ABSTRACT
Rheumatoid arthritis (RA), the most common inflammatory arthropathy word wild, is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate. Metabolic mis-regulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction, while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA. Recently, natural active compounds from traditional Chinese medicines (TCMs) have potential therapeutic effects on RA and regulating immunometabolism. In this review, in addition to updating the connection between cellular metabolism and cell function in immune cells of RA, we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells, and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA.
ABSTRACT
Tumors are believed to consist of a heterogeneous population of tumor cells originating from rare cancer stem cells (CSCs). However, emerging evidence suggests that tumor may also originate from non-CSCs. To support this viewpoint, we are here to present definitive evidence indicating that the number of tumorigenic tumor cells is greater than that of CSCs in tumor, and tumor can also derive from non-CSCs. To achieve this, an idealized mathematical model was employed in the present study and theoretical calculation revealed that non-CSCs could initiate the occurrence of tumor if their proliferation potential was adequate. Further, experimental studies demonstrated that 17.7%, 38.6% and 5.2% of tumor cells in murine B16 solid melanoma, H22 hepatoma and Lewis lung carcinoma, respectively, were potentially tumorigenic. Thus, based on the aforementioned findings, we propose that the scarce CSCs, if exist, are not the sole source of a tumor.
ABSTRACT
Tumors are believed to consist of a heterogeneous population of tumor cells originating from rare cancer stem cells (CSCs). However, emerging evidence suggests that tumor may also originate from non-CSCs. To support this viewpoint, we are here to present definitive evidence indicating that the number of tumorigenic tumor cells is greater than that of CSCs in tumor, and tumor can also derive from non-CSCs. To achieve this, an idealized mathematical model was employed in the present study and theoretical calculation revealed that non-CSCs could initiate the occurrence of tumor if their proliferation potential was adequate. Further, experimental studies demonstrated that 17.7%, 38.6% and 5.2% of tumor cells in murine B16 solid melanoma, H22 hepatoma and Lewis lung carcinoma, respectively, were potentially tumorigenic. Thus, based on the aforementioned findings, we propose that the scarce CSCs, if exist, are not the sole source of a tumor.
Subject(s)
Animals , Algorithms , Carcinogenesis , Pathology , Carcinoma, Lewis Lung , Pathology , Cell Differentiation , Cell Line, Tumor , Cell Proliferation , Liver Neoplasms, Experimental , Pathology , Melanoma, Experimental , Pathology , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Biological , Neoplasms, Experimental , Pathology , Neoplastic Stem Cells , Pathology , Time Factors , Tumor Stem Cell Assay , MethodsABSTRACT
The negative signal provided by interactions of costimulatory molecules, programmed death-1 (PD-1) and its ligands, PD-L1 (also B7-H1) and PD-L2 (also B7-DC), is involved in the mechanisms of tumor immune evasion. To block PD-Ls-PD-1 interactions by a soluble receptor of PD-1, we constructed a eukaryotic expression plasmid that expresses extracellular region (aa1-aa167) of murine PD-1 (pPD-1A) and, another version of pPD-1A, pPD-1B, carrying cDNAs encoding for both extracellular region of PD-1 and green fluorescent protein (GFP) reporter gene, which was inserted downstream of PD-1. Experiment of BHK cells transfected with pPD-1B determined that most expression product (sPD-1) in the cells was secreted out. FACS analysis revealed that sPD-1 was specific and bound efficiently to PD-1 ligands. Cytotoxicity assay showed that blocking PD-Ls on either tumor cells or spleen cells by sPD-1 mediated enhanced lysis of H22 cells by Hsp70-H22 peptides complexstimulated spleen cells. The constructed plasmid vector would provide a novel method of tumor gene therapy of blocking PD-Ls-PD-1 interactions by expression of soluble receptor of PD-1 in tumor sites, which could increase the antitumor activity.