The copy number variation of DMBT1 gene effects body traits in two Chinese cattle breeds.

Copy number variations (CNVs) belong to mutations in the genome level with loci in the region of genic or intergenic. It is through different effects (such as position effect and dose effect) that influence complex traits and diseases. Deleted in Malignant Brain Tumors 1 (DMBT1) gene is a member of the scavenger receptor cysteine-rich super family. In cattle, this gene has been associated with the susceptibility to bovine tuberculosis. In this study, a new CNV was found in DMBT1 gene of Chinese cattle breeds and tested in two different Chinese cattle breeds (Jiaxian red and Pinan) for frequency distribution analysis. Besides, the body size data such as body length, body height, chest girth, chest width, rump length, and rump girth for Jiaxian (JX) and Pinan (PN) cattle were collected and associated with the newly identified CNV. The CNV was significantly associated with the body length and chest girth of JX cattle, and the rump length of PN cattle (P < 0.05). Furthermore, the expression profile of the DMBT1 gene was tested in calves' tissues and the myoblasts differentiation. It was found that the DMBT1 gene expression was high in tuberculosis susceptible tissues (liver and lungs) at the calf stage and high in myoblast early differentiation. These tests were done using the qPCR method. As the result, the CNV of DMBT1 gene could be used as a candidate marker for bovine growth and health in marker-assisted selection (MAS) breeding.

Effect of copy number variation of PLA2G2A gene to growth traits in Chinese cattle.

SIMPLE SUMMARY: As a member of genetic polymorphism, copy number variation has been a commonly used method in the world for investigating effect of genetic polymorphism on gene expression. Effect of genetic polymorphism made on livestock development has been more and more important in beef cattle molecular breeding. The characteristics of Chinese cattle are excellent meat quality, tolerant to rough feeding, good environmental adaptability and so on. But there are some obvious weaknesses still exist in the process of cattle growth and development, such as weak hindquarters and growth slowly. To improve the growth performance and market competitiveness of Chinese cattle, a lot of studies have been made about finding and investigating effective molecular marker. In this study, Q-PCR and data association analysis were used for PLA2G2A gene copy number variation detection and related effect analysis in Chinese cattle. Results showed that PLA2G2A gene has a significant effect on two breeds of Chinese cattle on growth traits, which could be a basic materials and effective information of cattle molecular markers breeding. PLA2G2A, member of secreted phospholipases A2 (sPLA2) in superfamily of phospholipase A2, could catalyze the process of glycerophospholipids hydrolysis from position of sn-2 acyl with the release of free fatty acids and lysophospholipids. Researches about PLA2G2A gene are mostly focus on disease, including tumors and diabetes, the number of study occurred on animal breeding is weak. In this study, blood samples were collected from five breeds of Chinese cattle (Qingchuan cattle, Xianan cattle, Yunling cattle, Pinan cattle and Guyuan cattle) for PLA2G2A gene CNV type detection. SPSS 20.0 software and method of ANOVA were used to analyzed the association between types of CNV and growth traits. Results reveal that the distribution of different copy number types in different cattle breeds is different. In QC, XN and GY cattle, the frequencies of Deletion and Duplication are about 40%; in YL cattle, the frequency of Deletion type exceeds 60%; in PN cattle, the frequency of Duplication is closed to 80%. Association analysis indicate that CNV of PLA2G2A gene showed a positive effect in cattle growth: in QC cattle, Chest depth with Normal type copy number possess a increased trend (P < 0.05); individuals with Deletion type copy number have better performance on Height at sacrum, Heart girth and Body height in GY cattle (P < 0.05). The functional role and molecular mechanism of PLA2G2A gene in animal growth and development are still unclear, and it is necessary for processing a further research. This research aims to provide basic materials for molecular breeding of Chinese cattle.

M2 macrophage-derived exosomes carry miR-1271-5p to alleviate cardiac injury in acute myocardial infarction through down-regulating SOX6.

BACKGROUND: Emerging evidence has indicated that exosomes serve as key regulators in acute myocardial infarction (AMI). This study was determined to investigate the effect of M2 macrophage-derived exosomes (M2-Exos) in AMI and the further mechanism. METHODS: M2 macrophages were induced and M2-exos were isolated and verified. The AMI mouse model was prepared by ligation of the left anterior descending coronary artery (LAD) and then intravenously injected with the isolated M2-exos. The mouse cardiac function was assessed by echocardiography. Hematoxylin and eosin (HE) staining and TUNEL assay were conducted to examine myocardial lesion and apoptosis in cardiac tissues. The expressions of associated molecules were detected by quantitative real time-PCR (qRT-PCR) and western blot. MTT assay, Flow cytometry and Dual-luciferase reporter assay were carried out to detect cell viability, apoptosis and the interaction of miRNA and the target. RESULT: M2-Exos could promote cardiac repair in AMI mice. M2-Exos suppressed apoptosis and enhanced viability of hypoxia-induced cardiomyocytes through delivery of miR-1271-5p. SOX6 is a direct target of miR-1271-5p. miR-1271-5p decreased cardiomyocyte apoptosis induced by hypoxia and alleviated cardiac injury in AMI via down-regulating SOX6 expression. CONCLUSION: We identified that M2-Exos could carry miR-1271-5p to reduce apoptosis of cardiomyocytes and promote cardiac repair via down-regulating SOX6.

Bone marrow mesenchymal stem cells-derived exosomes reduce Aß deposition and improve cognitive function recovery in mice with Alzheimer's disease by activating sphingosine kinase/sphingosine-1-phosphate signaling pathway.

Exosomes are associated with the development and progression of Alzheimer's disease (AD), although the impact of these extracellular vesicles in brain pathological condition remains incompletely understood. Therefore, this study aimed to investigate the role and mechanism of exosomes signaling in AD. Double transgenic APP/PS1 mice were injected with bone marrow mesenchymal stem cells (BM-MSCs)-derived exosomes or combined with SKI-Ⅱ (sphingosine kinase [SphK] inhibitor) or VPC23019 (sphingosine-1-phosphate [S1P] 1 receptor blocker). We observed the spatial learning and memory ability of mice, and assessed the levels of amyloid and proteins. We found that exosomes improved spatial learning and memory ability of APP/PS1 mice, and enhanced the expression of SphK1 and S1P1. Moreover, exosomes inhibited the levels of amyloid and enhanced the expression of NeuN in cortex and hippocampus of APP/PS1 mice. Exosomes repressed the levels of Aß1-40, Aß1-42, BACE1, and PS1, and promoted the expression of neprilysin in APP/PS1 mice. The influence conferred by exosomes was abolished by SKI-Ⅱ or VPC23019. In conclusion, our article confirms that BM-MSCs-derived exosomes reduce Aß deposition and promote cognitive function recovery in AD mice by activating SphK/S1P signaling pathway. Thus, our data suggest that S1P/SphK-containing exosomes should be explored as potential AD cure.

Development and validation of a simple risk model to predict major cancers for patients with nonalcoholic fatty liver disease.

OBJECTIVE: To recognize risk factors and build up and validate a simple risk model predicting 8-year cancer events after nonalcoholic fatty liver disease (NAFLD). METHODS: This was a retrospective cohort study. Patients with NAFLD (n = 5561) were randomly divided into groups: training (n = 1254), test (n = 627), evaluation (n = 627), and validation (n = 3053). Risk factors were recognized by statistical method named as a Cox model with Markov chain Monte Carlo (MCMC) simulation. This prediction score was established based on the training group and was further validated based on the testing and evaluation group from January 1, 2007 to December 31, 2009 and another 3053 independent cases from January 1, 2010 to February 13, 2014. RESULTS: The main outcomes were NAFLD-related cancer events, including those of the liver, breast, esophagus, stomach, pancreas, prostate and colon, within 8 years after hospitalization for NAFLD diagnosis. Seven risk factors (age (every 5 years),LDL, smoking, BMI, diabetes, OSAS, and aspartate aminotransferase (every 5 units)) were identified as independent indicators of cancer events. This risk model contained a predictive range of 0.4%-37.7%, 0.3%-39.6%, and 0.4%-39.3% in the training, test, evaluation group, respectively, with a range 0.4%-30.4% for validation groups. In the training group, 12.6%, 76.9%, and 10.5% of patients, which corresponded to the low -, moderate -, and high-risk groups, had probabilities of, <0.01, <0.1, and 0.23 for 8-year events. CONCLUSIONS: Seven risk factors were recognized and a simple risk model were developed and validated to predict the risk of cancer events after NAFLD based on 8 years. This simple risk score system may recognize high-risk patients and reduce cancer incidence.