TEAD4: A key regulator of tumor metastasis and chemoresistance - Mechanisms and therapeutic implications.

Cancer metastasis is a complex process influenced by various factors, including epithelial-mesenchymal transition (EMT), tumor cell proliferation, tumor microenvironment, and cellular metabolic status, which remains a significant challenge in clinical oncology, accounting for a majority of cancer-related deaths. TEAD4, a key mediator of the Hippo signaling pathway, has been implicated in regulating these factors that are all critical in the metastatic cascade. TEAD4 drives tumor metastasis and chemoresistance, and its upregulation is associated with poor prognosis in many types of cancers, making it an attractive target for therapeutic intervention. TEAD4 promotes EMT by interacting with coactivators and activating the transcription of genes involved in mesenchymal cell characteristics and extracellular matrix remodeling. Additionally, TEAD4 enhances the stemness of cancer stem cells (CSCs) by regulating the expression of genes associated with CSC maintenance. TEAD4 contributes to metastasis by modulating the secretion of paracrine factors and promoting heterotypic cellular communication. In this paper, we highlight the central role of TEAD4 in cancer metastasis and chemoresistance and its impact on various aspects of tumor biology. Understanding the mechanistic basis of TEAD4-mediated processes can facilitate the development of targeted therapies and combination approaches to combat cancer metastasis and improve treatment outcomes.

HDAC11: A novel target for improved cancer therapy.

Histone deacetylase 11 (HDAC11) is a unique member of the histone deacetylase family that plays an important role in the regulation of gene expression and protein function. In recent years, research on the role of HDAC11 in tumors has attracted increasing attention. This review summarizes the current knowledge on the subcellular localization, structure, expression, and functions of HDAC11 in tumors, as well as the regulatory mechanisms involved in its network, including ncRNA and substrates. Moreover, we focus on the progress made in targeting HDAC11 to overcome tumor therapy resistance, and the development of HDAC11 inhibitors for cancer treatment. Collectively, this review provides comprehensive insights into the potential clinical implications of HDAC11 for cancer therapy.

Study on the Degradation of Methylene Blue by Cu-Doped SnSe.

Treatment of organic wastewater is still a difficult problem to solve. In this paper, Cu-doped SnSe powder was synthesized by a convenient and efficient hydrothermal method. Meanwhile, the degradation effect of different doping concentrations of SnSe on methylene blue was investigated. It was found that at low doping concentrations, the degradation effect on methylene blue was not obvious because Cu was dissolved in the lattice of the SnSe matrix at low concentrations. As the doping concentration increased, SnSe changed from a layered structure to a nanocluster structure with reduced particle size, and a mixed phase of SnSe and Cu2SnSe4 appeared. In fact, the degradation effect on methylene blue was significantly enhanced, and we found that the catalytic degradation effect on methylene blue was best at a doping concentration of 10 wt.%.

New insights into the roles of peroxiredoxins in cancer.

Oxidative stress is one of the hallmarks of cancer. Tumorigenesis and progression are accompanied by elevated reactive oxygen species (ROS) levels and adaptive elevation of antioxidant expression levels. Peroxiredoxins (PRDXs) are among the most important antioxidants and are widely distributed in a variety of cancers. PRDXs are involved in the regulation of a variety of tumor cell phenotypes, such as invasion, migration, epithelial-mesenchymal transition (EMT) and stemness. PRDXs are also associated with tumor cell resistance to cell death, such as apoptosis and ferroptosis. In addition, PRDXs are involved in the transduction of hypoxic signals in the TME and in the regulation of the function of other cellular components of the TME, such as cancer-associated fibroblasts (CAFs), natural killer (NK) cells and macrophages. This implies that PRDXs are promising targets for cancer treatment. Of course, further studies are needed to realize the clinical application of targeting PRDXs. In this review, we highlight the role of PRDXs in cancer, summarizing the basic features of PRDXs, their association with tumorigenesis, their expression and function in cancer, and their relationship with cancer therapeutic resistance.

Association Between Left Atrial Volume Index and Ventricular Repolarization Heterogeneity: A Cross-Sectional Study of a Healthy Chinese Population.

BACKGROUND: Electromechanical coupling may play a significant role in the association between abnormal myocardial mechanics and heterogeneity of repolarization. This study sought to assess the potential relationship between the left atrial volume index (LAVI), which is an important marker of cardiac diastolic function, and ventricular repolarization variables, such as the QT interval, Tpeak-to-Tend (Tpe) interval and Tpe/QT ratio, in an apparently healthy Chinese population. METHODS: This was a community-based cross-sectional study conducted in Shenyang, China. A total of 414 healthy subjects aged 35-91 years, including 186 men (44.9%), were enrolled. In addition to performing clinical and laboratory measurements, all subjects underwent comprehensive echocardiography and standard 12-lead electrocardiography. Echocardiographic and electrocardiographic results were analysed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations. RESULTS: Subjects were divided into four groups according to quartile of LAVI levels (<16.0, 16.0-18.9, 19.0-22.5 and >22.5 mL/m2). Ventricular repolarization variables, such as QT interval and QTc interval, gradually increased with the progression from low to high LAVI levels (P<0.05). LAVI was positively and significantly correlated with the QT interval, the QTc interval, and the Tpe interval (P<0.01). After adjusting for age and other possible confounders, LAVI showed significant and independent associations with the QT interval and the QTc interval (P<0.001; P=0.003). CONCLUSION: Echocardiographic LAVI is linearly associated with ventricular repolarization variables even in healthy people.

Severity of COVID-19 and Treatment Strategy for Patient With Diabetes.

Coronavirus disease 2019 (COVID-19), which was named by the World Health Organization (WHO) in February 2020, has quickly spread to more than 200 countries around the world and was declared as a global pandemic in March 2020. The severity of the disease makes it more prone to severe symptoms and higher mortality rates in patients, especially those who are with comorbidities, including high blood pressure, cardiovascular disease, obesity, and diabetes, increases the concern over the consequences of this pandemic. However, initial reports do not clearly describe whether diabetes itself or associated comorbidities or treatment strategies contribute to the severe prognosis of COVID-19 infections. Various clinical trials are being conducted on glucose-lowering agents but to date, there is no standard treatment protocol approved for COVID-19 cases with pre-existing diabetes. This review is aimed to decipher the potential risk factors of COVID-19 involved from existing evidence. Identification of a novel therapeutic strategy could be beneficial for combating SARS-CoV-2, which might be dreadful to debilitating people who have diabetes.

A Role of Glucose Overload in Diabetic Cardiomyopathy in Nonhuman Primates.

Type 2 diabetes (T2D) plays a major role in the development of heart failure. Patients with T2D have an increased risk to develop HF than healthy subjects, and they always have very poor outcomes and survival rates. However, the underlying mechanisms for this are still unclear. To help develop new therapeutic interventions, well-characterized animal models for preclinical and translational investigations in T2D and HF are urgently needed. Although studies in rodents are more often used, the research findings in rodents have often failed to be translated into humans due to the significant metabolic differences between rodents and humans. Nonhuman primates (NHPs) serve as valuable translational models between basic studies in rodent models and clinical studies in humans. NHPs can recapitulate the natural progress of these diseases in humans and study the underlying mechanism due to their genetic similarity and comparable spontaneous T2D rates to humans. In this review, we discuss the importance of using NHPs models in understanding diabetic cardiomyopathy (DCM) in humans with aspects of correlations between hyperglycemia and cardiac dysfunction progression, glucose overload, and altered glucose metabolism promoting cardiac oxidative stress and mitochondria dysfunction, glucose, and its effect on cardiac resynchronization therapy with defibrillator (CRT-d), the currently available diabetic NHPs models and the limitations involved in the use of NHP models.

Hypoxia-induced alterations of transcriptome and chromatin accessibility in HL-1 cells.

Cardiac hypoxia plays a significant role in various types of heart disease, and improper treatment of hypoxia often leads to myocardial cell damage or even death. Transcriptome profiling and open chromatin mapping have been used as powerful tools to understand the development of heart disease, but the interplay between gene expression and chromatin accessibility has not been extensively investigated in hypoxia-induced cardiac damage. In this study, with HL-1 cardiomyocytes as a model, we performed temporal profiling of transcriptome and chromatin accessibility to show the cardiac responses to hypoxia (for 4 and 8 hr) and reoxygenation (for 24 hr). With RNA-seq and ATAC-seq, we identified a total of 2,912 differentially expressed genes and 3,004 differential peaks across the whole genome and showed that these data were in good agreement with each other. For hypoxia-related genes, we also discovered high correlations between their ATAC-seq signals and mRNA levels, such as VEGF, Angpt1, Slc2a1, Bnip3, and Casp3 with Pearson correlations >0.7. Interestingly, after 24 hr reoxygenation, the expression levels of 235 genes were still significantly different from the counterparts in the control, suggesting that these genes need a longer recovery time after reoxygenation. In conclusion, our study shows the close relationship between alterations of transcriptome and chromatin accessibility after hypoxia exposure and reoxygenation, emphasizing the importance of open chromatin profiling in related studies. In addition, the profiled molecular responses here will be valuable resources for better understanding of the mechanisms responsible for hypoxia-induced heart disease in future.

Relationship between Long Noncoding RNA H19 Polymorphisms and Risk of Coronary Artery Disease in a Chinese Population: A Case-Control Study.

METHODS: We collected 732 samples from Liaoning Province, China, and three polymorphisms in long noncoding RNA H19 were genotyped using the KASP platform. RESULTS: Our data showed that H19 rs2735971 and rs3024270 variant genotypes were associated with a decreased risk of CAD (rs2735971, P = 0.003, odds ratio (OR) = 0.6195, 95% confidence interval = 0.44 - 0.84; rs3024270, P = 0.030, OR = 0.65, 95% confidence interval = 0.44 - 0.96). No significant association with the risk of CAD was found for H19 rs2839698 polymorphism (P > 0.05). In haplotype analysis, H19 polymorphisms of rs2735971-rs2839698-rs3024270 A-C-C haplotype reduced the risk of CAD by 0.61-fold (P = 0.004, OR = 0.61, 95% confidence interval = 0.43-0.86). In addition, we found that rs2839698 interacted with smoking (P interaction = 0.027), and according to multifactor dimensionality reduction analysis, the three-factor model including H19 rs2839698-smoking-drinking was the best model for the risk of CAD (testing balanced accuracy = 0.6979). CONCLUSION: Our study demonstrated that some genotypes of H19 rs2735971 and rs3024270 polymorphisms, as well as rs2735971-rs2839698-rs3024270 A-C-C haplotype, were associated with the risk of CAD in a Chinese population, and these genotypes have the potential to be biomarkers for predicting CAD risk. We also found that rs2735971-rs2839698-rs3024270 A-C-C may have a significantly lower risk of CAD. The recessive genetic model of rs3024270 could predict the severity of CAD.

LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case-control study in a Chinese population.

Background: Coronary artery disease (CAD) is one of the main fatal diseases all over the world. CAD is a complex disease, which has multiple risk factors mechanisms. In recent years, genome-wide association study (GWAS) had revealed single nucleotide polymorphism genes (SNPs) which were closely related with CAD risks. The relationship between long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and CAD risk is largely unknown. To our knowledge, this is the first study which demonstrated the interaction effects of SNP-SNP and SNP-environment with CAD risk. In general, our case-control study is to detect the association between MALAT1 (rs619586, rs4102217) SNPs and CAD risk. Methods: Three hundred and sixty-five CAD patients and three hundred and eighty-four matched control participants blood samples were collected in Liaoning province, China. Two polymorphisms (rs619586, rs4102217) in lncRNA MALAT1 were genotyped by KASP platform. Results: In a stratified analysis, we found that non-drinkers with GC genotype and the recessive model of rs4102217 had higher CAD risk (P=0.010, odds ratio (OR): 1.96, 95% confidence interval (CI) = 1.17-3.28; P=0.026, OR: 1.73, 95% CI = 1.07-2.79) and diabetes mellitus (DM) history group (P=0.010, OR: 4.07, 95% CI = 1.41-11.81; P=0.019, OR: 3.29, 95% CI = 1.22-8.88). In SNP-SNP interactions analysis between MALAT1 and CAD risk, we found rs4102217 had an increase in smokers (GG: OR: 2.04, 95% CI = 1.42-2.92; CC+GC: OR: 2.64, 95% CI = 1.64-4.26) and a decrease in drinkers (CC+GC: OR: 0.33, 95% CI = 0.20-0.55). Smokers with MALAT1 rs619586 AA genotype (OR: 2.20, 95% CI = 1.57-3.07) and GG+AG genotype (OR: 2.11, 95% CI = 1.17-3.81) had a higher risk of CAD. Moreover, drinkers with AA genotype (OR: 0.22, 95% CI = 0.10-0.48) and GG+AG genotype (OR: 0.38, 95% CI = 0.22-0.65) had a lower risk of CAD. According to the MDR software, MALAT1 rs4102217 polymorphism-smoking-drinking was the best interaction model, which has higher risk of CAD (Testing Bal.ACC. = 0.6979). Conclusion: Our study demonstrated that the GC genotype and the recessive model of rs4102217 potentially increased CAD risk in some specific group.

BmTudor-sn Is a Binding Protein of Destruxin A in Silkworm Bm12 Cells.

Destruxin A (DA), a hexa-cyclodepsipeptidic mycotoxin secreted by the entomopathogenic fungus Metarhizium anisopliae, was reported to have an insecticidal effect and anti-immunity activity. However, its molecular mechanism of action remains unclear. Previously, we isolated several potential DA-affinity (binding) proteins in the Bombyx mori Bm12 cell line. By docking score using MOE2015, we selected three proteins-BmTudor-sn, BmPiwi, and BmAGO2-for further validation. First, using Bio-Layer Interferometry in vitro, we found that BmTudor-sn had an affinity interaction with DA at 125, 250, and 500 µM, while BmPiwi and BmAGO2 had no interaction signal with DA. Second, we employed standard immunoblotting to verify that BmTudor-sn is susceptible to DA, but BmPiwi and BmAGO2 are not. Third, to verify these findings in vivo, we used a target engagement strategy based on shifts in protein thermal stability following ligand binding termed the cellular thermal shift assay and found no thermal stability shift in BmPiwi and BmAGO2, whereas a shift was found for BmTudor-sn. In addition, in BmTudor-sn knockdown Bm12 cells, we observed that cell viability increased under DA treatment. Furthermore, insect two-hybrid system results indicated that the key site involved in DA binding to BmTudor-sn was Leu704. In conclusion, in vivo and in vitro experimental evidence indicated that BmTudor-sn is a binding protein of DA in silkworm Bm12 cells at the 100 µM level, and the key site of this interaction is Leu704. Our results provide new perspectives to aid in elucidating the molecular mechanism of action of DA in insects and developing new biopesticide.

Associations between circulating IgG antibodies to Apolipoprotein B100-derived peptide antigens and acute coronary syndrome in a Chinese Han population.

Objectives: Acute coronary syndrome (ACS) is the major cause of mortality worldwide and caused mainly by atherosclerosis of coronary arteries. Apolipoprotein B100 (ApoB100) is a major component of low-density lipoprotein (LDL) and its oxidation can trigger inflammation in vascular endothelial cells leading to atherosclerosis. The association between antibodies to ApoB100-derived antigens and atherosclerotic diseases has been studied in recent years, but the findings appear to be controversial. The present study developed an ELISA in-house with ApoB100-derived peptide antigens to circulating anti-ApoB100 IgG antibodies in patients with ACS. Methods: Fifteen ApoB100-derived peptide antigens (Ag1-Ag15) were designed to develop an in-house ELISA for the detection of circulating anti-ApoB100 IgG levels in 350 patients with ACS and 201 control subjects amongst a Chinese population. Binary logistic regression was applied to examine the differences in anti-ApoB IgG levels between the patient group and the control group with adjustment for a number of confounding factors; the correlation between anti-ApoB100 IgG levels and clinical characteristics was also tested. Results: Patients with ACS had significantly higher levels of plasma IgG for Ag1 (adjusted P<0.001) and Ag10 antigens (adjusted P<0.001). There was no significant increase in the levels of IgG to the other 13 antigens in these ACS patients. In the control group, anti-Ag10 IgG levels were positively correlated with age, high-density lipoprotein (HDL), and ApoA levels (P≤0.001 for all) and negatively correlated with blood triglyceride (TG) (P=0.008); in the patient group, anti-Ag10 IgG levels were positively correlated with LDL (P=0.003), and negatively correlated with ApoA (P=0.048) and systolic blood pressure (SBP) (P=0.036). The area under ROC (receiver operator characteristic) curve (AUC) was 0.612 (95% confidence interval (CI): 0.560-0.664; P<0.001) in anti-Ag1 IgG assay and 0.621 (95% CI: 0.569-0.672; P<0.001) in anti-Ag10 IgG assay. Conclusion: Circulating IgG for ApoB100-derived peptide antigens may be a useful biomarker of ACS, although anti-ApoB IgG levels were not associated with the coronary artery plaque burden characterized by the coronary Gensini score.

A brief review: the therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction.

Myocardial infarction (MI) results in dysfunction and irreversible loss of cardiomyocytes and is among the most serious health threats today. Bone marrow mesenchymal stem cells (BMSCs), with their capacity for multidirectional differentiation, low immunogenicity, and high portability, can serve as ideal seed cells in cardiovascular disease therapy. In this review, we examine recent literature concerning the application of BMSCs for the treatment of MI and consider the following aspects: activity of transplanted cells, migration and homing of BMSCs, immunomodulatory and anti-inflammatory effects of BMSCs, anti-fibrotic activity of BMSCs, the role of BMSCs in angiogenesis, and differentiation of BMSCs into cardiomyocyte-like cells and endothelial cells. Each aspect is complementary to the others and together they promote the repair of cardiomyocytes by BMSCs after MI. Although transplantation of BMSCs has enabled new options for MI treatment, the critical issue we must now address is the reduced viability of transplanted BMSCs due to inadequate blood supply, poor nourishment of cells, and generation of free radicals. More clinical trials are needed to prove the therapeutic potential of BMSCs in MI.

Destruxin A Induces and Binds HSPs in Bombyx mori Bm12 Cells.

Destruxin A (DA) is a cyclodepsipeptidic mycotoxin isolated from the entomopathogenic fungus, Metarhizium anisopliae. It has insecticidal activity against host insect's innate immunity system, but the molecular mechanism is not yet elucidated. In our previous experiment, four HSPs (heat shock proteins, BmHSP70-3, BmHSP75, BmHSP83, and BmHSCP) were characterized from the specific protein electrophoretic bands of Bombyx mori Bm12 cell line treated with DA in the test of drug affinity responsive target stability (DARTS), which implied that these HSPs might be kinds of DA-affinity proteins, or DA induces them up-regulated expression. Therefore, in current research, the interactions of DA and HSPs were explored through analysis of bio-layer interferometry (BLI) employing FortBio OcteteQK. The expression levels of HSPs genes were surveyed by quantitative real-time polymerase chain reaction (qPCR). The results indicated that DA had no interactions with BmHSP70-3, BmHSP75, and BmHSP83, but had affinity to BmHSCP with a KD value of 88.1 µM, in BLI analysis. However, the expression levels of all HSPs genes were significantly up-regulated after the Bm12 cells were treated by DA. In conclusion, DA can induce the four HSPs expression in Bm12 cells, but DA only binds to BmHSCP. Our research provides new insights on understanding of the action mechanisms of destruxins.

The Effects of Destruxin A on Relish and Rel Gene Regulation to the Suspected Immune-Related Genes of Silkworm.

Destruxin A (DA), a cyclodepsipeptidic mycotoxin of entomopathogenic fungus, Metarhizium anisopliae, has anti-immunity activity against insects, but the mechanism of immune regulation is not clear yet. In our previous experiment, the significant expression changes of Bm_nscaf2838_045, Bm_nscaf2674_066, and Bm_nscaf2767_133 genes in a silkworm's hemocytes were found, which suggested that these genes might be involved in insect's innate immunity. In the current experiment, the silkworm cell line Bm12 was used to survey the expression levels of these genes after the cells were treated with DA and the transcription factors BmRel, BmRelish1 and BmRelish2 were silenced by specific siRNA. The results indicated that, after the cells were treated by DA, the gene expression level of BmRelish2 was significantly downregulated, but BmRel and BmRelish1 were not changed. The results also showed that the gene expression levels of Bm_nscaf2838_045 and Bm_nscaf2674_066 had similar phenomena, i.e., downregulation with individual BmRelish1 gene silence or DA treatment, upregulation with combination of BmRelish1 gene silence and DA treatment, upregulation with individual BmRelish2 gene silence, and downregulation with combination of BmRelish2 gene silence plus DA treatment, but no changes in the BmRel gene silence combined with DA treatment. For the Bm_nscaf2767_133 gene, the downregulated expressions were found in individual BmRelish2 gene silence or DA treatment, upregulation in the combination treatment of BmRelish2 gene silence plus DA, and the individual treatment of BmRel or BmRelish1 silence. It is suggested that expressions of the Bm_nscaf2838_045 and Bm_nscaf2674_066 genes are closely related to the Imd signal pathway, but Bm_nscaf2767_133 genes might involve in both Toll and Imd pathways. Furthermore, the BmRelish1 gene acts as an activator and the BmRelish2 gene acts as a repressor for both Bm_nscaf2838_045 and Bm_nscaf2674_066 gene expressions. It also implies that DA may participate in the splicing process of BmRelish where BmRelish2 was promoted. Our research will provide new insights on the understanding of the activity mechanisms of destruxins.

Effects of acetaldehyde and L-carnitine on morphology and enzyme activity of myocardial mitochondria in rats.

This study aimed to investigate the effects of acetaldehyde (AA) and L-carnitine (LC) on morphology and enzyme activity of myocardial mitochondria in rats. Sixty-five Wistar rats were randomly divided into 4 groups: the control group (n = 20), the AA low-dose group (n = 15), the AA high-dose group (n = 15) and the AA + LC group (n = 15). Different doses (110 mg/kg and 220 mg/kg) AA was injected intraperitoneally once a day for 4 weeks. After 4 weeks administration, transmission electron microscope (TEM) observation of morphology of rat myocardial mitochondria was performed. Serum levels of succinate dehydrogenase (SDH), superoxide dismutase (SOD), malondialdehyde (MDA) and cardiac troponin I (cTnI) were detected to evaluate mitochondrial enzymes activities. Light micrograph of rat myocardiocytes in the control group showing normal architecture of myocytes. The numerical density and number of mitochondria in both low-dose and high-dose AA groups were lower than that of the control group. After administration of LC, the rats in the AA + LC group showed an obvious increase in the numerical density and number of mitochondria. TEM showed that both low-dose and high-dose AA could induce myocardial mitochondrial damage in rats in a dose-dependent manner, such as mitochondrial swelling, disruptions of crest and membrane, mitochondrial deficiency. The degree of mitochondrial damage of the AA + LC group was significantly decreased after administration of LC. Our results showed that serum levels of SDH and SOD in the AA + LC and control groups were also higher than those of the low-dose and high-dose AA groups; while the MDA level in the AA + LC and control groups were lower than that of the low-dose and high-dose AA groups. The low-dose AA, high-dose AA and AA + LC groups exhibited a higher level of serum cTnI than that of the control group. However, there was no significant difference in serum cTnI level among the low-dose AA, high-dose AA and AA + LC groups. Our findings indicate that AA may lead to myocardial mitochondrial damage and the induction of enzyme activity in rats, while administration of LC could alleviate AA-related damage of rat myocardial mitochondria.

Common polymorphisms in the interleukin-6 gene and myocardial infarction risk: a meta-analysis.

BACKGROUND: Interleukin-6 (IL-6) plays a critical role in the development and progression of cardiovascular disease. Emerging evidence suggests that two common polymorphisms (-174 G/C and -572 G/C) in the IL-6 gene might have an impact on an individual's susceptibility to myocardial infarction (MI), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationship between IL-6 -174 G/C and -572 G/C polymorphisms and MI risk. METHOD: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases from their inception through August 1st, 2013. A meta-analysis was then performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Eleven case-control studies were included with a total of 10,252 subjects, including 5429 MI patients and 4823 healthy controls. Our meta-analysis results indicated that IL-6 -174 G/C polymorphism may increase the risk of MI (C allele vs. G allele: OR=1.07, 95% CI: 1.01-1.14, p=0.018; GC+CC vs. GG: OR=1.14, 95% CI: 1.04-1.24, p=0.003; respectively). However, our results showed no significant association between IL-6 -572 G/C polymorphism and MI risk (C allele vs. G allele: OR=0.88, 95% CI: 0.75-1.03, p=0.098; GC+CC vs. GG: OR=0.87, 95% CI: 0.70-1.07, p=0.173; respectively). No publication bias was detected in this meta-analysis. CONCLUSION: The current meta-analysis suggests that IL-6 -174 G/C polymorphism may contribute to MI susceptibility. Thus, detection of IL-6 -174 G/C polymorphisms may be a promising biomarker for the early detection of MI. However, IL-6 -572 G/C polymorphism may not associate with the risk of MI.

Glutathione S-transferase M1 polymorphism and coronary heart disease susceptibility: a meta-analysis involving 47,596 subjects.

BACKGROUND: Many studies have investigated the association between glutathione S-transferase M1 (GSTM1) null genotype and the risk of coronary heart disease (CHD). However, the effect of the GSTM1 null genotype on CHD is still unclear because of apparent inconsistencies among those studies. A meta-analysis was performed to characterise the relationship more accurately. METHODS: Pubmed, Embase, and Web of Science were searched. We estimated the summary odds ratio (OR) with a 95% confidence interval (95% CI) to assess the association. RESULTS: Up to 26 case-control studies with 13,929 CHD cases and 33,667 control cases were included into this meta-analysis. Meta-analysis of the 26 studies showed that GSTM1 null genotype was associated with the risk of CHD (random effects OR=1.35, 95% CI 1.00 to 1.83). After adjustment for heterogeneity, meta-analysis showed that GSTM1 null genotype was not associated with increased risk of CHD in the total population (fixed effects OR=1.01, 95% CI 0.95 to 1.07). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR=1.36, 95% CI=0.96-1.92) or Asians (OR=1.28, 95% CI=0.91-1.80). When stratified by smoking status, in the subgroup of smokers, GSTM1 null genotype was significantly associated with increased CHD risk (random effects OR=1.64, 95% CI 1.02 to 2.64). No evidence of publication bias was observed. CONCLUSION: In conclusion, this meta-analysis suggested that there is overall lack of association between GSTM1 genotypes and CHD risk, however, GSTM1 null genotype when combining with smoking history may contribute to CHD susceptibility.

SELP genetic polymorphisms may contribute to the pathogenesis of coronary heart disease and myocardial infarction: a meta-analysis.

We conducted a meta-analysis of case-control studies to determine whether SELP genetic polymorphisms contribute to the pathogenesis of coronary heart disease (CHD) and myocardial infarction (MI). A range of electronic databases were searched: MEDLINE (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese biomedical database (1982-2013) without language restrictions. Meta-analysis was performed with the use of the STATA statistical software. Nine case-control studies with a total of 3,154 CHD patients, 1,608 MI patients and 17,304 healthy controls were involved in this meta-analysis. Six common polymorphisms in the SELE gene were assessed, including -1969G/A (rs1800805 G>A), -1817T/C (rs1800808 T>C), -2123C/G (rs1800807 C>G), Thr715Pro (rs6136 A>C), Leu599Val (rs6133 G>T), and Ser290Asn (rs6131 C>T). Our findings illustrated significantly positive associations of SELE genetic polymorphisms with the development of CHD and MI. The results of subgroup analysis by SNP type indicated that -1969G/A, -1817T/C, -2123C/G, Thr715Pro and Ser290Asn in the SELP gene might be strongly correlated with CHD and MI risk, but no similar results were found in SELP Leu599Val polymorphism. In the subgroup analysis by ethnicity, our results indicated significant relationships between SELE genetic polymorphisms and the pathogenesis of CHD and MI among Asians and Caucasians. However, we observed no significant associations between SELP genetic polymorphisms and the risk of CHD and MI among Africans. Our findings provide empirical evidence that SELE genetic polymorphisms may contribute to the pathogenesis of CHD and MI, especially among Asians and Caucasians. Thus, SELP genetic polymorphisms could be potential and practical biomarkers for early diagnosis of CHD and MI.

ABCB1 C3435T polymorphism and the risk of coronary heart disease: a meta-analysis.

BACKGROUND: ATP-binding cassette transporter 1 (ABCB1) plays a critical role in the development and progression of cardiovascular disease. Emerging evidence suggests that common functional polymorphisms in the ABCB1 gene might have an impact on an individual's susceptibility to coronary heart disease (CHD), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationship between ABCB1 C3435T polymorphism and CHD risk. METHOD: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases from their inception through August 1st, 2013. Meta-analysis was performed using the STATA 12.0 software. The crude odds ratio (OR) with 95% confidence interval (CI) were calculated. RESULTS: Seven clinical studies were included with a total of 13,074 CHD patients, including 378 variant angina pectoris (VAP) patients, 2290 myocardial infarction (MI) patients, and 10,406 acute coronary syndrome (ACS) patients. Our meta-analysis results indicated that ABCB1 C3435T polymorphism may be associated with an increased risk of CHD, especially for MI and ACS among Caucasian populations. However, no statistically significant association was found between ABCB1 C3435T polymorphism and VAP risk, especially among Asian populations. Meta-regression analyses showed that clinical subtype and ethnicity may be the main sources of heterogeneity. No publication bias was detected in this meta-analysis. CONCLUSION: The current meta-analysis suggests that ABCB1 C3435T polymorphism may contribute to the risk of CHD, especially for MI and ACS, among Caucasian populations. Thus, detection of ABCB1 C3435T polymorphism may be a promising biomarker for the early detection of CHD.