Diversity and functional prediction of fungal communities in different segments of mongolian horse gastrointestinal tracts.

BACKGROUND: Anaerobic fungi are effective fibre-degrading microorganisms in the digestive tract of horses. However, our understanding of their diversity and community structure is limited, especially in different parts of the gastrointestinal tract. RESULTS: For the first time, high-throughput sequencing technology was used to analyse and predict fungal microbial diversity in different parts of the gastrointestinal tract of Mongolian horses. The results revealed that the richness and diversity of fungi in the hindgut of Mongolian horses were much higher than those in the foregut. The foregut was dominated by Basidiomycota and Ascomycota, whereas the hindgut was dominated by Neocallimastigomycota and Basidiomycota. At the genus level, the relative abundance of many pathogenic fungi (Cryptococcus, Cladosporium, Alternaria, and Sarocladium) in the foregut was significantly higher than that in the posterior gut, indicating that Mongolian horses have strong disease resistance. The prediction of fungal function also showed significant differences in the fungal flora between the foregut and the hindgut. The fungi in Mongolian horses' foreguts were mainly pathologically nutritive and contained many animal and plant pathogens, particularly in the small intestine (jejunum and ileum). This indicates that the foregut may be the most important immune site in the digestive system of Mongolian horses, which explains the high disease resistance of Mongolian horses. The number of unassigned functional groups in the posterior gut was significantly higher than that in the anterior gut, indicating that the functions of fungal groups in the posterior gut have not been fully explored, and further studies are required in the future. CONCLUSIONS: Analysis of high-throughput sequencing results revealed that the fungal composition varied greatly among different gastrointestinal tract segments in Mongolian horses, whose hindgut contains many anaerobic fungi involved in plant cellulose degradation. This provides important basic data for studying fungal diversity in the digestive system of healthy horses, which can be used for the health assessment of horses and provides clues for further research on the disease resistance and digestive capacity of horses, as well as a reference for the early diagnosis of intestinal diseases and innovative treatment methods.

Association of the L3MBTL3 rs1125970 and rs4897367 Gene Polymorphisms With Coronary Heart Disease Susceptibility in the Chinese Population: A Case-Control Study.

ABSTRACT: Coronary heart disease (CHD) is a prevalent heart disease with high incidence and mortality rates worldwide, and its pathogenesis is related to genetic factors. L3MBTL3 has been reported to be potentially linked to CHD susceptibility. This study aims to explore the correlation between L3MBTL3 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese population. Three SNPs (rs1125970 A/T, rs4897367 T/C, and rs2068957 A/G) in L3MBTL3 from 649 patients with CHD and 649 healthy controls were genotyped using the Agena MassARRAY platform. The relationship between SNPs and CHD risk was evaluated by logistic regression analysis. Our study indicated that rs1125970 (TT: odds ratio [OR] = 0.76, P = 0.014) and rs4897367 (TT: OR = 0.74, P = 0.021) were related to a decreased susceptibility to CHD. Stratified analyses showed that rs1125970 could reduce the risk of CHD in males, subjects aged <60 years, with a body mass index <24 kg/m 2 , and nonhypertensive patients. rs4897367 exerted a risk-decreasing influence on CHD in nondiabetic patients. In the haplotype analysis, individuals with the T rs4897367 A rs2068957 haplotype were less likely to develop CHD (OR = 0.74, P = 0.024). In summary, L3MBTL3 rs1125970 and rs4897367 were significantly correlated with a decreased susceptibility to CHD in the Chinese population.

The association study between CYP20A1, CYP4F2, CYP2D6 gene polymorphisms and coronary heart disease risk in the Han population in southern China.

BACKGROUND: Coronary heart disease (CHD) is a disease that seriously harms human health. Genetic factors seriously affect the CHD susceptibility. The CYP20A1, CYP4F2 and CYP2D6 are important drug metabolism enzymes in the human body. OBJECTIVE: We aimed to explore the association between CYP20A1, CYP4F2, CYP2D6 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese Southern Han population. METHODS: Based on the 'case-control' experimental design (505 cases and 508 controls), we conducted an association study between 5 candidate SNPs selected from CYP20A1 (rs2043449), CYP4F2 (rs2108622, rs3093106, rs309310), CYP2D6 (rs1065852) and CHD risk. Logistic regression was used to analyze the CHD susceptibility under different genetic models. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction of 'SNP-SNP' in CHD risk. RESULTS: Our results showed that under multiple genetic models, CYP2D6 rs1065852 significantly increased the CHD risk in these participants who are ≤ 60 years old (OR 1.40, CI 1.07-1.82, p = 0.013), smokers (OR 1.40, CI 1.02-1.93, p = 0.039), or have family history (OR 1.24, CI 1.02-1.51, p = 0.035). CYP4F2 SNPs rs2108622 (OR 0.63, CI 0.43-0.93, p = 0.020), rs3093106 (OR 0.52, CI 0.29-0.92, p = 0.023), and rs309310 (OR 0.55, CI 0.31-0.96, p = 0.033) were potentially associated with the course of CHD patients. CONCLUSION: Our study found that CY2D6 rs1065852 has an outstanding and significant association with increased CHD risk. Our study provided data supplements for CHD genetic susceptibility loci, and also provided a new and valuable reference for CHD drug treatment.

Effects of oat (Avena sativa L.) hay diet supplementation on the intestinal microbiome and metabolome of Small-tail Han sheep.

Supplementation of the sheep diet with oats (Avena sativa L.) improves animal growth and meat quality, however effects on intestinal microbes and their metabolites was not clear. This study aimed to establish the effect of dietary oat supplementation on rumen and colonic microbial abundance and explore the relationship with subsequent changes in digesta metabolites. Twenty Small-tail Han sheep were randomly assigned to a diet containing 30 g/100 g of maize straw (Control) or oat hay (Oat). After 90-days on experimental diets, rumen and colon digesta were collected and microbial diversity was determined by 16S rRNA gene Illumina NovaSeq sequencing and metabolomics was conducted using Ultra-high performance liquid chromatography Q-Exactive mass spectrometry (UHPLC-QE-MS). Compared to Control group, oat hay increased the abundance of Bacteroidetes and Fibrobacteres as well as known short-chain fatty acid (SCFA) producers Prevotellaceae, Ruminococcaceae and Fibrobacteraceae in rumen (p < 0.05). In rumen digesta, the Oat group showed had higher levels of (3Z,6Z)-3,6-nonadienal, Limonene-1,2-epoxide, P-tolualdehyde, and Salicylaldehyde compared to Control (p < 0.05) and these metabolites were positively correlated with the abundance of cecal Prevotellaceae NK3B31. In conclusion, supplementation of the sheep diet with oat hay improved desirable microbes and metabolites in the rumen, providing insight into mechanisms whereby meat quality can be improved by oat hay supplementation.

The effect of CYP7B1 polymorphisms on the risk of coronary heart disease in Hainan Han population.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of human death worldwide. Genetic factors play an important role in the occurrence of CHD. Our study is designed to investigate the influence of CYP7B1 polymorphisms on CHD risk. METHODS: In this case-control study, 508 CHD patients and 510 healthy individuals were recruited to determine the correlation between CYP7B1 polymorphisms (rs7836768, rs6472155, and rs2980003) and CHD risk. The associations were evaluated by computing odds ratios (OR) and 95% confidence intervals (CI) with logistic regression analysis. The association between SNP-SNP interaction and CHD susceptibility was carried out by multifactor dimensionality reduction analyses. RESULTS: Our study found that rs6472155 is significantly associated with an increased risk of CHD in age > 60 years (OR 2.20, 95% CI = 1.07-4.49, p = 0.031), women (OR 3.17, 95% CI = 1.19-8.44, p = 0.021), and non-smokers (3.43, 95% CI = 1.16-10.09, p = 0.025). Rs2980003 polymorphism has a lower risk of CHD in drinkers (OR 0.47, 95% CI = 0.24-0.91, p = 0.025). Further analyses based on false-positive report probability validated these significant results. Besides, it was found that rs6472155 polymorphism was associated with uric acid level (p = 0.034). CONCLUSION: Our study indicated that CYP7B1 polymorphisms are related to the risk of CHD, which provides a new perspective for prevent of CHD.

Characterization of chilled chicken spoilage using an integrated microbiome and metabolomics analysis.

Spoilage of chilled chicken can occur as a result of microbial development and consumption of meat nutrients by spoilage bacteria, ultimately resulting in the release of undesired metabolites. Characterizing the profiles of the microbiota and metabolites and clarifying their relationships will contribute to an improved understanding of the mechanism underlying chilled chicken spoilage. In the present study, 16S rRNA gene sequencing and ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS)-based untargeted metabolomics analyses were applied to determine the microbial and metabolic profiles in chicken during chilled storage. The microbial and metabolic datasets were subjected to combined analysis using weighted gene co-expression network analysis (WGCNA) and Spearman's correlation analysis. Brochothrix, Carnobacterium, Photobacterium, Pseudomonas, Acinetobacter, Serratia, Kurthia, Shewanella, and Obesumbacterium genera were identified as the dominant spoilage bacteria in chilled chicken. Ten metabolic pathways, including histidine metabolism and purine metabolism, were identified as potential mechanisms underlying chilled chicken spoilage. Correlation analysis demonstrated that spoilage bacterial genera were highly correlated with spoilage-related metabolites. Taken together, the present study proposed an integrated microbiome and metabolomics approach to investigate the mechanism of chilled chicken spoilage caused by microbial activity. The results obtained by this approach provide a comprehensive insight into changes in the microbial and metabolic profiles of chilled chicken during spoilage.

Analytical Solution to Assess the Induced Seismicity Potential of Faults in Pressurized and Depleted Reservoirs.

Displaced faults crossing the reservoir could significantly increase the induced earthquake frequency in geo-energy projects. Understanding and predicting the stress variation in such cases is essential to minimize the risk of induced seismicity. Here, we adopt the inclusion theory to develop an analytical solution for the stress response to pore pressure variations within the reservoir for both permeable and impermeable faults with offset ranging from zero to the reservoir thickness. By analyzing fault stability changes due to reservoir pressurization/depletion under different scenarios, we find that (1) the induced seismicity potential of impermeable faults is always larger than that of permeable faults under any initial and injection conditions-the maximum size of the fault undergoing failure is 3-5 times larger for impermeable than for permeable faults; (2) stress concentration at the corners results in the occurrence of reversed slip in normal faults with a normal faulting stress regime; (3) while fault offset has no impact on the slip potential for impermeable faults, the slip potential increases with the offset for permeable faults, which indicates that non-displaced permeable faults constitute a safer choice for site selection; (4) an impermeable fault would rupture at a lower deviatoric stress, and at a smaller pressure buildup than a permeable one; and (5) the induced seismicity potential is overestimated and the injectivity underestimated if the stress arching (i.e., the poromechanical coupling) is neglected. This analytical solution is a useful tool for site selection and for supporting decision making during the lifetime of geo-energy projects.

ANGPTL8 enhances insulin sensitivity by directly activating insulin-mediated AKT phosphorylation.

ANGPTL8 is a 22-KDa protein in the angiopoietin-like family. It is a liver-derived hormone that dynamically regulates glucose metabolism after refeeding. The mechanism of its regulation of glucose metabolism is unclear. We analyzed the effect of ANGPTL8 overexpression on glucose tolerance in the mouse liver by tail vein hydrodynamic transfection. The mechanism of ANGPTL8 improving insulin sensitivity was analyzed by the overexpression or knockdown of ANGPTL8 in mouse primary hepatocytes through in vitro synthetic mRNA and siRNA technology. The key site of ANGPTL8 protein regulating this signal pathway was screened by DNA point mutation and fragment truncation. The results showed that ANGPTL8 may directly regulate AKT protein phosphorylation in the insulin-mediated PI3K/AKT signaling pathway to improve insulin sensitivity. Ser94 and Thr98 are the key sites of ANGPTL8 protein in activating AKT protein phosphorylation. Present results indicate that ANGPTL8 may be a potential new agent to reduce postprandial blood glucose.

Differences in root surface adsorption, root uptake, subcellular distribution, and chemical forms of Cd between low- and high-Cd-accumulating wheat cultivars.

The differences in the mechanism of cadmium (Cd) accumulation in the grains of different wheat (Triticum aestivum L.) cultivars remain unclear. Thus, we conducted a hydroponic experiment in a greenhouse to compare root surface adsorption, root uptake, subcellular distribution, and chemical forms of Cd between low- and high-Cd-accumulating wheat cultivars at seedling stage, to improve our understanding of the differences between cultivars. The results showed that Cd adsorbed on the root surface was mainly in a complexed form, and the total amount of Cd on the Yaomai16 (YM, high-Cd-accumulating genotypes) root surface was higher (p < 0.05) than that on Xinmai9817 (XM, low-Cd-accumulating genotypes). A large amount of Cd ions adsorbed on root surface would cause plant damage and inhibit growth. Comparing the root-to-shoot translocation factors of Cd, the transfer coefficients of YM were 1.017, 1.446, 1.464, and 1.030 times higher than those of XM under 5, 10, 50, and 100 µmol L-1 Cd treatments, respectively. The subcellular distribution of Cd under Cd exposure is mainly in the cell wall and soluble fraction. The proportions of Cd in YM shoot soluble fraction were higher than those in XM, which was the main detoxification mechanism limiting the activity of Cd and may be responsible for low Cd accumulation in grains, while the effects of the chemical forms of Cd on migration and detoxification were not found to be related to Cd accumulation in the kernels.

Identification of Long Non-Coding RNA-Associated Competing Endogenous RNA Network in the Differentiation of Chicken Preadipocytes.

Emerging evidence indicates that long noncoding RNAs (lncRNAs) play important roles in the regulation of cell differentiation by acting as competing endogenous RNA (ceRNA). However, the regulatory mechanisms of lncRNA and the lncRNA-associated ceRNA network involved in adipogenic differentiation of chicken preadipocytes remain elusive. Here, we first constructed the chicken preadipocyte in vitro induction model. Then, we identified differentially expressed lncRNAs (DELs), miRNAs (DEMis), and mRNAs (DEMs) between differentiated and undifferentiated preadipocytes. Furthermore, we constructed the lncRNA associated ceRNA network by gene expression correlation analysis and target prediction of DELs, DEMis, and DEMs. Finally, we determined twelve candidate lncRNA-miRNA-mRNA interactions from the lncRNA associated ceRNA network. Eight out of the twelve interactions were validated by RT-qPCR, indicating their potential role in the regulation of chicken preadipocytes differentiation. Among the eight interactions, TCONS_00026544-gga-miR-128-1-5p-RASD1, TCONS_00055280-gga-miR-135a-5p-JAM3, TCONS_00055280-gga-miR-135a-5p-GPR133, TCONS_00055280-gga-miR-135a-5p-CLDN1, and TCONS_00055280-gga-miR-135a-5p-TMEM123 may promote adipogenic differentiation of chicken preadipocytes while TCONS_00057272-gga-miR-146a-3p-FOXO6, TCONS_00057242-gga-miR-6615-3p-FOXO6, and TCONS_00057242-gga-miR-6615-3p-ENSGALT00000043224 have the opposite effects. Our results not only provide novel insights into ceRNA roles of lncRNAs in chicken preadipocytes differentiation and but also contribute to a better understanding of chicken fat deposition.

Hypolipidemic and antioxidant potential of bitter gourd (Momordica charantia L.) leaf in mice fed on a high-fat diet.

The purpose of this study was to investigate the antioxidant and hypolipidemic potential of bitter gourd (BG) leaf ethanol extract (LE) in mice fed a high-fat diet (HFD). Fifty mice were randomly separated into five groups with 10 animals of each group. The animals received normal diet (NC), HFD diet (HF), 200mg/kg/day LE with HFD (LLE), 400 mg/kg/day LE with HFD (MLE), 800mg/kg/day LE with HFD (HLE), respectively. After six weeks, HF group showed meaningfully (P<0.05) increased body weight, fat index, serum lipid and oxidant stress compared to NC group. However, serum TC, TG and LDL-c concentrations were lower in all LE treated groups compared with HF group (P<0.05). In addition to LLE group, HLD-c levels in LE treated groups were higher that that in HF group (P<0.05). Moreover, LE attenuated significantly (P<0.05) the MDA content and elevated the SOD activities of the liver tissues in a dose effect relationship. The histopathological examination confirmed the hepatoprotective effect of LE against liver damage induced by HFD. These findings illustrate that bitter gourd leaves may be valuable for preventing hyperlipidemia and oxidative stress induced by HFD.

Survey of Antithrombotic Treatment in Rural Patients (>60 years) with Atrial Fibrillation in East China.

The prevalence and antithrombotic treatment of atrial fibrillation (AF) in Chinese rural population is not well known. The aim of this study was to investigate the extent to which antithrombotic treatment was prescribed for rural AF patients >60 years. We identified 828 AF patients from 36734 rural residents >60 years in Shanghai China. Our data indicated the overall prevalence rate of AF was 2.3% in rural population >60 years in East China and 38.9% of AF patients underwent antithrombotic therapy, including warfarin (5.9%), aspirin (29.6%), clopidogrel (2.9%) and aspirin combined with clopidogrel (0.5%). Of enrolled subjects, 98.4% had CHA2DS2-VASc score ≥1, 72.0% had HAS-BLED score <3 and 59.2% had CHA2DS2-VASc score ≥2 with HAS-BLED score <3. Missing early detection (34.9%), delay in seeking treatment for asymptomatic AF (25.5%) and doctors's incomplete inform of AF-related risk of stroke to patients (21.7%) were three dominant causes for failing anticoagulant usage. In conclusion, most AF patients were with a high risk of thrombosis and a low risk of bleeding in China, but a large majority of them failed to take anticoagulants mainly for missing an early screening of AF and lack of awareness on AF for both patients and primary care physicians.

MicroRNA-30c suppresses the pro-fibrogenic effects of cardiac fibroblasts induced by TGF-ß1 and prevents atrial fibrosis by targeting TGFßRII.

Atrial fibrosis serves as an important contributor to atrial fibrillation (AF). Recent data have suggested that microRNA-30c (miR-30c) is involved in fibrotic remodelling and cancer development, but the specific role of miR-30c in atrial fibrosis remains unclear. The purpose of this study was to investigate the role of miR-30c in atrial fibrosis and its underlying mechanisms through in vivo and in vitro experiments. Our results indicate that miR-30c is significantly down-regulated in the rat abdominal aortic constriction (AAC) model and in the cellular model of fibrosis induced by transforming growth factor-ß1 (TGF-ß1). Overexpression of miR-30c in cardiac fibroblasts (CFs) markedly inhibits CF proliferation, differentiation, migration and collagen production, whereas decrease in miR-30c leads to the opposite results. Moreover, we identified TGFßRII as a target of miR-30c. Finally, transferring adeno-associated virus 9 (AAV9)-miR-30c into the inferior vena cava of rats attenuated fibrosis in the left atrium following AAC. These data indicate that miR-30c attenuates atrial fibrosis via inhibition of CF proliferation, differentiation, migration and collagen production by targeting TGFßRII, suggesting that miR-30c might be a novel potential therapeutic target for preventing atrial fibrosis.

The Role of Angle in the Evaluation of Ablation Accuracy in Pulmonary Vein Isolation Navigated by Image Integration.

BACKGROUND: The conventional index for ablation accuracy is to compare the distance between mapping points with and without treatment by using image integration. We attempted to quantitatively evaluate the role of angle as an index in the ablation accuracy in patients with atrial fibrillation (AF). METHODS: A total of 48 patients with AF were included in the present study. Virtual fluoroscopy planes were predicted by pulmonary vein (PV) angiography, and the standard image planes were defined on the basis of the computed tomography images. Ablations were performed, guided by image integration; and the ablation planes were defined by the actual ablation rings. The predicted angle (distance) was defined as the angle (distance) between the fluoroscopy (predicted) plane and image (standard) plane, whereas the actual angle (distance) was defined as the angle (distance) between the ablation (actual) planes and the image (standard) planes. RESULTS: We found that all actual angles were significantly smaller than the predicted angles (P <.05), but only the actual distances in the left PV, right inferior PV, right superior PV, and right PV were significantly smaller; the distances in the left inferior PV and left superior PV were not significantly different (P >.05). CONCLUSION: Our finding indicates that both the angle and the distance can be significantly reduced by navigation with image integration, but that the angle exhibited better sensitivity than the conventional index of distance. We suggest that the angle should be considered as a new index for ablation accuracy.

Association of SCN10A Polymorphisms with the Recurrence of Atrial Fibrillation after Catheter Ablation in a Chinese Han Population.

The nonsynonymous SCN10A single nucleotide polymorphism (SNP) rs6795970 has been reported to associate with PR interval and atrial fibrillation (AF) and in strong linkage disequilibrium (LD) with the AF-associated SNP rs6800541. In this study, we investigated whether rs6795970 polymorphisms are associated with AF recurrence after catheter ablation. A total of 502 consecutive patients with AF who underwent catheter ablation were included. AF recurrence was defined as a documented episode of any atrial arrhythmias lasting ≥30 s after a blanking period of 3 months. AF recurrence was observed between 3 and 12 months after catheter ablation in 24.5% of the patients. There was a significant difference in the allele distribution (p = 7.86 × 10-5) and genotype distribution (p = 1.42 × 10-5) of rs6795970 between the AF recurrence and no recurrence groups. In a multivariate analysis, we identified the following independent predictors of AF recurrence: the rs6795970 genotypes in an additive model (OR 0.36, 95%CI 0.22~0.60, p = 7.04 × 10-5), a history of AF ≥36 months (OR 3.57, 95%CI 2.26~5.63, p = 4.33 × 10-8) and left atrial diameter (LAD) ≥40 mm (OR 1.85, 95%CI 1.08~3.19, p = 0.026). These data suggest that genetic variation in SCN10A may play an important role in predicting AF recurrence after catheter ablation in the Chinese Han population.

Common variants predict recurrence after nonfamilial atrial fibrillation ablation in Chinese Han population.

BACKGROUND: Genome-wide association studies (GWAS) have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between susceptibility loci and clinical recurrence of AF after catheter ablation have not been examined in Chinese Han populations. To the personalization of catheter ablation for AF, we examined whether these single nucleotide polymorphisms (SNPs) can predict clinical outcomes after catheter ablation for AF in Chinese Han population. METHODS AND RESULTS: The association between 8 SNPs and AF was studied in 1418 AF patients and 1424 controls by the unconditional logistic regression analysis. The survival analyses were used to compare AT/AF recurrence differences among 438 AF patients, which were classified by the genotype of rs2200733. rs2200733 and rs6590357 were significantly associated with AF in Chinese Han population. In addition, rs2200733 was associated with clinical recurrence of AF after catheter ablation. In Kaplan-Meier survival analysis, the recurrence-free rates for AF with TT and with TC+CC were 35.5% and 61.9%, respectively (P=0.0009). In multivariate Cox regression analysis, rs2200733 was strong independent risk factor for recurrence. CONCLUSION: rs2200733 risk allele at the 4q25 predicted impaired clinical response to catheter ablation for AF in Chinese Han population. Our findings suggested rs2200733 polymorphism may be used as a clinical tool for selection of patients for AF catheter ablation.

Identification of acetyltransferase genes (HAT1 and KAT8) regulating HBV replication by RNAi screening.

BACKGROUND: The initiation of hepatitis B virus (HBV) replication involves the formation of covalently closed circular DNA (cccDNA) and its transcription into pregenomic RNA (pgRNA) in hepatocyte nuclei. The regulatory mechanism of HBV replication by acetyltransferase is thus far not well understood, but human acetyltransferase has been reported as being involved in the regulation of HBV replication. RESULTS: Depletion of KAT8 or HAT1 via RNA interference (RNAi) markedly down-regulated HBV-DNA and pgRNA levels in HepG2.2.15 cells, with KAT8 knockdown reducing both HBsAg and HBeAg more than HAT1 knockdown. Consistent with these observations, HBV replication regulators hepatocyte nuclear factor-4-α (HNF4α) and peroxisome proliferator-activated receptor gamma coactivator- (PPARGC-) 1-α were decreased following knockdown of HAT1 or KAT8. CONCLUSIONS: These data suggest that KAT8 or HAT1 regulate HBV replication and may be potential drug targets of anti-HBV therapy.

The mammalian target of rapamycin signaling pathway regulates myocyte enhancer factor-2C phosphorylation levels through integrin-linked kinase in goat skeletal muscle satellite cells.

Mammalian target of rapamycin (mTOR) signaling pathway plays a key role in muscle development and is involved in multiple intracellular signaling pathways. Myocyte enhancer factor-2 (MEF2) regulates muscle cell proliferation and differentiation. However, how the mTOR signaling pathway regulates MEF2 activity remains unclear. We isolated goat skeletal muscle satellite cells (gSSCs) as model cells to explore mTOR signaling pathway regulation of MEF2C. We inhibited mTOR activity in gSSCs with PP242 and found that MEF2C phosphorylation was decreased and that muscle creatine kinase (MCK) expression was suppressed. Subsequently, we detected integrin-linked kinase (ILK) using MEF2C coimmunoprecipitation; ILK and MEF2C were colocalized in the gSSCs. We found that inhibiting mTOR activity increased ILK phosphorylation levels and that inhibiting ILK activity with Cpd 22 and knocking down ILK with small interfering RNA increased MEF2C phosphorylation and MCK expression. In the presence of Cpd 22, mTOR activity inhibition did not affect MEF2C phosphorylation. Moreover, ILK dephosphorylated MEF2C in vitro. These results suggest that the mTOR signaling pathway regulates MEF2C positively and regulates ILK negatively and that ILK regulates MEF2C negatively. It appears that the mTOR signaling pathway regulates MEF2C through ILK, further regulating the expression of muscle-related genes in gSSCs.

Association of IPS1 polymorphisms with peginterferon efficacy in chronic hepatitis B with HBeAg-positive in the Chinese population.

AIMS: To investigate whether IPS1 polymorphisms affect peginterferon alpha (PEG-IFN) efficacy in chronic hepatitis B (CHB) patients using a tag- single nucleotide polymorphism (SNP) approach. METHODS: A total of 212 hepatitis B e antigen (HBeAg)-positive patients treated with a 48weeks of PEG-IFN monotherapy were enrolled initially and 127 patients were followed for 48weeks posttreatment. Genotype analysis was performed for 10 tag-SNPs in IPS1. RESULTS: The end of virological response (EVR) rate was 45.8% (97/212) and the sustained virological response (SVR) rate was 45.7% (58/127). Meanwhile, 35.4% (75/212) achieved HBeAg seroconversion at the end of treatment. In a multivariate analysis, the rs2464 CC genotype was independently associated with EVR (OR 2.21, 95% CI 1.23-3.98, P=0.008) and SVR (OR 2.34, 95% CI 1.05-5.20, P=0.037) after adjustment for sex, age, HBV genotype, baseline levels of HBV DNA and ALT. Meanwhile, rs2464 CC genotype were also independently associated with decline of HBsAg levels below 1500IU/mL at 12weeks of treatment (OR 2.52, 95% CI 1.01-6.29, P=0.047). Furthermore, three SNPs were found to be independently associated with HBeAg seroconversion at the end of treatment. (1) The rs2326369 CC genotype was independently associated with no HBeAg seroconversion (OR 0.52, 95% CI 0.29-0.95, P=0.034); (2) The rs6515831 TT genotype was independently associated with HBeAg seroconversion (OR 2.11, 95% CI 1.14-3.90, P=0.017); (3) The rs2464 CC genotype was independently associated with HBeAg seroconversion (OR 2.36, 95% CI 1.26-4.42, P=0.007). CONCLUSIONS: Polymorphisms in IPS1 are independently associated with treatment response to PEG-IFN among Chinese HBeAg-positive CHB patients.