Project description:Hepatitis B virus (HBV) is an enveloped, coated, non-cytopathic and hepatotropic partially double-stranded DNA virus in the family Hepadnaviridae genus Orthohepadnavirus. Despite significant progress in the availability of safe vaccines and antiviral therapies against HBV, it still affects approximately 257 million people worldwide and is responsible for about 887,000 deaths per year around the world [4]. HBV infection, which are associated with acute and chronic liver failure responses to viruses attacked the liver, can result in inactive carrier state, chronic hepatitis, or fulminant hepatitis and put them at high risk to develop advanced liver fibrosis and cirrhosis, and even hepatocellular cancer. Many viral factors, which could affect the disparity of clinical outcomes or disease prognosis during chronic HBV infection, have been reported in previous studies; among them, the viral genotype, as well as HBV mutations ascribing the virus to a certain phenotype, was reported to be the most important factor influencing viral pathogenesis, including the change of host immune recognition, the enhanced virulence with increased HBV replication and the facilitation of cell attachment or penetration.
Project description:Increasing studies suggested the treatment potential of mesenchymal stem cells in variety diseases. Evidence showed that MSCs could promote injured tissue repair and improve disease mortality. These indicated that MSC transplantation may be an ideal candidate for cholestasis treatment.We found that MenSC transplantation could significantly improve the symptoms and pathological changes of DDC-induced cholestasis liver injury in mice.
Project description:In Proteobacteria, the outer membrane protein TamA and the inner membrane-anchored protein TamB form the Translocation and Assembly Module (TAM) complex, which facilitates the transport of autotransporters, virulence factors, and likely lipids across the two membranes. In Bacteroidetes, TamB co-occurs with TamL, a TamA-like lipoprotein with a lipid modification at its N-terminus that likely anchors it to the outer membrane. This structural difference suggests that TamL may have a distinct function compared to the TamA homologue in Proteobacteria. However, the role of TAM in bacterial phyla other than Proteobacteria remains unexplored. Our study aimed to elucidate the functional importance of TamL in Flavobacterium johnsoniae, an environmental Bacteroidetes. Unlike its homologues in Proteobacteria, we found that TamL and TamB are essential in F. johnsoniae. Through genetic, phenotypic, proteomic, and lipidomic analyses, we discovered that TamL depletion severely compromises outer membrane integrity, as evidenced by reduced cell viability, altered cell shape, increased susceptibility to membrane-disrupting agents, and elevated levels of outer membrane lipoproteins. Notably, we did not observe any impact on outer membrane lipid composition. Via pull-down protein assays, we confirmed that TamL interacts with TamB in F. johnsoniae, likely forming the TAM complex. Furthermore, our in silico analysis revealed that the presence of TamL and TamB monocistronic genes is a shared genetic feature among Bacteroidetes members, including the human pathogen Capnocytophaga canimorsus where we confirmed the essentiality of the TamL and TamB homologs. To our knowledge, this study is the first to provide functional insights into a TAM subunit beyond Proteobacteria.
Project description:Background: Schistosoma japonicum (S. japonicum) is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatuous lesions, the main pathogenic factor of schistosomiasis. Although global awareness of the association between schistosomiasis-indued hepatic fibrosis and s. japonicum infection is increasing, little is known about the molecular differences associated with rapid progression to schistosomiasis in cirrhotic patients. Methods: We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. Results: On the basis of our analysis, we identified 1,144 proteins, among which 66 were differentially expressed between the healthy control and SHF-F2 groups and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). Furthermore, our results indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing patients with SHF-F2 and SHF-F4 resulting from S. japonicum infection. Conclusions: This report is the first to provide a global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. C1QA and CFD are potentially diagnostic markers for patients with SHF-F2 and SHF-F4 resulting from S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals with different stages of advanced S. japonicum-induced hepatic fibrosis and might provide fundamental information for further detailed investigations.
Project description:Given that CVB3 is able to impair myocardial contractility, which finally leads to acute heart failure (AHF) and even sudden death, we tried to analyze the related myocardial function of these groups of mice
Project description:Fungal infections, especially for candidiasis and aspergillosis, claim an unacceptably high fatality. However, the determining mechanism that promote fungal lethal infections are still elusive. The energy ATP necessary for fungal cell growth and function is synthesized mainly through oxidative phosphorylation, whose key enzyme is F1Fo-ATP synthase. Nonetheless, it remians unknown how this enzyme affects fungal pathogenicity. Here we show that F1Fo-ATP synthase subunit deletion completely abrogates C. albicans lethal infection rather than leading to remarkable intracellular ATP concentration and growth defect. Mechanically, subunit deletion reduces PFK1 activity via interrupting PFK1 phosphorylation to trigger its conformational change, decreases downstream FBP level, blocks Ras1-dependent and -independent cAMP-PKA pathway, and curtails virulence factors. Based on these findings, we engineer a small molecule compound aimed at subunit that effectively protects mice from succumbing to invasive candidiasis. In summary, our findings reveal that F1Fo-ATP synthase δ subunit determines the lethal infection of pathogenic fungi and represents a potential new therapeutic target.
Project description:Atopic dermatitis (AD) is a serious inflammatory skin disorder characterized by increased levels of proinflammatory cytokines that contribute to a vicious cycle of inflammation. While the in-flammatory recombinant human epidermal (RHE) models related to AD have been established, there is currently lack of comprehensive understanding. To reveal the alterations and identify potential hub genes in AD-related inflammation, related RHE models induced by inflammatory cocktail (polyinosinic-polycytidylic acid, TNF-α, IL-4 and IL-13) are constructed and analyzed through TMT-proteomic in combination with RNA-seq transcriptomic.
Project description:Insomnia is an economic burden and public health problem. This study aimed to explore potential biological pathways and protein networks for insomnia characterized by wakefulness after sleep. Proteomics analysis was performed in the insomnia group with wakefulness and the control group. The differentially expressed proteins (DEPs) were enriched, then hub proteins were identified by protein-protein interaction (PPI) network and verified by parallel reaction monitoring (PRM). Compared with the control group, the sleep time and efficiency of insomnia patients were decreased, awakening time and numbers after sleep onset were significantly increased (P < 0.001).
Project description:Insomnia is an economic burden and public health problem. This study aimed to explore potential biological pathways and protein networks for insomnia characterized by wakefulness after sleep. Proteomics analysis was performed in the insomnia group with wakefulness and the control group. The differentially expressed proteins (DEPs) were enriched, then hub proteins were identified by protein-protein interaction (PPI) network and verified by parallel reaction monitoring (PRM). Compared with the control group, the sleep time and efficiency of insomnia patients were decreased, awakening time and numbers after sleep onset were significantly increased (P < 0.001). The results of proteomic sequencing found 68 DEPs in serum under 1.2-fold changed standard. These DEPs were significantly enriched in humoral immune response, complement and coagulation cascades, cholesterol metabolism. Through PPI network, we identified 10 proteins with the highest connectivity as hub proteins. Among them, differential expression of 9 proteins was verified by PRM.We identified the hub proteins and molecular mechanisms of insomnia patients characterized by wakefulness after sleep. It provided potential molecular targets for the clinical diagnosis and treatment of these patients, and indicated the immune and metabolic systems may be closely related to insomnia characterized by wakefulness after sleep.
Project description:Vesicoureteral reflux (VUR) is a common pediatric condition that predisposes children to renal damage after urinary tract infection (UTI). We profiled the urinary proteome of VUR patients with recurrent UTI and renal scarring to identify potential biomarkers characterizing this condition. Urine was obtained from 22 age-matched controls and 22 patients with low grade VUR (1-3 out of 5), renal scarring, and history of recurrent UTI. Proteins extracted from these samples were analyzed by mass spectrometry for protein identification and quantitation for comparison.