Chronic hepatitis B virus infection in women is not associated with IVF/ICSI outcomes

Objective

This study was to evaluate whether chronic HBV (Hepatitis B virus) infection in women is associated with poor performance following IVF/ICSI (in vitro fertilization/intracytoplasmic sperm injection) treatments.

Materials and methods

123 cycles with female chronic HBV infection were compared with 246 cycles with no-infected couples, matched for female age, D3 serum FSH (follicles stimulation hormone) levels, body mass index and assisted reproductive technology approach used (IVF or ICSI), in a ratio of 1:2.

Results

The details in IVF/ICSI cycles, including the dosage of gonadotrophin used, the serum estradiol levels and the endometrial thickness on the day of hCG (human chorionic gonadotrophin) injection, the mean number of oocytes retrieved, and the embryology data, were similar among seropositive and seronegative women. And there was no significant differences in implantation rates and live birth rates between seropositive women group and matched control (30.52 versus 28.34 % per transfer; 42.28 versus 40.65 %).

Conclusions

The results indicated that women with chronic HBV infection is not associated with outcomes of IVF/ICSI treatments.     

Current evidence on the relationship between four polymorphisms in the matrix metalloproteinases (MMP) gene and breast cancer risk: a meta-analysis

The matrix metalloproteinases (MMP) can degrade various components of the extracellular matrix and its functional genetic polymorphisms may be associated with breast cancer risk. However, this relationship remains controversial. A meta-analysis was conducted in order to investigate the potential association between four polymorphisms in the MMP gene and breast cancer risk. A database search yielded a total of 9 studies involving 2,597 cases and 2,618 controls. Four polymorphisms were included in the meta-analysis: MMP-1 −1607 2G/1G (rs1799750), MMP-2 −1306 C/T (rs243865), MMP-3 −1171 6A/5A (rs3025058) and MMP-9 −1562 C/T (rs3918242). Crude odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, we found that breast cancer cases had a significantly higher frequency of CC genotype (OR = 1.27, 95% CI = 1.10, 1.47; P = 0.001) and lower frequency of CT genotype (OR = 0.78, 95% CI = 0.67, 0.91; P = 0.001) of MMP-2. No significant difference was found in any genotype of MMP-1, MMP-3 or MMP-9. In conclusion, this meta-analysis suggested that MMP-2 −1306 C/T polymorphism may contribute to breast cancer susceptibility. More studies were needed especially in Asians in the future.     

The association between COMT Val158Met gene polymorphism and antipsychotic-induced tardive dyskinesia risk

Purpose: Catechol-O-methyltransferase (COMT) Val158Met gene polymorphism has been implicated the association with Tardive dyskinesia (TD) risk. However, lots of studies have reported contradictory results, so we conducted a meta-analysis to investigate the association between the COMT Val158Met gene polymorphism and TD susceptibility. Materials and methods: The PubMed, Embase, China National Knowledge Internet and Wanfang Database were researched up to 5 January 2015. The odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the relationship, and the statistical analyses were carried out by STATA 11.0 software. Results: In total, 1206 cases and 1680 controls from 11 case-control studies were included in the present study. The overall and subgroup pooled results indicated no significant association between COMT Val158Met gene polymorphism and TD susceptibility in all gene models (AA + AG vs. GG, OR: 0.98, 95% CI = 0.76–1.26, P = 0.87; AA vs. AG + GG, OR: 1.15, 95% CI = 0.93–1.42, P = 0.271; AA vs. GG, OR: 1.15, 95% CI = 0.90–1.49, P = 0.27; AG vs. GG, OR: 0.95, 95% CI = 0.80–1.14, P = 0.59; A vs. G, OR: 1.05, 95% CI = 0.93–1.17, P = 0.43). Conclusion: The study suggested COMT Val158Met gene polymorphism may not be an independent risk factor for TD susceptibility, especially in East Asians.     

颠胃酸口服液的消化活力测定

目的 建立颠胃酸口服液消化活力测定方法.方法 用酪氨酸为对照品,牛血红蛋白为底物,水浴温度37℃±0.5℃,紫外分光光度法,测定波长275 nm.结果 颠胃酸口服液平均消化活力为33.8μ·mL-1,高于标示量(24μ·mL-1),回收率为98.2％,RSD为0.96％(n=6).结论 该方法用于颠胃酸口服液的消化活力测定,操作便利,试验条件稳定,结果重复性好.     

Integrated Pharmacokinetic-Driven Approach to Screen Candidate Anticancer Drugs for Brain Tumor Chemotherapy

The goal of the study was to develop an effective screening strategy to select new agents for brain tumor chemotherapy from a series of low molecular weight anticancer agents [ON123x] by the combined use of in silico, in vitro cytotoxicity, and in vitro ADME profiling studies. The results of these studies were cast into a pipeline of tier 1 and tier 2 procedures that resulted in the identification of ON123300 as the lead compound. Of the 154 ON123xx compounds, 13 met tier 1 screening criteria based on physicochemical properties [i.e., MW < 450 Da, predicted log P between 2 and 3.5] and in vitro glioma cell cytotoxicity [i.e., IC50 < 10 μM] and were further tested in tier 2 assays. The tier 2 profiling studies consisted of metabolic stability, MDCK-MDR1 cell permeability and plasma and brain protein binding that were combined to globally assess whether favorable pharmacokinetic properties and brain penetration could be achieved in vivo. In vivo cassette dosing studies were conducted in mice for 12 compounds that permitted examination of in vitro/in vivo relationships that confirmed the suitability of the in vitro assays. A parameter derived from the in vitro assays accurately predicted the extent of drug accumulation in the brain based on the area under the drug concentration–time curve in brain measured in the cassette dosing study (r² = 0.920). Overall, the current studies demonstrated the value of an integrated pharmacokinetic-driven approach to identify potentially efficacious agents for brain tumor chemotherapy.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-012-9428-4) contains supplementary material, which is available to authorized users.KEY WORDS: brain tumor, CNS, drug development, pharmacokinetics, preclinical     

Participation of epoxygenase activation in saikogenin D-induced inhibition of prostaglandin E(2) synthesis

We examined the effect of saikogenin D on arachidonic acid metabolism in C6 rat glioma cells to clarify its anti-inflammatory mechanism. Incubation of C6 cells with saikogenin D for 20 min resulted in the inhibition of prostaglandin E(2) production and the accumulation of an arachidonic acid metabolite that was found to be 11,12-dihydroxyeicosatrienoic acid, a metabolite of 11,12-epoxyeicosatrienoic acid. C6 cells expressed rat epoxygenase mRNAs, CYP1A1, CYP2B1 and CYP2J3, which converted arachidonic acid to epoxyeicosatrienoic acids. 11,12-Epoxyeicosatrienoic acid inhibited A23187-induced prostaglandin E(2) production and SKF-525A, an inhibitor of epoxygenase, attenuated the saikogenin D-induced inhibition of prostaglandin E(2) production in C6 cells. Furthermore, 11,12-epoxyeicosatrienoic acid and 11,12-dihydroxyeicosatrienoic acid, but not saikogenin D, inhibited the activity of cyclooxygenase in a cell-free condition. These data suggest that saikogenin D activates epoxygenases that rapidly convert arachidonic acid to epoxyeicosanoids and dihydroxyeicosatrienoic acids, and then the metabolites secondarily inhibit prostaglandin E(2) production.     

Identifying dysfunctional miRNA-mRNA regulatory modules by inverse activation,cofunction, and high interconnection of target genes: A case study of glioblastoma

Background

Accumulating evidence demonstrates that complex diseases may arise from cooperative effects of multiple dysfunctional miRNAs. Thus, identifying abnormal functions cooperatively regulated by multiple miRNAs is useful for understanding the pathogenesis of complex diseases.

Methods

In this study, we proposed a multistep method to identify dysfunctional miRNA-mRNA regulatory modules (dMiMRMs) in a specific disease, in which a group of miRNAs cooperatively regulate a group of target genes involved in a specific function. We identified dysfunctional miRNAs, which were differentially expressed and inversely regulated most of their target genes, by integrating paired miRNA and mRNA expression profiles and miRNA target information. Then, we identified cooperative functional units, in each of which a pair of miRNAs cooperatively repressed function-enriched and highly interconnected target genes. Finally, the cooperative functional units were assembled into dMiMRMs.

Results

We applied our method to glioblastoma (GBM) and identified GBM-associated dMiMRMs at the population, subtype, and individual levels. We identified 5 common dMiMRMs using all GBM samples, 3 of which were associated with the prognosis in patients with GBM and were better predictors of prognosis than were miRNAs or mRNAs alone. By applying our approach to GBM subtypes, we found consistent dMiMRMs across GBM subtypes, and some subtype-specific dMiMRMs were observed. Furthermore, personalized dMiMRMs were identified, suggesting significant individual differences in different patients with GBM.

Conclusions

Our method provides the capability to identify miRNA-mediated dysfunctional mechanisms underlying complex diseases.     

Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesis

Netrins are secreted molecules with roles in axonal growth and angiogenesis. The Netrin receptor UNC5B is required during embryonic development for vascular patterning, suggesting that it may also contribute to postnatal and pathological angiogenesis. Here we show that unc5b is down-regulated in quiescent adult vasculature, but re-expressed during sprouting angiogenesis in matrigel and tumor implants. Stimulation of UNC5B-expressing neovessels with an agonist (Netrin-1) inhibits sprouting angiogenesis. Genetic loss of function of unc5b reduces Netrin-1-mediated angiogenesis inhibition. Expression of UNC5B full-length receptor also triggers endothelial cell repulsion in response to Netrin-1 in vitro, whereas a truncated UNC5B lacking the intracellular signaling domain fails to induce repulsion. These data show that UNC5B activation inhibits sprouting angiogenesis, thus identifying UNC5B as a potential anti-angiogenic target.     

Chemokine Signaling Pathway Involved in CCL2 Expression in Patients with Rheumatoid Arthritis

Purpose

Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Chemokines are involved in RA pathogenesis. In this study, we investigated the chemokine signaling pathway associated with CCL2 in peripheral blood (PB) and synovial tissues (ST) of RA patients based on our previous work about chemokine signaling pathway involved in the activation of CCL2 production in collagen-induced arthritis rat ST.

Materials and Methods

Total RNA was isolated from PB leukocytes and synovium of the knee joint in both RA patients and control populations. Real-time polymerase chain reaction was used to determine CCL4, CCR5, c-Jun, c-Fos, and CCL2 expressions. Serum level of CCL2 was assessed by enzyme-linked immunosorbent assay, and the production of CCL2 in ST was analyzed immunohistochemically.

Results

The expressions of CCL4, CCR5, c-Jun, c-Fos, and CCL2 messenger RNA in RA patients were significantly higher than those in healthy controls, both in ST and on PB leukocyte. Serum CCL2 levels were elevated in RA patients. Histological examination of rheumatoid joints revealed extensive CCL2 expression in RA ST.

Conclusion

CCL2, CCL4, c-Jun, c-Fos, and CCR5 may play an important role in the recruitment of PB leukocytes into the RA joints. These data provide evidence that the chemokine signaling pathway is involved in CCL2 expression in RA patient tissues, which may contribute to chronic inflammation associated with RA. Targeting this signaling pathway may provide a novel therapeutic avenue in RA.