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Background: Previous studies have investigated the vitamin D status in patients with chronic hepatitis B virus (HBV) infection and its relationship with HBV replication, the results however were inconsistent. The present meta-analysis was carried out to compare the vitamin D levels between patients with chronic hepatitis B (CHB) and healthy controls, and to determine whether vitamin D levels were correlated with HBV viral loads significantly.Methods: A systematic search was conducted via PubMed, Web of Science, EMBASE and the Cochrane Library to identify eligible studies until September 28, 2017. We calculated pooled mean difference (MD) and 95% confidence intervals (CI) to quantitatively estimate the difference of vitamin D levels between CHB patients and controls. In addition, correlation between serum vitamin D levels and HBV viral loads was defined by summary correlation coefficient (r value) and the corresponding 95% CI.Results: A total of 7 studies involving 814 CHB patients and 696 healthy controls were included. A significantly decreased vitamin D levels was found in CHB patients compared with healthy controls: pooled MD (95% CI) was - 2.03 ng/mL (- 2.60, - 1.46). Latitude-stratified subgroup analysis indicated this difference was more obvious in low latitude areas, with a bigger pooled MD (95% CI) of - 2.72 ng/mL (- 4.57, - 0.87). In addition, we observed an inverse correlation between serum vitamin D levels and HBV viral loads: pooled r (95% CI) was - 0.41(- 0.54, - 0.27).Conclusions: Our results showed that vitamin D levels were lower in CHB patients than that of healthy controls and inversely correlated with HBV viral loads, although future comprehensive studies are needed to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Recently, accumulating studies have unveiled that circRNAs exert critical function in a variety of tumor biological processes including chemoresistance. Our previous study has found circACTR2 is significantly down-regulated in acquired gemcitabine (GEM)- resistant pancreatic cancer (PC) cells, which has not been well-explored. Our study aimed to research the function and molecular mechanism of circACTR2 in PC chemoresistance. Methods: qRT-PCR and western blot analysis was performed to detect gene expression. The effect of circACTR2 on PC GEM resistance were examined by CCK-8 and flow cytometry assays. Whether circACTR2 could sponge miR-221-3p and regulate PTEN expression were determined by bioinformatics analysis, RNA pull-down, and Dual-luciferase reporter assay. Results: circACTR2 was notably down-regulated in a panel of GEM-resistant PC cells lines, and negatively associated with aggressive phenotype and poor prognosis of PC. circACTR2 downregulation contributed to GEM chemoresistance of PC cells with decreased S phase ratio of cell cycle and cell apoptosis, as confirmed by gain- and loss-of-function assays in vitro. In addition, circACTR2 overexpression retarded GEM resistance in vivo. Further, circACTR2 acted as a ceRNA against miR-221-3p, which directly targeted PTEN. The mechanistic studies revealed that loss of circACTR2 promoted GEM resistance in PC through activating the PI3K/AKT signaling pathway by downregulating PTEN expression in a miR-221-3p dependent manner. Conclusions: circACTR2 reversed the chemoresistance of PC cells to GEM through inhibiting PI3K/AKT signaling pathway by sponging miR-221-3p and upregulating PTEN expression. [ABSTRACT FROM AUTHOR]

Background: Alternaria sp. MG1, an endophytic fungus isolated from grape, is a native producer of resveratrol, which has important application potential. However, the metabolic characteristics and physiological behavior of MG1 still remains mostly unraveled. In addition, the resveratrol production of the strain is low. Thus, the whole-genome sequencing is highly required for elucidating the resveratrol biosynthesis pathway. Furthermore, the metabolic network model of MG1 was constructed to provide a computational guided approach for improving the yield of resveratrol. Results: Firstly, a draft genomic sequence of MG1 was generated with a size of 34.7 Mbp and a GC content of 50.96%. Genome annotation indicated that MG1 possessed complete biosynthesis pathways for stilbenoids, flavonoids, and lignins. Eight secondary metabolites involved in these pathways were detected by GC–MS analysis, confirming the metabolic diversity of MG1. Furthermore, the first genome-scale metabolic network of Alternaria sp. MG1 (named iYL1539) was reconstructed, accounting for 1539 genes, 2231 metabolites, and 2255 reactions. The model was validated qualitatively and quantitatively by comparing the in silico simulation with experimental data, and the results showed a high consistency. In iYL1539, 56 genes were identified as growth essential in rich medium. According to constraint-based analysis, the importance of cofactors for the resveratrol biosynthesis was successfully demonstrated. Ethanol addition was predicted in silico to be an effective method to improve resveratrol production by strengthening acetyl-CoA synthesis and pentose phosphate pathway, and was verified experimentally with a 26.31% increase of resveratrol. Finally, 6 genes were identified as potential targets for resveratrol over-production by the recently developed methodology. The target-genes were validated using salicylic acid as elicitor, leading to an increase of resveratrol yield by 33.32% and the expression of gene 4CL and CHS by 1.8- and 1.6-fold, respectively. Conclusions: This study details the diverse capability and key genes of Alternaria sp. MG1 to produce multiple secondary metabolites. The first model of the species Alternaria was constructed, providing an overall understanding of the physiological behavior and metabolic characteristics of MG1. The model is a highly useful tool for enhancing productivity by rational design of the metabolic pathway for resveratrol and other secondary metabolites. [ABSTRACT FROM AUTHOR]

Background: Pseudorabies virus (PRV) of the family Herpesviridae is the causative agent of Aujeszky's disease. Attenuation of PRV by serial passaging in vitro is a well-established method; however, the dynamic variations occurring on viral genome during this process have not been characterized. Methods: Genome sequencing and comparative genomic analyses of a virulent pseudorabies virus and a series of its plaque-purified strains via serial passaging in vitro were performed, and the properties in vitro and in vivo of which were further characterized. Results: Compared to the parental virus, replication in vitro was enhanced in the highly passaged F50, F91, and F120. In contrast, lethality in mice decreased gradually with passage number. Genome sequencing of F50, F91, and F120 showed deletion of a large fragment containing gE, which is likely related to their attenuation. In addition, single nucleotide variations were identified in many genes of F50, F91, and F120. In-frame and frameshift indels were also detected in specific genes of passaged strains. Particularly frameshift mutations were observed in highly passaged strains, resulting in a truncated but overexpressed pUL46. Conclusion: During attenuation of PRV by serial passaging in Vero cells, dynamic variation patterns including a large deletion, single nucleotide variations, small in-frame indels, and also frameshifts mutations successively emerged, contributing to evolution of the viral population and enabling the gradual attenuation of the virus. These data provide clues to better understand PRV attenuation during passaging. [ABSTRACT FROM AUTHOR]

Background: Salmonella is one of the most important foodborne pathogens, causing outbreaks of human salmonellosis worldwide. Owing to large scales of consumption markets, pork and poultry that contaminated by Salmonella could pose a tremendous threat to public health. The aim of this study was to investigate the contamination of Salmonella from chicken, pork and the environment in slaughtering and retail processes in Chongqing, China. Results: A total of 115 Salmonella isolates were recovered from 1112 samples collected from pork, chicken and the environment. Compared with the isolation rate of samples from chicken (9.50%) and the environment (6.23%), samples from pork had a significant higher isolation rate (44.00%). The isolation rates in slaughterhouses (10.76%) and in supermarkets (10.07%) showed no statistical difference. Thirty different serotypes were identified among all the isolates. S. Derby (n = 26), S. London (n = 16) and S. Rissen (n = 12) were the dominant serotypes. Antimicrobial susceptibility testing revealed that 73.04% isolates were resistant to tetracycline, followed by 66.96% to ampicillin and 59.13% to doxycycline. More than half (50.43%) of the isolates were multidrug resistant (MDR), and most of the MDR isolates were from supermarkets. Multilocus sequence typing results showed 24 out of 115 isolates were ST40, which was the most prevalent. Furthermore, isolates from supermarkets had 20 different sequence types while isolates from slaughterhouses only had 8 different sequence types. Conclusion: Our study highlighted that Salmonella was more frequently isolated in pork production chain than that in chicken. Compared with isolates from slaughterhouses, isolates from supermarkets had more MDR profiles and represented a wider range of serotypes and sequence types, indicating that the retail process had more diverse sources of Salmonella contamination than that of slaughtering process. [ABSTRACT FROM AUTHOR]

Background: Chronic low-grade inflammation and oxidative stress play important roles in the development of obesity-induced cardiac hypertrophy. Here, we investigated the role of Fibronectin type III domain containing 5 (FNDC5) in cardiac inflammation and oxidative stress in obesity-induced cardiac hypertrophy.Methods: Male wild-type and FNDC5-/- mice were fed normal chow or high fat diet (HFD) for 20 weeks to induce obesity, and primary cardiomyocytes and H9c2 cells treated with palmitate (PA) were used as in vitro model. The therapeutic effects of lentiviral vector-mediated FNDC5 overexpression were also examined in HFD-induced cardiac hypertrophy.Results: High fat diet manifested significant increases in body weight and cardiac hypertrophy marker genes expression, while FNDC5 deficiency aggravated cardiac hypertrophy evidenced by increased Nppa, Nppb and Myh7 mRNA level and cardiomyocytes area, in association with enhanced cardiac inflammatory cytokines expression, oxidative stress level and JAK2/STAT3 activation in HFD-fed mice. FNDC5 deficiency in primary cardiomyocytes or FNDC5 knockdown in H9c2 cells enhanced PA-induced inflammatory responses and NOX4 expression. Exogenous FNDC5 pretreatment attenuated PA-induced cardiomyocytes hypertrophy, inflammatory cytokines up-regulation and oxidative stress in primary cardiomyocytes and H9c2 cells. FNDC5 overexpression attenuated cardiac hypertrophy as well as cardiac inflammation and oxidative stress in HFD-fed mice.Conclusions: FNDC5 attenuates obesity-induced cardiac hypertrophy by inactivating JAK2/STAT3 associated-cardiac inflammation and oxidative stress. The cardio-protective role of FNDC5 shed light on future therapeutic interventions in obesity and related cardiovascular complications. [ABSTRACT FROM AUTHOR]

Backgroud: Variations in HPV LCR/E6/E7 have been shown to be associated with the viral persistence and cervical cancer development. So far, there are few reports about the polymorphisms of the HPV-58 LCR/E6/E7 sequences in Southwest China. This study aims to characterize the gene polymorphisms of the HPV-58 LCR/E6/E7 sequences in women of Southwest China, and assess the effects of variations on the immune recognition of viral E6 and E7 antigens. Methods: Twelve LCR/E6/E7 of the HPV-58 isolates were amplified and sequenced. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED v3.3. The selection pressure acting on the HPV-58 E6 and E7 coding regions was estimated by Bayes empirical Bayes analysis of PAML 4.8. Meanwhile, the MHC class-I and II binding peptides were predicted by the ProPred-I server and ProPred server. The transcription factor binding sites in the HPV-58 LCR were analyzed using the JASPAR database. Results: Twenty nine SNPs (20 in the LCR, 3 in the E6, 6 in the E7) were identified at 27 nucleotide sites across the HPV-58 LCR/E6/E7. From the most variable to the least variable, the nucleotide variations were LCR > E7 > E6. The combinations of all the SNPs resulted in 11 unique sequences, which were clustered into the A lineage (7 belong to A1, 2 belong to A2, and 2 belong to A3). An insertion (TGTCAGTTTCCT) was found between the nucleotide sites 7280 and 7281 in 2 variants, and a deletion (TTTAT) was found between 7429 and 7433 in 1 variant. The most common non-synonymous substitution V77A in the E7 was observed in the sequences encoding the α-helix. 63G in the E7 was determined to be the only one positively selected site in the HPV-58 E6/E7 sequences. Six non-synonymous amino acid substitutions (including S71F and K93 N in the E6, and T20I, G41R, G63S/D, and V77A in the E7) were affecting multiple putative epitopes for both CD4+ and CD8+ T-cells. In the LCR, C7265G and C7266T were the most variable sites and were the potential binding sites for the transcription factor SOX10. Conclusion: These results provide an insight into the intrinsic geographical relatedness and biological differences of the HPV-58 variants, and contribute to further research on the HPV-58 epidemiology, carcinogenesis, and therapeutic vaccine development. [ABSTRACT FROM AUTHOR]