2019 is coming along with new dreams and ambitions on top of the current progresses. This article has compiled 10 major events happened in 2018 for infectious diseases, and further discussed the developing trends in the field.
Nine prognostic models for end-stage liver diseases were used to assess the prognosis of the patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and the influencing factors of mortality were analyzed. A total of 91 HBV-ACLF patients who received treatment in Huashan Hospital, Fudan University, from July 2014 to July 2018 were selected. The predictive value of nine prognostic models was assessed by the areas under receiver operating characteristic curves (AUROCs), and the influencing factors of mortality were analyzed by logistic regression model. Among 91 patients with HBV-ACLF, 46 died within 90 d. COSSH-ACLF score model presented the best predictive value (AUROC: 0.946 for 28-day mortality and 0.920 for 90-day mortality). AUROCs of the patients graded by the number of organ failure were: grades 0-1: 0.900 for 28-day mortality and 0.846 for 90-day mortality; grades 2-3: 0.957 for 28-day mortality and 0.917 for 90-day mortality. The cutoff of COSSH-ACLF score was 6.245. The survival rate of the patients with COSSH-ACLF score >6.245 was significantly lower than those ≤6.245 (10.7% vs. 81.8%, P<0.000 1). The independent predictors of mortality were age, total bilirubin, coagulation failure, hepatic encephalopathy and platelet count. The platelet count in the survival group was significantly higher than that in the death group (P<0.002 2). The results suggest that COSSH-ACLF score model is clinically practical for the prognosis of HBV-ACLF patients, and platelet count is associated with the severity and prognosis of HBV-ACLF patients.
During the translation process, the translation would be terminated prematurely when abnormal mRNA (such as the deletion of the stop codon) is translated, resulting in the ribosome stalling and causing the bacteria to initiate ribosome rescue pathway. The trans-translation system mediated by tmRNA-SmpB is the main ribosome rescue pathway in Mycobacterium tuberculosis (M. tuberculosis), which has a significant impact on its growth and physiology. In order to explore the initiation and other functional characteristics of the trans-translation pathway in mycobacteria, Mycobacterium smegmatis (M. smegmatis) was selected as the experimental strain and a reporting system that reflects trans-translational expression in cells by adding Escherichia coli (E. coli) terminator at the 3′ end of the reporter genes was constructed. mCherry and egfp were chosen as reporter genes respectively. The results showed that the immature mCherry protein expressed in the experimental strain was quickly hydrolyzed compared with the normal mCherry expressed in the control strain, and the color of the former strain was significantly lighter than that of the latter strain. In addition, the quantitative detection data of enhanced green fluorescent protein (EGFP) also showed that the error EGFP level was significantly lower. These results suggested that both trans-translational reporting systems were successfully constructed. Dynamic expression data of the reporter genes showed that M. smegmatis could initiate the trans-translation pathway and completely hydrolyze the immature error proteins at 40 h to 45 h. This study will help us carry out functional researches on the trans-translation pathway of mycobacteria and screen for new anti-tuberculosis drugs.
This study aimed to explore the optimal culture conditions for transcriptional expression of leukocidin ED (lukED) of Staphylococcus aureus (S. aureus). The transcription level of lukE in S. aureus strain Newman was detected at different growth phases (early-exponential, middle-exponential, late-exponential and stationary phases) in TSB, BHI, YCP, MHB and LB media by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Based on the medium mediating the lowest transcription level of lukE, the different compositions of medium producing the highest mRNA level of lukE was added to discover the substances promoting lukED expression. The findings showed that lukE mRNA level was highest at the late-exponential phase in YCP medium, in which yeast extract, casamino acids and sodium pyruvate could all strikingly increase the expression of lukE, with the first two being better.
The present paper aimed to find the metabolic biomarkers of Candida albicans (C. albicans) infection in early stage. The model of C. albicans-infected Wistar rats was established by tail vein injection of C. albicans liquid. Twenty rats were divided into control group and C. albicans group according to the random number table, 10 in each group. The samples were analyzed by ultra-high performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS) combined with data-dependent acquisition. The measured data were analyzed using SIMCA-P software. Partial least squares discrimination analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA) and principal component analysis (PCA) were used for pattern recognition analysis, respectively, to distinguish the differences in plasma metabolites between the C. albicans group and the control group. The possible metabolic markers were screened according to the variable importance in the projection (VIP) values of OPLS-DA model. The results showed that plasma metabolites in the two groups differed significantly. The OPLS-DA, PLS-DA and PCA models were effective methods to distinguish the two groups. The differences in 18 metabolites were preliminary confirmed. Receiver operating characteristic curve (ROC) analysis demonstrated that the areas under ROC (AUCs) of LysoPC (14∶0), LysoPC (18∶1(9Z)), LysoPC (18∶0), L-tryptophan, L-gulonic acid γ-lactone were all higher than 0.90. The study indicates that the corresponding compounds might be potential markers of Candida infection in Wistar rats, which may help the early diagnosis and treatment of C. albicans infection.
Influenza A virus (IAV) is the dominant type of seasonal influenza and is also an important viral agent of acute respiratory tract infections in children worldwide. Nonstructural protein 1 (NS1) is a protein encoded by viral genome, expressed in the infected cells but not in virions. In recent years, large number of studies have shown that NS1 is an important virulence factor of IAV. NS1 plays multiple roles in antagonizing host antiviral response, inhibiting host cell apoptosis, and modifying host and itself gene expression via NS1-RNA and NS1-protein binding. In-depth study on interaction between NS1 and host cells can not only deepen the comprehending of the pathogenesis of IAV, but also lay a theoretical foundation for the prevention and control of IAV. It also has important application value in the development of new antiviral drugs and vaccines.
Hepatitis C virus (HCV) infection has become a serious global public health problem. Interferon (IFN) therapy is the traditional anti-HCV method, playing antiviral role through Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway. Suppressor of cytokine signaling 3 (SOCS3) is one of the important negative regulatory factors in this pathway. The expression level of SOCS3 is closely related with host IFN resistance. HCV infection and IFN therapy can change the expression level of host microRNA, and microRNA targeting SOCS3 can participate in host anti-HCV replication by regulating SOCS3 expression level.
The survival period of human immunodeficiency virus (HIV)-infected patients has been gradually extended due to effective combination antiretroviral therapy. The immune response of HIV-infected individuals also plays a crucial role in the recovery of the host’s immune system during viral suppression phase. HIV infection activates the interferon signaling pathway and induces up-regulated expression of interferon-stimulated genes (ISGs) that exert antiviral effects. The ubiquitin-like protein ISG15 is one of the most significantly up-regulated host factors in HIV-infected patients, inhibiting the budding and release of HIV viral particles through ISGylation, while the non-structural proteins of HIV interfere with ISGylation process or bind to key molecules of interferon signaling pathways to reverse the inhibitory effect of ISG15 on the virus. Herein we review the biological characteristics of ISG15, its expression in different cell populations, antiviral effects, and mechanism of escaping from the host immune restriction, in order to further understand the role of ISG15 in HIV infection, and to explore the opportunities of functional cure of HIV-infected patients with the strategies using host factors.
Aspergillus fumigatus (A. fumigatus) is an ubiquitous opportunistic fungus, which could cause serious pulmonary infection through inhalation of conidia. The infection is difficult to treat, and severity is strongly related to host immune status, especially innate immune functions. Monocytes are important effector cells in innate immune, which could be differentiated into dendritic cells and macrophages. Three subsets of monocytes defined by specific surface molecules exert distinguished functions in phagocytosis, antigen-presentation and conidiacidal activity. Based on the continuous development of assays, such as fluorescent tag, perfusion culture, spectral imaging, gene knockout technology, it is proven that monocytes play important roles in control of A. fumigatus infection in human and mouse. Monocytes could directly kill spores or improve neutrophil conidiacidal activity in the early A. fumigatus infection via interleukins signaling molecules.