Local Bone Marrow Renin-Angiotensin System and COVID-19

Çiftçiler, Rafiye; Ciftciler, Ali Erdinc; Haznedaroğlu, İbrahim C.

doi:10.4999/uhod.204171

Cited by 5 publications

(5 citation statements)

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“…In a previous paper, it was stated that SARS-CoV-2 can affect HSC and hematopoiesis via local bone marrow RAS system. 49 IFN-gamma is known to affect the differentiation of most hematopoietic progenitor cells. 50 It was shown that increased expression of IFN-gamma caused impairments in HSC regulations, supporting differentiation rather than self-renewal of HSCs.…”

Section: Effects Of Ifns On Hematopoietic Stem Cells Upon Viral Entrymentioning

confidence: 99%

Interferon-Gene Family Alterations Following the SARS-Cov Infection in Association with Iron Metabolism and Lymphoid Biology

Malkan¹,

Turk²,

Turk³

et al. 2021

UHOD

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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 (IF-NAR1, 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.

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Section: Effects Of Ifns On Hematopoietic Stem Cells Upon Viral Entrymentioning

confidence: 99%

Interferon-Gene Family Alterations Following the SARS-Cov Infection in Association with Iron Metabolism and Lymphoid Biology

Malkan¹,

Turk²,

Turk³

et al. 2021

UHOD

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“…Appropriate inflammatory response is crucial for combatting against SARS-CoV-2 [21] , [30] . Thus, excessive or uncontrolled inflammatory response in cellular level is the major cause of disease severity and mortality in the patients with COVID-19 [31] .…”

Section: Covid-19 Related Inflammation and The Role Of Proteinase- Acmentioning

confidence: 99%

Ankaferd hemostat (ABS) as a potential mucosal topical agent for the management of COVID-19 syndrome based on its PAR-1 inhibitory effect and oestrogen content

Beyazıt

Tanoğlu³

et al. 2020

Medical Hypotheses

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COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.

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“…Systemic COVID-19 syndrome could affect numerous organs including lungs, heart, gastrointestinal (GI) system, brain, kidneys, and bone marrow (BM) with the exaggerated or disproportionate immunological activation. SARS-CoV-2 virus or its spike protein attacks on hematopoietic stem cells (HSC), hematopoietic progenitor cells (HPC), together with the precursor and mature blood cells (4)(5)(6). Within this hematopoietic viral spread context, it is crucial to search the clinicopathological correlations of COVID-19 in order to develop specific potential therapeutics against pleiotropic SARS-CoV-2 actions (2,4,7).…”

Section: Introductionmentioning

confidence: 99%

“…SARS-CoV-2 virus or its spike protein attacks on hematopoietic stem cells (HSC), hematopoietic progenitor cells (HPC), together with the precursor and mature blood cells (4)(5)(6). Within this hematopoietic viral spread context, it is crucial to search the clinicopathological correlations of COVID-19 in order to develop specific potential therapeutics against pleiotropic SARS-CoV-2 actions (2,4,7). COVID-19 syndrome has three clinicopathological courses comprising initial, propagating and complicating phase (8).…”

Section: Introductionmentioning

confidence: 99%

The pathobiological harmony between the local pulmonary/ bone marrow RAS and its management via tissue-RAS modulating agents in COVID-19

Çetin

Beyazıt

et al. 2022

Journal of Health Sciences and Medicine

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Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to public health and healthcare systems. It presents unusual pathophysiological effects mainly characterized by immune-inflammatory response and prothrombotic state causing acute respiratory distress syndrome and multiple organ failure. SARS-CoV-2 enters target cells after binding to the angiotensin-converting enzyme 2 (ACE2) receptor and therefore has a direct effect on the renin-angiotensin system (RAS). Apart from affecting numerous organs including lungs, heart, gastrointestinal system, spleen, brain and kidneys, the spike protein of SARS-CoV-2 could attack hematopoietic stem cells and hematopoietic progenitor cells in bone marrow (BM) microenvironment together with the precursor and mature blood cells. Within this hematopoietic viral spread context, it is crucial to search the clinicopathological correlations of COVID-19 in order to develop specific potential therapeutics against pleiotropic SARS-CoV-2 actions. Therefore, pharmacological disruption of the pathological cross-talk of local BM RAS and pulmonary RAS via administration of the tissue-RAS modulating agents such as soluble ACE2, angiotensin (1-7), TXA127 and MAS receptor agonists may prevent the clinical progression of the COVID-19 syndrome via reducing the hematopoietic virus propagation and systemic multi-organ spread.

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Local Bone Marrow Renin-Angiotensin System and COVID-19

Cited by 5 publications

References 0 publications

Interferon-Gene Family Alterations Following the SARS-Cov Infection in Association with Iron Metabolism and Lymphoid Biology

Interferon-Gene Family Alterations Following the SARS-Cov Infection in Association with Iron Metabolism and Lymphoid Biology

Ankaferd hemostat (ABS) as a potential mucosal topical agent for the management of COVID-19 syndrome based on its PAR-1 inhibitory effect and oestrogen content

The pathobiological harmony between the local pulmonary/ bone marrow RAS and its management via tissue-RAS modulating agents in COVID-19

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