Screening and verification of genes related to polycystic ovary syndrome.

OBJECTIVE: To identify key genes involved in occurrence and development of polycystic ovary syndrome (PCOS). METHODS: By downloading the GSE85932 dataset from the GEO database, we used bioinformatical analysis to analyse differentially expressed genes (DEGs) from blood samples of eight women with PCOS and eight matched controls. Following bioinformatic analysis, we performed a cross-sectional study of serum samples taken from 79 women with PCOS and 36 healthy controls. RESULTS: From the 178 DEGs identified by bioinformatical analysis, 15 genes were identified as significant, and of these, ORM1 and ORM2 were selected for further verification as potential biomarkers for PCOS. Serum ORM1 and ORM2 levels were significantly increased in women with PCOS, and had a high diagnostic value. ORM1 and ORM2 were positively correlated with testosterone, cholesterol, and triglycerides. ORM1 levels were negatively correlated with high density lipoprotein (HDL) while ORM2 levels showed no significant correlation. CONCLUSIONS: ORM may be an effective biomarker for the diagnosis of PCOS and its monitoring may be a useful therapeutic strategy.

High-Temperature-Induced Shape Memory Copolyimide.

A series of polyimide (PI) films with a high-temperature-induced shape memory effect and tunable properties were prepared via the facile random copolymerization of 4,4'-oxydianiline (ODA) with 4,4'-(hexafluoroisopropyl)diphthalic anhydride (6FDA) and 4,4'-oxydiphthalic anhydride (ODPA). The trigger temperature can be controlled from 294 to 326 °C by adjusting the ratio of monomers. The effects of monomer rigidity on the chain mobility, physical properties, and shape memory performance of as-prepared copolyimide were systematically investigated. The introduction of ODPA could enhance the mobility of PI macromolecular chains, which made chain entanglement more likely to occur and increased the physical crosslinking density, thereby improving the PI's shape recovery up to 97%. Meanwhile, the existence of 6FDA enabled PI films to set quickly at low temperatures with a shape fixation of 98%. The shape memory cycling characteristics of the polyimide films are also studied, and the relationship between the PI chemical structure and the film properties are further discussed.

Evaluation of loop-mediated isothermal amplification assays for rapid detection of blaKPC producing Serratia spp. in clinical specimens: A prospective diagnostic accuracy study.

The prevalence of carbapenem-resistant Serratia spp. is increasing owing to the propagation of ß lactamase Klebsiella pneumoniae carbapenemase (blaKPC) and it has become one of the major global health concerns. As effective therapies for such resistant pathogens are limited, there is a great need for the rapid and sensitive characterization of the pathogen. In the present study, a loop-mediated isothermal amplification (LAMP) method for the rapid detection of Serratia spp. with blaKPC in pure cultures and clinical specimens was developed. A calcein indicator and real-time turbidity recording system were used to assess the LAMP reaction. The LAMP assay was compared with conventional PCR and real-time PCR kits for the target pathogen. The desired amplification was achieved using selected primers and detection was possible using both the calcein indicator method and the real-time turbity recording system at 65˚C for 60 min. The sensitivity of the detection system for blaKPC-producing Serratia spp. reached a detection limit of 3.92 pg/µl DNA, which was 10 times more sensitive than conventional PCR. Specificity testing indicated that the primers were highly specific. Compared with conventional culture methods and real-time PCR, the LAMP assay was more sensitive, easier for laboratory staff to master and less influenced by the clinical specimen matrix. In conclusion, a LAMP assay for blaKPC-producing Serratia spp. that permitted rapid, sensitive and economical detection for this pathogen was successfully developed. Comparisons with alternative methods indicated that the LAMP assay was more feasible in a clinical setting.

LncRNA GAS5 is upregulated in polycystic ovary syndrome and regulates cell apoptosis and the expression of IL-6.

BACKGROUND: GAS5 contains a hormone response element that can induce cell apoptosis in breast cancer. It is known that cell apoptosis and hormone response play crucial roles in polycystic ovary syndrome (PCOS), indicating the potential involvement of GAS5 in PCOS. This study was performed to investigate the potential involvement of GAS5 and IL-6 (a critical player in PCOS) in PCOS. METHODS: Research subjects of this study included 60 PCOS patients and 60 healthy controls. The expression levels of GAS5 and IL-6 in plasma of both patients and controls were measured by qPCR and ELISA, respectively. Cell transfections were performed to analyze the interaction between GAS5 and IL-6. Cell apoptosis was analyzed by cell apoptosis assay. RESULTS: GAS5 was upregulated in plasma of PCOS patients. The expression levels of GAS5 were positively correlated with the expression levels of IL-6. Altered expression levels of GAS5 and IL-6 distinguished PCOS patients from healthy controls. In cells of a granulosa-like tumor cell line (KGN), overexpression of GAS5 led to upregulated IL-6, while silencing of GAS5 played an opposite role. Cell apoptosis analysis showed that overexpression of GAS5 significantly decreased apoptosis rate of KGN cells. Silencing of GAS5 increased the rate of KGN cell apoptosis. CONCLUSIONS: GAS5 is upregulated in PCOS and regulates cell apoptosis and the expression of IL-6.

Aberrant Expression of Cancer-Testis Antigen FBXO39 in Breast Cancer and its Clinical Significance.

BACKGROUND: Cancer/testis antigen (CTA) is a class of antigen molecules expressed only in the germinal epithelium of testis and some tumor tissues. As an important CTA molecule, the expression of F-box protein 39 (FBXO39) in breast cancer (BC) and its clinical significance remain unclear. The objective of this study is to explore the value of FBXO39 in the diagnosis, efficacy monitoring, and prognostic evaluation of BC. METHODS: The expression of FBXO39 mRNA in the serum exosomes of patients with BC before and after the initial diagnosis and treatment was detected by qRT-PCR, and the corresponding ROC curve was plotted. The expression of FBXO39 protein in BC cancer tissues was detected by immunohistochemistry, along with the analysis of the correlation between FBXO39 expression and clinical pathological features as well as prognosis of BC cases. RESULTS: The serum-derived exosomes were successfully isolated and identified. The positive rate of FBXO39 mRNA in serum exosomes of patients with BC was up to 86%; there was a correlation between the expression level of serum exosomal FBXO39 and clinical staging, HER2, and Ki-67 expression (all with p < 0.05). The sensitivity of serum exosomal FBXO39 in distinguishing BC patients from healthy controls was 88%, with the specificity as 86%, and AUC as 0.9432. The expression change of FBXO39 in serum-sourced exosomes of patients with BC was related to their treatment situation, indicating that the level of FBXO39 decreased significantly after treatment. The expression of FBXO39 in cancer tissue was related to the clinical stage (p = 0.023) and lymphatic metastasis (p = 0.015) of the BC patients. Survival analysis showed that the expression of FBXO39 was negatively correlated with the prognosis of BC patients, with the high expression of FBXO39 indicating poor prognosis. CONCLUSIONS: Serum-derived exosomal FBXO39 could serve as an important indicator of BC diagnosis and efficacy evaluation; FBXO39 could be rated as an important indicator of BC prognosis evaluation.

Appraising circular RNAs as novel biomarkers for the diagnosis and prognosis of gastric cancer: A pair-wise meta-analysis.

BACKGROUND: Circular RNAs (circRNAs), proven as single-stranded closed RNA molecules, have been implicated in the onset and development of multiple cancers. This study aimed to summarize existing evidences regarding the clinicopathologic, diagnostic, and prognostic significances of circRNAs in gastric cancer (GC). METHODS: Eligible studies were identified using online databases. The quality of the included studies was judged, and patients' clinical characteristics, diagnostic data, and overall survival (OS) were extracted from the electronic medical record. Fisher's method was adopted to determine P values for clinicopathologic features. The diagnostic and prognostic data from all included studies were merged. RESULTS: Thirty eligible studies were comprised of 2687 GC patients were enrolled in the meta-analyses. Altered expressions of circRNAs in GC tissues were significantly associated with worse clinicopathologic features. Abnormally expressed circRNAs yielded a pooled sensitivity of 0.76 (95% CI: 0.69-0.81) and a specificity of 0.77 (95% CI: 0.70-0.83) in distinguishing GC from noncancerous controls, which corresponded to an area under the curve (AUC) of 0.83. The survival analysis showed that the oncogenic circRNA signature could be an independent risk factor of OS (HR = 2.11, 95% CI: 1.60-2.78, P = .000). Patients with down-regulated circRNAs (tumor suppressor genes) presented a significantly shorter OS time than those with high-level circRNAs (HR = 0.33, 95% CI: 0.27-0.42, P = .000). Stratified analyses based on sample type, control source, circRNA expression status, and cutoff setting also produced robust results. CONCLUSIONS: CircRNAs may play an important role as potential diagnostic and prognostic biomarkers of GC.

Catechol-O-methyltransferase 158G/A polymorphism and endometriosis/adenomyosis susceptibility: A meta-analysis in the Chinese population.

PURPOSE: An association between catechol-O-methyltransferase (COMT) 158G/A polymorphism and endometriosis/adenomyosis susceptibility has been reported in the previous studies, but the results were inconsistent. This study was conducted to explore this association in the Chinese population using meta-analysis. MATERIALS AND METHODS: PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine were searched for all relevant studies published up to December 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. RESULTS: A total of 7 case-control studies including 782 cases and 700 controls were included in this meta-analysis. Overall, COMT 158G/A polymorphism was found to be significantly associated with endometriosis and adenomyosis risk in the Chinese population (A vs. G, OR = 1.21, 95% CI: 1.02-1.42; AA vs. GG, OR = 1.47, 95% CI: 1.01-2.14; AA vs. GG + GA, OR = 1.42, 95% CI: 0.99-2.03; AA + GA vs. GG, OR = 1.20, 95% CI: 0.97-1.49). In subgroup analyses stratified by ethnicity, source of controls and disease groups, the significant risk was found in Chinese not mentioned the ethnicity, in population-based studies and adenomyosis. CONCLUSIONS: COMT 158G/A polymorphism may contribute to the risk of endometriosis and adenomyosis in Chinese, particularly for adenomyosis.

Correction: Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.14712.].

miR-338-3p inhibits the invasion of renal cell carcinoma by downregulation of ALK5.

BACKGROUND: The current study aims to elucidate the role of miRNA-338-3p (miR-338-3p) in the invasion of renal cell carcinoma (RCC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-338-3p in human RCC cell lines with high metastatic potential (Caki-1) and low metastatic potential (786-O), respectively. The Caki-1 and 786-O cells were transfected with miR-338-3p mimic or inhibitor. Wound healing assay, Transwell assay and western blotting were performed to analyze the invasive ability and expression of activin receptor-like kinase 5 (ALK5) in the RCC cell lines. During the 36-month follow-up, we detected the expressions of miR-338-3p and ALK5 in 22 RCC cases with metastasis and 60 cases achieving a remission. RESULTS: miR-339-3p was significantly downregulated in the Caki-1 cells as compared with the 786-O cells. The transfection with miR-338-3p inhibitor caused an increased invasive ability of both two cell lines. However, the transfection with miR-338-3p mimic caused a reduction of the invasiveness. In RCC cells, the expression of ALK5 was negatively correlated to miR-338-3p. Upregulation of ALK5 partially counteracted the miR-338-3p-induced invasiveness of RCC cells. We subsequently found the negative correlations between miR-338-3p and metastasis/ALK5 expression could be also observed in human RCC tissues. CONCLUSION: Taken together, these results indicate that miR-338-3p acts as a novel tumor suppressor to inhibit the invasion of RCC by regulating ALK5 expression.

Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis.

Fibulin-3 has emerged as a promising novel biomarker in conforming or monitoring malignant pleural mesothelioma (MPM). This study sought to evaluate the diagnostic and prognostic efficacies of humoral fibulin-3 for MPM. Seven eligible publications comprising 468 MPM cases for diagnosis, and 138 for prognosis were identified. Results manifested that humoral fibulin-3 sustained a pooled sensitivity of 0.62 (95% CI: 0.45-0.77) and specificity of 0.82 (95% CI: 0.73-0.89) in discriminating MPM patients from cancer-free individuals, corresponding to an AUC (area under the curve) of 0.81. For the survival analysis, fibulin-3 expression was not markedly associated with overall survival (OS) time of the MPM patients [HR (hazard ratio): 1.84, 95% CI: 0.75-4.56, P = 0.185]. In the subgroup analyses stratified by test matrix and ethnicity, data revealed that serum-based fibulin-3 examination achieved superior accuracy than plasma-based analysis (sensitivity: 0.77 versus 0.54; specificity: 0.85 versus 0.77; AUC: 0.92 versus 0.69); additionally, testing of fibulin-3 in Europeans retained higher efficacy than those in Americans and Australians. Taken together, fibulin-3 confers a relatively high diagnostic efficacy and is acceptable to be an auxiliary biomarker to aid in MPM identification.

Extracellular matrix metalloproteinase inducer enhances host resistance against pseudomonas aeruginosa infection through MAPK signaling pathway.

This study aims to explore the role of extra-cellular matrix metalloproteinase inducer (EMMPRIN) in the drug resistance of the pseudomonas aeruginosa (PA). The BALB/c mice were transfected with PA, then the mice were infected with the siRNA of EMMPRIN to silence the EMMPRIN gene. The EMMPRIN mRNA and protein were detected by using RT-PCR and western blot, respectively. In order to examine the function of EMMPRIN in drug resistance of PA, the BALB/c and C57BL/6 mice were treated with EMMPRIN siRNA. The cytokines, EMMPRIN and MMP9 were examined by the RP-PCR and ELISA, respectively, undergoing the silence of EMMPRIN siRNA. Moreover, the western blot assay was also used to test the phosphorylated MAPK in the murine macrophages after silenced by the EMMPRIN siRNA. The EMMPRIN was activated, with lipopolysaccharide stimulation and treated with the MAPK inhibitor, to evaluate whether the MAPK participates in the EMMPRIN-triggered drug resistance. The results indicated that the EMMPRIN expression was elevated in the infected BALB/c at 3 or 5 days post-infection. Silence of EMMPRIN Enhanced the Production of pro-inflammatory cytokines in PA keratitis. Silence of EMMPRIN significantly up-regulated Th1-type cytokines IFN-γ, IL-12, and IL-18, but down-regulated Th2-type cytokines IL-4, IL-5, and IL-10. MMP9 was increased in the cells with rEMMPRIN treatment. EMMPRIN inhibits pro-inflammatory cytokine production via a MAPK signaling pathway. In conclusion, EMMPRIN promotes host resistance against pseudomonas aeruginosa infection via MAPK signaling pathway.

Characterization by phenotypic and genotypic methods of metallo-ß-lactamase-producing Pseudomonas aeruginosa isolated from patients with cystic fibrosis.

Pseudomonas aeruginosa continues to be a predominant cause of infections with high intrinsic resistance to antibiotics, resulting in treatment failure. P. aeruginosa is the leading cause of respiratory infections among cystic fibrosis (CF) patients. Resistance to carbapenem antibiotics among P. aeruginosa has been reported. Thus, this study was undertaken to characterize the metallo-ß-lactamase (MBL) production of P. aeruginosa by phenotypic and genotypic methods. A total of 572 sputum samples were collected from cystic fibrosis patients along with the patient demographic details in a questionnaire. In total, 217 P. aeruginosa isolates were collected and an antibiogram revealed that 159 (73.3%) and 141 (64.9%) of these colonies exhibited resistance to imipenem and meropenem, respectively. Ceftazidime and tobramycin resistance were both identified in 112 (51.6%) isolates, and resistance to piperacillin-tazobactam, gatifloxacin and netilmicin was detected in 96 (44.2%) respective samples. A total of 62 (28.6%) respective samples were resistant to cefoperazone, cefepime and ceftriaxone. The least antibiotic resistance was shown to amikacin and ceftizoxime with 51 (23.5%) and 32 (14.7%) respective colonies resistant to the antibiotics. The minimum inhibitory concentration (MIC) for imipenem revealed a reduction in the MIC values. MBL screening by the zone enhancement method using ceftazidime plus EDTA discs demonstrated that 63 (56.25%) of the colonies were positive for MBL. A total of 53 (84.1%) samples expressed blaVIM and 48 (76.1%) expressed blaIMP genes, as detected by duplex polymerase chain reaction. In conclusion, carbapenem resistance is of great clinical concern in cystic fibrosis patients with P. aeruginosa infection. Therefore, mandatory regular screening and monitoring the resistance in P. aeruginosa among CF patients is required.