Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes.

Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

GPX4 Plays a Crucial Role in Fuzheng Kang'ai Decoction-Induced Non-Small Cell Lung Cancer Cell Ferroptosis.

Background: Fuzheng Kang'ai decoction (FZKA) has been widely used to treat Non-Small Cell Lung Cancer (NSCLC) patients in China for decades, showing definitively curative effects in clinic. Recently, we found that FZKA could induce NSCLC cell ferroptosis, another type of programmed cell death (PCD), which is totally different from cell apoptosis. Therefore, in the present study, we aim to discover the exact mechanism by which FZKA induces NSCLC cell ferroptosis, which is rarely studied in Traditional Chinese Medicine (TCM). Methods: Cell proliferation assay were performed to detect the cell viability. Cell ferroptosis triggered by FZKA was observed by performing lipid peroxidation assay, Fe2+ Ions assay, and mitochondrial ultrastructure by transmission electron microscopy. Ferroptosis inhibitors including liproxstatin-1 and UAMC 3203 were used to block ferroptosis. The ratio of GSH/GSSG was done to measure the alteration of oxidative stress. Western blot and qRT-PCR were carried out to detect the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4 (GPX4) at protein and mRNA levels, respectively. Lentivirus transfection was performed to overexpress GPX4 stably. Animal model was done to verify the effect of FZKA-induced ferroptosis in NSCLC in vivo and immunohistochemistry was done to detect the expression of SLC7A11, SLC3A2 and GPX4 at protein level. Results: First of all, in vitro experiments confirmed the inhibition effect of FZKA on NSCLC cell growth. We then, for the first time, found that FZKA induced NSCLC cell ferroptosis by increasing lipid peroxidation and cellular Fe2+ Ions. Moreover, characteristic morphological changes of NSCLC cell ferroptosis was observed under transmission electron microscopy. Mechanistically, GPX4, as a key inhibitor of lipid peroxidation, was greatly suppressed by FZKA treatment both at protein and mRNA levels. Furthermore, system xc- (SLC7A11 and SLC3A2) were found to be suppressed and a decreased GSH/GSSG ratio was observed at the same time when treated with FZKA. Notably, overexpressing GPX4 reversed the effect of FZKA-induced NSCLC cell ferroptosis significantly. Finally, the above effect was validated using animal model in vivo. Conclusion: Our findings conclude that GPX4 plays a crucial role in FZKA-induced NSCLC cell ferroptosis, providing a novel molecular mechanism by which FZKA treats NSCLC.

Liraglutide for the treatment of type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials.

INTRODUCTION: Liraglutide has been widely used in the treatment of type 2 diabetes mellitus (T2DM), however, the results of a number of randomized placebo-controlled trials on the effects of liraglutide for the treatment of T2DM have varied. The purpose of this study was to assess the effects of liraglutide versus placebo for the treatment of T2DM. METHODS: We searched randomized controlled trials comparing liraglutide and placebo for the treatment of T2DM in the following databases: MEDLINE; EMBASE; Cochrane Library Central Register of Controlled Trials; and Clinical Trials Gov (through August 2014). The standard mean difference (SMD) was calculated for the continuous data and a χ (2) test was used to evaluate heterogeneity. RESULTS: Initially, 103 articles were retrieved through the literature search and 11 studies met the requirements for the meta-analysis. The effects of liraglutide on lowering glycosylated hemoglobin, fasting plasma glucose, reducing weight, lowering blood pressure, and the prevalence of adverse events were significantly different from placebo (P < 0.0001, SMD = -0.96, 95% CI = [-1.20, -0.73]; P < 0.0001, SMD = -0.72, 95% CI = [-0.99, -0.45]; P = 0.004, SMD = -0.24, 95% CI = [-0.40, -0.07]; P = 0.021, SMD = -0.15, 95% CI = [-0.27, -0.02], and P = 0.007, respectively). CONCLUSION: Liraglutide had greater hypoglycemic, weight-reducing and systolic blood pressure-lowering effects than placebo. However, there were more adverse events in the treatment with liraglutide. It is suggested that additional well-designed, large, studies be conducted to further support the use of liraglutide and provide objective guidance for clinical application of liraglutide.

Comparative effects of sitagliptin and metformin in patients with type 2 diabetes mellitus: a meta-analysis.

BACKGROUND: Sitagliptin has been widely used in the treatment of type 2 diabetes mellitus (T2DM); however, the therapeutic efficacy of sitagliptin remains inconclusive in randomized controlled studies on T2DM in which metformin has served as a control. OBJECTIVES: The present meta-analysis aimed to compare the therapeutic efficacy of sitagliptin and metformin in the treatment of T2DM. METHODS: We searched the following databases (Medline, Embase, Cochrane databases, Chinese Medical Journal Database, and the Chinese National Knowledge Infrastructure from inception until April 2013), and identified randomized controlled trials (RCTs) involving sitagliptin and metformin for T2DM. Two independent authors determined whether or not these trials met the inclusion criteria. Then, the variance of results from each study was calculated, and I(2) was employed for evaluation of heterogeneity. RESULTS: One hundred and twenty-one studies were identified, of which seven were included for further analysis. For T2DM, the therapeutic efficacy of sitagliptin and metformin was comparable in reducing HbA1c (P = 0.148, standard mean difference [SMD] = 0.13, 95% confidence interval [CI] = -0.05, 0.30), decreasing BMI (P = 0.063, SMD = 0.26, 95% CI = -0.01, 0.54), and improving the homeostasis model assessment (HOMA)-ß (P = 0.285, SMD = -0.05, 95% CI = -0.15, 0.04), but sitagliptin was inferior to metformin in improving HOMA-IR (P = 0.003, SMD = 0.16, 95% CI = 0.06, 0.27). CONCLUSIONS: Sitagliptin is similar to metformin in reducing HbA1c, decreasing body weight, and improving the function of beta cells, but is inferior to metformin in improving insulin sensitivity. More RCTs with large sample sizes are required to provide evidence for the rational application of sitagliptin.

Effects of thiazolidinediones on polycystic ovary syndrome: a meta-analysis of randomized placebo-controlled trials.

INTRODUCTION: Thiazolidinedione (TZD) is one of the therapy options for polycystic ovary syndrome (PCOS) patients; however, the effectiveness of TZD in the treatment of PCOS remains controversial. The aim of this metaanalysis was to clarify the role that TZDs play in the treatment of PCOS. METHODS: The authors searched the following databases for any date up to June 2012 for randomized controlled trials on PCOS treatment in which interventions for the experimental and control groups were TZDs and placebo, respectively: Medline, Embase, and the Cochrane library. RESULTS: The search strategy identified 173 potential publications, eight of which were included. In the treatment of PCOS, the insulin-lowering effects of TZDs were superior to placebo (95% CI -1.50 to -0.12; P=0.021), and the lowering of fasting blood glucose was superior to placebo (95% CI -1.06 to -0.05; P=0.031). There was no difference in reduction of the Ferriman-Gallwey scores or the androgen levels between TZDs and placebo (95% CI -0.57 to 0.10; P=0.169 and 95% CI -0.64 to 0.09; P=0.141, respectively). The effects of TZDs on body weight reduction were inferior to placebo (95% CI 0.13 to 0.66; P=0.003). Significant between-study heterogeneity was detected for several variables assessed. CONCLUSION: This is the first meta-analysis to evaluate the role that TZDs plays in the treatment of PCOS compared with placebo. The currently available data showed that TZDs can effectively reduce insulin and fasting blood glucose levels in patients with PCOS, but TZDs may not effectively reduce the Ferriman-Gallwey score or androgen levels and may increase body weight.

A systematic review and meta-analysis of randomized controlled trials comparing pioglitazone versus metformin in the treatment of polycystic ovary syndrome.

OBJECTIVE: Evidence indicates that metformin and pioglitazone both improve insulin resistance and hirsutism among patient with polycystic ovarian syndrome (PCOS). However, the effectiveness of pioglitazone versus metformin in the treatment of PCOS remains controversial. To summarize the relative efficacy of pioglitazone and metformin in PCOS patients, a systematic review and meta-analysis of randomized controlled trials (RCTs) was performed. METHODS: The authors searched MEDLINE, EMBASE, CNKI and WANFANG DATA for articles published up to November 2011 to identify those comparing pioglitazone versus metformin as a treatment for PCOS. RESULTS: Of the 161 studies retrieved, six trials were included in this analysis, including a total of 278 women with PCOS. Pioglitazone was found to be significantly more effective than metformin at reducing fasting insulin level (P = 0.002, standardized mean differences [SMD] = -0.37, 95% confidence interval [CI] [-0.61, -0.13]). Similarly, pioglitazone was found to be significantly more effective than metformin at improving the HOMA-IR index (P = 0.014, SMD = -0.32, 95% CI [-0.57, -0.06]). However, pioglitazone was significantly less effective than metformin at reducing body mass index (BMI; P = 0.038, SMD = 0.25, 95% CI [0.01, 0.49]). The effect of pioglitazone on fasting glucose levels, testosterone levels, and Ferriman-Gallwey scores was not significantly different from that of metformin (P greater than 0.05 for all). CONCLUSION: This systematic review and meta-analysis suggests that pioglitazone was more suitable for treating hyperinsulinemia and insulin resistance among PCOS patients, while metformin was more effective in reducing body weight. Well designed RCTs are needed to provide better evidence.

Variations of author origins in World Journal of Gastroenterology during 2001-2007.

AIM: To discuss the variations and distributions of authors who published their papers in World Journal of Gastroenterology (WJG) during 2001-2007 and evaluate the development of WJG and gastroenterology core journals in recent years by comparing the contributions of the authors. METHODS: WJG articles published in 2001-2007 were searched from MEDLINE database (by ISI Web of Knowledge). The variations (cooperation degree, cooperation rate) and distributions of the first authors were analyzed with bibliometric methods. SCIE was used to collect articles published in Am J Gastroenterol, Gastroenterology, Scand J Gastroenterol and WJG in 2007, and comparison of the data was made. Comparison indicators included the article number of annual journals, cooperation degree of authors, cooperation rate, mean number of articles published in each WJG issue, number of countries of the first WJG authors, geographical distribution and article contribution ratio of all WJG authors and domestic authors. RESULTS: Of the 5851 articles covered in MEDLINE, 173, 236, 633, 826, 1496, 1382 and 1105 articles were cited from 2001 to 2007. The cooperation degree was 5.11, 5.56, 5.75, 5.76, 6.31, 5.90 and 5.64 respectively. The cooperation rates was 94.80%, 99.15%, 98.89%, 98.55%, 99.13%, 96.67% and 95.66%, respectively. The mean number of articles published in each WJG issue from 2001 to 2007 was 28, 39, 52, 34, 31, 28 and 23, respectively. The number of countries of the first WJG authors was 8, 8, 27, 32, 49, 61 and 56, respectively. The first authors of WJG came from 3 continents in 2001 and covered 6 continents in 2006-2007. The number of articles written by Asian authors was 136 (79.07%), 227 (96.19%), 575 (90.98%), 713 (87.81%), 1111 (75.32%), 712 (53.98%) and 555 (53.21%), respectively in 2001-2007. The number of articles written by European & American authors increased from 36 (20.93%) and 8 (3.39%) in 2001-2002 to 563 (42.68%) and 452(43.34%) in 2006-2007. The number of countries except for China contributing papers was increased. The number of articles written by first authors of Japan rose from 0 (0%) in 2001-2002 to 287 (12.15%) in 2006-2007. The number of articles written by American authors increased from 6 (1.47%) in 2001-2002 to 158 (6.69%) in 2006-2007. The number of articles written by Chinese authors was 136 (79.07%), 227 (96.19%), 548 (86.71%), 669 (82.39%), 884 (59.93%), 380 (28.81%) and 320 (30.68%), respectively, in 2001 to 2007. The number of articles published in Am J Gastroenterol, Gastroenterology, Scand J Gastroenterol and WJG was 565, 586, 238 and 1118, respectively in 2007. The cooperation degree was 4.77, 6.14, 5.95 and 5.64, respectively, in 2007. The cooperation rate was 95.40%, 84.18%, 96.63% and 95.66%, respectively, in 2007. The number of countries of authors contributing papers was 44, 35, 42 and 62, respectively, in 2007. CONCLUSION: The geographical distribution of WJG authors is wide for the past 2 years. WJG has made a step onto international publishing, and drawn even more attentions from gastroenterology researchers. Its authors are distributed over 74 countries in 6 global continents, and the journal has become the main intermediary for international gastroenterology researchers to demonstrate their research accomplishments.

[Analysis of published articles and authors in Chinese Journal of Preventive Medicine from 1996 to 2005].

OBJECTIVE: To analyze the authors, the organizations and regional distribution of these authors of Chinese Journal of Preventive Medicine, and ascertain the core authors, core organizations and core regions. METHODS: Using quantitative analysis method, the authors, co-authors and the core authors of papers published in between 1996 to 2005 were analysed. Also, the distributions of districts and highly quantitative organization were determined statistically. RESULTS: There were 722 articles published during the last ten years; 510 authors had only published one paper, accounting for 70.64% of the total first authors. There were 712 articles having one or more co-authors, the cooperatively rate and degree were 98.61% and 5.54, respectively. There were 10 papers with single author, which accounted for 1.39% of total papers. The number of papers from universities, institutes and affiliated hospitals were 366 (50.69%), 229 (31.72%) and 78 (10.80%), respectively. There were 90 core authors publishing 212 (29.36%) papers, while 13 highly-quantities organizations published 303 (41.97%) papers. The core region was Beijing, in which there were published 231 (31.99%) articles. CONCLUSION: Authors of the Chinese Journal of Preventive Medicine should have a wide distribution and highly cooperative rate. There are a group of active and talented core authors, who have offered a great influence on the Journal.

[Analysis of authors of articles published in Chinese Journal of Ophthalmology from 1995 to 2004].

OBJECTIVE: We aimed to analyze the authors, the organizations and regional distribution of these authors of Chinese Journal of Ophthalmology, and ascertain the core authors, core organizations and core regions. METHODS: Using quantitative analysis method, we analysed the authors, co-authors and the core authors of papers published between 1995 to 2004. Also, the distributions of districts and highly quantitative organization were determined statistically. RESULTS: There were 2143 articles published during the last ten years; 912 author had published only one paper, accounted for 70.59% of total first authors. There were 1853 articles with one or more co-authors, the cooperative rate and degree were 86.47% and 3.56, respectively. There were 290 papers with single author, which accounted for 13.53% of total papers. The number of papers from universities, institutes, affiliated hospitals and hospitals were 246 (11.48%), 176 (8.21%), 969 (45.22%) and 423 (19.74%), respectively. There were 82 core authors published 553 (25.81%) papers, while 20 highly-quantities organizations published 1016 (47.41%) papers. Core region was Beijing, which published 574 (26.78%) articles. CONCLUSIONS: Authors of the Chinese Journal of Ophthalmology have a wide distribution and highly cooperative rate. There are a group of active and talented core authors, who have a great influence on this journal.