BackgroundType 2 diabetes mellitus (T2D) is a metabolic disease characterized by dysfunction of pancreatic beta cell and insulin resistance. Liraglutide, which has many special anti-diabetes biological effects, is found to inhibit beta cell death and ameliorate endoplasmic reticulum stress (ERs) induced by free fatty acid (FFA). Macroautophagy (hereafter referred to as autophagy) altered by FFA is also associated with the dysfunction or death of pancreatic beta cells.ObjectivesWe aim at proving that Liraglutide improves the survival of INS-1 cells by promoting autophagy.Materials and MethodsCell survival was assessed by CCK8 assay. The percentage of apoptotic cells was determined by flow cytometric assay after Annexin V-FITC/PI staining. Expression of LC3 was detected by western blotting. MDC staining and transmission electron microscopy (TEM) were used in the measurement of autophagy.ResultsApoptosis induced by PA in INS-1 cells was significantly resolved after Liraglutide treatment. Simultaneously, autophagy was enhanced with the treatment of PA and Liraglutide. Conclusions: Liraglutide appears to protect INS-1 cells from apoptosis FFA-induced by promoting autophagy.ConclusionsThese findings provide a novel role for GLP-1 analogue in preventing or treating with T2D.

Serum cTnT concentration measured within 2 weeks of the onset of PPCM was correlated negatively with LVEF at follow-up. This marker offers a simple, quick, inexpensive, non-invasive method for predicting a persistent LVEF of < or =50%. A cTnT concentration of >0.04 ng/ml predicted persistent left ventricular dysfunction with a sensitivity of 54.9% and a specificity of 90.9%.

BackgroundThis study was to investigate the effects and safety of cathepsin B-cleavable doxorubicin (DOX)-prodrug (PDOX) for targeting therapy of metastatic human hepatocellular carcinoma (HCC) using DOX as a positive control drug.MethodsThe orthotopic nude mice model of highly metastatic HCC was established and the animals were randomized and treated with PDOX, DOX and saline, respectively. Hematology, biochemistry and tumor markers were studied. At autopsy, liver tumor weight and size, ascites, abdominal lymph nodes metastases, experimental peritoneal carcinomatosis index (ePCI), and tumor-host body weight ratio were investigated. Immunohistochemical studies and western blotting were done to investigate key molecules involved in the mechanism of action.ResultsCompared with Control, both PDOX and DOX could similarly and significantly reduce liver tumor weight and tumor volume by over 40%, ePCI values, retroperitoneal lymph node metastases and lung metastases and serum AFP levels (P < 0.05). The PDOX group had significantly higher WBC than the DOX group (P < 0.05), and higher PLT than Control (P < 0.05). Serum BUN and Cr levels were lower in the PDOX group than DOX and Control groups (P < 0.05). Compared with Control, DOX increased CK and CK-MB; while PDOX decreased CK compared with DOX (P < 0.05). Multiple spotty degenerative changes of the myocardium were observed in DOX-treated mice, but not in the Control and PDOX groups. PDOX could significantly reduce the Ki-67 positive rate of tumor cells, compared with DOX and Control groups. PDOX produced the effects at least via the ERK pathway.ConclusionCompared with DOX, PDOX may have better anti-metastatic efficacy and reduced side effects especially cardio-toxicities in this HCC model.

Background Secondary hyperparathyroidism (SHPT) usually required parathyroidectomy (PTX) when drugs treatment is invalid. Analysis was done on the impact of different intact parathyroid hormone (iPTH) after the PTX on all-cause mortality. Methods An open, retrospective, multicenter cohort design was conducted. The sample included 525 dialysis patients with SHPT who had undergone PTX. Results 404 patients conformed to the standard, with 36 (8.91%) deaths during the 11 years of follow-up. One week postoperatively, different levels of serum iPTH were divided into four groups: A: ≤20 pg/mL; B: 21–150 pg/mL; C: 151–600 pg/mL; and D: >600 pg/mL. All-cause mortality in groups with different iPTH levels appeared as follows: A (8.29%), B (3.54%), C (10.91%), and D (29.03%). The all-cause mortality of B was the lowest, with D the highest. We used group A as reference (hazard ratio (HR) = 1) compared with the other groups, and HRs on groups B, C, and D appeared as 0.57, 1.43, and 3.45, respectively. Conclusion The all-cause mortality was associated with different levels of iPTH after the PTX. We found that iPTH > 600 pg/mL appeared as a factor which increased the risk of all-cause mortality. When iPTH levels were positively and effectively reducing, the risk of all-cause mortality also decreased. The most appropriate level of postoperative iPTH seemed to be 21–150 pg/mL.

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