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Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)-protein kinase A (PKA)-nuclear factor kappa-B (NF-
ABSTRACT
Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.
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Objective To analyze fungal isolates from patients with superficial fungal infections during 1960-2006.Methods Fungal strains isolated from patients with superficial (mucocutaneous and cutaneous)fungal infections and identified in the Medical Mycology Clinical Laboratory,Department of Dermatology and Venereology,Union Hospital,from 1960 to 2006 (data from September 1991 to July 1992 were unavailable),were subjected to a classification and statistical analysis.Clinical samples for mycological examination were taken from outpatients or inpatients of different departments in hospitals of Hubei province and surrounding areas.Morphological,physiological and biochemical methods were applied for species identification.Results A total of 11 989 Candida strains were isolated,which belonged to 23 species and 16 genera.They fell into 3 groups,i.e.,dermatophytes,Candida and yeasts (including Malassezia),and non-dermatophyte moulds.Since 287 strains of moulds were suspected to be contaminating fungi,11 702 residual isolates were analyzed.Of the analyzed isolates,Candida species (5642/11 702,48.2％ )and dermatophytes (5279/11 702,45.1％ )predominated,followed by yeasts (449/11 702,3.8％) and Malassezia species (332/11 702,2.8％).The most frequently isolated species was Trichophyton rubrum (3865/11 702,33.0％),Candida albicans (3110/11 702,26.6％ ) and non-albicans Candida species (2532/11 702,21.6％ ).Dermatophyte strains were mostly isolated from lesions of smooth skin with an exception of palmoplantar and interdigit regions (1787/5279,37.7％).The most common dermatophyte species was Trichophyton rubrum,followed by Trichophyton violanceum.Candida was mainly isolated from mucous membrane lesions (4099/5642,72.7％),with Candida albicans being the predominant species.Conclusions Candida species and dermatophytes predominate in patients with superficial fungal infections during 1960-2006,with Trichophyton rubrum being the most common species.