Description: Background: NDRG2, a member of N-Myc downstream regulated gene family, plays some roles in cellular stress, cell differentiation and tumor suppression. We have found that NDRG2 expression in cervical cancer Hela cells increases significantly upon stimulation with cisplatin, the most popular chemotherapeutic agent currently used for the treatment of advanced cervical cancer. This interesting phenomenon drove us to evaluate the role of NDRG2 in chemosensitivity of Hela cells. Methods: In the present study, RNA interference was employed to down-regulate NDRG2 expression in Hela cells. RT-PCR and Western blot were used to detect expression of NDRG2, Bcl-2 and Bax in cancer cells. Real-time PCR was applied to detect miR-15b and miR-16 expression levels. Drug sensitivity was determined with MTT assay. Cell cloning efficiency was evaluated by Colony-forming assay. Apoptotic cells were detected with annexin V staining and flow cytometry. Results: In vitro drug sensitivity assay revealed that suppression of NDRG2 could sensitize Hela cells to cisplatin. Down-regulation of NDRG2 didn't influence the colony-forming ability but promoted cisplatin-induced apoptosis of Hela cells. Inhibition of NDRG2 in Hela cells was accompanied by decreased Bcl-2 protein level. However, Bcl-2 mRNA level was not changed in Hela cells with down-regulation of NDRG2. Further study indicated that miR-15b and miR-16, two microRNAs targetting Bcl-2, were significantly up-regulated in NDRG2-suppressed Hela cells. Conclusions: These data suggested that down-regulation of NDRG2 could enhance sensitivity of Hela cells to cisplatin through inhibiting Bcl-2 protein expression, which might be mediated by up-regulating miR-15b and miR-16.

Description: Background: Given that hearing loss occurs in 1 to 3 of 1,000 live births and approximately 90 to 95 percent of them are born into hearing families, it is of importance and necessity to get better understanding about the carrier rate and mutation spectrum of genes associated with hearing impairment in the general population. Methods: 7,263 unrelated women of childbearing age with normal hearing and without family history of hearing loss were tested with allele-specific PCR-based universal array. Further genetic testing were provided to the spouses of the screened carriers. For those couples at risk, multiple choices were provided, including prenatal diagnosis. Results: Among the 7,263 normal hearing participants, 303 subjects carried pathogenic mutations included in the screening chip, which made the carrier rate 4.17%. Of the 303 screened carriers, 282 harbored heterozygous mutated genes associated with autosomal recessive hearing loss, and 95 spouses took further genetic tests. 8 out of the 9 couples harbored deafness-causing mutations in the same gene received prenatal diagnosis. Conclusions: Given that nearly 90 to 95 percent of deaf and hard-of-hearing babies are born into hearing families, better understanding about the carrier rate and mutation spectrum of genes associated with hearing impairment in the female population of childbearing age may be of importance in carrier screening and genetic counseling.

Description: Background: DNA damage repair genes JWA, XRCC1 and BRCA1 were associated with clinical outcomes and could convert the response to the cisplatin-based therapy in some carcinomas. The synergistic effects of JWA, XRCC1 and BRCA1 mRNA expression on personalized therapy remain unknown in advanced esophageal squamous cell carcinoma (ESCC). Methods: We employed quantitative real-time polymerase chain reaction (qPCR) to determine the expression of JWA, XRCC1 and BRCA1 mRNA in paraffin-embedded specimen from 172 patients with advanced ESCC who underwent the first-line cisplatin-or docetaxel-based treatments. Results: High JWA or XRCC1mRNA expression was correlated with longer median overall survival (mOS) in all the patients (both P 

Description: Background: Statin therapy plays a pivotal role in stabilizing the plaque for unstable angina (UA) patients although its mechanism(s) remains largely unexplored. Here we aim to identify microRNAs (miRNAs) mediating the protective effect of statins in UA patients. Methods: MiRNAs Array was carried out to compare the circulating whole blood miRNA profile of UA patients treated with (n = 10) and without statin (n = 10) and plasma miRNA profile UA patients treated with (n = 5) and without statin (n = 5). 22 whole blood miRNAs and 19 plasma miRNAs were found significantly upregulated in statin group. Targets of these miRNAs were predicted by algoritms: Targetscan, Miranda and Diana microT, then clustered according to functions and cell types by using the Database for Annotation, Visualization and Integrated Discovery(DAVID. To reveal the enriched function pathways in human atherosclerotic plaque, we analyzed microarray data from GEO database, Coronary atherosclerotic plaque (n = 80); macrophages in ruptured plaque (n = 11); carotid atheroma plaque (n = 64); advanced carotid atherosclerotic plaque (n = 29) using Reactome database. Integrated analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion. In vulnerable plaque, additional immune system signaling was also targeted. Results: The data showed target genes regulated by these statin induced miRNAs majorly expressed in i) plaque macrophage and platelet, where they were involved in hemostasis process; ii) in monocyte to regulate NGF apoptosis; iii) and in endothelial cell function in Rho GTPase pathway. Integrate analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion. Conclusions: Our study suggest that statin induces the expression of multiple miRNAs in the circulation of UA patient, which play important roles by regulating signal pathways critical for the pathogenesis of UA.

Description: Background: Although most reported biogenic Mn oxides are hexagonal birnessites, other types of biogenic Mn oxides also commonly occur in the environment. However, sorption characteristics and underlying mechanisms of the adsorption of heavy-metal ions on these biogenic Mn oxides are still rarely addressed. In this study, the sorption mechanisms of Cu(II) on a low valence biogenic Mn oxide, poorly crystallized bixbyite-like Mn2O3 (α-Mn2O3), were investigated. Results: The maximum adsorption capacity of Cu(II) onto this biogenic Mn oxide at pH 6.00 was 796 mmol/kg (0.45 mol Cu mol−1 Mn). The complex structure of adsorbed Cu(II) was constrained using Cu extended X-ray absorption fine structure (EXAFS) analysis, combined with structural parameters of the biogenic Mn oxide with alternately arranged regular and distorted MnO6 octahedra obtained through multiple-FEFF fitting of Mn EXAFS data. The sorbed Cu(II) was found to coordinate with the biogenic Mn oxide particle edges as inner-sphere complexes. At a relatively low Cu2+ loading (233 mmol/kg, pH 6.00), Cu(II) adsorbed onto the biogenic Mn oxide with two types of coordinated complexes, i.e., (1) coordinated with one regular/distorted MnO6 octahedron as a monodentate-mononuclear complex and (2) with two adjacent MnO6 octahedra as a bidentate-binuclear complex. While, at a relatively high Cu2+ loading (787 mmol/kg, pH 6.00), only one type of coordinated complex was constrained, the adsorbed Cu(II) coordinated with one regular/distorted MnO6 octahedron as a monodentate-mononuclear complex. Conclusions: This research extends further insight into the bacterial Mn(II) oxidation in the environment and serves as a good reference for understanding the interactions between metal ions and biogenic low valence Mn oxides, which are still poorly explored either theoretically or practically.

Description: Background: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that α7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-κB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear. Methods: In this report, an aggravating role of α7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (α7 −/− mice) blockages of α7 nAChR. Results: As shown in our in vivo studies, BBB injury was significantly reduced in α7 −/− mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the α7 −/− animals. C. neoformans and gp41-I90 could activate NF-κB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-κB inhibitor). Conclusions: Collectively, our data suggest that α7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders.

Description: Background: CXC chemokine receptor 2 (CXCR2) has been reported to play an important role in the proliferation and invasion of gastric cancer cells. The present study aims to investigate the impact of CXCR2 expression on the overall survival (OS) of gastric cancer patients after radical resection. Methods: Intratumoral CXCR2 expression was evaluated with immunohistochemistry on tissue microarrays containing tumor samples of 357 gastric cancer patients from a single center. CXCR2 expression levels were correlated to clinicopathological variables and OS. Results: CXCR2 expression was mainly located in the cytoplasm of gastric carcinoma cells. High CXCR2 expression was associated with poor tumor differentiation (p = 0.021), increased tumor depth (p 

Description: Thalidomide has been reported to cause numerous thromboembolic events. Deep vein thrombosis and pulmonary embolism are more common. It can also cause bradycardia and even total atrioventricular block. Rarely, ...

Description: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disease due mainly to inherited deficiencies in the proteins or enzymes involved in the clearance of triglycerides from circulation. It usu...

Description: This study aimed to investigate the prevalence of healthcare-associated infection (HAI) in the China-Japan Friendship Hospital, a tertiary level hospital in Beijing, China.