Livin, a novel member of the human inhibitors of apoptosis protein (IAP) family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. To investigate its possibility as a therapeutic target for human malignancies, we established two genetically different stable tumor cell lines (LoVo and SPCA-1) and RNA interference (RNAi) technique was employed to downregulate Livin expression in two human tumor cell lines. The specific downregulation of Livin expression in tumor cell lines significantly inhibited in vitro cell proliferation and in vivo tumorigenicity. Furthermore, Livin knockdown led to cell arrest in the G 1 /G 0 phase of cell cycle, eventual apoptosis and chemosensitivity enhancement in tumor cells. All these results indicate that RNAi-mediated downregulation of Livin expression can lead to potent antitumor activity and chemosensitizing effects in human cancers.
This study was to investigate the change of high-molecula-weight (HMW) adiponectin (APN) isoform, the association between type 2 diabetes mellitus (T2DM) and HMW APN isoform, the variation of Disulfide-bond A oxidoreductase-like protein (DsbA-L), the effect of HMW APN isoform on AMP-dependent protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) in Chinese T2DM. 169 patients aged at (48.7±9.4) years and 107 healthy control subjects aged at (42.6±7.8) years took part in this study. Anthropometric measures of the characters were assayed and different APN isoforms, DsbA-L, AMPK and eNOS levels were determined. Ln(sRAGE) and Ln(Adiponectin) were significantly lower and significantly higher for the other characteristics in T2DM. Ln(Adiponectin) was negatively and significantly correlated with WHR, Ln(triglycerides), fasting plasma glucose, HbA1c (%) in control subjects and T2DM patients. Plasma and adipose tissue total APN and HMW APN were significantly reduced in newly diagnosed T2DM patients. DsbA-L was markedly down-regulated in diabetic adipose tissue. HMW APN caused significant decreases in AMPK and eNOS phosphorylation levels of human umbilical vein endothelial cells (HUVECs). Our results demonstrated that total APN levels was closely related to the risk of T2DM and HMW APN reduction was involved in the diabetic vascular AMPK/eNOS signal pathway. The findings will provide insight into novel therapeutic approaches for reducing the elevated cardiovascular risk associated with T2DM.
Background Regurgitation following TAVR impacts all-cause mortality. So far, no quantitative comparison of regurgitation by the same core lab has been performed among the various commercially available transcatheter heart valves (THV) We aimed to compare quantitative angiographic aortic regurgitation (AR) of 11 different types of THVs. Method This is a multicentre retrospective corelab pooled analysis of aortograms from 2704 consecutive patients treated with 11 different THV devices. Analysis was done by quantitative videodensitometric aortography (LVOT-AR), which is an objective, accurate, and reproducible tool for assessment of AR following TAVR. This method relies on time density changes in contrast medium after injection in the ascending aorta and its regurgitation (and subsequent density increase) in the LVOT. The ratio between the areas under the two-time density curves of these regions quantifies the AR in absolute percentage. The valves evaluated include ACURATE neo2 (n=120), Lotus (n=546), Myval (n=108), VitaFlow (n=105), Evolut PRO (n=95), SAPIEN 3 (n=397), Evolut R (n=295), SAPIEN XT (n=239), ACURATE neo (n=120), Venus-A (n=113) and CoreValve (n=532). Stratification of continuous variable regurgitation into categorical variables was performed according to the following pre-determined threshold criteria: 1) none/trace regurgitation (LVOT-AR<6%); 2) mild (6%≤ LVOT-AR ≤17%); and 3) moderate or severe (LVOT-AR >17%). Results The addition of anti PVR sealing features to the new generations ACURATE neo2 THV proved to be effective in reduction the incidence of significant PVR In comparison with the first generation ACURATE neo. Myval, VitaFlow and Venus-A THVs are showing promising results. Although the incidence of moderate/severe AR has regressed over time with new generations of THVs, the incidence of mild AR is still prominent with all THVs still exhibiting mild AR with an incidence ranging between 30% and 50% with the exception of the Lotus valve that had an 19% incidence of mild AR Conclusion ACURATE neo2 had the lowest severe/moderate percentage of AR showing significant improvements in comparison to ACURATE neo. Myval, VitaFlow and Venus-A are promising options in the THV armamentarium. These results should be confirmed in prospective randomized, head-to-head comparisons between THVs. Funding Acknowledgement Type of funding sources: None.
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