Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome

BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

Correlation of RUNX3 expression with microvessel density in colorectal adenocarcinoma tissues and clinical significance

Objective: To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density(MVD),and investigate the clinical pathological prognostic significance of RUNX3 and MVD in patients with colorectal cancer,Methods: The expression value of RUNX3 and MVD in 70 specimens' colorectal adenocarcinoma tissues were detected by immunohistochemistry staining technique,The correlation between their expression and the clinicopathologic features was also investigated,Results: The expression value of RUNX3 and the positive rates of RUNX3 in colorectal adenocarcinoma tissues were 3.25±1.14 and 25.71%(18/70),The expression value of MVD in colorectal adenocarcinoma tissues was 13.14±3.23,Expression of RUNX3 and MVD value were correlated with CEA,serosal invasion,liver metastasis,lymph node metastasis,and TNM stage(P<0.01),The expression value of RUNX3 had negative correlations with that of MVD,Conclusions: The high expression of RUNX3 could inhibit tumor microvascular generation in order to have negative control response on invasion and distant metastasis.

Correlation of caveolin-1 expression with microlymphatic vessel density in colorectal adenocarcinoma tissues and its correlation with prognosis

Objective: To study the expression of caveolin-1 in colorectal adenocarcinoma tissues and its correlation with microlymphatic vessel density(LMVD), and to investigate the clinical pathological prognostic significance of caveolin-1 and LMVD in patients with colorectal cancer. Methods: The expression of caveolin-1 and LMVD in 45 specimens of normal colorectal tissues, and 90 specimens of colorectal adenocarcinoma tissues were detected by immunohistochemistry technique. The correlation between their expression and the clinicopathologic features was analyzed. Muhivariable Cox regression was used to analyze the association between the laboratory indices and overall survival time. Results: The positive rates of caveolin-1 in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues(P<0.01). LMVD in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues(P<0.01). Mean LMVD in group with caveolin-1 positive was significantly higher than in that with caveolin-1 negative. The median survival time was 26.7 months. Cox regression analysis showed that the caveolin-1 expression, invation depth, lymph nodemetastasis, TNM stage, liver metastasis and LMVD were independent risk factors of overall survival time of patients with colorectal carcinoma. Conclusions: Caveolin-1 may contribute to the lymphangiogenesis in the tumor. During the occurrence and development of colorectal adenocarcinoma, there is a close relationship between the expression of caveolin-1 and lymphatic microvessel of tumor. Caveolin-1 expression and microlymphatic vessel density are significant prognostic value of colorectal carcinoma.

Four-manifolds with positive isotropic curvature

We give a survey on 4-dimensional manifolds with positive isotropic curvature. We will introduce the work of B. L. Chen, S. H. Tang and X. P. Zhu on a complete classification theorem on compact four-manifolds with positive isotropic curvature （PIC）. Then we review an application of the classification theorem, which is from Chen and Zhu＇s work. Finally, we discuss our recent result on the path-connectedness of the moduli spaces of Riemannian metrics with positive isotropic curvature.