metabolism in obesity as well as the interplay of obesity and asthma. These lay the foundations for targeted therapies in terms of direct and indirect immune regulators of lipid metabolism, which ultimately help provide effective control of obesity-related asthma with a feasible treatment strategy.

Protective Effect of Yinhua Miyanling Tablet on Lipopolysaccharide-Induced Inflammation through Suppression of NLRP3/Caspase-1 Inflammasome in Human Peripheral Blood Mononuclear Cells.

Yinhua Miyanling Tablet (YMT), the Chinese formula, has long been administrated in clinical practice for the treatment of acute pyelonephritis and acute urocystitis. In the current study, we aimed to investigate the anti-inflammatory effect of YMT in vitro and to evaluate the association between anti-inflammation and innate immune response. Human peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll density gradient centrifugation and then were stimulated by Lipopolysaccharide (LPS). The differential gene expression of inflammation-related genes after drug administration was assessed using PCR array, and the protein levels of differential genes were measured by ELISA and Western blot. The result showed that YMT significantly inhibited the expression of NLRP3, Caspase-1, and the downstream cytokine IL-1ß and suppressed the production of inflammatory mediators TNF-α, IL-6, IL-10, and MCP-1 in a dose-dependent manner compared to the LPS group (P < 0.01). The finding indicated that YMT exhibited anti-inflammatory effect in vitro by suppressing the NLRP3/Caspase-1 inflammasome, and that may have therapeutic potential for the treatment of inflammatory diseases.