Aim:The aim is to summarize the association between ejaculation frequency and risk of prostate cancer. Methods:The Pub Med, EMBASE and Web of Science were searched to identify articles about ejaculation frequency and risk of prostate cancer without date or language restrictions (last search up to April,2016).We included prospective cohort studies about ejaculation frequency and risk of prostate cancer.We only did a descriptive analysis because of without suitable data. Results:The result of descriptive analysis indicated that higher ejaculation frequency is associated with reducing risk of prostate cancer and lower ejaculation frequency is not associated with reducing risk of prostate cancer. Conclusion:This systematic review showed that higher ejaculation frequency shows beneficial effect in decreasing risk of prostate cancer and lower ejaculation frequency shows no effect in decreasing risk of prostate cancer.Studies with high methodological quality are required to confirm these findings.
Objective: To study the relationships between single nucleotide polymorphisms (SNPs) in the intron of the tumor necrosis factor α (TNFα) gene and the susceptibility and severity of disease associated with adenovirus infection in children. Methods: Four polymorphic loci of the TNFα gene (rs3093661, rs1800610, rs3093662, and rs3093664) were characterized allelically and genotypically in 320 children with adenovirus-associated pneumonia (AP) and compared with 320 healthy controls. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the plasma TNFα protein levels in all subjects. Results: The TNFα gene rs3093661 locus A allele, the rs1800610 locus A allele, the rs3093662 locus G allele, and the rs3093664 locus G allele were identified as susceptibility alleles for development of AP, and they were also positively correlated with the severity of AP. In children who had the GGAA haplotype, AP susceptibility was significantly reduced (0.28-fold) (95% confidence interval, CI: 0.20–0.40, p < 0.001). Conversely, among the subjects with the AGGG haplotype, their AP susceptibility risk was significantly increased (2.76-fold) (95% CI: 1.77–4.29, p < 0.001); and in the subjects with the AP GGGG haplotype their AP susceptibility risk was significantly increased (2.49-fold) (95% CI: 1.67–3.72, p < 0.001). The TNFα rs3093661, rs1800610, rs3093662, and rs3093664 SNPs were significantly correlated with plasma TNFα levels (p < 0.05). Conclusion: The TNFα gene rs3093661, rs1800610, rs3093662, and rs3093664 loci are associated with AP susceptibility and severity. This relationship might be due to the effect on TNFα levels found in the plasma. Clinical Trial Registration number: LL20190723.
// Ming Ming Yang 1 , Xiao Yuan Wang 1 , Ying Wei Liu 2 , Li Dong 1 , De Ju Kong 1 , Hong Yan Sun 1 , Jiao Jie Fan 1 , Xu Hui Yu 1 , and Jun Wang 3 1 Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China 2 Department of Ophthalmology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, China 3 Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China Correspondence to: Jun Wang, email: wangjun4622@163.com Keywords: complement system; C5; ocular inflammation; uveitis; molecular genetics Received: September 19, 2017 Accepted: February 13, 2018 Published: February 17, 2018 ABSTRACT Objective: Uveitis is a major cause for visual impairment, our previous studies have made significant advancements in depicting the genetic profile of complement genes in uveitis. This study aimed to further investigate whether the terminal pathway gene, Complement component 5 ( C5 ), confers susceptibility to uveitis. Methods: Six tagging SNPs in C5 were genotyped in 592 unrelated study subjects: 141 anterior uveitis patients, 158 patients with non-infectious intermediate and posterior uveitis, and 293 controls. Multiple in-depth analyses have been conducted. Results: Among the six C5 SNPs, rs17611 was significantly associated with uveitis after adjusted for gender and SNP-gender interaction ( P = 0.017). After stratification by gender, rs17611 G allele and GG homozygosity confers an increased risk for uveitis in males ( P = 0.004, OR = 1.67 and P = 0.009, OR = 2.69, respectively) but not in females. Moreover, genotype-phenotype correlation analysis revealed an association between rs17611 and disease recurrence ( P = 0.045). The haplotype GC, defined by rs17611 and rs2269066, was also found to be associated with total uveitis and specific intermediate and posterior uveitis subtype ( P = 0.0055, OR = 1.51 and P = 0.0084, OR = 1.58, respectively). Other polymorphisms were not significantly associated with either investigated uveitis entities. Conclusions: This study shows a gender-specific association of C5 -rs17611 with uveitis, indicating that C5 may have an epistatic effect with gender in the pathogenesis of uveitis. This study help us depict the disease profile and estimate the contribution of each complement activation pathway in ocular immunologic process.
Abstract Aim Pemetrexed, a new generation antifolate drug, is approved for the treatment for locally advanced or metastatic breast cancer, but factors affecting the efficacy and resistance of it have yet to be fully explicit. ATP-binding cassette transporters have been reported as prognostic and adverse effects predictors of many xenobiotics. This study was designed to explore whether ABC transporters affect pemetrexed resistance and may contribute to treatment regimen optimization for breast cancer. Methods Firstly, the expression of ABC transporters family members was measured in cell lines, thereafter examined the potential role of ABC transporter in conferring resistance to pemetrexed in primary cancer cell lines isolated from 34 breast cancer patients, and then the role of ABCC5 in mediating transport of pemetrexed and apoptosis pathway in MCF-7 cell lines was assessed. Finally, the functions of ABCC5 on therapeutic effect of pemetrexed was evaluated in breast cancer bearing mice. Results The expressions of ABCC2, ABCC4, ABCC5 and ABCG2 were significantly increased in pan-resistance cell lines, and the ABCC5, the most obvious one, was 5.21 times higher than that of the control group. The expression of ABCC5 was inversely correlated with sensitivity (IC 50 ) of pemetrexed (r = 0.741; p <0.010) in breast cancer cell lines from 34 patients. Further, we found expression of ABCC5 influenced the efflux and cytotoxicity of pemetrexed in MCF-7 cell line, and the IC 50 were 0.06 μg/ml and 0.20 μg/ml in ABCC5 knock-down and over-expression cells, respectively. In vivo study, we found ABCC5 affected sensitivity of pemetrexed in breast cancer bearing mice, and the tumor volume was much larger in ABCC5 over-expression group than that in control group (2.7 folds vs 1.2 folds). Conclusions Our results indicated ABCC5 was associated with pemetrexed sensitivity and resistance in vitro and in vivo, and may be a biomarker for regimen optimization of pemetrexed in breast cancer treatment.
Diabetic retinopathy (DR) is a complication of diabetes that has a serious impact on the quality of life of patients. VEGFA is necessary in the physiological state to maintain endothelial activity and physical properties of blood vessels. VEGFA plays an important role in the promotion of neovascularization; therefore, inhibition of VEGFA can degrade the structure of blood vessels and reduce neovascularization. In the present study, HERB, a high-throughput experimental and reference-oriented database of herbal medicines, was used for compound mining targeting VEGFA. The compounds most likely to interact with VEGFA were screened by molecular docking. Next, the compounds were used to verify whether it could inhibit the activity of the VEGF signaling pathway in vitro and neovascularization in vivo. In vitro, we found that dioscin could inhibit the activation of the VEGFA-VEGFR2 signaling pathway and cell proliferation of human retinal microvascular endothelial cells in a high-glucose (HG) environment. A more important dioscin intervention inhibits the expression of pro-angiogenic factors in the retinas of db/db mice. In conclusion, our study indicates that dioscin reduces the vascular damage and the expression of pro-angiogenic factors in the retina of db/db mice and implies an important and potential application of dioscin for treatment of DR in clinics.
Our previous studies demonstrated that reexpression of the alpha2beta1 integrin by a poorly differentiated breast carcinoma cell line, Mm5MT, resulted in dramatic reversion of a malignant phenotype to a differentiated epithelial phenotype. We hypothesized that reexpression of the alpha2beta1 integrin may regulate expression of other genes, the expression of which contributed to the dramatic phenotypic change. We now show that reexpression of the alpha2beta1 integrin results in up-regulation of both the alpha6 and beta4 integrin subunits but no change in the alpha1, alpha3, alpha5, or beta1 integrin subunits or E-cadherin. To further investigate the role of the alpha6 and beta4 integrin subunits in mediating the phenotypic changes elicited by reexpression of the alpha2beta1 integrin, the alpha6 or beta4 integrin subunit was expressed in our Mm5MT model. Expression of either subunit increased adhesion to laminin-1. Although adhesion to collagen was unaltered, contraction of three-dimensional collagen gels was reduced. Expression of either the alpha6 or beta4 integrin subunit also restored some aspects of a less malignant phenotype, including the acquisition of contact inhibition and diminution of anchorage-dependent and anchorage-independent growth rates. The alpha6 and beta4 transfectants formed three-dimensional organized structures when grown in gels of reconstituted basement membrane but did not form the highly branched, duct-like structures formed by the alpha2 transfectants. In contrast to the reduced invasiveness of the alpha2 transfectants, the alpha6 and beta4 transfectants retained an invasive phenotype. These results suggest that expression of the alpha6beta4 integrin contributes to some but not all of the phenotypic changes elicited by reexpression of the alpha2 integrin subunit and modulates the function of other integrins on these cells. Using our Mm5MT model, we are defining the cascade of integrin expression required for maintenance of the differentiated mammary epithelial cell phenotype.
To use green fluorescent protein as a marker to study the localization of the fusion protein, the mutant full length cDNAs of human ZNF230 and mouse znf230 with their stop codon TGA changed to TGG were obtained by PCR amplification, and then cloned into pGEM-Teasy vector. After the double enzyme cutting, the mutated human and mouse ZNF230(znf230) were inserted into mammalian expression plasmid pEGFP-N1. Thus we constructed the plasmid with fusion gene of ZNF230 and green fluorescent protein(GFP). Then the Cos cell was transfected with the fused gene by liposome. Fluorescence microscopy showed that green fluorescence protein expressed over the whole cell when transfected with vector pEGFP-N1. While after the transfection with pEGFP-ZNF230, the fluorescence located mainly on the nuclei of the cells. We demonstrated that the transfected Cos cell line can express human ZNF230 and mouse znf230 with high efficiency. When transfected with the constructed recombinant pEGFP-ZNF230 vector, the ZNF230 protein localizes mainly on the nucleus.
Abstract Background Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin‐dependent kinase 5 (CDK5) regulatory subunit‐associated protein 1‐like 1 (CDKAL1). Objective To examine whether this polymorphism was involved in the susceptibility in first‐episode drug‐naive schizophrenic patients (FDSP), and further influenced their clinical symptoms. Methods This polymorphism was genotyped in 239 FDSP and 368 healthy controls. The clinical symptoms in FDSP were assessed using the Positive and Negative Syndrome Scale (PANSS) five‐factor models. Results There was no significant difference in the allelic and genotypic frequencies of this polymorphism between two groups (both p > 0.05) after adjusting for covariates. However, the PANSS depressive score significantly differed by genotype in FDSP after adjusting for covariates ( F = 5.25, p = 0.006). This significant difference also persisted after Bonferroni correction ( p < 0.05). FDSP with C/C genotype had significantly higher PANSS depressive score than those with C/G genotype ( p = 0.007) and those with G/G genotype ( p = 0.005). Moreover, further stepwise multivariate regression analysis showed the significant association between the rs7754840 polymorphism and PANSS depressive score in FDSP ( β = −1.07, t = −2.75, p = 0.007). Conclusions Our findings demonstrated that although the CDKAL1 rs7754840 polymorphism did not contribute to the susceptibility to FDSP, it might be implicated in depressive symptoms in this patient group.
To study the effect of Shugan Jiangu Recipe (SJR) on bone mineral density (BMD) and serum bone metabolic biochemical markers in postmenopausal breast cancer patients with osteopenia.Totally 38 patients of postmenopausal women with breast cancer, who received aromatase inhibitors (AIs), were assigned to the treatment group (21 cases) and the control group (17 cases) by using random digit table. All patients took Caltrate D Tablet (containing Ca 600 mg and Vit D3 125 IU), one tablet daily. Patients in the treatment group took SJR, 6 g each time, twice daily for 6 successive months. The bone mineral density (BMD) level was detected before treatment and at months 6 after treatment. Levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type II collagen (CTX-II) were detected by enzyme linked immunosorbent assay (ELISA). The drug safety was also assessed.Compared with before treatment, BMD of L2-4 and femur neck obviously increased in the treatment group at month 6 after treatment (P < 0.01), serum BALP and TRAP decreased (P < 0.05). Compared with before treatment, BMD of L2-4 and femur neck obviously decreased in the control group at month 6 after treatment (P < 0.05), serum BALP and TRAP increased (P < 0.01). Compared with the control group, lumbar and femur neck BMD obviously increased, serum levels of BGP and BALP obviously decreased, and serum levels of CTX-II and TRAP obviously increased in the treatment group at month 6 after treatment (P < 0.01). No serious adverse event occurred during the treatment period. Bone fracture occurred in one case of the control group (5.8%).SJR could attenuate bone loss of postmenopausal women with breast cancer who received AIs, increase BMD and improve abnormal bone metabolism.
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