Diagnostic accuracy of the Berlin questionnaire and therapeutic effect of nasal continuous positive airway pressure in OSAHS patients with glucose metabolic dysfunction.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with alterations in glucose metabolism. The Berlin questionnaire (BQ) is effective in identifying subjects with high risk of OSAHS. However, its validity in patients with glucose metabolic dysfunction remains unclear. Our study aims to examine the diagnostic efficacy of the BQ in detecting OSAHS in patients with glucose metabolic dysfunction and to explore the effect of nasal CPAP on glucose metabolism. METHODS: Patients with glucose metabolic dysregulation were first asked to complete the BQ and then recruited for polysomnogram (PSG). The diagnostic accuracy of the BQ and the relationships between groups with normal glucose tolerance (NGT), elevated fasting blood glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were analyzed. Subjects with both OSAHS and glucose dysregulation received CPAP treatment and underwent an oral glucose tolerance test. Changes in apnea-hypopnea indices (AHI) and glycemic parameters were calculated to determine the efficacy of CPAP. RESULTS: Glycosylated hemoglobin and insulin levels were statistically different between the high-risk and low-risk groups according to the BQ. For diagnosis of subjects with OSAHS who also had glucose metabolic dysfunction, the sensitivity and specificity of the BQ using AHI cut-off values at 5 events per hour were 73% and 67%. CPAP therapy effectively reduced the blood glucose, HOMA-IR, and insulin levels. CONCLUSIONS: The BQ can be considered to be an effective and economical screening tool for patieints with OSAHS who also have glucose metabolic dysfunction. Treatment with CPAP may improve glycemic parameters.

High flow nasal cannula versus conventional oxygen therapy in postoperative patients at high risk for pulmonary complications: A systematic review and meta-analysis.

BACKGROUND: The effects of high flow nasal cannula (HFNC) on postoperative patients at high risk for pulmonary complications(PC) are controversial. We aimed to further determine the effectiveness of HFNC in postoperative patients at high risk for PC by comparison to conventional oxygen therapy (COT). METHODS: We performed a comprehensive search that compared HFNC with COT in postoperative patients at high risk for PC. The main outcomes were length of hospital stay (hospital LOS) and respiratory complications. RESULTS: Six trials with a total of 733 patients were pooled in our final studies. Except for Hospital LOS (I2  = 53%, χ2  = 8.51, P = .07) and rate of intubation or non-invasive ventilation (NIV) for respiratory failure (RF) (I2  = 49%, χ2  = 1.97, P = .16) between HFNC and COT, no significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with a lower rate of intubation or NIV for RF (RR 0.23, 95% CI 0.08-0.66, P = .006) and rate of hypercapnia (RR 0.37, 95% CI 0.20-0.68, P = .002). As for the Hospital LOS, ICU LOS, rate of requirement of O2 after discontinuous and hypoxemia, HFNC did not show any advantage over COT. Trial Sequential Analysis (TSA) for Hospital LOS showed that monitoring boundaries were finally not surpassed and required information size (RIS) was not met. CONCLUSIONS: The available randomised controlled trials (RCTs) suggest that, among the postoperative patients at high risk for PC, HFNC therapy compared with the COT significantly reduces rate of incubation or NIV for RF and rate of hypercapnia, meanwhile is safely administered. Further large-scale, multicenter, randomised and controlled studies are needed to confirm our results.

Predictors of acute cardiovascular events following acute exacerbation period for patients with COPD: a nested case-control study.

BACKGROUND: It has been noted that there is an increase in the incidence of acute cardiovascular events (CVEs) in patients with chronic obstructive pulmonary disease (COPD) during an acute exacerbation (AE), thereby causing increased inpatient mortality. Thus, we have tried to identify predictors of acute CVEs in patients with AECOPD via a nested case-control study. METHODS: A total of 496 cases hospitalized for AECOPD were included in this study, and followed-up for up to 6 months after discharge. Acute CVEs in the AE period were defined as a new or worsening acute coronary syndrome (ACS), arrhythmia, or left ventricular disfunction (LVD). Predictors of CVEs were selected from several variables, including baseline characteristics and treatments in the stable period as well as symptoms, laboratory tests, complications and treatments in the AE period. RESULTS: Thirty cases (6.05%) had acute CVEs, namely 2 had ACS, 13 had LVD and 19 experienced some form of arrhythmia. Four deaths were observed in the CVE group, with significantly increased death risk compared with the non-CVE group (P = 0.001, OR = 5.81). Moreover, patients who had CVEs were more prone to have re-exacerbation within 3 months. Multivariate analysis showed that previous LVD history (P = 0.004, OR = 5.06), 20% increase in heart rate (HR) (P = 0.003, OR = 10.19), electrolyte disturbance (P = 0.01, OR = 4.24) and diuretics (P = 0.002, OR = 6.37) were independent predictors of CVEs. In addition, usage of theophylline, fluoroquinolone and inhaled beta agonists in the AE period were not statistically associated with acute CVEs. CONCLUSIONS: Our preliminary study indicates that patients hospitalized for AECOPD with previous LVD history or increased HR need close observation and diuretics should be cautiously used with regular electrolyte monitoring. These findings need to be confirmed in a large cohort.

Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway.

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/-) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1ß elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

Hsp70 Gene Polymorphisms Are Associated With Disease Susceptibility and HRQOL Improvement in Chinese Han Population With Systemic Lupus Erythematosus.

OBJECTIVES: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

Micro-RNA-143 inhibits proliferation and promotes apoptosis of thymocytes by targeting CXCL13 in a myasthenia gravis mouse model.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, affecting the quality of life of millions of people worldwide. The present study aims to determine the relationship between micro-RNA-143 (miR-143) and C-X-C motif chemokine 13 (CXCL13) and whether it influences the pathogenesis of myasthenia gravis (MG). Thymus specimens were resected from patients with thymic hyperplasia combined with MG and then infused into normal mouse cavities to establish MG mouse models. Immunohistochemistry, reverse transcription-quantitative PCR, in situ hybridization detection, and Western blot analysis were employed to identify the expression of miR-143 and CXCL13 in MG and normal mice. The obtained thymocytes were cultured in vitro and transfected with a series of miR-143 mimic, miR-143 inhibitor, overexpression of CXCL13, or siRNA against CXCL13. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and flow cytometry assays were employed to assess cell viability, cycle entry, and apoptosis of the thymocytes. Dual-luciferase reporter assay provided verification, confirming that CXCL13 was the target gene of miR-143. Low miR-143 expression in the thymus tissues of the MG mice was detected, which presented with a reciprocal relationship with the expression rate of CLCX13. Observations in relation to the interactions between miR-143 mimic or siRNA-CXCL13 exposure showed reduced cell viability, with a greater number of cells arrested at the G0/G1 phase and a greater rate of induced apoptosis. Furthermore, overexpression of CXCL13 rescued miR-143 mimic-induced apoptosis. The findings have identified the potential role of miR-143 as a MG development mediator by targeting CXCL13. The key results obtained provide a promising experimental basis for targeted intervention treatment with miR-143.

Low expression of CRISP3 predicts a favorable prognosis in patients with mammary carcinoma.

The discovery of cysteine-rich secretory protein 3 (CRISP3) has been made in human neutrophils for the first time. Cloning of the complementary DNA (cDNA) for CRISP3 was performed from a cDNA library of human bone marrow. In patients with mammary carcinoma, we found that lower expression of CRISP3 was connected to a significantly improved DFS (disease-free survival) and OS (overall survival). Furthermore, the CRISP3 protein level was significantly associated with negative ANXA1 protein level. In addition, the heterogeneous expression of CRISP3 had been exhibited in diverse mammary carcinoma cells. A significant higher mRNA and the protein level of CRISP3 were seen in T-47D as well as SK-BR-3 cells compared with those in other types of mammary carcinoma cells. Knockdown of CRISP3 in T-47D or SK-BR-3 cells resulted in the weakened migration or invasion abilities. Furthermore, CRISP3 knockdown significantly inhibited the ERK1/2 MAPK signaling pathway in T-47D or SK-BR-3 cells. Research results indicated that the lowering in the expression of CRISP3 is likely to serve as an unprecedented approach for the treatment of mammary carcinoma.

Long noncoding RNA nuclear enriched abundant transcript 1 impacts cell proliferation, invasion, and migration of glioma through regulating miR-139-5p/ CDK6.

AIMS: We aimed to explore the impact of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) on cell proliferation, invasion, and migration of glioma. METHODS: Differentially expressed genes were screened out from Gene Expression Omnibus data set based on the microarray analysis. The expression levels of lncRNA NEAT1, miR-139-5p, and CDK6 in glioma cells and tissues were examined by quantitative reverse transcription polymerase chain reaction, and the protein level of CDK6 in glioma cells was determined by western blot and immunohistochemistry. Glioma cell viability, cell cycle, and apoptosis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and flow cytometry, respectively, whereas cell invasion and migration were analyzed by transwell assay. The target relationships among NEAT1, miR-139-5p, and CDK6 were confirmed by dual-luciferase reporter gene assay. The effects of lncRNA NEAT1 on tumor growth were further testified through glioma xenografts in nude mice. RESULTS: LncRNA NEAT1 and CDK6 were highly expressed in glioma tissues and cells, whereas miR-139-5p was lowly expressed. There were target relationships and correlations on expressions between miR-139-5p and NEAT1/ CDK6. NEAT1 and CDK6 could promote cell proliferation and metastasis of glioma cells and impeded cell apoptosis, whereas miR-139-5p exerted suppressive effects on the biological functions of glioma cells. NEAT1 regulated CDK6 to affect glioma growth through sponging miR-139-5p. CONCLUSIONS: LncRNA NEAT1 promotes cell proliferation, invasion, and migration of glioma through regulating miR-139-5p/CDK6 pathway.

Purple sweet potato color attenuated NLRP3 inflammasome by inducing autophagy to delay endothelial senescence.

Autophagy is a vital negative factor regulating cellular senescence. Purple sweet potato color (PSPC), one type of flavonoid, has been demonstrated to suppress endothelial senescence and restore endothelial function in diabetic mice by inhibiting the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. However, the roles of autophagy in the inflammatory response during endothelial senescence are unknown. Here, we found that PSPC augmented autophagy to restrict high-glucose-induced premature endothelial senescence. In addition, PSPC administration impaired endothelium aging in diabetic mice by increasing autophagy. Inhibition of autophagy accelerated endothelial senescence, while enhancement of autophagy delayed senescence. Moreover, deactivation of the NLRP3 inflammasome triggered by PSPC was autophagy-dependent. Autophagy receptor microtubule-associated protein 1 light chain 3 and p62 interacted with the inflammasome component NLRP3, suggesting that autophagosomes target the NLRP3 inflammasome and deliver it to the lysosome for degradation. Altogether, PSPC amplified cellular autophagy, subsequently attenuated NLRP3 inflammasome activity and finally delayed endothelial senescence to ameliorate cardiovascular complication. These results suggest a potential therapeutic target in senescence-related cardiovascular diseases.

High expression of LASS2 is associated with unfavorable prognosis in patients with ovarian cancer.

Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), is a gene isolated from a human liver complementary DNA library. In this study, we found that LASS2 protein level was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage and LASS2-negative tumors showed significant association with longer disease-free survival (DFS) and overall survival (OS) in ovarian cancer patients. The heterogeneous expression of LASS2 had been exhibited in diverse ovarian cancer cells. A significantly lower messenger RNA (mRNA) and protein level of LASS2 was seen in 3AO cell compared with those in other types of ovarian cancer cells. Meanwhile, the mRNA and protein levels of LASS2 in ES-2 and NIH:OVCAR-3 cells were obviously higher. LASS2 overexpression in 3AO cell could promote migration, invasion, and metastasis abilities in vitro and in vivo, while LASS2 knockdown in ES-2 and NIH:OVCAR-3 cells had the opposite effects. The oncogenic capacity of LASS2 in ovarian cancer may be mediated by increased expression of YAP/TAZ. It is indicated that lowering the expression of LASS2 is likely to serve as an unprecedented approach for the treatment of ovarian cancer.

Retracted: The role of HOTAIR-induced downregulation of microRNA-126 and interleukin-13 in the development of bronchial hyperresponsiveness in neonates.

Long noncoding RNAs, including HOTAIR, are involved in the pathogenesis of a wide range of diseases. This study aimed to explore the mechanism underlying the involvement of HOTAIR in neonatal bronchial hyperresponsiveness (BHR). A total of 105 newborns were recruited in this study to collect their peripheral blood mononuclear cell and serum samples, which were then divided into different genotype groups based on the genotypes of rs4759314, rs874945, and rs7958904. The real-time polymerase chain reaction, western blot analysis, computational analyses, and luciferase assays were performed to establish the regulatory relationships between the HOTAIR, microRNA-126 (miR-126), and interleukin-13 (IL-13). The level of HOTAIR, miR-126, and IL-13 among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups was similar. However, the level of HOTAIR was increased in the rs7958904 GG group, accompanied by a decreased level of miR-126 and IL-13. In addition, the level of airway responsiveness was comparable among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups. However, the airway responsiveness in the groups rs7958904 CG and CC was much stronger than that of the GG group. We also demonstrated that, by directly binding to miR-126, HOTAIR reduced the expression of miR-126, which in turn decreased the expression of IL-13. In summary, we demonstrated the role of HOTAIR-induced downregulation of miR-126 and IL-13 in the development of BHR in neonates.

Suppression of microRNA-342-3p increases glutamate transporters and prevents dopaminergic neuron loss through activating the Wnt signaling pathway via p21-activated kinase 1 in mice with Parkinson's disease.

Development of effective therapeutic drugs for Parkinson's disease (PD) is of great importance. Aberrant microRNA (miRNA) expression has been identified in postmortem human PD brain samples, in vitro and in vivo PD models. However, the role of miR-342-3p in PD has been understudied. The study explores the effects of miR-342-3p on expression of glutamate (Glu) transporter, and dopaminergic neuron apoptosis and proliferation by targeting p21-activated kinase 1 (PAK1) through the Wnt signaling pathway in PD mice. After establishment of PD mouse models, gain- or loss-of-function assay was performed to explore the functional role of miR-342-3p in PD. Number of apoptotic neurons and Glu concentration was then determined. Subsequently, PC12 cells were treated with miR-342-3p mimic, miR-342-3p inhibitor, dickkopf-1 (DKK1), and miR-342-3p inhibitor + DKK1. The expression of miR-342-3p, PAK1, the Wnt signaling pathway-related and apoptosis-related genes, Glutamate transporter subtype 1 (GLT-1), l-glutamate/ l-aspartate transporter (GLAST), tyrosine hydroxylase (TH) was measured. Also, cell viability and apoptosis were evaluated. PD mice exhibited increased miR-342-3p, while decreased expression of PAK1, GLT-1, GLAST, TH, and the Wnt signaling pathway-related and antiapoptosis genes. miR-342-3p downregulation could promote expression of PAK1, the Wnt signaling pathway-related and antiapoptosis genes. GLT-1, GLAST, and TH as well as cell viability, but reduce cell apoptosis rate. The results indicated that suppression of miR-342-3p improves expression of Glu transporter and promotes dopaminergic neuron proliferation while suppressing apoptosis through the Wnt signaling pathway by targeting PAK1 in mice with PD.

Low expression of ENC1 predicts a favorable prognosis in patients with ovarian cancer.

Ectodermal-neural cortex 1 (ENC1) belongs to a member of the kelch family of genes. It is an actin-binding protein and plays a pivotal role in neuronal and adipocyte differentiation. Here, we found that lower expression of ENC1 in the ovarian cancer patients was associated with favorable prognosis. In addition, ENC1 was heterogeneously expressed in various ovarian cancer cells. The messenger RNA and protein expression levels of ENC1 in HO-8910PM and NIH:OVCAR-3 cells were obviously higher than that in the other types of ovarian cancer cells. Knockdown of ENC1 in HO-8910PM or NIH:OVCAR-3 cells could significantly increase the reactive oxygen species levels, resulting in inhibition of in vitro proliferation, migration, and invasion. Our findings suggest that decreasing expression of ENC1 may be a new approach that can be used for ovarian cancer treatment.

FBXW7 suppresses HMGB1-mediated innate immune signaling to attenuate hepatic inflammation and insulin resistance in a mouse model of nonalcoholic fatty liver disease.

BACKGROUND: Innate immune dysfunction contributes to the development and progression of nonalcoholic fatty liver disease (NAFLD), however, its pathogenesis is still incompletely understood. Identifying the key innate immune component responsible for the pathogenesis of NAFLD and clarifying the underlying mechanisms may provide therapeutic targets for NAFLD. Recently, F-box- and WD repeat domain-containing 7 (FBXW7) exhibits a regulatory role in hepatic glucose and lipid metabolism. This study aims to investigate whether FBXW7 controls high-mobility group box 1 protein (HMGB1)-mediated innate immune signaling to improve NAFLD and the mechanism underlying this action. METHODS: Mice were fed a high-fat diet (HFD) for 12 or 20 weeks to establish NAFLD model. Hepatic overexpression or knockdown of FBXW7 was induced by tail-vein injection of recombinant adenovirus. Some Ad-FBXW7-injected mice fed a HFD were injected intraperitoneally with recombinant mouse HMGB1 to confirm the protective role of FBXW7 in NAFLD via inhibition of HMGB1. RESULTS: FBXW7 improves NAFLD and related metabolic parameters without remarkable influence of body weight and food intake. Moreover, FBXW7 markedly ameliorated hepatic inflammation and insulin resistance in the HFD-fed mice. Furthermore, FBXW7 dramatically attenuated the expression and release of HMGB1 in the livers of HFD-fed mice, which is associated with inhibition of protein kinase R (PKR) signaling. Thereby, FBXW7 restrains Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) signaling in HFD-fed mouse livers. In addition, exogenous HMGB1 treatment abolished FBXW7-mediated inhibition of hepatic inflammation and insulin resistance in HFD-fed mouse livers. CONCLUSIONS: Our results demonstrate a protective role of FBXW7 in NAFLD by abating HMGB1-mediated innate immune signaling to suppress inflammation and consequent insulin resistance, suggesting that FBXW7 is a potential target for therapeutic intervention in NAFLD development.

MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K/Akt signaling pathway.

Glioma is known to be the most prevalent primary brain tumor. In recent years, there has been evidence indicating myeloid cell leukemia-1 (MCL1) plays a role in brain glioblastoma. Therefore, the present study was conducted with aims of exploring the ability of MCL1 silencing to influence glioma cell senescence and apoptosis through the mediation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Glioma and tumor-adjacent tissues were collected in order to detect the presence of higher levels of MCL1 protein expression. Next, the mRNA and protein expression of MCL1, PI3K, Akt, B cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), and phosphatase and tensin homolog (PTEN) were determined. Cell counting kit-8 assay was applied to detect cell proliferation, ß-galactosidase staining for cell senescence, and flow cytometry for cell cycle entry and apoptosis. Initially, the results revealed higher positive expression rate of MCL1 protein, increased mRNA and protein expression of MCL1, PI3K, Akt, Bmi-1, and Bcl-2 and decreased that of Bax and PTEN in human glioma tissues. The silencing of MCL1 resulted in a decrease in mRNA and protein expression of PI3K, Akt, Bmi-1, and Bcl-2 and an increase in Bax and PTEN expressions in glioma cells. Moreover, silencing of MCL1 also inhibited cell proliferation and cell cycle entry in glioma cells, and promoted glioma cell senescence and apoptosis. In conclusion, the aforementioned results collectively suggested that the silencing of MCL1 promotes senescence and apoptosis in glioma cells through inhibiting the PI3K/Akt signaling pathway. Thus, decreasing the expression of MCL1 might have therapeutic functions in glioma. © 2018 IUBMB Life, 71(1):81-92, 2019.

Association of oestrogen receptor alpha gene polymorphisms with systemic lupus erythematosus risk: An updated meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease, and oestrogen is considered to be a predisposing factor for SLE. Although some studies are conducted to explore the association between oestrogen receptor alpha (ERα) gene polymorphisms and SLE susceptibility, their results are inconsistent. METHODS: Meta-analysis was conducted to confirm whether ERα gene polymorphisms were associated with SLE susceptibility, and the strength of association was anticipated by pooled ORs with 95% CIs. Stata software package version 12.0 was used to calculate all the statistical analyses. RESULTS: Twelve studies included 2494 cases and 4176 controls were incorporated in our meta-analysis. A significant association was found for ERα PvuII polymorphism in the overall population (CC+CT vs TT: OR = 1.334, 95% CI = 1.195-1.490, P < 0.001; CC vs TT: OR = 1.401, 95% CI = 1.096-1.791, P = 0.007; CT vs TT: OR = 1.284, 95% CI = 1.141-1.444, P < 0.001; C vs T: OR = 1.221, 95% CI = 1.084-1.375, P = 0.001), while there was no significant association for ERα XbaI polymorphism. Besides, in stratification analyses by ethnicity, the PvuII polymorphism was associated with an increased risk of SLE in Asians (CC+CT vs TT: OR = 1.379, 95% CI = 1.203-1.581, P < 0.001; CT vs TT: OR = 1.308, 95% CI = 1.130-1.515, P < 0.001; C vs T: OR = 1.240, 95% CI = 1.052-1.462, P = 0.010), while for ESR1 XbaI polymorphism, a significantly increased risk of SLE susceptibility was found in Asians (GA vs AA: OR = 1.271, 95% CI = 1.101-1.467, P = 0.001). CONCLUSION: Our meta-analysis indicated that the ERα PvuII polymorphism was significantly associated with SLE susceptibility in the overall and Asian populations, while the ERα XbaI GA genotype only played a key role in SLE susceptibility in Asian populations.

MircoRNA-1275 promotes proliferation, invasion and migration of glioma cells via SERPINE1.

This study was designed to explore the relationship between miR-1275 and SERPINE1 and its effects on glioma cell proliferation, migration, invasion and apoptosis. Differentially expressed miRNAs and mRNAs in glioma tissues were screened out by bioinformatic analysis. Dual-luciferase reporter gene assay was used to validate the targeted relationship between miR-1275 and SERPINE1. qRT-PCR was used to detect the expression of miR-1275 and SERPINE1 in glioma tissues. The expressions of SERPINE1 and p53 pathway-related proteins in glioma cells were detected by western blot. Glioma cell proliferation, apoptosis, migration and invasion were respectively detected by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Tumour xenograft model was developed to study the influence of miR-1275 and SERPINE1 on glioma growth in vivo. The results of microarray analysis, qRT-PCR and western blot showed that miR-1275 was low-expressed while SERPINE1 was high-expressed in glioma. Dual-luciferase assay showed that miR-1275 could bind to SERPINE1. Overexpression of miR-1275 could promote the p53 pathway-related proteins' expression. Highly expressed miR-1275 could repress the migration, proliferation and invasion of glioma cells while highly expressed SERPINE1 had inverse effects. Tumour xenograft showed that up-regulated miR-1275 or down-regulated SERPINE1 could repress glioma growth in vivo. Up-regulation of miR-1275 activated p53 signalling pathway via regulating SERPINE1 and therefore suppressed glioma cell proliferation, invasion and migration, whereas promoted cell apoptosis.

MicroRNA-140-5p elevates cerebral protection of dexmedetomidine against hypoxic-ischaemic brain damage via the Wnt/ß-catenin signalling pathway.

Hypoxia-ischaemia (HI) remains a major cause of foetal brain damage presented a scarcity of effective therapeutic approaches. Dexmedetomidine (DEX) and microRNA-140-5p (miR-140-5p) have been highlighted due to its potentially significant role in the treatment of cerebral ischaemia. This study was to investigate the role by which miR-140-5p provides cerebral protection using DEX to treat hypoxic-ischaemic brain damage (HIBD) in neonatal rats via the Wnt/ß-catenin signalling pathway. The HIBD rat models were established and allocated into various groups with different treatment plans, and eight SD rats into sham group. The learning and memory ability of the rats was assessed. Apoptosis and pathological changes in the hippocampus CA1 region and expressions of the related genes of the Wnt/ß-catenin signalling pathway as well as the genes responsible of apoptosis were detected. Compared with the sham group, the parameters of weight, length growth, weight ratio between hemispheres, the rate of reaching standard, as well as Bcl-2 expressions, were all increased. Furthermore, observations of increased levels of cerebral infarction volume, total mortality rate, response times, total response duration, expressions of Wnt1, ß-catenin, TCF-4, E-cadherin, apoptosis rate of neurons, and Bax expression were elevated. Following DEX treatment, the symptoms exhibited by HIBD rats were ameliorated. miR-140-5p and si-Wnt1 were noted to attenuate the progression of HIBD. Our study demonstrates that miR-140-5p promotes the cerebral protective effects of DEX against HIBD in neonatal rats by targeting the Wnt1 gene through via the negative regulation of the Wnt/ß-catenin signalling pathway.

Effect of microRNA-186 on oxidative stress injury of neuron by targeting interleukin 2 through the janus kinase-signal transducer and activator of transcription pathway in a rat model of Alzheimer's disease.

Recent studies have proposed that microRNAs (miR) function as novel diagnostic and prognostic biomarkers and therapeutic targets in Alzheimer's disease (AD), a common disease among the elderly. In the current study, we aim to explore the effect of miR-186 on oxidative stress injury of neuron in rat models of AD with the involvement of the interleukin-2 (IL2) and the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. AD rat models were established, and dual-luciferase reporter assay and online software were used to confirm the targeting relationship between miR-186 and IL2. Immunohistochemistry was used evaluating the positive rate of IL2. Afterward, to define the role of miR-186 in AD, miR-186, IL2, and JAK-STAT related protein (JAK2, STAT3) expressions were quantified. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and cell apoptosis was detected by flow cytometry. We observed downregulated miR-186 and IL2 and upregulated JAK-STAT signaling pathway related genes in AD. The overexpression of miR-186 was shown to significantly promote cell proliferation while suppressing cell apoptosis along with the expression of the IL2 and JAK-STAT signaling pathway related protein. Collectively, the key findings obtained from the current study define the potential role of miR-186 as an inhibitor of AD development by downregulation of IL2 through suppression of the JAK-STAT signaling pathway.

LncRNA LINC00880 promotes cell proliferation, migration, and invasion while inhibiting apoptosis by targeting CACNG5 through the MAPK signaling pathway in spinal cord ependymoma.

The present study was to investigate the effect of lncRNA LINC00880 targeting CACNG5 on cell proliferation, migration, invasion, and apoptosis in spinal cord ependymoma (SCE) through the MAPK signaling pathway. GEO database was used to download gene expression data related with SCE (GSE50161 and GSE66354) and annotation file. LncRNA with differential expression was predicted by Multi Experiment Matrix website (MEM). The target gene was analyzed by KEGG pathway enrichment analysis. SCE tissues and adjacent tissues were collected. The positive expression of CACNG5 protein was tested by immunohistochemistry. Expression of LINC00880, CACNG5, and MAPK signaling pathway-related proteins was measured with qRT-PCR and Western blotting. Cell proliferation, migration, invasion, cycle, and apoptosis were detected using MTT, Transwell assay, Scratch test, and Flow cytometry. SCE tissues showed increased LINC00880 expression. CACNG5 was a target gene of LINC00880 and correlated with MAPK signaling pathway. Compared with adjacent tissues, SCE tissues showed lower positive expression of CACNG5. Compared with the blank group, LINC00880 expression was higher in the LINC00880 vector and LINC00880 vector + CACNG5 vector groups, and lower in the si-LINC00880 and si-LINC00880 + si-CACNG5 groups; in the LINC00880 vector and si-CACNG5 groups, expression of survivin, p38MAPK, ERK1/2, JNK1/2/3 increased and CACNG5 and Bax expression reduced, the proliferation, invasion and migration of tumor cells increased, and apoptosis rate decreased. Opposite results were found in the si-LINC00880 and CACNG5 vector groups. The findings indicate that lncRNA LINC00880 targeting CACNG5 inhibits cell apoptosis and promotes proliferation, migration, and invasion in SCE through the MAPK signaling pathway.