A novel equine parvovirus, equine parvovirus-hepatitis (EqPV-H), was first discovered in a horse that died of equine serum hepatitis in the USA in 2018. EqPV-H was shown to be a novel etiological agent associated with equine serum hepatitis. Following this initial report, no additional studies on EqPV-H have been published. In this study, a total of 143 serum samples were collected from racehorses at 5 separate farms in China and were analyzed to detect EqPV-H DNA via nested PCR. The results indicated a high prevalence of EqPV-H (11.9%, 17/143) in the studied animals. In addition, a remarkably high coinfection rate (58.8%, 10/17) with 2 equine flaviviruses (equine hepacivirus and equine pegivirus) was observed in the EqPV-H positive equines. However, all equines tested negative for Theiler’s disease-associated virus, an etiological agent associated with equine serum hepatitis. The genomes of six field EqPV-H strains were sequenced and analyzed, with the results indicating that the Chinese EqPV-H strains have low genetic diversity and high genetic similarity with the USA EqPV-H strain BCT-01. A phylogenetic analysis demonstrated that the Chinese EqPV-H strains clustered with BCT-01 in the genus Copiparvovirus but were distantly related to another equine parvovirus identified in horse cerebrospinal fluid. In addition, liver enzyme levels were detected in the EqPV-H positive serum samples, and all the values were in the normal range, indicating that infection can occur without concurrent liver disease. This study will promote an understanding of the geographical distribution, genetic diversity, and pathogenicity of EqPV-H.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a common, chronic liver disease worldwide. Recent studies have shown that T helper (Th) 17 and regulatory T (Treg) cells play critical roles in various disorders of liver inflammation. Here, we explored the value of polyene phosphatidylcholine capsules (PPC) for regulating the imbalance of Th17/Treg cells in the pathogenesis of mice with NAFLD.MethodsC57BL/6 mice were randomly divided into three groups as follows:normal diet (ND), high-fat diet (HF),and HF plus PPC(HF + PPC). The frequencies of splenic Th17 and Treg cells were measured by flow cytometry, and their related cytokines were analyzed by CBA and real-time PCR.ResultsAt the end of 24 weeks, mice in the HF group had a higher frequency of intrahepatic Th17 cells,and a lower proportion of Treg cells compared with the ND group. The levels of Th17 cell-related cytokines (IL-6, IL-17 and IL-23) in serum and in liver tisse were increased,and the hepatic mRNA levels of RORγt, STAT3 and IL-6 were also increased. By contrast,the FoxP3 mRNA level was decreased in the HF group. Moreover, significant pathological and biochemical changes in the liver, as well as serum biochemical changes, were found in mice with NAFLD. Interestingly, following treatment with PPC, the levels of liver inflammation,frequencies of Th17/Treg cells and associated cytokines,and biochemical data were significantly altered.ConclusionThese findings demonstrate a critical role for PPC in partially attenuating liver inflammatory responses in mice with NAFLD that involves the imbalance of Treg/Th17 cells and associated cytokines.

Equine parvovirus-hepatitis (EqPV-H) was first reported in a horse that died of equine serum hepatitis in the USA in 2018, and was determined having a strong association with equine serum hepatitis in the following studies. As a newly discovered virus, the genomic sequences of only seven EqPV-H strains have been reported. Considering this, an epidemiological study was performed to investigate the prevalence of EqPV-H in equines in Guangdong Province in China, and obtain genomic sequences of the field prevalent EqPV-H strains. The detection rate of EqPV-H was finally determined to be 8.33% (95% CI: 2.8-18.4%), and EqPV-H's coinfection with equine hepacivirus and equine pegivirus was also determined. Then, the genomes of the Chinese field EqPV-H strains were obtained by PCR, sequencing, and assembly. Through bootscanning analysis, Simplot analysis, and phylogenetic analysis, strong evidence for natural recombination events were found in two Chinese field EqPV-H strains. The natural recombination events occurred between the Chinese and American strains, and were determined within VP protein. Finally, the genetic distance of EqPV-H strains was investigated. Nucleotide identities of 97.1-99.9% and 95.2-100% were found for NS and VP between EqPV-H strains, respectively. Together with other molecular evidence obtained in the present study, the genetic diversity of EqPV-H was determined. Taken together, the results of the present study expand our knowledge on the epidemiological characteristics, genetic variability, and evolution of EqPV-H.

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Pure total flavonoids from Citrus (PTFC) effectively reduce the symptoms of non-alcoholic fatty liver disease (NAFLD). Our previous microarray analysis uncovered the alterations of important signaling pathways in the treatment of NAFLD with PTFC. However, the underlying core genes that might be targeted by PTFC, which play important roles in the progression of NALFD are yet to be identified. In this study, we predicted the vascular endothelial growth factor-C (VEGF-C) as potential key molecular target of PTFC against NAFLD via network pharmacology analysis. The network pharmacology approach presented here provided important clues for understanding the mechanisms of PTFC treatment in the development of NAFLD.

IL-33 played an important role in inflammatory diseases as evidenced by their high levels of expression in diseased tissues. Previous studies showed that IL-33/ST2L signal transduction pathway participated in epithelial-mesenchymal transition (EMT) of A549 cells. Cytokine IL-1β can increase the expression of MMPs by activating NF-kB. The excessive or inappropriate expression of MMP-9 may randomly and non-selectively destroy the extracellular matrix. TIMP-1 (tissue inhibitor of MMP-9) effects on ebb and flow of ECM by inhibiting activation of MMP-9. Therefore, IL-33 may take part in the process of pulmonary fibrosis by regulating expressions of MMP-9 and TIMP-1. To explore the acting mechanism of IL-33 in pulmonary fibrosis, proliferation of the human embryonic lung fibroblasts and expressions of related signal molecules was analyzed in vitro. We cultured HELF cells and stimulated HELF with rhIL-33 at different time points (24, 48, 72 h) and different concentrations respectively. The expression of the receptor ST2L was analyzed by RT-PCR and the proliferative rate of HELF was tested by MTT. The expressions of collagen IV, MMP-9, TIMP-1, and critical signal transducer TRAF-6 and NF-kappaB were tested by Western blotting. The rhIL-33 can promote proliferation of HELF and the concentration of 10 ng/ml was most significant at 72 h (P < 0.05). Hence, this experiment chose 10 ng/ml as stimulated concentration at following experiments. The expressions of collagen IV, MMP-9, TIMP-1, TRAF-6, and NF-kappaB increased and then reduced in protein levels at different time points (0, 6, 12, 24, 48, 72 h) (P < 0.05). IL-33 participates in the production of profibrotic cytokines and formation of mesenchymal substances in early inflammatory responses of pulmonary fibrosis. IL-33 can regulate deposition of ECM and promote the process of pulmonary fibrosis by inducing the imbalance between MMP-9 and TIMP-1.

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