Causal association between brain structure and obstructive sleep apnea: A mendelian randomization study.

OBJECTIVE: Previous studies have reported contradictory findings regarding the relationship between obstructive sleep apnea (OSA) and abnormal brain morphology. Furthermore, the causal relationship between OSA and brain morphology has not been clearly established. The aim of this study was to utilize Mendelian randomization (MR) analysis to investigate the impact of obstructive sleep apnea (OSA) on brain morphology and determine its potential causal relationship. METHODS: Firstly, the inverse-variance weighted (IVW) method was employed to assess the causal effects of OSA on cortical surface area and brain structure volume. Additionally, two additional MR methods, namely weighted median and MR-Egger, were used to supplement the results from IVW. Subsequently, a reverse MR analysis was conducted to determine the direction of causality. Furthermore, sensitivity analyses were performed including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. RESULTS: The results of the study showed that OSA patients had a tendency towards decreased cortical surface area and hippocampal volume in the precuneus region compared to individuals without OSA, while the superior temporal cortical surface area showed an increase. The results from the weighted median and MR-Egger analyses were consistent with those from the IVW analysis. Sensitivity tests confirmed the reliability of the causal estimates. CONCLUSIONS: This study provides preliminary evidence of an association between OSA and brain structure using large-scale genome-wide association data. The results demonstrate that OSA is associated with changes in brain structure. Therefore, individuals with OSA should be vigilant about the risks of related diseases due to alterations in brain tissue.

Relationship between four insulin resistance surrogates and regression to normoglycemia from prediabetes among Chinese adults: A longitudinal Cohort Study.

PURPOSE: We aimed to investigate the association of the triglyceride glucose-body mass index(TyG-BMI), metabolic score for insulin resistance (METS-IR) with regression to normoglycaemia, and further to compare the value of the four insulin resistance(IR) related indices(TyG-BMI, METS-IR, TyG and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio) in identifying regressions to normoglycaemia from prediabetes. METHODS: A total of 15,025 patients with prediabetes from the DATA-DRYAD database were included. Cox proportional hazards regression models and restricted cubic spline functions were performed to explore the association and nonlinearity between the indices with the incidence rate of normoglycaemia. Sensitivity and subgroup analyses evaluated the robustness of our findings. RESULTS: Compared with the first quintile, TyG-BMI and METS-IR was negatively linked with the probability of regression to normoglycaemia from prediabetes, the adjusted effect size of the highest quintiles of METS-IR were the most obvious (HR:0.456,95% CI:0.4-0.519), followed by TG/HDL (HR:0.792, 95% CI:0.733-0.856), TyG-BMI (HR:0.816, 95% CI:0.73-0.911) and TyG (HR:0.841, 95% CI: 0.754-0.937) (all p for trend <0.001). A 1.0 SD increase in METS-IR induced a 43% decrease in the probability of regression to normoglycaemia, with 9.8% for TyG-BMI. There were nonlinear associations between TyG-BMI and METS-IR and outcomes, with the inflection point of the TyG-BMI being 218.2 and that of the METS-IR being 37. CONCLUSIONS: The METS-IR might be the most superior indicator among the four non-insulin indices in identifying regressions to normoglycaemia from prediabetes in clinical application. The inflection points of the METS-IR and TyG-BMI may be instructive therapeutic points for assessing the status of prediabetes in advance and making more appropriate management and health care decisions.

Cardiac arrhythmia in COVID-19 patients.

The coronavirus disease 2019 (COVID-19) was first introduced in December 2019, which is known as severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2) that is a serious and life-threatening disease. Although pneumonia is the most common manifestation of COVID-19 and was initially introduced as a respiratory infection, in fact, the infection of COVID-19 is a subset of complications and damage to various organs. There are several reports of cardiac involvement with COVID-19. A wide range of cardiac complications may occur following COVID-19 infection, including systolic heart failure, myocarditis, pericarditis, atrial and ventricular arrhythmias, and thromboembolic events. There are various hypotheses about the pathophysiology of cardiovascular involvement by this virus. At the top of these hypotheses is the release of cytokines to the heart. Although there are other assumptions, considering that one of the causes of death in patients with COVID-19 is arrhythmia. It is necessary to know correctly about its pathophysiology and etiology. Therefore, in this study, we have reviewed the articles of recent years in the field of pathophysiology and etiology of arrhythmia in patients with COVID-19 infection. The purpose of this study was to provide a basis for a correct and more comprehensive understanding of the pathogenesis of arrhythmia in patients with COVID-19 infection.

Exogenous hydrogen sulfide alleviates hepatic endoplasmic reticulum stress via SIRT1/FoxO1/PCSK9 pathway in NAFLD.

High-fat-induced endoplasmic reticulum (ER) stress has been the main reason for the occurrence and development of nonalcoholic fatty liver disease (NAFLD). Hydrogen sulfide (H2 S) produces a marked effect on regulating lipid metabolism and antioxidation, whose effects on ER stress of NAFLD are still unclear. Here, we studied the influence of exogenous H2 S on NAFLD and its potential mechanism. In vivo, NAFLD model was induced by high-fat diet (HFD) for 12 weeks, followed by intraperitoneal injection of exogenous H2 S intervention for 4 weeks. HepG2 cells exposure to lipid mixture (LM) were used as vitro model to explore the potential mechanism. We found exogenous H2 S significantly inhibited the hepatic ER stress and improved the liver fat deposition of HFD-fed mice. These similar results were also observed in HepG2 cells dealt with LM after exogenous H2 S treatment. Further mechanism studies showed exogenous H2 S strengthened the combination of FoxO1 with the PCSK9 promoter gene through SIRT1-mediated deacetylation, thereby inhibiting the PCSK9 expression to relieve the hepatic ER stress. However, SIRT1 knockout eliminated the effects of exogenous H2 S on FoxO1 deacetylation, PCSK9 inhibition, and remission of hepatic ER stress and steatosis. In conclusion, exogenous H2 S improved NAFLD by inhibiting hepatic ER stress through SIRT1/FoxO1/PCSK9 pathway. Exogenous H2 S and ER stress may be potential drug and target for the treatment of NAFLD, respectively.

Anisotropic conductive reduced graphene oxide/silk matrices promote post-infarction myocardial function by restoring electrical integrity.

Myocardial infarction (MI) remains the leading cause of death globally, often leading to impaired cardiac function and pathological myocardial microenvironment. Electrical conduction abnormalities of the infarcted myocardium not only induce adverse myocardial remodeling but also prevent tissue repair. Restoring the myocardial electrical integrity, particularly the anisotropic electrical signal propagation within the injured area after infarction is crucial for an effective function recovery. Herein, optimized reduced graphene oxide (rGO) functionalized electrospun silk fibroin (rGO/silk) biomaterials presenting anisotropic conductivity and enhanced suturablity were developed and investigated as cardiac patches for their potential in improving the post-MI myocardial function of rat models. The results show that the anisotropic conductive rGO/silk patches exhibit remarkable therapeutic effect on repairing the infarcted myocardium compared to the nonconductive silk and isotropic conductive rGO/silk patches as determined by the enhanced pumping function, reduced susceptibility to arrhythmias, thickened left ventricular walls and improved survival of functional cardiomyocytes. Their notable effect on promoting the angiogenesis of capillaries in the infarcted myocardium has also been demonstrated. This study highlights an effective and biomimetic reconstruction of the electrical myocardial microenvironment based on the anisotropic conductive rGO/silk biomaterials as a promising option for promoting the repair of infarcted myocardium. STATEMENT OF SIGNIFICANCE: The dysfunctional electrical microenvironment in the infarcted myocardium not only aggravates the adverse myocardial remodeling but also limits the effect of cardiac regenerative medicine. Although various conductive biomaterials have been employed to restore the electrical network in the infarcted myocardium in vivo, the anisotropic nature of the myocardial electrical microenvironment which enables directional electrical signal propagation were neglected. In this study, an anisotropic conductive rGO/silk biomaterial system is developed to improve the myocardial function post infarction by restoring the anisotropic electrical microenvironment in the infarcted myocardium. The promoted effects of anisotropic conductive grafts on repairing infarcted hearts are demonstrated with improved pumping function, cardiomyocyte survival, resistance to ventricular fibrillation, and angiogenesis of capillary network.

rGO/Silk Fibroin-Modified Nanofibrous Patches Prevent Ventricular Remodeling via Yap/Taz-TGFß1/Smads Signaling After Myocardial Infarction in Rats.

Objective: After acute myocardial infarction (AMI), the loss of cardiomyocytes and dysregulation of extracellular matrix homeostasis results in impaired cardiac function and eventually heart failure. Cardiac patches have emerged as a potential therapeutic strategy for AMI. In this study, we fabricated and produced reduced graphene oxide (rGO)/silk fibroin-modified nanofibrous biomaterials as a cardiac patch to repair rat heart tissue after AMI and investigated the potential role of rGO/silk patch on reducing myocardial fibrosis and improving cardiac function in the infarcted rats. Method: rGO/silk nanofibrous biomaterial was prepared by electrospinning and vacuum filtration. A rat model of AMI was used to investigate the ability of patches with rGO/silk to repair the injured heart in vivo. Echocardiography and stress-strain analysis of the left ventricular papillary muscles was used to assess the cardiac function and mechanical property of injured hearts treated with this cardiac patch. Masson's trichrome staining and immunohistochemical staining for Col1A1 was used to observe the degree of myocardial fibrosis at 28 days after patch implantation. The potential direct mechanism of the new patch to reduce myocardial fibrosis was explored in vitro and in vivo. Results: Both echocardiography and histopathological staining demonstrated improved cardiac systolic function and ventricular remodeling after implantation of the rGO/silk patch. Additionally, cardiac fibrosis and myocardial stiffness of the infarcted area were improved with rGO/silk. On RNA-sequencing, the gene expression of matrix-regulated genes was altered in cardiofibroblasts treated with rGO. Western blot analysis revealed decreased expression of the Yap/Taz-TGFß1/Smads signaling pathway in heart tissue of the rGO/silk patch group as compared with controls. Furthermore, the rGO directly effect on Col I and Col III expression and Yap/Taz-TGFß1/Smads signaling was confirmed in isolated cardiofibroblasts in vitro. Conclusion: This study suggested that rGO/silk improved cardiac function and reduced cardiac fibrosis in heart tissue after AMI. The mechanism of the anti-fibrosis effect may involve a direct regulation of rGO on Yap/Taz-TGFß1/Smads signaling in cardiofibroblasts.

MicroRNA-26a Protects the Heart Against Hypertension-Induced Myocardial Fibrosis.

Background Hypertensive myocardial fibrosis (MF) is characterized by excessive deposition of extracellular matrix and cardiac fibroblast proliferation, which can lead to heart failure, malignant arrhythmia, and sudden death. In recent years, with the deepening of research, microRNAs have been found to have an important role in blood pressure control and maintaining normal ventricular structure and function. Methods and Results In this study, we first documented the downregulation of microRNA-26a (miR-26a) in the plasma and myocardium of spontaneously hypertensive rats; more importantly, miR-26a-deficient mice showed MF, whereas overexpression of miR-26a significantly prevented elevated blood pressure and inhibited MF in vivo and angiotensin II-induced fibrogenesis in cardiac fibroblasts by directly targeting connective tissue growth factor and Smad4. miR-26a inhibited cardiac fibroblast proliferation by the enhancer of zeste homolog 2/p21 pathway. Conclusions Our study identified a novel role for miR-26a in blood pressure control and hypertensive MF and provides a possible treatment strategy for miR-26a to alleviate and reverse hypertensive MF.

Matrix stiffness controls cardiac fibroblast activation through regulating YAP via AT1 R.

Cardiac fibrosis is a common pathway leading to heart failure and involves continued activation of cardiac fibroblasts (CFs) into myofibroblasts during myocardium damage, causing excessive deposition of the extracellular matrix (ECM) and thus increases matrix stiffness. Increasing evidence has shown that stiffened matrix plays an important role in promoting CF activation and cardiac fibrosis, and several signaling factors mediating CF mechanotransduction have been identified. However, the key molecules that perceive matrix stiffness to regulate CF activation remain to be further explored. Here, we detected significantly increased expression and nuclear localization of Yes-associated protein (YAP) in native fibrotic cardiac tissues. By using mechanically regulated in vitro cell culture models, we found that a stiff matrix-induced high expression and nuclear localization of YAP in CFs, accompanied by enhanced cell activation. We also demonstrated that YAP knockdown decreased fibrogenic response of CFs and that YAP overexpression promoted CF activation, indicating that YAP plays an important role in mediating matrix stiffness-induced CF activation. Further mechanistic studies revealed that the YAP pathway is an important signaling branch downstream of angiotensin II type 1 receptor in CF mechanotransduction. The findings help elucidate the mechanism of fibrotic mechanotransduction and may contribute to the development of new approaches for treating fibrotic diseases.

iTRAQ-Based Differential Proteomic Analysis Reveals the Pathways Associated with Tigecycline Resistance in Acinetobacter baumannii.

BACKGROUND/AIMS: Acinetobacter baumannii is an aerobic and Gram-negative bacterial pathogen with high morbidity and mortality. It remains a serious public health problem arising from its multidrug-resistant and extensive antibiotic resistance spectrum. METHODS: In the present study, iTRAQ coupled with 2D LC-MS/MS was used to evaluate the proteome in standard Acinetobacter baumannii standard strains and tigecycline-resistant strains. RESULTS: A total of 3639 proteins were identified and 961 proteins were identified to be differentially expressed in tigecycline-resistant Acinetobacter baumannii strains compared to the standard strains. 506 (52.6%) proteins were up-regulated and 455 (47.4%) proteins were down-regulated. Based on the GO enrichment analysis and KEGG pathway analysis, we concluded that most differentially expressed proteins were associated with stress responses, cellular component organization, proteins synthesis, degradation and function. Moreover, ß-lactam resistance, the longevity regulating pathway and other related pathways were also involved in the regulation of tigecycline-resistant Acinetobacter baumannii. The differential expression of key proteins were evaluated by transcript analysis using quantitative RT-PCR. CONCLUSION: These results may provide new insights into the mechanisms of drug resistance in Acinetobacter baumannii.

CYP17 polymorphisms are associated with decreased risk of breast cancer in Chinese Han women: a case-control study.

INTRODUCTION: CYP17 is the second most important enzyme in estradiol synthesis. Epidemiological studies have shown the associations between CYP17 polymorphisms and cancer risk. We conducted a case-control study to evaluate the relationship between CYP17 polymorphisms (rs743572 and rs2486758) and breast cancer (BC) risk. PATIENTS AND METHODS: This case-control study included 560 BC patients and 583 age-matched healthy controls from Northwest China. Two polymorphisms (rs743572 and rs2486758) of CYP17 were genotyped by using Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship. RESULTS: Compared with the wild genotype of rs743572, we found a significantly reduced risk of BC associated with the variant genotypes (heterozygote model: OR=0.69, 95% CI=0.53-0.89; homozygote model: OR=0.68, 95% CI=0.49-0.95; dominant model: OR=0.69, 95% CI=0.54-0.87; overdominant model: OR=0.78, 95% CI=0.62-0.98; allele model: OR=0.79, 95% CI=0.66-0.93). For rs2486758 polymorphism, we did not find any difference in any of the genetic models. Further stratification analysis by clinical characteristics showed rs743572 was associated with estrogen receptor status (heterozygote model: OR=2.13, 95% CI=1.47-3.08; homozygote model: OR=3.29, 95% CI=1.94-5.58; dominant model: OR=2.39, 95% CI=1.69-3.37) and progesterone receptor status (homozygote model: OR=3.17, 95% CI=1.82-5.55), but there was no association between rs2486758 and clinical characteristics of BC. Haplotype analysis showed that Grs743572Crs2486758 haplotype was a protective factor of BC (OR=0.52, 95% CI=0.40-0.67). Survival analysis did not find that CYP17 rs743572 polymorphism was associated with triple-negative BC, either in terms of overall survival or progression-free survival. CONCLUSION: Our results suggest that CYP17 polymorphisms may reduce the susceptibility to BC in Chinese women.

Integrated analysis of microRNA and mRNA expression profiles in rats with selenium deficiency and identification of associated miRNA-mRNA network.

Selenium deficiency is closely related with various type of cardiovascular disease. However, the miRNA-mRNA regulatory network in Selenium deficiency related cardiac change remains to be understand. In the present study, a reliable Selenium deficiency rat model was established and confirmed by pathological and biochemical examination. The mRNA and miRNA expression profiles were conducted by microarray technology. Gene Ontology (GO) Analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Analysis was performed to investigate the function of targeted genes, and the relationship between miRNA and mRNA was studied by network analysis. A total of 4931 mRNAs and 119 miRNAs was differentially expressed between any two groups (control group, low-selenium group and selenium supplementation group). GO and KEGG pathway analysis of selected miRNAs target genes found that selenium deficiency was related to several different biological processes. Furthermore, a miRNA-mRNA regulatory network was conducted to illustrate the interaction of miRNAs and these targeted genes. In conclusion, our present study provides a new insight that potential molecular mechanism of Selenium deficiency was a multiply miRNAs and mRNA caused biological change.

Successful treatment of toxic epidermal necrolysis using plasmapheresis: A prospective observational study.

Toxic epidermal necrolysis (TEN) is a rare, severe, life-threatening skin disease and it requires urgent critical care, including admission to the intensive care unit (ICU). It is characterized by fatal sequelae and high mortality. Currently, insufficient evidence exists to support the use of any systemic adjuvant therapy, such as cyclophosphamide, intravenous immunoglobulin (IVIg), or corticosteroids. However, plasmapheresis has been increasingly valued by clinicians due to its significant efficacy and little adverse side effects. To assess the efficacy of such treatment, 28 patients who were diagnosed with TEN or SJS/TEN overlap were continuously recruited in the ICU from February 2009 to August 2016. These patients including both children and adults were randomly divided into two groups based on whether or not plasmapheresis therapy was performed after admission, which resulted in a plasmapheresis group (n=13) and a non-plasmapheresis group (n=15). Severity of the disease and the efficacy of treatments were evaluated by the severity-of-illness score for TEN. The results indicated that plasmapheresis may be superior to conventional therapies, such as IVIg or corticosteroids. Furthermore, plasmapheresis combined with other treatments might not be advantageous compared to the effect of plasmapheresis alone.

The underlying risks of circadian blood pressure variation for carotid plaque in treated hypertensive patients with normal blood pressure.

OBJECTIVES: The aim of this study was to investigate the relationship between 24 h variation of blood pressure (BP) and carotid plaque in essential hypertensive patients with normal BP under anti-hypertensive treatment. PARTICIPANTS AND METHODS: A total of 322 hypertensive patients with systolic BP (SBP) and diastolic BP (DBP) within the normal range after routine treatment were continuously recruited and evaluated by ambulatory BP monitoring from 1 January 2014 to 31 July 2015. The exclusion criteria included participants younger than 18 or older than 90 years of age, pregnancy, night-work employment, and suffering from secondary hypertension. The prevalence of carotid plaque between different circadian BP pattern groups was analyzed using a χ-test. Logistic regression was applied to analyze the relationship between carotid plaque and ambulatory BP monitoring variables. RESULTS: All the individuals were divided into a 'carotid plaque' group (n=197) and a 'non-plaque' group (n=125) on the basis of whether the thickness of each plaque was at least 0.5 mm under the carotid ultrasound. In addition, patients were grouped into a dipper (10-20% nocturnal fall of BP in SBP) group and a nondipper (<10% nocturnal fall of BP in SBP) group on the basis of individual SBP variation. In the nondipper group, the number of patients with carotid plaque was higher than the patients without plaque (P=0.017). Logistic analysis showed that the nondipper pattern of BP was significantly associated with the formation of carotid plaque (odds ratio=1.731, P=0.041). CONCLUSION: A nondipper pattern of BP may serve as a risk factor for carotid plaque in treated hypertensive individuals with normal BP.

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study.

Previous studies have found associations between polymorphisms in T cell immunoglobulin and mucin domain 3 (TIM-3) and increased risks of various cancers. However, the association between TIM-3 polymorphisms and breast cancer (BC) remains uncertain. In this study, a total of 560 BC patients and 583 age, sex, and ethnicity-matched healthy controls from Northwest China were included. The polymorphisms were genotyped using Sequenom MassARRAY. The expression level of TIM-3 protein was detected by immunohistochemistry. We observed rs10053538 had a significantly increased risk of BC, comparing with the wild-type genotype even after Bonferroni correction. In addition, the rs4704853 G>A variants were more frequent among BC patients than the controls (GA + AA vs. GG: OR = 1.32, 95% CI = 1.03-1.69, P = 0.026); However, the significance was lost after Bonferroni correction (P = 0.078). Furthermore, rs10053538 was associated with lymph node metastasis. Age stratification revealed that among patients aged <49 years, those with the rs4704853 GA/AA genotype had a higher risk of BC; But there was no difference when Bonferroni correction was conducted. Immunohistochemical analysis showed that the expression of TIM-3 protein in the breast cancer tissues was higher in patients carrying the rs10053538 GT+TT genotype than those with GG genotype (P = 0.012). However, we failed to find any difference between BC patients and controls in any rs1036199 genetic model. These findings suggested that rs10053538 in TIM-3 might increase susceptibility to BC and promote the progression of BC in Chinese women.

Genetic association of deleted in colorectal carcinoma variants with breast cancer risk: A case-control study.

Deleted in colorectal carcinoma (DCC), a netrin-1 dependence receptor, is correlated with cell progression, migration, and adhesion. Evidence indicated that DCC was frequently down-regulated in many cancers. However, the association of DCC with breast cancer remains uncertain. We conducted a case-control study to investigate the impact of three DCC gene variants (rs2229080, rs7504990, and rs4078288) on breast cancer susceptibility in Chinese women. This study included 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. The three gene variants were genotyped via Sequenom MassARRAY. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to evaluate the associations. We found that individuals with the rs2229080 C/G, C/C, and C/G-CC genotypes had a higher breast cancer risk, and the minor allele C was associated with increased breast cancer risk in an allele model. We observed a significantly decreased breast cancer risk with the rs7504990 C/T, T/T, and C/T-T/T genotypes, and the minor allele T was protective against breast cancer in an allele model. In addition, rs2229080 was associated with the axillary lymph node (LN) metastasis status. An age-stratified analysis revealed an association between rs2229080 and reduced breast cancer risk among older patients (≥ 49 years). Furthermore, the haplotype analysis showed that the Crs2229080Crs7504990Ars4078288 haplotype was associated with a decreased breast cancer risk. However, the results indicated a lack of association between rs4078288 and breast cancer risk. These findings affirmed that rs2229080 and rs7504990 polymorphisms in DCC might be related with breast cancer susceptibility in Chinese women.

The Associations of Single Nucleotide Polymorphisms in miR196a2, miR-499, and miR-608 With Breast Cancer Susceptibility: A STROBE-Compliant Observational Study.

MicroRNAs (miRNAs) play an important role as regulators of tumor suppressors and oncogenes in cancer-related processes. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to be relevant to various different cancers, including breast cancer (BC). The aim of this study was to estimate the associations between miRNA-related gene polymorphisms (miR-196a2, miR-499, and miR-608) and the risk of BC in a Chinese population. Gene polymorphisms were analyzed in 1143 subjects (controls = 583; BC = 560). The 3 SNPs were genotyped using the Sequenom Mass-ARRAY platform. The associations between the SNP frequencies and BC were assessed by computing odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as by applying Chi-square tests. The miR-196a2 (rs11614913) T allele was associated with a decreased risk of BC based on results from dominant (OR = 0.67, 95% CI = 0.52-0.86), recessive (OR = 0.65, 95% CI = 0.48-0.86), and allele models (OR = 0.73, 95% CI = 0.62-0.86). In contrast, the miR-499 (rs3746444) AG/GG genotypes were associated with an increased risk of BC (OR = 1.45, 95% CI = 1.10-1.91), and miR-608 (rs4919510) was not significantly associated with BC risk. Our study suggested that the polymorphisms of rs11614913 and rs3746444 may be associated with BC risk in Chinese individuals.

Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study.

Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61-0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55-0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff-Bloom-Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.

Complete mitochondrial genome of Undaria pinnatifida (Alariaceae, Laminariales, Phaeophyceae).

Undaria pinnatifida is one of the most important economic marine algae and key components of coastal ecosystems. Undaria pinnatifida owns a typical heteromorphic, diplohaplontic life cycle. We present the complete sequence of mitochondrial genome of U. pinnatifida, focusing on genome organization and phylogenetic relationship between different brown algae lineages. The size of U. pinnatifida mitochondrial DNA is 37,402 bp, including 3 rRNAs, 25 tRNAs, 35 proteins, as well as 3 ORFs. No intron is found and most genes are encoded on the H-strand. The phylogenetic trees (BI) constructed on 35 protein-coding genes from 17 species proved that Saccharina has a closer relationship with Laminaria than that with Undaria. The results supported the conclusion that Alariaceae is sister genus to the Laminariaceae. Above researches will facilitate the understanding of evolutionary relationship within brown algae.