Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. Systemic administration of CNTF or leptin led to rapid induction of the tis-11 primary response gene in the arcuate nucleus, suggesting that both cytokines can signal to hypothalamic satiety centers. Consistent with this idea, CNTF treatment of ob͞ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. Unlike leptin, CNTF also reduced obesity-related phenotypes in db͞db mice, which lack functional leptin receptor, and in mice with diet-induced obesity, which are partially resistant to the actions of leptin. The identification of a cytokine-mediated anti-obesity mechanism that acts independently of the leptin system may help to develop strategies for the treatment of obesity associated with leptin resistance.

Culotte stenting for UPLMCA bifurcation lesions was associated with significantly increased MACEs, mainly due to the increased TVR. (Double Kissing [DK] Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-00000151).

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Background Ulcerative colitis is a type of chronic inflammatory bowel disease closely associated with gut microbiota dysbiosis and intestinal homeostasis dysregulation. Barley leaf (BL) has a long history of use in Traditional Chinese Medicine with potential health-promoting effects on intestinal functions. However, its mechanism of action is not yet clear. Here, we explore the potential modulating roles of gut microbial metabolites of BL to protect against colitis and elucidate the underlying molecular mechanisms. Results Using 16S rRNA gene-based microbiota analysis, we first found that dietary supplementation of BL ameliorated dextran sulfate sodium (DSS)-induced gut microbiota dysbiosis. The mechanisms by which BL protected against DSS-induced colitis were resulted from improved intestinal mucosal barrier functions via the activation of peroxisome proliferator-activated receptor (PPAR)γ signaling. In addition, metabolomic profiling analysis showed that the gut microbiota modulated BL-induced metabolic reprograming in the colonic tissues particularly by the enhancement of glycolysis process. Notably, dietary BL supplementation resulted in the enrichment of microbiota-derived purine metabolite inosine, which could activate PPARγ signaling in human colon epithelial cells. Furthermore, exogenous treatment of inosine reproduced similar protective effects as BL to protect against DSS-induced colitis through improving adenosine 2A receptor (A2AR)/PPARγ-dependent mucosal barrier functions. Conclusions Overall, our findings suggest that the gut microbiota-inosine-A2AR/PPARγ axis plays an important role in the maintenance of intestinal homeostasis, which may represent a novel approach for colitis prevention via manipulation of the gut microbial purine metabolite.

Fusarium oxysporum f. sp. cucumerinum is a destructive pathogen on cucumber (Cucumis sativus L.) seedlings and the causal organism of crown and root rot of cucumber plants. An isolate of B579, which was identified as Bacillus subtilis by 16S rDNA sequences analysis, was selected from 158 bacteria isolates as the best antagonist against F. oxysporum by dual plate assay. The production of chitinase, b-1, 3-glucanase, siderophores, indole-3-acetic acid (IAA), hydrogen cyanide (HCN), and phosphate solubilization, by B579 were screened with the selected medium by in vitro tests. The cell-free culture filtrate of B579, with a concentration of 20% (v/v), could result in the vacuolation, swelling and lysis of hyphae. Besides, it could blacken, shrunk and hindered the germination of conidia of F. oxysporum at the concentration of C80% (v/v). When applied as inoculants, B579 (10 8 c.f.u. ml -1 ) was able to reduce disease incidence by 73.60%, and promote seedling growth in pot trial studies. The activities of plant defenserelated enzyme, peroxidase (POX), polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL) were significantly increased in plants treated with B579. Interestingly, a higher content of IAA, an important plant growth regulator, was detected in B579 treated plants. Furthermore, seed-soaking with B579 exhibited a better biological control effect (Biocontrol effect 73.60%) and plant growth promoting ability (Vigor Index 4,177.53) than root-irrigation (50.88% and 3,575.77, respectively), suggesting the potential use of B579 as a seed-coating agent.

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