Dietary carotenoid intake and dental fluorosis in relation to SOD2 (rs 11968525) polymorphisms in Guizhou, China.

BACKGROUND AND OBJECTIVES: Genetic and dietary factors are important contributors to the development of dental fluorosis (DF). This study investigated the association between DF and dietary carotenoids, and explored whether the association was modified by polymorphisms of the antioxidant enzyme superoxide dismutase 2 (SOD2 rs11968525) in Guizhou, China. METHODS AND STUDY DESIGN: A cross-sectional study with a total of 899 adults aged 18-75 years were enrolled in the study. Face-to-face interviews were conducted to assess dietary habits using a validated 75 item food frequency questionnaire (FFQ). Sociodemographic and lifestyle information, and blood and urine samples were also collected. Genotypes were evaluated using TaqMan single nucleotide polymorphism (SNP) Genotyping Assay. RESULTS: There were significant dose-dependent inverse associations of the prevalence of DF with intake of α-carotene, ß-carotene, lutein/zeaxanthin, lycopene and total carotenoids (p-trend ranged from <0.001-0.004). The odds ratios (ORs) and 95% confidence intervals (CIs) of DF comparing the highest against lowest quartile were 0.56 (0.35, 0.92) for α-carotene, 0.53 (0.35, 0.81) for ß-carotene, 0.44 (0.27, 0.74) for lycopene, 0.35 (0.21, 0.58) for lutein/zeaxanthin in combination and 0.42 (0.25, 0.69) for total carotenoids (all p-trend<0.005). Intake of ß-cryptoxanthin was not found to be related to DF. The inverse association of DF with dietary intake of α-carotene and ß-carotene was more evident in individuals with the AG+AA genotype (p-interaction<0.05). CONCLUSIONS: Higher dietary carotenoids were associated with a lower occurrence of DF, polymorphisms in SOD2 (rs 11968525) modified the associations between dietary intake of carotene and DF. These findings provide evidence for precision prevention of fluorosis.

Increased expression of TAZ and associated upregulation of PD-L1 in cervical cancer.

BACKGROUND: As an important component of the Hippo pathway, WW domain-containing transcription regulator 1 (TAZ), is a transcriptional coactivator that is responsible for the progression of various types of cancers. Programmed cell death protein 1 (PD-1) receptors in activated T cells and their ligand programming death force 1 (PD-L1) are the main checkpoint signals that control T cell activity. Studies have shown high levels of PD-L1 in various cancers and that PD-L1/PD-1 signals to evade T-cell immunity. Recent data have demonstrated that TAZ can regulate the characteristics of cancer cells via PD-L1. Cervical cancer is a common gynecological disease worldwide. In this study, we attempted to evaluate the effects of TAZ and PD-L1 on cervical cancer. METHODS: Hela cervical cancer cells were transfected with TAZ plasmid or TAZ siRNA or PD-L1 siRNA by using Lipofectamine 2000. The relationship between TAZ and PD-L1 in cervical cancer cells was determined by qRT-PCR and western blotting. The functional roles of TAZ were confirmed via CCK-8, Transwell and flow cytometry assays. Western blotting was utilized to observe the expression of BCL-2 and Caspase-3. The clinicopathological correlation of TAZ and PD-L1 was evaluated via relevant databases. RESULT: TAZ is upregulated in cervical cancer and induces the growth and metastasis of cervical cancer cells by targeting PD-L1and inhibiting the ratio of apoptotic of cancer cells. High TAZ and PD-L1 expression was observed in different stage, grade, histological patterns, and ages of cervical cancer groups compared with normal cervix groups. Furthermore, high TAZ expression was positively correlated with the infiltration levels of immune cells and the expression of PD-L1.

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin.

Background: The evolution of adriamycin (ADR) resistance in the treatment of breast cancer often leads to a poor prognosis in patients. Ubiquitin-specific peptidase 37 (USP37) has been recently identified as a modulator in regulating the stemness of breast cancer cells, but its underlying mechanism remains unclear. In this study, we investigated whether USP37 knockdown could hamper the chemical resistance of MCF-7 and MCF-7/ADR cells to adriamycin and elucidated the potential mechanism. Methods: Immunohistochemistry, western blotting, and RT-qPCR assays were performed to detect the USP37 expression in MCF-7 and MCF-7/ADR cells. The efficiency of USP37 knockdown in breast cancer cells was confirmed by western blotting and RT-qPCR assays. We also performed CCK-8 assay, flow cytometry, western blotting, and TUNEL assays to evaluate cell viability and apoptosis in breast cancer cells. In vivo study was performed to detect the tumorigenicity of MCF-7/ADR cells transfected with shScramble or shUSP37#1 under adriamycin treatment. Results: Bioinformatic analysis indicated that USP37 overexpression was positively correlated with adriamycin resistance. The expression levels of USP37 in both MCF-7 and MCF-7/ADR cells increased significantly with the exposure to adriamycin in a dose-dependent manner. It was verified by the observation that USP37 downregulation elevated the inhibitory effects of adriamycin on breast cancer cells, suppressed cell proliferation caused by cell cycle arrest in G1/S transition, as well as induced apoptosis. Furthermore, in vivo study showed that knockdown of USP37 expression also decreased tumorigenicity of MCF-7/ADR cells in mice. TUNEL assay and observation of cell morphology magnified USP37 knockdown synergized with Adriamycin could elevate the apoptosis of MCF-7 and MCF-7/ADR cells. Western blotting assay illustrated that the combination of USP37 knockdown with adriamycin treatment significantly upregulated the expression levels of cleaved caspase 3 and Bax, whereas the expression level of Bcl-2 was inhibited. Conclusion: Knockdown of USP37 gene expression can reverse the resistance of breast cancer cells to adriamycin, and down-regulating USP37 might be a valuable strategy against ADR resistance in breast cancer therapy.

IL-6 induces tumor suppressor protein tyrosine phosphatase receptor type D by inhibiting miR-34a to prevent IL-6 signaling overactivation.

Protein tyrosine phosphatase receptor type D (PTPRD) is a tumor suppressor gene that is epigenetically silenced and mutated in several cancers, including breast cancer. Since IL-6/STAT3 signaling is often hyperactivated in breast cancer and STAT3 is a direct PTPRD substrate, we investigated the role of PTPRD in breast cancer and the association between PTPRD and IL-6/STAT3 signaling. We found that PTPRD acts as a tumor suppressor in breast cancer tissues and that high PTPRD expression is positively associated with tumor size, lymph node metastasis, PCNA expression, and patient survival. Moreover, breast cancers with high PTPRD expression tend to exhibit high IL-6 and low phosphorylated-STAT3 expression. IL-6 was found to inhibit miR-34a transcription and induce PTPRD expression in breast cancer and breast epithelial cells, whereas PTPRD was shown to mediate activated STAT3 dephosphorylation and to be a conserved, direct target of miR-34a. IL-6-induced PTPRD upregulation was blocked by miR-34a mimics, whereas experimental PTPRD overexpression suppressed MDA-MB-231 cell migration, invasion, and epithelial to mesenchymal transition, decreased STAT3 phosphorylation, and increased miR-34a transcription. Our findings suggest that PTPRD mediates activated STAT3 dephosphorylation and is induced by the IL-6/STAT3-mediated transcriptional inhibition of miR-34a, thereby establishing a negative feedback loop that inhibits IL-6/STAT3 signaling overactivation.

rApoptin induces apoptosis in human breast cancer cells via phosphorylation of Nur77 and Akt.

Breast cancer is the leading cause of cancer incidence and cancer-related mortality among women and is becoming a major public health problem around the world. The current study aims to investigate the possible role and mechanism of recombinant Apoptin (rApoptin), a potential anticancer candidate that minimally impacts normal cells, in the breast cancer cell proliferation and apoptosis in vitro and in vivo. We found that rApoptin could effectively inhibit the proliferation and apoptosis in MCF-7 and MDA-MB-231 cells in vitro, which was further confirmed by flow cytometry analysis. Apoptin partially inhibited MCF-7 cell xenograft tumor development in vivo. Furthermore, we found via western blot that rApoptin-induced apoptosis in MCF-7 and MDA-MB-231 cells was associated with the phosphorylation of Nur77 (p-Nur77) and Akt (p-Akt). In addition, compared with the control groups, rApoptin-treated tissues showed significantly higher expression of Bax and Cyt c while Bcl-2 expression was decreased by rApoptin treatment. Together, our results are the first to demonstrate that rApoptin was able to effectively induce breast cancer cell apoptosis both in vitro and in vivo and that this activity could be regulated by the phosphorylation of Nur77 and Akt and the mitochondrial pathway. Our findings highlight the potential application of rApoptin as a breast cancer treatment.

MicroRNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway.

MicroRNAs play pivotal roles in cancer stem cell regulation. Previous studies have shown that microRNA-34a (miR-34a) is downregulated in human breast cancer. However, it is unknown whether and how miR-34a regulates breast cancer stem cells. Notch signaling is one of the most important pathways in stem cell maintenance and function. In this study, we verified that miR-34a directly and functionally targeted Notch1 in MCF-7 cells. We reported that miR-34a negatively regulated cell proliferation, migration, and invasion and breast cancer stem cell propagation by downregulating Notch1. The expression of miR-34a was negatively correlated with tumor stages, metastasis, and Notch1 expression in breast cancer tissues. Furthermore, overexpression of miR-34a increased chemosensitivity of breast cancer cells to paclitaxel (PTX) by downregulating the Notch1 pathway. Mammosphere formation and expression of the stemness factor ALDH1 were also reduced in the cells treated with miR-34a and PTX compared to those treated with PTX alone. Taken together, our results indicate that miR-34a inhibited breast cancer stemness and increased the chemosensitivity to PTX partially by downregulating the Notch1 pathway, suggesting that miR-34a/Notch1 play an important role in regulating breast cancer stem cells. Thus miR-34a is a potential target for prevention and therapy of breast cancer.

Expression and activation of EGFR and STAT3 during the multistage carcinogenesis of intrahepatic cholangiocarcinoma induced by 3'-methyl-4 dimethylaminoazobenzene in rats.

The purpose of this study was to investigate whether the epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription-3 (STAT3) signal pathway contributes to the carcinogenesis of intrahepatic cholangiocarcinoma (ICC) induced by 3'-methyl-4 dimethylaminoazobenzene (3'Me-DAB) in rats. EGFR, TGFα, STAT3 and p-STAT3 in different stages of carcinogenesis were detected by immunohistochemistry (IHC). In situ hybridization (ISH) was applied to investigate the expression of STAT3 mRNA. Oval cells were verified by the immunohistochemical staining of alpha-fetoprotein (AFP), CD133 and epithelial cell adhesion molecules (EpCAM). Sequential development of necrosis, oval cell proliferation, cholangiofibrosis (CF) and ICC was observed in the liver of rats administered 3'Me-DAB. Oval cells showed positive expression of AFP, CD133 and EpCAM. The expression of EGFR was significantly higher in the ICC than in oval cells, CF or normal bile ducts (p<0.05), but there was no difference in EGFR expression between the other groups. The highest expression of p-STAT3 and TGFα was observed in CF. The expression of these two molecules in the ICC and oval cells was significantly higher than in normal bile ducts (p<0.05). Elevation of STAT3 mRNA was detected during carcinogenesis as shown by ISH, strong intensity was observed in the ICC and moderate intensity was observed in oval cells and CF. These observations suggest that the EGFR and STAT3 signal pathway contributes to the carcinogenesis of ICC. High activity of STAT3 during the carcinogenesis of ICC may be the result of high activity of EGFR triggered by TGFα.

[Inhibitory effect of salinomycin on human breast cancer cells MDA-MB-231 proliferation through Hedgehog signaling pathway].

OBJECTIVE: To investigate the inhibitory effect of salinomycin on human breast cancer cells in vitro, and to explore the related molecular mechanism. METHODS: Human breast cancer MDA-MB-231 cells were treated with salinomycin at different concentrations and at various time points. The effect of salinomycin on MDA-MB-231 cells proliferation was studied by CCK-8 method. The cell cycle status was examined by flow cytometry. RT-PCR and Western blot were used to detect the expression of Shh, Smo and Gli1 in the Hedgehog pathway at mRNA and protein levels. RESULTS: Proliferation of MDA-MB-231 cells treated with salinomycin was markedly inhibited in a concentration and time dependent manner. Salinomycin at concentrations of 0, 0.4, 0.8 and 1.6 µmol/L inhibited the growth at the rates of 11.18%, 25.88%, 50.03%, 92.65%, respectively. Salinomycin prevented MDA-MB-231 cells from G1 into S phase. Salinomycin at concentrations of 0, 0.8 and 1.6 µmol/L resulted in S-phase percentage of 25.03%, 11.85% and 35.21%, respectively (P < 0.05). RT-PCR and Western blot showed that the expression of key elements Shh, Smo and Gli1 in the Hedgehog pathway was inhibited by salinomycin in a concentration dependent manner (P < 0.05). CONCLUSION: Salinomycin prevents breast cancer cell transition from G1 to S phase through downregulation of the target genes of Hedgehog signaling pathway, leading to an effective inhibition of MDA-MB-231 cells.

[microRNA-140 suppresses the migration and invasion of colorectal cancer cells through targeting Smad3].

OBJECTIVE: To investigate the effect of microRNA-140 (miR-140) on the migration and invasion of colorectal cancer (CRC) cells and the possible mechanism. METHODS: miR-140 mimics, miR-140 specific inhibitor or small interfering RNA (siRNA) against Smad3 were transfected into human CRC cell line RKO cells respectively, using Oligofectamine or Lipofectamine2000. Quantitative real-time PCR (real-time PCR) was used to measure the expression levels of miR-140 and Smad3 mRNA. Smad3 protein was analyzed by Western blot. The in vitro cell migrating and invasive abilities were determined by wound-healing and Transwell chamber assay after up-regulating or down-regulating miR-140 or knocking down Smad3. RESULTS: The Western blot assays showed that the Smad3 protein level was significantly reduced after up-regulating miR-140 (0.04 ± 0.01), compared with that of (0.47 ± 0.02, P < 0.05) in the control group and that of (0.52 ± 0.06) in the negative control group (P < 0.05 for both). The results of real-time PCR indicated that no significant difference was found in the levels of Smad3 mRNA between miR-140 transfection and NC groups (1.11 ± 0.13 vs. 1.00 ± 0.06, P > 0.05). The wound-healing assay showed that the migrating ability was dramatically attenuated by miR-140 compared with that in the control and NC groups, whereas no significance was found when compared with that of the Smad3 siRNA transfected cells. The number of cells migrating through Transwell chamber without matrigel in the miR-140 group was (76.2 ± 4.4), remarkably lowered than that in the control (267.1 ± 4.9) and NC (336.1 ± 5.7) groups (P < 0.05 for both), but no significant difference between the miR-140 (76.2 ± 4.4) and Smad3 siRNA (83.5 ± 7.3) groups. Transwell chamber with matrigel assay showed that number of cells penetrating through the membrane was (109.5 ± 7.4) in the miR-140 group, significantly lower than that in the control (403.1 ± 5.1) and NC (392.6 ± 8.4) groups (P < 0.05 for both), while Smad3 siRNA transfection had a similar effect (138.8 ± 3.6)(P > 0.05). Down-regulation of miR-140 increased the level of smad3 protein expression, and partially reversed the inhibition of the cell migration and invasion mediated by miR-140. Co-transfection of miR-140 inhibitor and Smad3 siRNA had no significant effect on the Smad3 protein expression and the abilities of cell migration and invasion. CONCLUSIONS: miR-140 regulates the Smad3 expression at the post-transcriptional level. miR-140 suppresses the migrating and invasive abilities of CRC cells, possibly through down-regulation of Smad3. The findings of this study suggest that miR-140 may have a unique potential as a possible biomarker candidate for diagnosis and therapy of tumor metastasis.

[Down-regulation of Smoothened gene expression inhibits proliferation of breast cancer stem cells].

OBJECTIVE: To investigate the influence of down-regulating Smoothened (SMO) gene expression through short hairpin RNA (shRNA) on the proliferation of breast cancer stem cells. METHODS: Human SMO shRNA was designed, synthesized chemically, and transfected into MCF-7 cells to down-regulate SMO gene. By using G418, stable cells with down-regulated SMO were selected. In vitro proliferation of these cells was measured by CCK8 assay. The proportion of CD44(+)/CD24(-) cells was detected by flow cytometry and the mammospheres formation was determined by suspension sphere culture. The expression of SMO, GLI1 and Oct4 was detected by Western blot. In vivo, the volume of tumor was measured every 3 days and the expression of SMO, GLI1 and Oct4 detected by Western blot. RESULTS: In vitro, the cells were transfected with SMO-shRNA and selected by G418 after 21 days. SMO-shRNA effectively down-regulated the expression of SMO gene and protein, and inhibited the proliferation of MCF-7 and markedly reduced the proportion of CD44(+)/CD24(-) cells and mammospheres. In vivo, SMO-shRNA treatment of MCF-7 significantly inhibited the volume of tumor. The positive rate of SMO in negative control and SMO-shRNA group was 5/5 and 2/5, respectively. The expression of SMO, GLI1 and Oct4 in different groups were 0.72 ± 0.17 and 0.21 ± 0.09, 1.21 ± 0.21 and 0.47 ± 0.12, 0.83 ± 0.13 and 0.25 ± 0.07. SMO, GLI1 and Oct4 down-regulation significantly suppressed at protein levels (P < 0.05). CONCLUSION: The shRNA by chemical synthesis can effectively down-regulate SMO gene expression and inhibit the proliferation of breast cancer stem cells.

The interplay between H19 and HIF-1α in mitochondrial dysfunction in myocardial infarction.

Myocardial infarction(MI) causes prolonged ischemia of infarcted myocardial tissue, which triggers a wide range of hypoxia cellular responses in cardiomyocytes. Emerging evidence has indicated the critical roles of long non-coding RNAs(lncRNAs) in cardiovascular diseases, including MI. The purpose of this study was to investigate the roles of lncRNA H19 and H19/HIF-1α pathway during MI. Results showed that cell injury and mitochondrial dysfunction were induced in hypoxia-treated H9c2 cells, accompanied by an increase in the expression of H19. H19 silencing remarkably diminishes cell injury, inhibits the dysfunctional degree of mitochondria, and decreases the injury of MI rats. Bioinformatics analysis and dual-luciferase assays revealed that H19 was the hypoxia-responsive lncRNA, and HIF-1α induced H19 transcription through direct binding to the H19 promoter. Moreover, H19 participates in the HIF-1α pathway by stabilizing the HIF-1α protein. These results indicated that H19 might be a potential biomarker and therapeutic target for myocardial infarction.

Regulation of breast cancer tumorigenesis and metastasis by miRNAs.

miRNAs are a family of 17- to 23-nucleotide noncoding small RNAs that primarily function as gene expression fine regulators. A number of studies have shown that miRNAs play an important role in breast tumorigenesis, metastasis, proliferation and differentiation of breast cancer stem cells. This short review summarizes the progression of miRNA-mediated breast tumorigenesis and metastasis through various signaling pathways associated with drug resistance.

Lactobacillus salivarius SNK-6 Activates Intestinal Mucosal Immune System by Regulating Cecal Microbial Community Structure in Laying Hens.

The production performance and disease resistance of laying hens decrease obviously with age. This study aimed to investigate the effects of supplementary Lactobacillus salivarius (L. salivarius) SNK-6 on laying performance, the immune-related gene expression in cecal tonsil, and the cecal microbial composition of laying hens. Here, 384 Xinyang black commercial hens (55 weeks old) were randomly allocated to three groups under the same husbandry and dietary regimes: basal diet (Con), the low L. salivarius SNK-6 group (T1: 1.0 × 106 CFU/g), and the high L. salivarius SNK-6 group (T2: 1.0 × 107 CFU/g). The results showed that the feed intake and broken-egg rate in the T1 group were significantly higher than the Con group (p < 0.05). Meanwhile, expressions of intestinal mucosal immune-related genes were significantly upregulated. The 16S rRNA gene sequencing indicated that supplementary L. salivarius SNK-6 had no significant difference in α -diversity and only displayed a trend difference in the ß-diversity of cecal microbiota (p = 0.07). LEfSe and random forest were further used to identify bacteria family Enterobacteriaceae, order RF39, genera Ochrobactrum, and Eubacterium as biomarkers between the Con and T1 groups. Genera Ochrobactrum, which had high relative abundance and nodal degree in the T1 and T2 groups, showed a significant positive correlation with the expression of TLR-6, IL-10, MHC-II, and CD40 in cecal tonsils and might play a critical role in activating the host intestinal mucosal immune responses. Overall, dietary supplementary L. salivarius SNK-6 can display an immunomodulatory function, possibly by regulating cecal microbial composition. However, the changes in immune responses may be at the expenditure of corresponding production performance, which needs to be weighed up in practical application.

Retraction Notice to: MicroRNA-140 Inhibits the Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer.

[This retracts the article DOI: 10.1016/j.omtn.2017.12.022.].

Association Between Antioxidant Nutrients, Oxidative Stress-Related Gene Polymorphism and Skeletal Fluorosis in Guizhou, China.

Background: Oxidative stress plays an important role in the pathogenesis of endemic fluorosis. We analyzed associations between oxidative stress-related gene polymorphisms (PON1 rs662, CAT rs769217, rs2300182, and SOD2 rs11968525) and skeletal fluorosis, and examined potential gene-environment interactions with dietary vitamin C, vitamin E, zinc, and selenium intake. Methods: A cross-sectional study was conducted in the Zhijin County, Guizhou Province of China. Skeletal fluorosis was identified according to the Chinese Diagnostic Criteria of Endemic Skeletal Fluorosis. Dietary information was assessed through face-to-face interviews by trained interviewers using a 75-item food frequency questionnaire. The genotype was detected by high throughput TaqMan-MGB RT-PCR technology. Odds ratios (ORs) and 95% CIs were calculated using an unconditional logistic regression model. Results: Intake of vitamin E, zinc, and selenium was found to be inversely associated with the risk of skeletal fluorosis. The multivariable-adjusted ORs were 0.438 (95% CI: 0.268 to 0.715, P-trend < 0.001) for vitamin E, 0.490 (95% CI: 0.298 to 0.805, P-trend = 0.001) for zinc, and 0.532 (95% CI: 0.324 to 0.873, P-trend = 0.010) for selenium when comparing the highest with the lowest quartile. The relationship for vitamin C was not observed after adjustment for risk factors. Furthermore, participants with PON1 rs662 AA genotype had a significantly decreased risk of skeletal fluorosis compared with those with the GG genotype (OR = 0.438, 95% CI: 0.231 to 0.830). GG + AG genotype carriers were 2.212 times more likely to have skeletal fluorosis than AA carriers (OR = 2.212, 95% CI: 1.197 to 4.090). Compared with AA carriers, AG carriers had a 2.182 times higher risk of skeletal fluorosis (OR = 2.182, 95% CI: 1.143 to 4.163). Although we observed the risk of skeletal fluorosis was higher with a lower intake of antioxidant nutrients, the potential interactions between nutrient intake and genetic polymorphisms were not observed. Conclusion: Participants with a higher intake of vitamin E, zinc, and selenium have a lower likelihood of skeletal fluorosis. In addition, the PON1 rs662 polymorphism is related to skeletal fluorosis.

Retraction Notice to: A Novel Mechanism of Doxorubicin Resistance and Tumorigenesis Mediated by MicroRNA-501-5p-Suppressed BLID.

[This retracts the article DOI: 10.1016/j.omtn.2018.06.011.].

Association of BLK (rs13277113, rs2248932) polymorphism with systemic lupus erythematosus: a meta-analysis.

The B-cell lymphocyte kinase (BLK) is a src-family protein tyrosine kinase specifically expressed in B-lineage cells that has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) and has been investigated in numerous ethnically diverse studies. However, genetic association studies that have examined the association between BLK gene variants and SLE have produced conflicting results. To shed further light on this issue, we performed a meta-analysis of the association between rs13277113, rs2248932 polymorphism and SLE in different ethnic groups. An updated literature-based meta-analysis of six original articles involving 20,271 control individuals and 11,796 subjects with SLE was conducted. Crude ORs with 95% CIs were used to assess the strength of association between rs13277113, rs2248932 polymorphism and SLE risk. Publication bias was estimated using Egger's linear regression test. The authors assessed the evidence of genotypic association using STATA Version 10.0. The combined overall odds ratio, calculated for SLE and the risk A-allele of rs13277113 was 1.416 (95% CI: 1.358, 1.477). An odds ratio of 1.264 (95% CI: 1.208, 1.322) was found for the T-allele of rs2248932. Significant associations of rs13277113 and SLE were observed for dominant model (AA + AG vs. GG, OR: 1.518; 95% CI: 1.411, 1.632), and recessive model (AA vs. AG + GG, OR: 1.553; 95% CI: 1.461, 1.651); so were rs2248932 and SLE for dominant model (TT + TC vs. CC, OR: 1.342; 95% CI: 1.233, 1.460), and recessive model (TT vs. TC + CC, OR: 1.338; 95% CI: 1.257, 1.424). All of these were conducted in fixed effects model as heterogeneity was not detected. Tests for bias revealed no evidence of biases. On the assessment of available evidence, the authors concluded that moderate evidence exists for an association between the BLK rs13277113, rs2248932 variants and SLE. Therefore, further research is warranted on the role of BLK polymorphisms in the etiology of SLE.

Lack of association of FcγRIIIb polymorphisms with systemic lupus erythematosus: a meta-analysis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Fcγ receptor genes have been suggested to play an important role in the pathogenesis of SLE and lupus nephritis (LN). This study aims to assess the association between FcγRIIIb-NA1/NA2 polymorphism and the susceptibility to SLE and lupus nephritis. Relevant studies were identified from electronic databases. A meta-analysis was performed for heterogeneity test and pooled OR calculation. The overall OR of NA2/NA2 homozygous genotype and NA2 allele frequency showed no significant association with SLE and lupus nephritis. Similarly, the association between FcγRIIIb-NA1/NA2 polymorphism and SLE and lupus nephritis was not found in European and Asian population. Taken together, our results suggest that FcγRIIIb might not be a susceptibility gene for SLE and lupus nephritis.

The Roles of lncRNA in Myocardial Infarction: Molecular Mechanisms, Diagnosis Biomarkers, and Therapeutic Perspectives.

In recent years, long non-coding RNAs (lncRNAs) have been demonstrated to be associated with many physiological and pathological processes in cardiac. Recent studies have shown that lncRNAs are expressed dynamically in cardiovascular diseases and participate in regulation through a variety of molecular mechanisms, which have become a critical part of the epigenetic and transcriptional regulatory pathways in heart development, as well as the initiation and progress of myocardial infarction. In this review, we summarized some current research about the roles of lncRNAs in heart development and myocardial infarction, with the emphasis on molecular mechanisms of pathological responses, and highlighted their functions in the secondary changes of myocardial infarction. We also discussed the possibility of lncRNAs as novel diagnostic biomarkers and potential therapeutic targets for myocardial infarction.

Comprehensive Analysis of ceRNA Regulation Network Involved in the Development of Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD) is one of the most common causes of sudden death with high morbidity in recent years. This paper is aimed at exploring the early peripheral blood biomarkers of sudden death and providing a new perspective for clinical diagnosis and forensic pathology identification by integrated bioinformatics analysis. METHODS: Two microarray expression profiling datasets (GSE113079 and GSE31568) were downloaded from the Gene Expression Omnibus (GEO) database, and we identified differentially expressed lncRNAs, miRNAs, and mRNAs in CAD. Gene Ontology (GO) and KEGG pathway analyses of DEmRNAs were executed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified. Finally, we constructed a competitive endogenous RNA (ceRNA) regulation network among lncRNAs, miRNAs, and mRNAs. Also, the 5 miRNAs of the ceRNA network were verified by RT-PCR. RESULTS: In total, 86 DElncRNAs, 148 DEmiRNAs, and 294 DEmRNAs were dysregulated in CAD. We received 12 GO terms and 5 pathways of DEmRNAs. 31 nodes and 78 edges were revealed in the PPI network. The top 10 genes calculated by degree method were identified as hub genes. Moreover, there were a total of 26 DElncRNAs, 5 DEmiRNAs, and 13 DEmRNAs in the ceRNA regulation network. We validated the 5 miRNAs of the ceRNA network by RT-PCR, which were consistent with the results of the microarray. CONCLUSIONS: In this paper, a CAD-specific ceRNA network was successfully constructed, contributing to the understanding of the relationship among lncRNAs, miRNAs, and mRNAs. We identified potential peripheral blood biomarkers in CAD and provided novel insights into the development and progress of CAD.