ABSTRACT
As the most abundant liver-specific microRNA, microRNA-122 (miR-122) is involved in various physiological processes in hepatic function as well as in liver pathology. There is now compelling evidence that miR-122, as a regulator of gene networks and pathways in hepatocytes, plays a central role in diverse aspects of hepatic function and in the progress of liver diseases. This liver-enriched transcription factors-regulated miRNA promotes differentiation of hepatocytes and regulates lipid metabolism. With regard to liver diseases, miR-122 was shown to stimulate hepatitis C virus (HCV) replication through a unique and unusual interaction with two binding sites in the 5'-UTR of HCV genome to mediate the stability of the viral RNA, whereas inhibit the expression and replication of hepatitis B virus (HBV) by a miR-122-cylin G1/p53-HBV enhancer regulatory pathway. In addition, miR-122 acts as a suppressor of cell proliferation and malignant transformation of hepatocytes with remarkable tumor inhibition activity. Notably, a clinical trial targeting miR-122 with the anti-miR-122 oligonucleotides miravirsen, the first miRNA targeted drug, has been initiated for treatment of HCV infection. With further understanding of the comprehensive roles of miR-122 in hepatic functions and the mechanisms involved in miR-122 down-regulation in chronic hepatitis or hepatocellular carcinoma, miR-122 appears to be a promising candidate for effective therapeutic approaches against tumor and infectious diseases.
Subject(s)
Humans , Lipid Metabolism , Genetics , Liver , Metabolism , Liver Diseases , Genetics , MicroRNAs , Genetics , Metabolism , Models, BiologicalABSTRACT
Heat-shock protein gp96 associates with antigenic peptides derived from tumor and virus. Exogenous gp96-peptide complexes are taken up by antigen-presenting cells through interaction with its receptor CD91 on the cell surface, and cross-present antigenic peptides to MHC class I molecules by a peptide relay line in the endoplasmic reticulum for specific T-cell activation. Meanwhile, gp96 has been shown to initiate innate immune responses through interaction with toll-like receptor 2 and toll-like receptor 4. Recent studies have shown a gp96-mediated immune balance between CTL and Tregs. With the further understanding of counteracting immunosuppressive mechanisms in gp96-induced cellular immune responses, and establishment of high level production of recombinant gp96 by the yeast, gp96 appears to be a promising candidate for designing effective therapeutic vaccines against tumor and infectious diseases.
Subject(s)
Animals , Humans , Communicable Diseases , Therapeutics , Heat-Shock Proteins , Allergy and Immunology , Therapeutic Uses , Immunotherapy, Active , Methods , Neoplasms , Therapeutics , T-Lymphocytes, Regulatory , Allergy and ImmunologyABSTRACT
While currently therapeutic vaccines for chronic hepatitis B virus (HBV) infection are actively being developed to complement standard antiviral treatments, their immune activity, especially T cell activity, remains to be further improved. Here, we investigated the role of heat shock proteins HSP70 and gp96 on cellular and humoral immunity, using the main structure antigens of hepatitis core (HBcAg) and surface (HBsAg) as the DNA vaccine. By ELISPOT (enzyme linked immunospot assay), IFN-gamma intracellular staining, [3H]-thymidine incorporation and ELISA (enzyme linked immunosorbent assay) analyses, we showed that immunization with HBsAg/HBcAg DNA formulation along with HSP70 or gp96 induced significant increase of T-cell (about 1-6-fold) and antibody (about 20%-60%) immunity against HBsAg and HBcAg. These results may provide bases for designing HSP70- and gp96-based vaccines aimed at eliciting T-cell responses for therapeutic applications.
Subject(s)
Animals , Female , Humans , Mice , Adjuvants, Immunologic , Pharmacology , HSP70 Heat-Shock Proteins , Allergy and Immunology , Hepatitis B Core Antigens , Allergy and Immunology , Hepatitis B Surface Antigens , Allergy and Immunology , Hepatitis B Vaccines , Allergy and Immunology , Hepatitis B virus , Allergy and Immunology , Hepatitis B, Chronic , Allergy and Immunology , Therapeutics , Immunoglobulin G , Allergy and Immunology , Membrane Glycoproteins , Allergy and Immunology , Mice, Inbred BALB C , T-Lymphocytes , Allergy and Immunology , Vaccines, DNA , Allergy and ImmunologyABSTRACT
Sixty-eight cases of naevus fusco-caeruleus zygomaticus were observed from 1990 to 1996 in our clinic. In order to differentiate easily from other pigmented disorders, detailed analysis was carried out. The results showed that this condition principally occurred in young or middle-aged women, manifested as dark greyish spots scattered bilaterally and symmetrically on the zygomatic region. Histopathologically, there were elongated, slender spindle-shaped melanocytes scattered in the upper portion of the dermis, their long axes run parallel to the collagen fibres. It suggests that the naevus reported differs clinically and histopathologieally from naevus of Ota.