ABSTRACT
On July 3, 2023, an interdisciplinary Council of Experts "The burden of COVID-19 in a heterogeneous population of immunocompromised patients - post-pandemic realities" was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.
Subject(s)
COVID-19 , Rheumatology , Humans , COVID-19/epidemiology , Immunization, Passive , Immunocompromised Host , Delivery of Health CareABSTRACT
In acute leukemia, the stromal microenvironment of the bone marrow that regulates hematopoiesis is modified under the influence of malignant cells. Chemotherapy also adversely affects stromal cells. Multipotent mesenchymal stromal cells (MSC) are involved in the formation of the stromal microenvironment and in the regulation of normal and tumor hematopoietic cells. The properties of MSC from the bone marrow of patients with acute myeloid and lymphoid leukemia were studied at the onset of the disease and after achieving remission. The immunophenotype and the level of gene expression were analyzed in MSC of 34 patients. In MSC from patients with acute leukemia, the expression of CD105 and CD274 was significantly reduced in comparison with MSC from healthy donors. At the onset of the disease, the expression of IL6, JAG1, PPARG, IGF1, and PDGFRA was enhanced, while the expression of IL1B, IL8, SOX9, ANG1, and TGFB was reduced. All these changes affect the course of the disease in patients and can be the targets of therapeutic intervention.
Subject(s)
Leukemia, Myeloid, Acute , Mesenchymal Stem Cells , Humans , Leukemia, Myeloid, Acute/metabolism , Bone Marrow/metabolism , Mesenchymal Stem Cells/metabolism , Hematopoiesis , Stromal Cells/pathology , Bone Marrow Cells/metabolism , Tumor MicroenvironmentABSTRACT
In patients with acute leukemia, not only normal hematopoiesis, but also bone marrow stromal microenvironment is damaged. Multipotent mesenchymal stromal cells (MSC) are essential for the formation and function of the stromal microenvironment. Analysis of changes in MSC is important for the development of new approaches to leukemia therapy. The metabolism of mitochondria in MSC, relative content of mitochondrial DNA, and expression levels of genes encoding PGC-1α and Nrf2 proteins, important regulators of biogenesis, were studied using real-time PCR. Relative content of mitochondrial DNA does not change in MSC of acute leukemia patients at the onset of disease or in remission. Relative expression level of the gene encoding PGC-1α protein in MSC does not change significantly. However, relative expression level of the gene encoding Nrf2, an important antioxidant activity regulator, insignificantly decreases in patients at the onset of acute leukemia, and this decrease becomes significant upon reaching remission.
Subject(s)
Leukemia, Myeloid, Acute , Mesenchymal Stem Cells , Humans , NF-E2-Related Factor 2/metabolism , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Mitochondria/genetics , Mitochondria/metabolism , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Mesenchymal Stem Cells/metabolism , Tumor MicroenvironmentABSTRACT
The effect of N-nitrozo-N-methylbiuret (NMB) on various features of Didymocladium ternatum, an organism producing termatin was studied. It was found that the lethal effect of NMB depended on the exposure time, prolongation of which resulted in increased numbers of the plus variants, morphological mutations and reverses into the populations. Variants possessing 8 times higher activity as compared to the initial culture were obtained as a result of selection of active variants.