ABSTRACT
A locally active renin–angiotensin system (RAS) present in the bone marrow, which controls the growth, production, proliferation, and differentiation of hematopoietic cells. Local bone marrow RAS has also a role in neoplastic hematopoiesis such as genesis of leukemia and other malignancies. The local RAS in bone marrow plays important roles in atherosclerosis. The "bone marrow response-to-lipid” hypothesis integrates the knowledge that proatherogenic features of hematopoietic and nonhematopoietic progenitors are determined by the local actions of modified LDL on the expression of local RAS genes. There is a relationship between the autonomic nervous system and bone marrow cells. This association between bone marrow stromal cells, hematopoietic stem cell, and nerve terminals has been described as the "neuroreticular complex.” A characteristic feature of early hypertension is endothelial dysfunction. Bone marrow–related endothelial progenitor cells contribute in the healing of injured endothelium. Relationship between autonomous nervous system and bone marrow vasculature could be an important mechanism of the pathophysiology of hypertension. Local bone marrow RAS has important role in COVID-19 syndrome. ACE2 receptor is presented on the surface of hematopoietic stem/progenitor cells within the context of local bone marrow RAS that characterizes a target for the SARS-CoV-2 attack on bone marrow hematopoiesis. Bone marrow and lung tissue are in a harmony in hematopoiesis under the control of tissue RAS. RAS genes are critical at the initiation of the infections initiated by coronavirus family members and can have an important association with the exchange of immune genes in due clinical course following the infection. The aim of this chapter is to focus on the impacts of the local bone marrow RAS on definitive and neoplastic hematopoiesis, as well as its interrelationships among atherosclerosis, hypertension, and COVID-19 syndrome. © 2023 Elsevier Inc. All rights reserved.
ABSTRACT
OBJECTIVE: Viral infections could complicate hematopoiesis and, in some cases, they may worsen the clinical prognosis of blood disorders. SARS-CoV-2 and COVID-19, as a viral disease, can have serious impact on the disease course of hematological neoplastic diseases and can cause hematological complications. The aim of this paper is to review the hematologic aspects of COVID-19 syndrome and the potential management options for SARS-CoV-2 including the convalescent plasma, hemostatic agents and proper anticoagulant treatment. MATERIALS AND METHODS: Up to February 2022, literature searches were performed using the internet search engines MEDLINE and EMBASE: (i) COVID-19; (ii) Hematology. PRISMA flow diagram described the COVID-19 and hematology search. RESULTS: According to our COVID-19 and hematology research on research databases, we included 82 studies in the current paper. The issues of the impact of the COVID-19 pandemic on hematological diseases, the role of t-lymphocytes in donor lymphocyte infusion and viruses, hemato-immunologic research in COVID-19, local bone marrow renin-angiotensin system and viral infections, clinical management of COVID-19 infection via hemostatic agents, immune plasma treatment of COVID-19, anticoagulant treatment of COVID-19 associated thrombosis are comprehensively described in this paper. CONCLUSIONS: The final episode of this pandemic will include the "chimerism-mediated immunotherapy" that will eventually lead to end of the COVID-19 process. The recent Omicron variant seems to have unique evasion effects on the interferon gene expression which will boost the chimerism-mediated immunotherapy without high mortality rates.
Subject(s)
COVID-19 , SARS-CoV-2 , Anticoagulants/therapeutic use , COVID-19/therapy , Humans , Immunization, Passive , Pandemics , Syndrome , COVID-19 SerotherapyABSTRACT
The distinctive clinical course and outcomes of COVID-19 infection in multiple myeloma patients are still not well established. In this study, we aimed to assess the clinical outcomes and associated factors of COVID-19 in patients with multiple myeloma (MM). This is a multi-center retrospective cohort study. Multiple myeloma patients treated in two tertiary centers were investigated, and the patients diagnosed with COVID-19 during follow-up were included. The main characteristics and clinical outcomes of patients were analyzed. A total of thirty patients were included for analysis. In this cohort, autologous hematopoietic stem cell transplantation (AHSCT) was performed in 63.3% of the patients, and 36.7% were in complete remission when COVID-19 was detected. The total fatality rate (FR) was 36%, and the COVID-19-related case fatality rate (CFR) was 30% for MM patients in our cohort. There was two non-COVIDrelated mortality. The CFR was associated with intensive care unit admission (26.7%, p< 0.001), mechanical ventilation (26.6%, p< 0.001), increased lactate dehydrogenase (p= 0.008) and lymphopenia (p= 0.042). Older age (> 65-years), stem cell transplantation, and comorbidities were not effective on the fatality rate. This study shows that the CFR rate was high in MM patients, irrespective of AHSCT status. Therefore, we suggest strict monitoring and adequate vaccination in this group. However, further studies, including vaccination data with a larger group of patients, are needed to clarify the literature.
ABSTRACT
A group of non-histone nuclear proteins with high electrophoretic mobility was discovered almost 40 years ago and referred to as high-mobility group (HMG) proteins. HMGB, HMGN, and HMGA are members of HMG families. HMGB has a family of three nuclear proteins including HMGB1, HMGB2, and HMGB3. HMGB1 is a DNA binding protein responsible for the maintenance of nucleosome structure and regulation of gene transcription. Recent studies suggest that HMGB1 has critical roles in DNA recombination, repair, replication, and gene transcription. This situation makes it a multifunctional protein involved in a variety of cellular biological processes. The unique features of HMGB1 allow it to be suggested as a novel target for cancer therapy and managing COVID-19 infection. However, there is still not any regulated drug by any authorities directly targeting HMGB1. The present study is aimed to systematically present the reported herbal medicinal plants and/or their active seconder metabolites to target HMGB1. First, the potential role of targeting HMGB1 on cancer therapy and COVID-19 management was discussed and then the reported herbal medicinal plants for this feature were presented. The active components for these medicinal plants were evaluated and their roles in cancer therapy and antiviral features besides targeting HMGB1 were discussed. Thus, a potential non-toxic phytotherapy solution primary intending to target HMGB1 and simultaneously to impact cell proliferation was suggested for supporting conventional cancer therapy. In addition, the well-known antiviral herbal medicinal plant extracts were considered whether they already include some components having features targeting HMGB1, or not. This critical point of view allowed us to suggest potential oral topical antiviral herbal solutions to be used in the management of COVID-19. © 2023 by Nova Science Publishers, Inc. All rights reserved.
ABSTRACT
Interferon (IFN) family has a significant impact on both SARS-CoV and SARS-CoV-2. The aim of this current bioinformatics study is to assess IFN-gene family alterations following the SARS-CoV infection in association with the iron metabolism and lymphoid biology.Gene expression data of human bronchial epithelial cells treated with SARS-CoV for 12, 24, 48 hours were obtained from Array Express (GSE17400). In order to use the obtained data in other targeted analyses,the raw data were normalized by robust multisequence analysis in accordance with the procedure in the Affy package in R. These data consist of 23344 genes (54675 probe sets). In addition, each gene has three repeated expression data values for 12, 24, 48 hours, respectively. For the 48 hours group,positive regulations of the natural killer (NK) cell activation and NK cell-mediated cytotoxicity, as well as hematopoietic stem cells proliferation,were found to be more significant regard to their nominal p-value, family-wise error rate, and false discovery rate (q-value) calculated by gen set enrichment analysis. The gene sets with nominal (NOM) p-value < 0.01, false discovery rate (FDR) q-value <= 1, and familywise error rate (FWER) < 1 considered as significantly correlate between compared groups. Our study exhibited that important IFN genes (IFNAR2, IFNA10, IFNA1, IFNLR1, IFNA21, IFNA4, IFNL2, IFNL1, IFNA16, IFNA17) behave like immune genes that show low expression in 12 hours virus exposure, unlike demonstrate high gene expression at 48 hours virus exposure. Likewise, three IFN genes (IFNAR1, IFNGR1, IFNG) have high expression levels at the 12 hours exposure and low expressions at the 48 hours virus expression. All of these interferon genes expression were highly correlated and statistically significant (p< 0.05, pearson r-value > 0.8) with exposure time to the virus. These results suggest that hematopoietic stem cell proliferation pathway is affected by the viral SARS-CoV infection.
ABSTRACT
OBJECTIVE: COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection. Pathobiological transitions and clinical stages of the COVID-19 syndrome following the attack of SARS-CoV-2 on the human body have not been fully explored. The aim of this review is to outline the three critical prominent phase regarding the clinicogenomics course of the COVID-19 immune syndrome. MATERIALS AND METHODS: In the clinical setting, the COVID-19 process presents as "asymptomatic/pre-symptomatic phase", "respiratory phase with mild/moderate/severe symptoms" and "multi-systemic clinical syndrome with impaired/disproportionate and/or defective immunity". The corresponding three genomic phases include the "ACE2, ANPEP transcripts in the initial phase", "EGFR and IGF2R transcripts in the propagating phase" and the "immune system related critical gene involvements of the complicating phase". RESULTS: The separation of the phases is important since the genomic features of each phase are different from each other and these different mechanisms lead to distinct clinical multi-systemic features. Comprehensive genomic profiling with next generation sequencing may play an important role in defining and clarifying these three unique separate phases for COVID-19. From our point of view, it is important to understand these unique phases of the syndrome in order to approach a COVID-19 patient bedside. CONCLUSIONS: This three-phase approach may be useful for future studies which will focus on the clinical management and development of the vaccines and/or specific drugs targeting the COVID-19 processes. ANPEP gene pathway may have a potential for the vaccine development. Regarding the specific disease treatments, MAS agonists, TXA127, Angiotensin (1-7) and soluble ACE2 could have therapeutic potential for the COVID-19 course. Moreover, future CRISPR technology can be utilized for the genomic editing and future management of the clinical course of the syndrome.