miRNA-133a-UCP2 pathway regulates inflammatory bowel disease progress by influencing inflammation, oxidative stress and energy metabolism.

AIM: To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS: C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11. Body weight, stool consistency and rectal bleeding were recorded daily, and these composed the disease activity index (DAI) score for the assessment of disease severity. After cervical dislocation was performed on day 14, the length of the colon in each mouse was measured, and colonic tissue was collected for further study, which included the following: haematoxylin and eosin staining, UCP2 and miR-133a detection by immunohistochemical staining, western blot and quantitative real-time PCR, measurement of apoptosis by TUNEL assay, and the assessment of inflammation (TNF-α, IL-1ß, IL-6 and MCP1), oxidative stress (H2O2 and MDA) and metabolic parameters (ATP) by ELISA and colorimetric methods. RESULTS: An animal model of IBD was successfully established, as shown by an increased DAI score, shortened colon length and specific pathologic changes, along with significantly increased UCP2 and decreased miR-133a levels. Compared with the DSS group, the severity of IBD was alleviated in the UCP2 and the miR-133a groups after successful UCP2 knockdown and miR-133a overexpression. The extent of apoptosis, as well as the levels of TNF-α, IL-1ß, MDA and ATP, were significantly increased in both the UCP2 and miR-133a groups compared with the DSS group. CONCLUSION: The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD.

Meta-analysis of the association of AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val polymorphisms and endometriosis risk in Asians.

PURPOSE: Several studies have suggested an association between the polymorphisms AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val and endometriosis, but results have been inconclusive. The aim of the present study was to assess these associations by meta-analysis. METHODS: Eligible literatures were retrieved from PubMed, ISI Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were calculated with a random or fixed-effect model. RESULTS: A total of six eligible studies were included. Regarding the AhR Arg554Lys and ARNT Val189Val polymorphisms, no obvious associations were found in either overall analysis or subgroup analysis based on the country, source of control, sample size, and genotyping method. For the AhRR Pro185Ala polymorphism, overall results suggested a marginal association with endometriosis susceptibility under the dominant model (OR = 1.65, 95 % CI = 1.00-2.72). Furthermore, a significantly increased risk for endometriosis was found in the subgroups which used the TaqMan method for genotype analysis or had a sample size ≥200. CONCLUSIONS: This meta-analysis suggested that the polymorphisms of AhR Arg554Lys and ARNT Val189Val are not associated with endometriosis, while the AhRR Pro185Ala polymorphism may be associated with endometriosis risk. However, further case-control studies with larger sample sizes are needed to confirm our results.

Circulating microRNAs in patients with polycystic ovary syndrome.

AIM: To explore the pattern of expression of circulating miRNAs in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Microarray and qRT-PCR were used to investigate circulating miRNAs in PCOS during clinical diagnosis. The targets of dys-regulated miRNAs were predicted using bioinformatics, followed by function and pathway analysis using the databases of Gene Ontology and the KEGG pathway. RESULTS: BMI, triglyceride, HOMA-IR, Testosterone and CRP levels were significantly higher, while estradiol was significantly lower in PCOS than in control groups. After SAM analysis, 5 circulating miRNAs were significantly up-regulated (let-7i-3pm, miR-5706, miR-4463, miR-3665, miR-638) and 4 (miR-124-3p, miR-128, miR-29a-3p, let-7c) were down-regulated in PCOS patients. Hierarchical clustering showed a general distinction between PCOS and control samples in a heat map. After joint prediction by different statistical methods, 34 and 41 genes targeted were up-and down-regulated miRNAs, in PCOS and controls, respectively. Further, GO and KEGG analyses revealed the involvement of the immune system, ATP binding, MAPK signaling, apoptosis, angiogenesis, response to reactive oxygen species and p53 signaling pathways in PCOS. CONCLUSIONS: We report a novel non-invasive miRNA profile which distinguishes PCOS patients from healthy controls. The miRNA-target database may provide a novel understanding of PCOS and potential therapeutic targets.

[Effect of modified cangfu daotan decoction in improving endometrial receptivity in infertility patients with polycystic ovarian syndrome].

OBJECTIVE: To study the effect and potential mechanism of Modified Cangfu Daotan Decoction (MCDD) on endometrial receptivity in infertility patients with polycystic ovarian syndrome (PCOS). METHODS: Totally 298 women having normal ovulation who underwent artificial insemination were recruited as the control group, and they received no drug therapy. Another 355 infertility patients with PCOS who received ovarian stimulation therapy were recruited as the treatment group. Then they were further assigned to the treatment group I (195 cases) and the treatment group II (160 cases) according to random digit table. Patients in the treatment group I received clomiphene (CC) + human menopause gonadotropin (HMG) +human chorionic gonadotropin (HCG), while those in the treatment group II received CC + HMG + HCG and additionally took modified MCDD. The therapeutic course for all was three menstrual cycles. The pregnancy ratio, the endometrial thickness, and spiral artery pulsatility index (PI), resistance index (RI), and homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Furthermore, the uncoupling protein 2 (UCP2) level was tested by Western blot. RESULTS: Compared with the control group, the endometrial thickness decreased and PI and RI increased in the treatment group I (all P < 0.05). Compared with the treatment group I , the endometrial thickness increased and PI and RI decreased in the treatment group II (all P < 0.05). Compared with before treatment, HOMA-IR levels were significantly decreased in the treatment group II after treatment (P < 0.05). Compared with the control group before treatment, the HOMA-IR level increased in the treatment group I and the treatment group II before treatment (P < 0.05). Compared with the control group after treatment, the HOMA-IR level increased in the treatment group I (P < 0.05). But there was no statistical difference in the post-treatment HOMA-IR level between the control group and the treatment group II (P < 0.05). Compared with the control group, the post-treatment UCP2 level was increased in the treatment group II (P < 0.05). After one year follow-up, the pregnancy rate was 16.1% (48/298) in the control group, 23.1% (37/160) in the treatment group I, and 33.8% (66/195) in the treatment group II. Compared with the control group, the pregnancy rate was significantly increased in the treatment group II (P < 0.05). CONCLUSION: MCDD was found to be capable of increasing the pregnancy rate of infertility patients with PCOS, which might be associated with improving endometrial blood flow and insulin resistance, increasing the UCP2 expression, and finally improving the endometrial receptivity.

[Prevalence of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome: a case-control study].

OBJECTIVE: To explore the prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with polycystic ovary syndrome (PCOS). METHODS: A case-control study employing 60 nonpregnant patients with PCOS and 60 non-pregnant patients without PCOS as control was conducted to compare the prevalence of NAFLD. RESULTS: The aminotransferase (ALT), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels were (29 +/- 15) U/L, (19 +/- 12) mU/L and 0.47 +/- 0.29 in PCOS group, which were significantly higher (P < 0.05) than corresponding parameters in control group [(15 +/- 13) U/L, (11 +/- 8) mU/L and 0.31 +/- 0.21)]. The occurrence of insulin resistance and NAFLD was63% (38/60) and 42% (25/60), higher than those in control group [35% (21/60) and 20% (12/60), P < 0.05]. The increment of ALT was 40% (24/60) in PCOS group, higher than that of 3% (2/60) in control group (P < 0.01). Compared with patients without NAFLD, patients with NAFLD had significantly increased body mass index (P < 0.01), waist-hip ratio, ALT, C-reaction protein, fasting insulin, insulin and HOMA-IR levels 2 hours after oral glucose tolerance test (P < 0. 05). CONCLUSION: The increased prevalence of NAFLD in PCOS patients suggests an association between these two conditions and the necessity of hepatic screening among PCOS patients for potential NAFLD.

Green tea consumption and liver disease: a systematic review.

OBJECTIVES: To present the effect of green tea consumption against liver disease. DATA SOURCES: Interventional and observational studies both in Western countries and in China and published between the years 1989 and December 2007. REVIEW METHODS: The articles were retrieved from Medline, Embase database, Chinese biomedicine web database and Chinese scientific journal's database using proper MESH headings and assessed by two independent investigators according to established inclusion criteria. The characteristics and outcomes of the chosen articles were displayed for further analysis and the quality of each study was also evaluated according to the widely acknowledged criteria. P<0.05 was defined as statistically significant in all enrolled trials. RESULTS: Ten qualified studies (eight from China, one from Japan and the other from the USA) with various outcomes such as liver cancer, cirrhosis and fatty liver disease were finally chosen. Among them, study designs differed in that there were four randomized-controlled clinical trials, two cohort, one case-control and three cross-sectional studies. The heterogeneity in the study design, outcomes, cofounders and amount of tea consumption precluded further meta-analysis. Nevertheless, eight studies showed a significant protective role of green tea against various liver diseases as determined by relative risk/odds ratio or P-value and among them, four studies showed a positive correlation between green tea intake and attenuation of liver disease. Moreover, the other two studies also presented the protective tendency of green tea against liver disease. CONCLUSIONS: An increased consumption of green tea may reduce the risk of liver disease.