Expression of apoptosis-related genes in the endometrium of polycystic ovary syndrome patients during the window of implantation

The present study investigated the expression of the apoptosis-related genes fas-associated via death domain (FADD) and Bcl-2 in the endometrium during the window of implantation in polycystic ovary syndrome (PCOS) patients. The aim was to explore the role of cell apoptosis in endometrial receptivity during this period. The subjects were divided into experimental and control group. The experimental group comprised 12 infertile women with PCOS, and the control group comprised 12 women who were infertile because of tubal pathological factors but had normal menstrual cycles. Endometria were collected by biopsy 7d after ovulation. Six samples from each group were randomly selected and subjected to gene chip analyses. The expression of endometrial FADD and Bcl-2 was determined by immunohistochemistry, and cell apoptosis was detected by the TUNEL method. Compared with the control group, 194 differentially expressed genes were found in the PCOS group, 102 of which were upregulated and 92 were downregulated. The differentially expressed genes were divided into 15 types according to function. Among the nine genes related to cell apoptosis, five (including Bcl-2) were upregulated and four were downregulated (including FADD). Bcl-2 expression during the window of implantation in the PCOS group increased compared with the control group, showing a significant difference (P<0.05). FADD expression in the PCOS group notably decreased compared with that in the control group, which also showed a significant difference (P<0.05). Cell apoptosis analysis showed a significant difference between the average apoptotic indices in the PCOS and control groups (P<0.05). Significant differences were observed between the endometrial gene expression in the PCOS and control groups. The decrease in cell apoptosis during the window of implantation in PCOS patients may be one of the causes of the reduced endometrial receptivity.     

A phenotypic and molecular characterization of the fmr1-tm1Cgr fragile X mouse

Fragile X Syndrome is the most common form of inherited mental retardation. It is also known for having a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always caused by inactivation of the X-linked FMR1 gene. A single knockout mouse model, fmr1-tm1Cgr, exists. In this report we further characterize the cognitive and behavioral phenotype of the fmr1-tm1Cgr Fragile X mouse through the use of F1 hybrid mice derived from two inbred strains (FVB/NJ and C57BL/6J). Use of F1 hybrids allows focus on the effects of the fmr1-tm1Cgr allele with reduced influence from recessive alleles present in the parental inbred strains. We find that the cognitive phenotype of fmr1-tm1Cgr mice, including measures of working memory and learning set formation that are known to be seriously impacted in humans with Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any fmr1-tm1Cgr cognitive deficit is surprisingly mild or absent. There is, however, clear support presented for a robust audiogenic seizure phenotype in all strains tested, as well as increased entries into the center of an open field. Finally, a molecular examination of the fmr1-tm1Cgr mouse shows that, contrary to common belief, it is not a molecular null. Implications of this finding for interpretation of the phenotype are discussed.     

Eight Functional Polymorphisms in the Estrogen Receptor 1 Gene and Endometrial Cancer Risk: A Meta-Analysis

Background and Objective

Emerging evidence indicates that common functional polymorphisms in the estrogen receptor 1 (ESR1) gene may have an impact on an individual’s susceptibility to endometrial cancer, but individually published results are inconclusive. The aim of this meta-analysis is to derive a more precise estimation of the associations between eight polymorphisms in the ESR1 gene and endometrial cancer risk.

Methods

A literature search of PubMed, Embase, Web of Science and China Biology Medicine (CBM) databases was conducted on publications published before November 1^st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software.

Results

Thirteen case-control studies were included with a total of 7,649 endometrial cancer cases and 16,855 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results indicated that PvuII (C>T) polymorphism was associated with an increased risk of endometrial cancer, especially among Caucasian populations. There were also significant associations between rs3020314 (C>T) polymorphism and an increased risk of endometrial cancer. Furthermore, rs2234670 (S/L) polymorphism may decrease the risk of endometrial cancer. However, no statistically significant associations were found in XbaI (A>G), Codon 325 (C>G), Codon 243 (C>T), VNTR (S/L) and rs2046210 (G>A) polymorphisms.

Conclusion

The current meta-analysis suggests that PvuII (C>T) and rs3020314 (C>T) polymorphisms may be risk factors for endometrial cancer, especially among Caucasian populations.     

Serum Concentrations of 15 Elements Among <Emphasis Type="Italic">Helicobacter Pylori</Emphasis>-Infected Residents from Lujiang County with High Gastric Cancer Risk in Eastern China

Data on the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS) are scarce. The objective of this study was to assess the effects of magnesium-zinc-calcium-vitamin D co-supplementation on hormonal profiles, biomarkers of inflammation, and oxidative stress in women with PCOS. Sixty PCOS women were randomized into two groups and treated with 100 mg magnesium, 4 mg zinc, 400 mg calcium plus 200 IU vitamin D supplements (n = 30), or placebo (n = 30) twice a day for 12 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were assessed at baseline and at end-of-treatment. After the 12-week intervention, compared with the placebo, magnesium-zinc-calcium-vitamin D co-supplementation resulted in significant reductions in hirsutism (?2.4 ± 1.2 vs. ?0.1 ± 0.4, P < 0.001), serum high sensitivity C-reactive protein (?0.7 ± 0.8 vs. +0.2 ± 1.8 mg/L, P < 0.001), and plasma malondialdehyde (?0.4 ± 0.3 vs. +0.2 ± 1.0 μmol/L, P = 0.01), and a significant increase in plasma total antioxidant capacity concentrations (+46.6 ± 66.5 vs. ?7.7 ± 130.1 mmol/L, P = 0.04). We failed to find any significant effect of magnesium-zinc-calcium-vitamin D co-supplementation on free androgen index, and other biomarkers of inflammation and oxidative stress. Overall, magnesium-zinc-calcium-vitamin D co-supplementation for 12 weeks among PCOS women had beneficial effects on hormonal profiles, biomarkers of inflammation, and oxidative stress.     

Anti-Prelog Reduction of Prochiral Carbonyl Compounds by Oenococcus oeni in a Biphasic System

An aqueous-organic biphasic system was established and used with whole cells of Oenococcus oeni to reduce 2-octanone to (R)-2-octanol. The conversion reached 99% when the Tris/borate buffer was increased from 50 mM to 300 mM in the aqueous phase. In addition, the conversion increased as the log P value of the organic solvent changed from 0.5 to 6.6. Under optimized conditions, the conversion of (R)-2-octanol reached 99% from 0.5 M 2-octanone with an optical purity of 99% e.e. The biphasic system allows the anti-Prelog reduction of aliphatic and aromatic ketones to furnish (R)-configurated alcohols in high optical purity as well.     

Aspirin Use and Lung Cancer Risk: A Possible Relationship? Evidence from an Updated Meta-Analysis

Background and Purpose

Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships.

Methods

We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR) and its 95% confidence interval (CI) were used for cohort studies, while odds ratio (OR) were employed for case-control studies. The random effects and fixed effects models were used for analyses.

Results

18 studies were identified including 19835 lung cancer cases, which were eligible for inclusion in the present meta-analysis. Pooled data from case-control studies showed a significant inverse association between regular aspirin use and lung cancer risk. But for cohort studies, insignificant association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI: 0.95 – 1.16; I²: 10.3%, p value: 0.351). In case-control studies, standard aspirin use (>325mg) was related to lower lung cancer incidence, compared with low-dose aspirin use (75–100mg). A similar trend was observed in cohort studies. Besides, when analysis was restricted to long time regular aspirin use (>5 years), insignificant results were reported in both cohort and case-control studies. Finally, regular aspirin use might result in higher reduction of non-small cell lung cancer incidence among men.

Conclusions

Our findings do not support the protective effect of regular aspirin use on lung cancer risk. Long time aspirin use, sex, dose and type of lung cancer might alter the effect of aspirin use on lung cancer risk. More well-designed studies are needed to further clarify these associations.     

Downstream bioprocessing of human pluripotent stem cell‐derived therapeutics

With the advancement in lineage‐specific differentiation from human pluripotent stem cells (hPSCs), downstream cell separation has now become a critical step to produce hPSC‐derived products. Since differentiation procedures usually result in a heterogeneous cell population, cell separation needs to be performed either to enrich the desired cell population or remove the undesired cell population. This article summarizes recent advances in separation processes for hPSC‐derived cells, including the standard separation technologies, such as magnetic‐activated cell sorting, as well as the novel separation strategies, such as those based on adhesion strength and metabolic flux. Specifically, the downstream bioprocessing flow and the identification of surface markers for various cell lineages are discussed. While challenges remain for large‐scale downstream bioprocessing of hPSC‐derived cells, the rational quality‐by‐design approach should be implemented to enhance the understanding of the relationship between process and the product and to ensure the safety of the produced cells.