Journal of Experimental Pathology最新文献

This is a Commentary of a review about extracellular vesicles of immune cells published two years ago in Clinical and Experimental Immunology, a prestigious journal of the field. The aim is to establish whether, and to what extent, results in scientific area of the review have been extended and strengthened by innovative findings of considerable interest. The analysis of the recently published results has revealed that in various areas of the review developments have occurred. However, innovative findings have been only about the extracellular vesicles secreted by mesenchymal stem cells, usually indicated as MSC-EVs. Based on these findings, the Commentary has been focused on recent MSC-EVs findings presented in three Sections dealing with 1. recently appeared, relevant functions of the latter vesicles; 2. therapeutic processes developed according well known criteria, however innovative in many respects; and 3. protection of COVID-19 disease patients from organ lesions induced by the specific virus, SARS-CoV-2, during the disease. As everybody knows, the COVID-19 pandemic started at the end of 2019, thus after the publication of the aforementioned review. Data of Section 3 are therefore innovative, of great potential interest also at the clinical level, applied by translational medicine to various organs, from lung to brain, heart, kidney, immune and other cells. In view of its relevance, the author expects that research and medical use of MSC-EV, active at present, will be further developed, acquiring additional relevance in the near future.

Human induced pluripotent stem cell (iPSC)-based model systems can be used to produce blood cells for the study of both hematologic and non-hematologic disorders. This commentary discusses recent advances that have utilized iPSC-derived red blood cells, megakaryocytes, myeloid cells, and lymphoid cells to model hematopoietic disorders. In addition, we review recent studies that have defined how microglial cells differentiated from iPSC-derived monocytes impact neurodegenerative disease. Related translational insights highlight the utility of iPSC models for studying pathologic anemia, bleeding, thrombosis, autoimmunity, immunodeficiency, blood cancers, and neurodegenerative disease such as Alzheimer's.

Previous studies showed that human cell line HEK293 lacking mitochondrial superoxide dismutase (MnSOD) exhibited decreased succinate dehydrogenase (SDH) activity, and mice lacking MnSOD displayed significant reductions in SDH and aconitase activities. Since MnSOD has significant effects on SDH activity, and succinate is a key regulator of TET enzymes needed for proper differentiation, we hypothesized that SOD2 loss would lead to succinate accumulation, inhibition of TET activity, and impaired erythroid precursor differentiation. To test this hypothesis, we genetically disrupted the SOD2 gene using the CRISPR/Cas9 genetic strategy in a human erythroleukemia cell line (HEL 92.1.7) capable of induced differentiation toward an erythroid phenotype. Cells obtained in this manner displayed significant inhibition of SDH activity and ~10-fold increases in cellular succinate levels compared to their parent cell controls. Furthermore, SOD2 ^-/- cells exhibited significantly reduced TET enzyme activity concomitant with decreases in genomic 5-hmC and corresponding increases in 5-mC. Finally, when stimulated with δ-aminolevulonic acid (δ-ALA), SOD2 ^-/- HEL cells failed to properly differentiate toward an erythroid phenotype, likely due to failure to complete the necessary global DNA demethylation program required for erythroid maturation. Together, our findings support the model of an SDH/succinate/TET axis and a role for succinate as a retrograde signaling molecule of mitochondrial origin that significantly perturbs nuclear epigenetic reprogramming and introduce MnSOD as a governor of the SDH/succinate/TET axis.

The prevalence and titre of IgG antibodies to human herpesvirus type 6 (HHV-6) were assayed in the serum samples from normal subjects and patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukaemia (ALL) and oral cancer (OC) using immunofluorescence and immunoperoxidase techniques. This forms the first study on the sero-prevalence and titre of antibodies to HHV-6 in India. There was no considerable difference in the prevalence (76%) and titre (10-160) of the antibodies in normal population from those reported for normal adults in other parts of the world. All the HL and ALL patients studied showed no significant elevation in the antibody titre, though a slight increase in the prevalence (95%) was noted. Antibody titre and prevalence were found highly elevated in OC. OC remained totally unstudied for the presence of anti-HHV-6 antibodies, and this is the first report of elevated levels of the antibody in this cancer. The role of HHV-6, if any, in the pathogenesis of OC is worth investigating.

Aortic lysosomal enzyme activities have been evaluated in relation to the extent and severity of aortic atherosclerosis in rhesus monkeys to see the biochemical and pathological effects of renal hypertension in experimental atherogenesis. The frequency and size of atherosclerotic plaques in aortas of atherogenic diet fed and/or hypertensive monkeys were calculated and an overall score of aortic atherosclerosis was computed on the basis of the gamut of pathological findings in relation to the biochemical alterations. This overall score of atherosclerosis was found to be significantly (p less than 0.01) greater in animals of all experimental groups as compared to the controls.