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  1. Article ; Online: COVID-19: Endogenous Retinoic Acid Theory and Retinoic Acid Depletion Syndrome.

    Sarohan, Aziz Rodan

    Medical hypotheses

    2020  Volume 144, Page(s) 110250

    Abstract: This study presents two new concepts and definitions to the medical literature. One of those is "endogenous retinoic acid theory" and the other "retinoic acid depletion syndrome". A new classification will be provided for the immune system: "retinoic ... ...

    Abstract This study presents two new concepts and definitions to the medical literature. One of those is "endogenous retinoic acid theory" and the other "retinoic acid depletion syndrome". A new classification will be provided for the immune system: "retinoic acid-dependent component" and "retinoic acid non-dependent component". If this theory is verified, all the diseases where the retinoic acid metabolism is defective and retinoic acid levels are low will be identified and new approaches will be developed fortreating such diseases. When the need for retinoic acids increases, such as acute infection, high fever, severe catabolic process, or chronic antigenic stimulation, cytochrome oxidase enzymes are inhibited by drugs or internal mechanisms. Metabolism and excretion of retinoic acids stored in the liver are prevented. In this way, retinoic acid levels in the blood are raised to therapeutic levels. This is called "Endogenous Retinoic Acid Theory". Retinoic acids also manage their metabolism through feedback mechanisms. Despite compensatory mechanisms, causes such as high fever, serious catabolic process and excessively large viral genome (SARS-CoV-2), excessive use of RIG-I and Type I interferon synthesis pathway using retinoic acid causes emptying of retinoic acid stores. As a result, the RIG-I pathway becomes ineffective, Type I IFN synthesis stops, and the congenital immune system collapses. Then the immune mechanism passes to TLR3, TLR7, TLR8, TLR9, MDA5 and UPS pathways in the monocyte, macrophage, neutrophil and dendritic cells of the adaptive immune defense system that do not require retinoic acid. This leads to excessive TNFα and cytokine discharge from the pathway. With the depletion of retinoic acid stores as a result of this overuse, the immune defense mechanism switches from the congenital immune system to the adaptive immune system, where retinoic acids cannot be used. As a result of this depletion of retinoic acids, the shift of the immune system to the NFκB arm, which causes excessive cytokine release, is called "retinoic acid depletion syndrome". COVID-19 and previously defined sepsis, SIRS and ARDS are each retinoic acid depletion syndrome. We claim that retinoic acid metabolism is defective in most inflammatory diseases, particularly COVID-19 (cytokine storm) sepsis, SIRS and ARDS. Finding a solution to this mechanism will bring a new perspective and treatment approach to such diseases.
    MeSH term(s) Autoimmunity ; COVID-19/immunology ; COVID-19/metabolism ; COVID-19/therapy ; Carotenoids/metabolism ; DEAD Box Protein 58/immunology ; Humans ; Immune System ; Interferon Type I/metabolism ; Interferons/metabolism ; Liver/metabolism ; Models, Theoretical ; Nervous System/metabolism ; Receptors, Immunologic ; Syndrome ; Tretinoin/metabolism ; Viral Load ; Vitamin A/pharmacology ; Vitamin A Deficiency/metabolism ; Zinc/metabolism
    Chemical Substances Interferon Type I ; Receptors, Immunologic ; Vitamin A (11103-57-4) ; Carotenoids (36-88-4) ; Tretinoin (5688UTC01R) ; Interferons (9008-11-1) ; RIGI protein, human (EC 3.6.1.-) ; DEAD Box Protein 58 (EC 3.6.4.13) ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2020-09-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2020.110250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: COVID-19

    Sarohan, Aziz Rodan

    Medical Hypotheses

    Endogenous Retinoic Acid Theory and Retinoic Acid Depletion Syndrome

    2020  Volume 144, Page(s) 110250

    Keywords General Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 193145-3
    ISSN 1532-2777 ; 0306-9877
    ISSN (online) 1532-2777
    ISSN 0306-9877
    DOI 10.1016/j.mehy.2020.110250
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: COVID-19: Endogenous Retinoic Acid Theory and Retinoic Acid Depletion Syndrome

    Sarohan, Aziz Rodan

    Med. Hypotheses

    Abstract: This study presents two new concepts and definitions to the medical literature. One of those is “endogenous retinoic acid theory” and the other “retinoic acid depletion syndrome”. A new classification will be provided for the immune system: “retinoic ... ...

    Abstract This study presents two new concepts and definitions to the medical literature. One of those is “endogenous retinoic acid theory” and the other “retinoic acid depletion syndrome”. A new classification will be provided for the immune system: “retinoic acid-dependent component” and “retinoic acid non-dependent component”. If this theory is verified, all the diseases where the retinoic acid metabolism is defective and retinoic acid levels are low will be identified and new approaches will be developed fortreating such diseases. When the need for retinoic acids increases, such as acute infection, high fever, severe catabolic process, or chronic antigenic stimulation, cytochrome oxidase enzymes are inhibited by drugs or internal mechanisms. Metabolism and excretion of retinoic acids stored in the liver are prevented. In this way, retinoic acid levels in the blood are raised to therapeutic levels. This is called “Endogenous Retinoic Acid Theory”. Retinoic acids also manage their metabolism through feedback mechanisms. Despite compensatory mechanisms, causes such as high fever, serious catabolic process and excessively large viral genome (SARS-CoV-2), excessive use of RIG-I and Type I interferon synthesis pathway using retinoic acid causes emptying of retinoic acid stores. As a result, the RIG-I pathway becomes ineffective, Type I IFN synthesis stops, and the congenital immune system collapses. Then the immune mechanism passes to TLR3, TLR7, TLR8, TLR9, MDA5 and UPS pathways in the monocyte, macrophage, neutrophil and dendritic cells of the adaptive immune defense system that do not require retinoic acid. This leads to excessive TNFα and cytokine discharge from the pathway. With the depletion of retinoic acid stores as a result of this overuse, the immune defense mechanism switches from the congenital immune system to the adaptive immune system, where retinoic acids cannot be used. As a result of this depletion of retinoic acids, the shift of the immune system to the NFκB arm, which causes excessive cytokine release, is called “retinoic acid depletion syndrome”. COVID-19 and previously defined sepsis, SIRS and ARDS are each retinoic acid depletion syndrome. We claim that retinoic acid metabolism is defective in most inflammatory diseases, particularly COVID-19 (cytokine storm) sepsis, SIRS and ARDS. Finding a solution to this mechanism will bring a new perspective and treatment approach to such diseases.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #753092
    Database COVID19

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  4. Article: Vitamin A Deficiency, COVID-19, and Rhino-Orbital Mucormycosis (Black Fungus): An Analytical Perspective.

    Sarohan, Aziz Rodan / Edipsoy, Sait / Özkurt, Zeynep Gürsel / Özlü, Can / Demir, Ayça Nur / Cen, Osman

    Advances in experimental medicine and biology

    2023  Volume 1436, Page(s) 153–166

    Abstract: Mucormycosis is a rare but serious opportunistic fungal disease characterized by rhino-orbito-cerebral and pulmonary involvement. It is mainly seen in people with secondary immunosuppression, isolated vitamin A deficiency, measles, and AIDS patients. It ... ...

    Abstract Mucormycosis is a rare but serious opportunistic fungal disease characterized by rhino-orbito-cerebral and pulmonary involvement. It is mainly seen in people with secondary immunosuppression, isolated vitamin A deficiency, measles, and AIDS patients. It showed a rise during the second wave of the COVID-19 epidemic in the spring of 2021 in India, especially in diabetic COVID-19 patients. Vitamin A deficiency is known to cause nutritional immunodeficiency and hence leading the way to increased opportunistic fungal, bacterial, and viral infections. In the eye, it causes keratitis, night blindness, xerophthalmia, conjunctivitis, Bitot spots, keratomalacia, and retinopathy. It also causes decreased tear secretion and deterioration of the anatomical/physiological defense barrier of the eye. The negative impact of vitamin A deficiency has been previously demonstrated in measles, AIDS, and COVID-19. We think that mucormycosis in COVID-19 might be rendered by vitamin A deficiency and that vitamin A supplementation may have preventive and therapeutic values against mucormycosis and other ocular symptoms associated with COVID-19. However, any vitamin A treatment regimen needs to be based on laboratory and clinical data and supervised by medical professionals.
    MeSH term(s) Humans ; Mucormycosis/epidemiology ; Vitamin A Deficiency/complications ; Vitamin A/therapeutic use ; Acquired Immunodeficiency Syndrome ; COVID-19 ; Eye Diseases ; Fungi
    Chemical Substances Vitamin A (11103-57-4)
    Language English
    Publishing date 2023-04-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 410187-X
    ISSN 0065-2598
    ISSN 0065-2598
    DOI 10.1007/5584_2023_774
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Retinol Depletion in COVID-19.

    Sarohan, Aziz Rodan / Akelma, Hakan / Araç, Eşref / Aslan, Özgür / Cen, Osman

    Clinical nutrition open science

    2022  Volume 43, Page(s) 85–94

    Abstract: Background and aims: COVID-19 has been a devastating pandemic. There are indications that vitamin A is depleted during infections. Vitamin A is important in development and immune homeostasis. It has been used successfully in measles, RSV and AIDS ... ...

    Abstract Background and aims: COVID-19 has been a devastating pandemic. There are indications that vitamin A is depleted during infections. Vitamin A is important in development and immune homeostasis. It has been used successfully in measles, RSV and AIDS infections. In this study, we aimed to measure the serum retinol levels in severe COVID-19 patients to assess the importance of vitamin A in the COVID-19 pathogenesis.
    Methods: The serum retinol level was measured in two groups of patients: the COVID-19 group, which consisted of 27 severe COVID-19 patients hospitalized in the intensive care unit with respiratory failure, and the control group, which consisted of 23 patients without COVID-19 symptoms.
    Results: The mean serum retinol levels were 0.37 mg/L in the COVID-19 group and 0.52 mg/L in the control group. The difference between the serum retinol levels in the two groups was statistically significant. There was no significant difference in retinol levels between different ages and genders within the COVID-19 group. Comorbidity did not affect serum retinol levels.
    Conclusion: The serum retinol level was significantly lower in patients with severe COVID-19, and this difference was independent of age or underlying comorbidity. Our data show that retinol and retinoic acid signaling might be important in immunopathogenesis of COVID-19.
    Language English
    Publishing date 2022-05-28
    Publishing country United States
    Document type Journal Article
    ISSN 2667-2685
    ISSN (online) 2667-2685
    DOI 10.1016/j.nutos.2022.05.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder.

    Sarohan, Aziz Rodan / Kızıl, Murat / İnkaya, Ahmet Çağkan / Mahmud, Shokhan / Akram, Muhammad / Cen, Osman

    Cellular signalling

    2021  Volume 87, Page(s) 110121

    Abstract: The SARS-CoV-2 virus has caused a worldwide COVID-19 pandemic. In less than a year and a half, more than 200 million people have been infected and more than four million have died. Despite some improvement in the treatment strategies, no definitive ... ...

    Abstract The SARS-CoV-2 virus has caused a worldwide COVID-19 pandemic. In less than a year and a half, more than 200 million people have been infected and more than four million have died. Despite some improvement in the treatment strategies, no definitive treatment protocol has been developed. The pathogenesis of the disease has not been clearly elucidated yet. A clear understanding of its pathogenesis will help develop effective vaccines and drugs. The immunopathogenesis of COVID-19 is characteristic with acute respiratory distress syndrome and multiorgan involvement with impaired Type I interferon response and hyperinflammation. The destructive systemic effects of COVID-19 cannot be explained simply by the viral tropism through the ACE2 and TMPRSS2 receptors. In addition, the recently identified mutations cannot fully explain the defect in all cases of Type I interferon synthesis. We hypothesize that retinol depletion and resulting impaired retinoid signaling play a central role in the COVID-19 pathogenesis that is characteristic for dysregulated immune system, defect in Type I interferon synthesis, severe inflammatory process, and destructive systemic multiorgan involvement. Viral RNA recognition mechanism through RIG-I receptors can quickly consume a large amount of the body's retinoid reserve, which causes the retinol levels to fall below the normal serum levels. This causes retinoid insufficiency and impaired retinoid signaling, which leads to interruption in Type I interferon synthesis and an excessive inflammation. Therefore, reconstitution of the retinoid signaling may prove to be a valid strategy for management of COVID-19 as well for some other chronic, degenerative, inflammatory, and autoimmune diseases.
    MeSH term(s) COVID-19/immunology ; COVID-19/metabolism ; COVID-19/pathology ; COVID-19/virology ; Central Nervous System/metabolism ; DEAD Box Protein 58/metabolism ; Humans ; Immune Tolerance ; Interferon Type I/metabolism ; Receptors, Immunologic/metabolism ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Signal Transduction/physiology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Viral Tropism/physiology ; Vitamin A/blood ; Vitamin A/metabolism
    Chemical Substances Interferon Type I ; Receptors, Immunologic ; Vitamin A (11103-57-4) ; RIGI protein, human (EC 3.6.1.-) ; DEAD Box Protein 58 (EC 3.6.4.13)
    Language English
    Publishing date 2021-08-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1002702-6
    ISSN 1873-3913 ; 0898-6568
    ISSN (online) 1873-3913
    ISSN 0898-6568
    DOI 10.1016/j.cellsig.2021.110121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Retinol Depletion in Severe COVID-19

    Sarohan, Aziz Rodan / Akelma, Hakan / Arac, Esref / Aslan, Ozgur

    medRxiv

    Abstract: Background and Purpose: Vitamin A is depleted during infections. Vitamin A has been used successfully in measles, RSV, and AIDS patients and is an effective vaccine adjuvant. In this study, low retinol levels were found in patients with severe COVID-19. ... ...

    Abstract Background and Purpose: Vitamin A is depleted during infections. Vitamin A has been used successfully in measles, RSV, and AIDS patients and is an effective vaccine adjuvant. In this study, low retinol levels were found in patients with severe COVID-19. Retinoid signaling impairment in COVID-19 disrupts Type-I interferon synthesis. Material and Method: Two groups were formed in the study. The patient group consisted of 27 (Group 1) severe COVID-19 patients hospitalized in the intensive care unit with respiratory failure, and the control group consisted of 23 (Group 2) patients without COVID-19 symptoms. Serum retinol levels were analyzed by ELIZA and HPLC in both groups. Findings: Retinol levels were found to be significantly lower in the patient group (P <0.001). There was no difference in retinol between two different age groups in the patient group (P> 0.05). There was no significant difference in retinol between men and women (P> 0.05). Comorbidity did not affect serum retinol levels (P >0.05). Conclusion: Serum retinol levels were low in patients with severe COVID-19. Drugs preventing retinol excretion were not stopped in the patient group. Some patients took vitamin A externally. Despite this, retinol was low in COVID-19 patients. Retinol depletion impairs Type-I interferon synthesis by impairing retinoid signaling. Retinoid signaling may be the main pathogenetic disorder in COVID-19. This pathogenesis can serve as a guide for adjuvants, drug targets, and candidate drugs. Retinol, retinoic acid derivatives, and some CYP450 inhibitors may work on COVID-19.
    Keywords covid19
    Language English
    Publishing date 2021-02-01
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.01.30.21250844
    Database COVID19

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