Effect of Xiaoqinglong decoction on mucus hypersecretion in the airways and cilia function in a murine model of asthma

Objective:Xiaoqinglong decoction (XQL) has been used in traditional Chinese medicine as a prescription for asthma treatment.We explored the effects of XQL on mucus hypersecretion and ciliophagy in the airways of mice in which asthma had been induced by ovalbumin (OVA).Methods:Thirty-six mice were sensitized by OVA injection (i.p.) on day-0 and day-14 and challenged with 1% OVA on day 18-22.Then,they were divided into three groups:model,carbocysteine and XQL.From day-15 to day-22,the XQL group was administered XQL (10 g/kg,p.o.) 1 hour before each aerosol challenge with OVA.To evaluate the effect of XQL on mucus hypersecretion,AB-PAS staining,measurement of serum levels of interleukin (IL)-13,bronchoalveolar lavage fluid (BALF) analyses,ciliophagy analyses,as well as coexpression of Light Chain 3 (LC3) and acetylated α-tubulin by immunofluorescence staining were undertaken.Results:Treatment with XQL (10 g/kg) attenuated mucus secretion in the airways,and reduced the positive areas of AB-PAS staining in histopathologic lung tissues (P <.05).IL-13 expression in serum (P <.01),OVA-induced inflammatory changes,and the number of white blood cells (P <.01) in BALF samples were also reduced.However,the effect on mucus secretion was less apparent in the carbocysteine group compared with the XQL group.XQL treatment also improved the cilia length and elicited a substantial reduction in ciliophagy and LC3 expression in the tracheal epithelium.Conclusion:XQL can attenuate cilia shortening,aid the clearance function of ciliated epithelial cells,and reduce mucus production in an OVA-induced asthma model in mice.XQL can inhibit mucus hypersecretion and could be a new type of pharmacotherapy.

Akkermansia muciniphila: a promising target for the therapy of metabolic syndrome and related diseases

The probiotic Akkermansia muciniphila(A. muciniphila) is an intestinal bacterium that was first identified in human feces in 2004. Its specialization in mucin degradation makes it a key microorganism that maintains intestinal mucosal barrier function. As an unique representative strain of the phylum Verrucomicrobia that can be cultured in vitro, A. muciniphila is much easier to detect by metagenomic analysis of intestinal flora. In the past few years, A. muciniphila has been getting increasing attention for the positive correlation between its intestinal colonization and host homeostatic metabolism. In this review, we summarize the relationship between A. muciniphila and host health and diseases, especially focusing on metabolic diseases and related mechanisms, as well as the natural food and drug-derived substrates affecting its colonization in the host, expecting to provide evidence and clues for the development of drugs targeting A. muciniphila.

Antagonism of toll-like receptor 2 attenuates the formation and progression of abdominal aortic aneurysm

Abdominal aortic aneurysm(AAA) is an inflammatory vascular disorder with high mortality.Accumulating evidence shows that toll-like receptor 2(TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury.We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression.In this study,enhanced expression of TLR2 and its ligands were observed in human AAA tissue.Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA.In addition,TLR2-deficient mice also failed to develop AAA.The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling,as indicated by the decreased expression or activity of MMP-2/9,α-SMA,inflammatory cytokines,and transcription factors NF-κB,AP-1 and STAT1/3 in AAA tissue.Mechanistically,blocking TLR2 decreased the expression and interaction of TLR2 and several endogenousligands,which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA.Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA.

Resistomycin attenuates triple-negative breast cancer progression by inhibiting E3 ligase Pellino-1 and inducing SNAIL/SLUG degradation

Dear Editor,The epithelial-to-mesenchymal transition(EMT)is a positive modulator of triple-negative breast cancer(TNBC)progression.1 Several EMT-inducing transcriptional factors(EMT-TFs)drive EMT process and enhance TNBC progression.2 Promoting the degradation of EMT-TFs to inhibit EMT and malignant actions holds therapeutic potential for TNBC patients.

1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome via promoting regulatory T cell-mediated resolution of inflammation

Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D_3[1,25(OH)_2D_3], the biologically active form of vitamin D_3, significantly attenuated monosodium glutamate(MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemiceuglycemic clamp. Moreover, 1,25(OH)_2D_3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)_2D_3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied byincreased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulintargeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)_2D_3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.