ABSTRACT
MicroRNAs (miRNAs) are endogenous non-coding single-stranded small RNAs that regulate gene expression by recognizing homologous sequences and interfering with transcriptional, translational or epigenetic processes. MiRNAs are involved in a variety of disease processes, and regulate the physiological and pathological status of diseases by modulating target cell activity, migration, invasion, apoptosis, autophagy and other processes. Among them, let-7i is highly expressed in various systems, which participates in the process of tumors, cardiovascular and cerebrovascular diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases and other diseases, and plays a positive or negative regulatory role in these diseases through different signal pathways and key molecules. Moreover, it can be used as an early diagnosis and prognostic marker for a variety of diseases and become a potential therapeutic target. As a biomarker, let-7i is frequently tested in combination with other miRNAs to diagnose multiple diseases and evaluate the clinical treatment or prognosis.
Subject(s)
Biomarkers , Apoptosis , Autophagy , Epigenesis, Genetic , MicroRNAs/geneticsABSTRACT
Objective:To investigate the molecular mechanism of VRC01 resistance in HIV-1 subtype B′ strains isolated from a patient (DRVI01) with broadly neutralizing antibody (bNAb).Methods:Sequences of the HIV-1 subtype B′ strains isolated from patient DRVI01 were compared with those of HIV-1 subtype B′ strains that were isolated at the same time but sensitive to VRC01 antibody. Key amino acids that might affect the neutralization of VRC01 were selected according to literature reports. Effects of the selected amino acids on VRC01 neutralization were verified by site-directed mutation and sequence exchange of membrane proteins from different patients.Results:Single-point mutations of E279D and R282K in LoopD region and N460A and N463Q in V5 region reversed the viral sensitivity to VRC01 neutralization. Combined mutations in two or three above-mentioned sites significantly increased the viral sensitivity to VRC01 antibody compared with single-point mutations. Contrary to literature reports, the glycosylation site mutation of N276 had no influence on the viral sensitivity to VRC01.Conclusions:HIV-1 subtype B′ strains isolated from patient DRV01 with bNAb carried the mutations of D279 and K282 in LoopD region and N460 and N463 in V5 region, resulting in resistance to VRC01 antibody.
ABSTRACT
Background and Objectives@#Systemic scleroderma (SSc) is a rare and serious connective tissue disease, an autoimmune disease, and a rare refractory disease. In this study, preventive effect of single systemic human umbilical cord mesenchymal stem cells (UC-MSCs) transfusion on SSc was preliminarily explored. @*Methods@#and Results: SSc mouse model was established by daily intradermal injection of Hypochlorite (HOCl). SSc mice were treated by single transfusion of UC-MSCs at 0.625×10 5 , 2.5×105 and 1×106 respectively. At the 42nd day of intradermal injection of HOCl, the symptoms showed up by skin and alveolar wall thickening, lymphocytic infiltration, increased collagen in skin/lung, and the increased proportion of CD3 ＋ CD4＋ CD25＋ FoxP3＋ cells (a Treg subset) in spleen. After UC-MSCs transfusion, the degree of skin thickening, alveolar wall thickening and lymphocyte infiltration were decreased, the collagen sedimentation in skin/lung was decreased, and the proportion of CD3＋ CD4＋ CD25＋FoxP3＋ cells was decreased. @*Conclusions@#UC-MSC can achieve a preventive effect in SSc mice by fibrosis attenuation and immunoregulation.
ABSTRACT
Background and Objectives@#Systemic scleroderma (SSc) is a rare and serious connective tissue disease, an autoimmune disease, and a rare refractory disease. In this study, preventive effect of single systemic human umbilical cord mesenchymal stem cells (UC-MSCs) transfusion on SSc was preliminarily explored. @*Methods@#and Results: SSc mouse model was established by daily intradermal injection of Hypochlorite (HOCl). SSc mice were treated by single transfusion of UC-MSCs at 0.625×10 5 , 2.5×105 and 1×106 respectively. At the 42nd day of intradermal injection of HOCl, the symptoms showed up by skin and alveolar wall thickening, lymphocytic infiltration, increased collagen in skin/lung, and the increased proportion of CD3 ＋ CD4＋ CD25＋ FoxP3＋ cells (a Treg subset) in spleen. After UC-MSCs transfusion, the degree of skin thickening, alveolar wall thickening and lymphocyte infiltration were decreased, the collagen sedimentation in skin/lung was decreased, and the proportion of CD3＋ CD4＋ CD25＋FoxP3＋ cells was decreased. @*Conclusions@#UC-MSC can achieve a preventive effect in SSc mice by fibrosis attenuation and immunoregulation.
ABSTRACT
Objective@#To amplify and identify monoclonal antibody genes from HIV-1-infected patients.@*Methods@#Single cell sorting was used to isolate antigen-specific single B cells. Sequence Identity Matrix and the international ImMunoGeneTics information system were used to analyze antibody variable region genes. Binding abilities were detected by enzyme linked immunosorbent assay. Neutralizing activities were tested by TZM-bl/pseudovirus assay.@*Results@#The heavy and light chain genes of four, seven, and eleven antibodies were amplified and sequenced from three HIV-1-infected patients, respectively. They were derived from various germline genes with flexible CDR3 lengths and somatic mutations. A1 and B3 antibodies bound to HIV-1 clade B, CRF01_AE, and CRF07_BC antigens. The half maximal inhibitory concentration values of A1 and B3 against MW965 virus were 0.04 μg/ml and 37.34 μg/ml.@*Conclusion@#In this study, we acquired a lot of monoclonal antibody genes and two HIV-1 monoclonal binding and neutralizing antibodies, which would provide basic data for further research on monoclonal antibody identification.