Cardiomyocyte nutrient deprivation is a common clinical event that mediates various cardiac ischemic processes and is associated with autophagy activation and cell survival or death. Luteolin-7-O-glucoside (LUTG) was one of the flavonoid glycosides isolated from Dracocephalum tanguticum. Previous research had showed that LUTG pretreatment had significant protective effects against doxorubicin-induced cardiotoxicity. However, whether LUTG could protect cardiomyocytes from starvation-induced injury was not clear. In this study, cardioprotection and mechanisms of LUTG against starvation-induced injury were investigated in vitro. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay showed starvation-induced autophagy is a homeostatic and protective response for H9c2 cell survival. LUTG could protect against injury induced by starvation in H9c2 cells. Acridine orange (AO) staining showed that pretreatment with LUTG enhanced lysosomal autophagy. Western blotting indicated that LUTG enhanced autophagy by down-regulating the expression of phospho-extracellular signal regulated kinase1/2 (p-ERK), phospho-protein kinase B (p-Akt) and phospho-mammalian target of rapamycin (p-mTOR). These results suggest that LUTG might act as a promising therapeutic agent for preventing starvation-induced cardiotoxicity by upregulation of autophagy through the Akt/mTOR and ERK signal pathway.
C35 is a novel tumor biomarker associated with metastasis progression. To investigate the interaction factors of C35 in its high expressed breast cancer cell lines, we constructed bait recombinant plasmids of C35 gene and T47D cell cDNA library for yeast two-hybrid screening. Full length C35 sequences were subcloned using RT-PCR from cDNA template extracted from T47D cells. Based on functional domain analysis, the full-length C351-348bp was also truncated into two fragments C351-153bp and C35154-348bp to avoid auto-activation. The three kinds of C35 genes were successfully amplified and inserted into pGBKT7 to construct bait recombinant plasmids pGBKT7-C351-348bp, pGBKT7-C351-153bp and pGBKT7-C35154-348bp, then transformed into Y187 yeast cells by the lithium acetate method. Auto-activation and toxicity of C35 baits were detected using nutritional deficient medium and X-α-Gal assays. The T47D cell ds cDNA was generated by SMARTTM technology and the library was constructed using in vivo recombination-mediated cloning in the AH109 yeast strain using a pGADT7-Rec plasmid. The transformed Y187/pGBKT7-C351-348bp line was intensively inhibited while the truncated Y187/pGBKT7-C35 lines had no auto-activation and toxicity in yeast cells. The titer of established cDNA library was 2 × 107 pfu/mL with high transformation efficiency of 1.4 × 106, and the insert size of ds cDNA was distributed homogeneously between 0.5-2.0 kb. Our research generated a T47D cell cDNA library with high titer, and the constructed two C35 "baits" contained a respective functional immunoreceptor tyrosine based activation motif (ITAM) and the conserved last four amino acids Cys-Ile-Leu-Val (CILV) motif, and therefore laid a foundation for screening the C35 interaction factors in a BC cell line.
This report aims to evaluate the usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget's disease for achieving maximum tumor resection. Between January 2014 and December 2015, 5 patients underwent surgical resection of a penile-scrotal extramammary Paget's disease in department of urology, Huashan hospital, Fudan University. All patients were coated with 5-ALA (concentration of 20%) throughout the scrotum and the visible range of the lesion plus a 2cm margin 3 hours before the induction of anesthesia. 5-ALA fluorescence was visualized using an ultraviolet (UV) light at 405 nm. Surgical margin was determined in a standardized manner. The extent of resection was evaluated on the basis of frozen and histology sections. If the fluorescence positive punctate lesions were found outside the resection range, we removed the lesions and sent them for pathological examination. All data were prospectively collected, and the short- and long-term outcomes of the treatment strategy were analyzed. Lesions in the blue light turns red after irradiation, the fluorescence-guided surgery delineated range is less than the naked eye, intraoperative frozen prompted negative margins, postoperative pathological diagnosis. A total of 31 scattered lesions were found. After biopsy pathology prompted four were positive. In conclusion, 5-ALA fluorescence-guided minimum range can be completely removed in penile-scrotal Paget's lesions, and it is able to detect distant scattered lesions.
It has been hypothesized that subjective well-being (SWB) is determined by a combination of individual characteristics, social environment, and physical environment. However, few studies have simultaneously examined the relationships of the social and physical attributes of a neighborhood with SWB. Accordingly, the present study aimed to examine these relationships among Chinese elders. A total of 2,719 elders aged 60 years or older were recruited from 47 neighborhoods in the Xinhua subdistrict of Shanghai by two-stage stratified random sampling and interviewed between July and September 2014. The social and physical attributes of each neighborhood were assessed using validated and psychometrically tested measures. The Chinese version of the international Personal Wellbeing Index was used to assess SWB. Control variables included sex, age, marital status, education level, years living in the neighborhood, self-rated health, chronic conditions, and leisure-time physical activity. Multilevel linear regression analysis was conducted to explore whether social and physical attributes were associated with SWB. The average level of SWB was 74.2 ± 15.7% of the scale maximum. After controlling for individual covariates, individual-level social cohesion and social interaction were positively correlated with SWB, and both individual-level and neighborhood-level aesthetic quality was positively correlated with SWB. In conclusion, both social and physical attributes of neighborhoods were associated with SWB among Chinese elderly. These findings suggest that creating aesthetic and cohesive neighborhoods may encourage Chinese elders to participate in social activities and promote their SWB.
Major portal vein invasion (MVI) by hepatocellular carcinoma (HCC) carries an extremely poor prognosis. Our aim was to clarify the indications of hepatic resection in the presence of MVI by HCC. Between 2001 and 2015, 1,306 patients undergoing primary treatment for HCC were analyzed (866 hepatic resections and 440 transarterial therapies). Significant prognostic factors were identified by retrospectively analyzing tumor status, liver function and treatment. Overall survival was compared in terms of the degree of vascular invasion and treatment. The 5-year survival rates according to the degree of vascular invasion (Vp) were Vp0: 51.9%, Vp1: 33.0%, Vp2: 16.7%, Vp3: 21.8%, and Vp4: 0%, respectively. Overall survival (OS) did not differ significantly between patients with Vp3 and Vp4 MVI (p = 0.153). Median survival following hepatic resection of Vp3 cases was significantly better than that for Vp4 cases (1,913 vs. 258 days, p = 0.014), while OS following transarterial therapy was not significantly different (164 vs. 254 days in Vp3 vs. Vp4, p = 0.137). Multivariate analysis revealed hepatic resection (Odds: 2.335 [95%CI: 1.236-4.718], p = 0.008) and multiple tumors (1.698 [1.029-2.826], p = 0.038) as independent predictors of survival. Hepatic resection in HCC patients with MVI should be indicate in patients with Vp3 invasion.
A recent systematic review and meta-analysis study suggested that higher alcohol consumption is associated with lower risks for frailty. However the apparent protective effect may not be true because of some limitations. Therefore we further explored potential linear and non-linear associations using a two-stage dose-response meta-analysis. Restricted cubic splines were applied with three fixed knots at percentiles (10%, 50%, and 90%). A two-stage dose-response meta-analysis showed a significant non-linear association (p for non-linearity < 0.001); incident frailty risk decreased until around 15 g/day of alcohol consumption and increased thereafter. This suggests that while moderate alcohol consumption is associated with a lower risk of frailty, at higher consumption levels this apparent protect effect is lost. Given these findings, non-linear associations should be considered in future research on alcohol and frailty.
Edited and published by : International Research and Cooperation Association for Bio & Socio-Sciences Advancement Produced and listed by : International Advancement Center for Medicine & Health Research