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Li X, Qu S. Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives. Mol Cell Biochem 2025; 480:3535-3551. [PMID: 39928210 DOI: 10.1007/s11010-024-05196-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 12/18/2024] [Indexed: 02/11/2025]
Abstract
Diabetic cardiomyopathy (DCM) is a cardiac complication specific to individuals with diabetes. It is defined as abnormalities of myocardial structure and function in diabetic patients who do not exhibit any obvious coronary artery disease, hypertensive heart disease, valvular heart disease, or inherited cardiomyopathy. A significant cardiovascular protective factor identified recently is angiotensin-converting enzyme 2 (ACE2), which is a rising star in the renin angiotensin system (RAS) and is responsible for the onset and progression of DCM. Nonetheless, there is not a comprehensive review outlining ACE2's effect on DCM. From the perspective of the pathogenesis of DCM, this review summarizes the myocardial protective role of ACE2 in the aspects of alleviating myocardial structure and dysfunction, correcting energy metabolism disorders, and restoring vascular function. Concurrently, we propose the connections between ACE2 and underlying signaling pathways, including ADAM17, Apelin/APJ, and Nrf2. Additionally, we highlight ACE2-related pharmaceutical treatment options and clinical application prospects for preventing and managing DCM. Further and underlying research is extensively required to completely comprehend the principal pathophysiological mechanism of DCM and the distinctive function of ACE2, switching experimental findings into clinical practice and identifying efficient therapeutic approaches.
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Affiliation(s)
- Xinyi Li
- Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Shunlin Qu
- Pathophysiology Department, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hongxiang Street, Hengyang, 421001, Hunan, China.
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2
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Tewari M, Rana P, Pande V. Nanomaterial-Based Biosensors for the Detection of COVID-19. Indian J Microbiol 2025; 65:120-136. [PMID: 40371045 PMCID: PMC12069788 DOI: 10.1007/s12088-024-01336-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 06/12/2024] [Indexed: 05/16/2025] Open
Abstract
The COVID-19 outbreak began in December 2019 and has affected people worldwide. It was declared a pandemic in 2020 by the World Health Organization. Developing rapid and reliable diagnostic techniques is crucial for identifying COVID-19 early and preventing the disease from becoming severe. In addition to conventional diagnostic techniques such as RT-PCR, computed tomography, serological assays, and sequencing methods, biosensors have become widely accepted for identifying and screening COVID-19 infection with high accuracy and sensitivity. Their low cost, high sensitivity, specificity, and portability make them ideal for diagnostics. The use of nanomaterials improves the performance of biosensors by increasing their sensitivities and limiting detection by several orders of magnitude. This manuscript briefly reviews the COVID-19 outbreak and its pathogenesis. Furthermore, it comprehensively discusses the currently available biosensors for SARS-CoV-2 detection, with a special emphasis on nanomaterials-based biosensors developed to detect this emerging virus and its variants efficiently.
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Affiliation(s)
- Manju Tewari
- Department of Biotechnology, Kumaun University, Sir J.C. Bose Technical Campus, Bhimtal, Uttarakhand 263136 India
| | - Prerna Rana
- Department of Biotechnology, Kumaun University, Sir J.C. Bose Technical Campus, Bhimtal, Uttarakhand 263136 India
| | - Veena Pande
- Department of Biotechnology, Kumaun University, Sir J.C. Bose Technical Campus, Bhimtal, Uttarakhand 263136 India
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3
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Kessler M, Vojtíšek T, Zeman T, Krajsa J, Srník M, Dziedzinska R, Šerý O. The protective effect of serum antibodies in preventing SARS-CoV-2 virus entry into cardiac muscle. Physiol Res 2024; 73:S715-S725. [PMID: 39808173 PMCID: PMC11827059 DOI: 10.33549/physiolres.935475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 08/19/2024] [Indexed: 01/18/2025] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with significant cardiovascular complications, including myocardial infection and pulmonary embolism. This study aims to elucidate the relationship between the presence of SARS-CoV-2 RNA in the myocardium of the left ventricle and the levels of IgG and IgM antibodies against the SARS-CoV-2 virus in deceased COVID-19 patients. We conducted a post-mortem examination on 91 individuals who succumbed to COVID-19-related complications. The presence of SARS-CoV-2 RNA in the myocardium of the left ventricle was analyzed reverse transcription real time PCR (RT-qPCR) (EliGene® COVID19 UKV/SAV RT kit, Elisabeth Pharmacon), and antibody levels in serum were analyzed by serological assays (VIDAS SARS-COV-2 IgM and VIDAS SARS-COV-2 IgG II tests, BioMérieux). Of the heart tissue samples, 44 % tested positive for SARS-CoV-2 RNA. Our findings indicate that any detectable level of IgG antibodies against SARS-CoV-2 reduces the risk of viral penetration into the myocardium by more than fourfold. Specifically, individuals with detectable levels of IgG and IgM antibodies exhibited a significantly reduced presence of SARS-CoV-2 RNA in cardiac tissues (p<0.0001 for IgG and p<0.001 for IgM). Notably, all patients who died from pulmonary embolism had elevated levels of IgG antibodies. The study underscores the protective role of IgG and IgM antibodies in preventing SARS-CoV-2 penetration into cardiac tissues. However, high antibody titers were associated with fatal outcomes such as pulmonary embolism, pointing to the intricate balance of immune response in COVID-19 pathology. Key words SARS-CoV-2, Antibody, IgG, IgM, Cardiac damage, qPCR, Pneumonia, Pulmonary embolism, Heart failure.
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Affiliation(s)
- M Kessler
- Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
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Ibrahim R. The effect of pre-hospital use of RAS inhibitors on COVID-19 mortality. J Investig Med 2024; 72:863-875. [PMID: 39075674 DOI: 10.1177/10815589241270417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2024]
Abstract
The effect of pre-hospital use of renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)) on clinical outcomes of hypertensive patients with COVID-19 has been questioned due to conflicting reports on this issue. After applying exclusion criteria, 175 COVID-19 hospitalized patients admitted to the Tishreen Hospital from January 1 to July 31, 2021 were retrospectively enrolled in this study. Baseline characteristics and in-hospital mortality rate were assessed between hypertensive (N = 91, 52%) and non-hypertensive (N = 84, 48%) patients, as well as between patients taking ACEis/ARBs and non-ACEis/ARBs within the hypertensive group. A lower mortality rate (51.2 versus 31.9%, p = 0.009) was observed in the hypertensive group (mean age 64.6 years, 64.8% males) compared to the non-hypertensive (mean age 62.6 years, 66.7% males). Patients' mortality in the non-hypertensive group was associated with lower blood oxygen saturation (SPO2 = 75 versus 86%, p = 0.002), increased levels of inflammatory (CRP, white blood cell and neutrophils count), and tissue/renal injury markers (LDH, urea, and creatinine). In the hypertensive group, a lower mortality rate was noted in the ACEis/ARBs group compared to the non-ACEis/ARBs (24.1 versus 45.5%, p = 0.036), and this was associated with a decrease in D-DIMER levels, although not significant (1723 versus 2683 ng/mL, p > 0.05). Death in the non-ACEis/ARBs group was associated with decreased SPO2 and tissue/renal injury markers (LDH, CK, AST, urea, and creatinine). We concluded that hypertension is not a direct cause of poor prognosis in COVID-19 patients and that multi-organ damage is a significant indicator of death from COVID-19. RAS inhibitors could improve the survival of hypertensive COVID-19 patients.
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Affiliation(s)
- Rama Ibrahim
- Department of Biochemistry and Microbiology, Faculty of Pharmacy,Al-Sham Private University (ASPU), Lattakia, Syria
- Department of Biochemistry and Microbiology, Faculty of Pharmacy, Tishreen University, Lattakia, Syria
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Nunes-Souza V, Alenina N, Qadri F, Mosienko V, Santos RAS, Bader M, Rabelo LA. ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner. Int J Mol Sci 2024; 25:9515. [PMID: 39273464 PMCID: PMC11394789 DOI: 10.3390/ijms25179515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Angiotensin converting enzyme 2 (ACE2) presents pleiotropic actions. It hydrolyzes angiotensin I (AngI) and angiotensin II (AngII) into angiotensin-(1-9) (Ang-(1-9)) and angiotensin-(1-7) (Ang-(1-7)), respectively, as well as participates in tryptophan uptake in the gut and in COVID-19 infection. Our aim was to investigate the metabolic effect of ACE2 deletion in young adults and elderly mice under conditions of high calorie intake. Male C57Bl/6 (WT) and ACE2-deficient (ACE2-/y) mice were analyzed at the age of 6 and 12 months under standard diet (StD) and high-fat diet (HFD). Under StD, ACE2-/y showed lower body weight and fat depots, improved glucose tolerance, enhanced insulin sensitivity, higher adiponectin, and lower leptin levels compared to WT. This difference was even more pronounced after HFD in 6-month-old mice, but, interestingly, it was blunted at the age of 12 months. ACE2-/y presented a decrease in adipocyte diameter and lipolysis, which reflected in the upregulation of lipid metabolism in white adipose tissue through the increased expression of genes involved in lipid regulation. Under HFD, both food intake and total energy expenditure were decreased in 6-month-old ACE2-/y mice, accompanied by an increase in liquid intake, compared to WT mice, fed either StD or HFD. Thus, ACE2-/y mice are less susceptible to HFD-induced obesity in an age-dependent manner, as well as represent an excellent animal model of human lipodystrophy and a tool to investigate new treatments.
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Affiliation(s)
- Valéria Nunes-Souza
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; (V.N.-S.); (F.Q.); (V.M.); (M.B.)
- Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife 50670-901, Brazil
- National Institute of Science and Technology in Nanobiopharmaceutics (Nanobiofar), Belo Horizonte 31270-901, Brazil;
| | - Natalia Alenina
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; (V.N.-S.); (F.Q.); (V.M.); (M.B.)
| | - Fatimunnisa Qadri
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; (V.N.-S.); (F.Q.); (V.M.); (M.B.)
| | - Valentina Mosienko
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; (V.N.-S.); (F.Q.); (V.M.); (M.B.)
- School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol BS8 1TD, UK
| | - Robson Augusto Souza Santos
- National Institute of Science and Technology in Nanobiopharmaceutics (Nanobiofar), Belo Horizonte 31270-901, Brazil;
- Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Michael Bader
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; (V.N.-S.); (F.Q.); (V.M.); (M.B.)
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany
- Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, 10117 Berlin, Germany
- Institute for Biology, University of Lübeck, 23562 Lübeck, Germany
| | - Luiza Antas Rabelo
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; (V.N.-S.); (F.Q.); (V.M.); (M.B.)
- National Institute of Science and Technology in Nanobiopharmaceutics (Nanobiofar), Belo Horizonte 31270-901, Brazil;
- Laboratory of Cardiovascular Reactivity, Metabolic Syndrome Center, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió 57072-900, Brazil
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Michaels TM, Essop MF, Joseph DE. Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells. Viruses 2024; 16:1243. [PMID: 39205219 PMCID: PMC11358987 DOI: 10.3390/v16081243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
The COVID-19 pandemic has revealed a bidirectional relationship between SARS-CoV-2 infection and diabetes mellitus. Existing evidence strongly suggests hyperglycemia as an independent risk factor for severe COVID-19, resulting in increased morbidity and mortality. Conversely, recent studies have reported new-onset diabetes following SARS-CoV-2 infection, hinting at a potential direct viral attack on pancreatic beta cells. In this review, we explore how hyperglycemia, a hallmark of diabetes, might influence SARS-CoV-2 entry and accessory proteins in pancreatic β-cells. We examine how the virus may enter and manipulate such cells, focusing on the role of the spike protein and its interaction with host receptors. Additionally, we analyze potential effects on endosomal processing and accessory proteins involved in viral infection. Our analysis suggests a complex interplay between hyperglycemia and SARS-CoV-2 in pancreatic β-cells. Understanding these mechanisms may help unlock urgent therapeutic strategies to mitigate the detrimental effects of COVID-19 in diabetic patients and unveil if the virus itself can trigger diabetes onset.
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Affiliation(s)
- Tara M. Michaels
- Centre for Cardio-Metabolic Research in Africa, Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch 7600, South Africa;
| | - M. Faadiel Essop
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa;
| | - Danzil E. Joseph
- Centre for Cardio-Metabolic Research in Africa, Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch 7600, South Africa;
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Carvajal JJ, García-Castillo V, Cuellar SV, Campillay-Véliz CP, Salazar-Ardiles C, Avellaneda AM, Muñoz CA, Retamal-Díaz A, Bueno SM, González PA, Kalergis AM, Lay MK. New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic. Front Immunol 2024; 15:1363572. [PMID: 38911850 PMCID: PMC11190347 DOI: 10.3389/fimmu.2024.1363572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Accepted: 04/24/2024] [Indexed: 06/25/2024] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.
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Affiliation(s)
- Jonatan J. Carvajal
- Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, University of Antofagasta, Antofagasta, Chile
| | - Valeria García-Castillo
- Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, University of Antofagasta, Antofagasta, Chile
| | - Shelsy V. Cuellar
- Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, University of Antofagasta, Antofagasta, Chile
| | | | - Camila Salazar-Ardiles
- Center for Research in Physiology and Altitude Medicine (FIMEDALT), Biomedical Department, Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile
| | - Andrea M. Avellaneda
- Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, University of Antofagasta, Antofagasta, Chile
- Department of Basic Sciences, Faculty of Sciences, Universidad Santo Tomás, Antofagasta, Chile
| | - Christian A. Muñoz
- Research Center in Immunology and Biomedical Biotechnology of Antofagasta (CIIBBA), University of Antofagasta, Antofagasta, Chile
- Department of Medical Technology, Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile
- Millennium Institute on Immunology and Immunotherapy, Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, Department of Medical Technology, Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile
| | - Angello Retamal-Díaz
- Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, University of Antofagasta, Antofagasta, Chile
- Research Center in Immunology and Biomedical Biotechnology of Antofagasta (CIIBBA), University of Antofagasta, Antofagasta, Chile
- Millennium Institute on Immunology and Immunotherapy, Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, Department of Medical Technology, Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile
| | - Susan M. Bueno
- Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Pablo A. González
- Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Alexis M. Kalergis
- Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
- Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Margarita K. Lay
- Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, University of Antofagasta, Antofagasta, Chile
- Research Center in Immunology and Biomedical Biotechnology of Antofagasta (CIIBBA), University of Antofagasta, Antofagasta, Chile
- Millennium Institute on Immunology and Immunotherapy, Department of Biotechnology, Faculty of Marine Sciences and Biological Resources, Department of Medical Technology, Faculty of Health Sciences, University of Antofagasta, Antofagasta, Chile
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Mendiola-Salazar XA, Munguía-Laguna MA, Franco M, Cano-Martínez A, Santamaría Sosa J, Bautista-Pérez R. SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2. Int J Mol Sci 2024; 25:6276. [PMID: 38892464 PMCID: PMC11172802 DOI: 10.3390/ijms25116276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 05/30/2024] [Accepted: 06/04/2024] [Indexed: 06/21/2024] Open
Abstract
In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.
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Affiliation(s)
- Xóchitl Andrea Mendiola-Salazar
- Department of Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City 14080, Mexico (M.A.M.-L.)
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City 54090, Mexico
| | - Melanie A. Munguía-Laguna
- Department of Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City 14080, Mexico (M.A.M.-L.)
| | - Martha Franco
- Department of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City 14080, Mexico; (M.F.); (J.S.S.)
| | - Agustina Cano-Martínez
- Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City 14080, Mexico;
| | - José Santamaría Sosa
- Department of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City 14080, Mexico; (M.F.); (J.S.S.)
| | - Rocío Bautista-Pérez
- Department of Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City 14080, Mexico (M.A.M.-L.)
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Bhullar SK, Dhalla NS. Adaptive and maladaptive roles of different angiotensin receptors in the development of cardiac hypertrophy and heart failure. Can J Physiol Pharmacol 2024; 102:86-104. [PMID: 37748204 DOI: 10.1139/cjpp-2023-0226] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Abstract
Angiotensin II (Ang II) is formed by the action of angiotensin-converting enzyme (ACE) in the renin-angiotensin system. This hormone is known to induce cardiac hypertrophy and heart failure and its actions are mediated by the interaction of both pro- and antihypertrophic Ang II receptors (AT1R and AT2R). Ang II is also metabolized by ACE 2 to Ang-(1-7), which elicits the activation of Mas receptors (MasR) for inducing antihypertrophic actions. Since heart failure under different pathophysiological situations is preceded by adaptive and maladaptive cardiac hypertrophy, we have reviewed the existing literature to gain some information regarding the roles of AT1R, AT2R, and MasR in both acute and chronic conditions of cardiac hypertrophy. It appears that the activation of AT1R may be involved in the development of adaptive and maladaptive cardiac hypertrophy as well as subsequent heart failure because both ACE inhibitors and AT1R antagonists exert beneficial effects. On the other hand, the activation of both AT2R and MasR may prevent the occurrence of maladaptive cardiac hypertrophy and delay the progression of heart failure, and thus therapy with different activators of these antihypertrophic receptors under chronic pathological stages may prove beneficial. Accordingly, it is suggested that a great deal of effort should be made to develop appropriate activators of both AT2R and MasR for the treatment of heart failure subjects.
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Affiliation(s)
- Sukhwinder K Bhullar
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre and Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada
| | - Naranjan S Dhalla
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre and Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada
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Jain R, Mathew D. Mechanisms influencing the high prevalence of COVID-19 in diabetics: A systematic review. MEDICAL RESEARCH ARCHIVES 2023; 11:4540. [PMID: 38933091 PMCID: PMC11198970 DOI: 10.18103/mra.v11i10.4540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/28/2024]
Abstract
Diabetics have an increased risk of contracting COVID-19 infection and tend to have more severe symptoms. This systematic review explores the potential mechanisms influencing the high prevalence of COVID-19 infections in individuals with diabetes. It reviews the emerging evidence about the interactions between viral and diabetic pathways, particularly how diabetes physiology could contribute to higher viral reception, viral entry and pathogenicity, and the severity of disease symptoms. Finally, it examines the challenges we face in studying these mechanisms and offers new strategies that might assist our fight against current and future pandemics.
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Affiliation(s)
- Roshni Jain
- Cell and Molecular Biology Program, University of Nevada, Reno, NV 89557
- Department of Biology, University of Nevada, Reno, NV 89557
| | - Dennis Mathew
- Cell and Molecular Biology Program, University of Nevada, Reno, NV 89557
- Department of Biology, University of Nevada, Reno, NV 89557
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11
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Salgado-Barreira A, Seijas-Amigo J, Rodriguez-Mañero M, Piñeiro-Lamas M, Eiras S, Cordero A, Gonzalez-Juanatey JR, Figueiras A. Effect of dapagliflozin on COVID-19 infection and risk of hospitalization. J Antimicrob Chemother 2023; 78:2335-2342. [PMID: 37549309 PMCID: PMC10477113 DOI: 10.1093/jac/dkad241] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 07/19/2023] [Indexed: 08/09/2023] Open
Abstract
BACKGROUND Dapagliflozin has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19) by reducing cytokine production and inflammation. However, there are limited data on its effectiveness. We aimed to evaluate the impact of dapagliflozin on COVID-19 severity (including hospitalization risk, ICU admission, in-hospital death and progression to severe COVID-19) and its potential on susceptibility to COVID-19 infection. METHODS We conducted a population-based case-control study. For aim 1, we assessed COVID-19 severity in cases (positive PCR patients requiring hospitalization) and matched controls (negative PCR patients or positive PCR patients not requiring hospitalization). For aim 2, we compared positive PCR cases (hospitalized and non-hospitalized) with controls. Adjusted odds ratios (aORs) were calculated using a generalized linear mixed model. RESULTS We analysed 86 602 subjects: 3060 were hospitalized cases, 26 757 were non-hospitalized cases and 56 785 were controls. Among the hospitalized COVID-19 patients, 228 were admitted to the ICU and 413 died. Dapagliflozin had no effect on the risk of hospitalization (aOR 0.98; 95% CI 0.65-1.48; P = 0.915), ICU admissions (aOR 1.21; 95% CI 0.34-4.25; P = 0.767) or in-hospital death (aOR 1.33; 95% CI 0.53-3.30; P = 0.543). Dapagliflozin reduced the risk of progression to severe COVID-19 by 35%, but this was not statistically significant (aOR 0.65; 95% CI 0.40-1.06; P = 0.086). Dapagliflozin was associated with a 30% increased risk of susceptibility to COVID-19 infection (aOR 1.31; 95% CI 1.05-1.62; P = 0.015). CONCLUSIONS Use of dapagliflozin prior to SARS-CoV-2 infection was not associated with an increased risk of hospitalization, ICU admission, mortality or progression to severe COVID-19. However, it was associated with an increased risk of susceptibility to COVID-19 infection.
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Affiliation(s)
- Angel Salgado-Barreira
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Carlos III Health Institute, Madrid, Spain
| | - Jose Seijas-Amigo
- Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
- Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - Moises Rodriguez-Mañero
- Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - María Piñeiro-Lamas
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Carlos III Health Institute, Madrid, Spain
| | - Sonia Eiras
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
- Translational Cardiology Group, Institute of Biomedical Research of Santiago de Compostela (IDIS-SERGAS), Santiago de Compostela, Spain
| | - Alberto Cordero
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
- Cardiology Department, Hospital Universitario de San Juan, Alicante, Spain
- Unidad de Investigación en Cardiología, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Valencia, Spain
| | - Jose Ramon Gonzalez-Juanatey
- Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - Adolfo Figueiras
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Carlos III Health Institute, Madrid, Spain
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Huo JL, Feng Q, Pan S, Fu WJ, Liu Z, Liu Z. Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions. Cell Death Discov 2023; 9:256. [PMID: 37479697 PMCID: PMC10362058 DOI: 10.1038/s41420-023-01553-4] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 07/06/2023] [Accepted: 07/12/2023] [Indexed: 07/23/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) mainly refers to myocardial metabolic dysfunction caused by high glucose, and hyperglycemia is an independent risk factor for cardiac function in the absence of coronary atherosclerosis and hypertension. DCM, which is a severe complication of diabetes, has become the leading cause of heart failure in diabetic patients. The initial symptoms are inconspicuous, and patients gradually exhibit left ventricular dysfunction and eventually develop total heart failure, which brings a great challenge to the early diagnosis of DCM. To date, the underlying pathological mechanisms of DCM are complicated and have not been fully elucidated. Although there are therapeutic strategies available for DCM, the treatment is mainly focused on controlling blood glucose and blood lipids, and there is a lack of effective drugs targeting myocardial injury. Thus, a large percentage of patients with DCM inevitably develop heart failure. Given the neglected initial symptoms, the intricate cellular and molecular mechanisms, and the lack of available drugs, it is necessary to explore early diagnostic biomarkers, further understand the signaling pathways involved in the pathogenesis of DCM, summarize the current therapeutic strategies, and develop new targeted interventions.
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Affiliation(s)
- Jin-Ling Huo
- Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P. R. China
- Henan Province Research Center For Kidney Disease, Zhengzhou, 450052, P. R. China
- Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P. R. China
| | - Qi Feng
- Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P. R. China
- Henan Province Research Center For Kidney Disease, Zhengzhou, 450052, P. R. China
- Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P. R. China
| | - Shaokang Pan
- Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P. R. China
- Henan Province Research Center For Kidney Disease, Zhengzhou, 450052, P. R. China
- Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P. R. China
| | - Wen-Jia Fu
- Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P. R. China
- Henan Province Research Center For Kidney Disease, Zhengzhou, 450052, P. R. China
- Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P. R. China
| | - Zhangsuo Liu
- Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P. R. China.
- Henan Province Research Center For Kidney Disease, Zhengzhou, 450052, P. R. China.
- Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P. R. China.
| | - Zhenzhen Liu
- Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China.
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13
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Kusumawardhani NY, Putra ICS, Kamarullah W, Afrianti R, Pramudyo M, Iqbal M, Prameswari HS, Achmad C, Tiksnadi BB, Akbar MR. Cardiovascular Disease in Post-Acute COVID-19 Syndrome: A Comprehensive Review of Pathophysiology and Diagnosis Approach. Rev Cardiovasc Med 2023; 24:28. [PMID: 39076856 PMCID: PMC11270463 DOI: 10.31083/j.rcm2401028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/09/2022] [Accepted: 12/23/2022] [Indexed: 07/31/2024] Open
Abstract
Long COVID or post-acute Coronavirus disease 2019 (COVID-19), a malady defined by the persistence of COVID-19 symptoms for weeks or even months, is expected to affect the lives of millions of individuals worldwide significantly. Cardiopulmonary symptoms such as chest discomfort, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia syndrome, and arrhythmias are prevalent and widely recognized. A variety of cardiovascular problems, including myocardial inflammation, myocardial infarction, ventricular dysfunction, and endothelial dysfunction, have been described in individuals following the initial acute phase. With over 10,000 published publications on COVID-19 and the cardiovascular system, presenting an unbiased thorough analysis of how SARS-CoV-2 affects the system is essentially challenging. This review will provide an overview of frequent cardiovascular manifestations, emphasizing consequences, proposed pathophysiology, and clinical diagnostic manifestation strategy.
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Affiliation(s)
- Nuraini Yasmin Kusumawardhani
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
- Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - Iwan Cahyo Santosa Putra
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - William Kamarullah
- Emergency Department, R. Syamsudin SH Regional Public Hospital, Sukabumi, 43341 West Java, Indonesia
| | - Rien Afrianti
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
- Department of Internal Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - Miftah Pramudyo
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - Mohammad Iqbal
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - Hawani Sasmaya Prameswari
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - Chaerul Achmad
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - Badai Bhatara Tiksnadi
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
| | - Mohammad Rizki Akbar
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Padjadjaran, 40132 Bandung, Indonesia
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14
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Kamthe DD, Sarangkar SD, Dalvi MS, Gosavi NA, Nikam VS. Angiotensin converting enzyme 2 level and its significance in COVID-19 and other diseases patients. Eur J Clin Invest 2023; 53:e13891. [PMID: 36222740 PMCID: PMC9874405 DOI: 10.1111/eci.13891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 10/03/2022] [Accepted: 10/11/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Angiotensin-converting enzyme 2 (ACE2) expressions and its modulation are of great interest as being a key receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and the protective arm of the rennin-angiotensin axis, maintaining cardiovascular homeostasis. However, ACE2 expressions and their modulation in the healthy and disease background are yet to be explored. METHOD We performed a meta-analysis, extracting the data for ACE2 expression in human subjects with various diseases, including SARS-CoV2 infection without or with co-morbidity. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Out of 203 studies, 39 met the inclusion criteria with SARS-CoV2 patients without co-morbidity, SARS-CoV2 patients with co-morbidity, cardiovascular (CVD) patients, diabetes patients, kidney disorders patients, pulmonary disease patients, and other viral infections patients. RESULTS Angiotensin-converting enzyme 2 expression was significantly increased in all diseases. There was an elevated level of ACE2, especially membrane-bound ACE2, in COVID-19 patients compared to healthy controls. A statistically significant increase in ACE2 expression was observed in CVD patients and patients with other viral diseases compared to healthy subjects. Moreover, subgroup analysis of ACE2 expression as soluble and membrane-bound ACE2 revealed a remarkable increase in membrane-bound ACE2 in CVD patients, patients with viral infection compared to soluble ACE2 and pooled standard mean difference (SMD) with the random-effects model was 0.37 and 2.23 respectively. CONCLUSION It was observed that utilizing the ACE2 by SARS-CoV2 for its entry and its consequence leads to several complications. So there is a need to investigate the underlying mechanism along with novel therapeutic strategies.
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Affiliation(s)
- Dipanjali Dhananjay Kamthe
- Department of Pharmacology, STES's, Smt. Kashibai Navale College of PharmacySavitribai Phule Pune UniversityPuneIndia
| | - Swapnil Dilip Sarangkar
- Department of Pharmacology, STES's, Smt. Kashibai Navale College of PharmacySavitribai Phule Pune UniversityPuneIndia
| | - Manali Suresh Dalvi
- Department of Pharmacology, STES's, Smt. Kashibai Navale College of PharmacySavitribai Phule Pune UniversityPuneIndia
| | - Netra Arun Gosavi
- Department of Pharmacology, STES's, Smt. Kashibai Navale College of PharmacySavitribai Phule Pune UniversityPuneIndia
| | - Vandana Sandeep Nikam
- Department of Pharmacology, STES's, Smt. Kashibai Navale College of PharmacySavitribai Phule Pune UniversityPuneIndia
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15
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Martínez JA, Alonso-Bernáldez M, Martínez-Urbistondo D, Vargas-Nuñez JA, Ramírez de Molina A, Dávalos A, Ramos-Lopez O. Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases. World J Gastroenterol 2022; 28:6230-6248. [PMID: 36504554 PMCID: PMC9730439 DOI: 10.3748/wjg.v28.i44.6230] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/07/2022] [Accepted: 11/16/2022] [Indexed: 11/25/2022] Open
Abstract
The liver is a key organ involved in a wide range of functions, whose damage can lead to chronic liver disease (CLD). CLD accounts for more than two million deaths worldwide, becoming a social and economic burden for most countries. Among the different factors that can cause CLD, alcohol abuse, viruses, drug treatments, and unhealthy dietary patterns top the list. These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis. High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma (HCC). Despite the advances achieved in this field, new approaches are needed for the prevention, diagnosis, treatment, and prognosis of CLD. In this context, the scientific com-munity is using machine learning (ML) algorithms to integrate and process vast amounts of data with unprecedented performance. ML techniques allow the integration of anthropometric, genetic, clinical, biochemical, dietary, lifestyle and omics data, giving new insights to tackle CLD and bringing personalized medicine a step closer. This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatory-related, hepatitis viruses-induced, and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.
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Affiliation(s)
- J Alfredo Martínez
- Precision Nutrition and Cardiometabolic Health, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | - Marta Alonso-Bernáldez
- Precision Nutrition and Cardiometabolic Health, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | | | - Juan A Vargas-Nuñez
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Madrid 28222, Majadahonda, Spain
| | - Ana Ramírez de Molina
- Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | - Omar Ramos-Lopez
- Medicine and Psychology School, Autonomous University of Baja California, Tijuana 22390, Baja California, Mexico
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16
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Murphy TR, Busse W, Holweg CTJ, Rajput Y, Raimundo K, Meyer CS, Seetasith A, Gupta S, Iqbal A, Kaner RJ. Patients with allergic asthma have lower risk of severe COVID-19 outcomes than patients with nonallergic asthma. BMC Pulm Med 2022; 22:418. [PMCID: PMC9660106 DOI: 10.1186/s12890-022-02230-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 10/17/2022] [Indexed: 11/16/2022] Open
Abstract
Background Although asthma does not appear to be a risk factor for severe coronavirus disease 2019 (COVID-19), outcomes could vary for patients with different asthma subtypes. The objective of this analysis was to compare COVID-19 outcomes in real-world cohorts in the United States among patients with asthma, with or without evidence of allergy. Methods In a retrospective analysis of the COVID-19 Optum electronic health record dataset (February 20, 2020–January 28, 2021), patients diagnosed with COVID-19 with a history of moderate-to-severe asthma were divided into 2 cohorts: those with evidence of allergic asthma and those without (nonallergic asthma). After 1:1 propensity score matching, in which covariates were balanced and potential bias was removed, COVID-19 outcomes were compared between cohorts. Results From a COVID-19 population of 591,198 patients, 1595 patients with allergic asthma and 8204 patients with nonallergic asthma were identified. After propensity score matching (n = 1578 per cohort), risk of death from any cause after COVID-19 diagnosis was significantly lower for patients with allergic vs nonallergic asthma (hazard ratio, 0.48; 95% CI 0.28–0.83; P = 0.0087), and a smaller proportion of patients with allergic vs nonallergic asthma was hospitalized within − 7 to + 30 days of COVID-19 diagnosis (13.8% [n = 217] vs 18.3% [n = 289]; P = 0.0005). Among hospitalized patients, there were no significant differences between patients with allergic or nonallergic asthma in need for intensive care unit admission, respiratory support, or COVID-19 treatment. Conclusions Asthma subtype may influence outcomes after COVID-19; patients with allergic asthma are at lower risk for hospitalization/death than those with nonallergic asthma.
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Affiliation(s)
- Thomas R. Murphy
- grid.478146.8ENT and Allergy Partners of Charleston, Charleston, SC USA
| | - William Busse
- grid.14003.360000 0001 2167 3675University of Wisconsin School of Medicine and Public Health, Madison, WI USA
| | - Cecile T. J. Holweg
- grid.418158.10000 0004 0534 4718Genentech, Inc., South San Francisco, CA USA
| | - Yamina Rajput
- grid.418158.10000 0004 0534 4718Genentech, Inc., South San Francisco, CA USA
| | - Karina Raimundo
- grid.418158.10000 0004 0534 4718Genentech, Inc., South San Francisco, CA USA
| | - Craig S. Meyer
- grid.418158.10000 0004 0534 4718Genentech, Inc., South San Francisco, CA USA
| | - Arpamas Seetasith
- grid.418158.10000 0004 0534 4718Genentech, Inc., South San Francisco, CA USA
| | - Sachin Gupta
- grid.418158.10000 0004 0534 4718Genentech, Inc., South San Francisco, CA USA
| | - Ahmar Iqbal
- grid.418158.10000 0004 0534 4718Genentech, Inc., South San Francisco, CA USA
| | - Robert J. Kaner
- grid.5386.8000000041936877XWeill Cornell Medicine, New York, NY USA
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17
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Gozzi-Silva SC, Oliveira LDM, Alberca RW, Pereira NZ, Yoshikawa FS, Pietrobon AJ, Yendo TM, de Souza Andrade MM, Ramos YAL, Brito CA, Oliveira EA, Beserra DR, Orfali RL, Aoki V, Duarte AJDS, Sato MN. Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients. Cells 2022; 11:cells11213359. [PMID: 36359755 PMCID: PMC9659290 DOI: 10.3390/cells11213359] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/15/2022] [Accepted: 10/20/2022] [Indexed: 11/24/2022] Open
Abstract
COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-α. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.
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Affiliation(s)
- Sarah Cristina Gozzi-Silva
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
- Correspondence: (S.C.G.-S.); (M.N.S.); Tel.: +55-11-3061-7499 (M.N.S.); Fax: +55-11-3081-7190 (M.N.S.)
| | - Luana de Mendonça Oliveira
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
| | - Ricardo Wesley Alberca
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
| | - Natalli Zanete Pereira
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
| | - Fábio Seiti Yoshikawa
- Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 263-8522, Japan
| | - Anna Julia Pietrobon
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
| | - Tatiana Mina Yendo
- Hospital das Clínicas of the University of São Paulo (HCFMUSP), University of São Paulo, São Paulo 05403-000, Brazil
| | - Milena Mary de Souza Andrade
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
| | - Yasmim Alefe Leuzzi Ramos
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
| | - Cyro Alves Brito
- Center of Immunology, Adolfo Lutz Institute, São Paulo 05403-000, Brazil
| | - Emily Araujo Oliveira
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
| | - Danielle Rosa Beserra
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
| | - Raquel Leão Orfali
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
| | - Valéria Aoki
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
| | - Alberto Jose da Silva Duarte
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
| | - Maria Notomi Sato
- Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil
- Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
- Laboratory of Dermatology and Immunodeficiencies 56 (LIM-56), Division of Dermatology, Medical School, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar 470, São Paulo 05403-000, Brazil
- Correspondence: (S.C.G.-S.); (M.N.S.); Tel.: +55-11-3061-7499 (M.N.S.); Fax: +55-11-3081-7190 (M.N.S.)
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Histologic, viral, and molecular correlates of heart disease in fatal COVID-19. Ann Diagn Pathol 2022; 60:151983. [PMID: 35660807 PMCID: PMC9148434 DOI: 10.1016/j.anndiagpath.2022.151983] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 12/13/2022]
Abstract
Cardiac manifestations are common in severe COVID-19. This study compared the histologic, viral, and molecular findings in cardiac tissue in fatal COVID-19 (n = 11) and controls (n = 11). In situ hybridization (SARS-CoV2 RNA) and immunohistochemistry for viral proteins and the host response were quantified for the samples and compared with qRTPCR and Western blot data. Control hearts showed a high resident population of macrophages that had variable ACE2 expression. Cardiac ACE2 expression was 10× greater in the heart tissues of cases and controls with obesity or type II diabetes. Multifocal endothelial cell swelling and degeneration, perivascular edema plus microvascular thrombi were unique to the cases. SARS-CoV2 RNA and nucleocapsid protein were rarely detected in situ in any COVID-19 heart. However, in each case abundant SARS-CoV-2 spike protein was evident. Co-expression experiments showed that the spike protein localized mostly to the ACE2+ interstitial macrophages/pericytes that were activated as evidenced by increased IL6 and TNFα expression. Western blots confirmed the presence of the viral spike protein, but not the nucleocapsid protein, in the cardiac homogenates. The intercalated disc proteins connexin 43, the primary cardiac gap junction protein, and NaV1.5, the predominant cardiac sodium channel, each showed marked lateral migration in the myocytes in the cases, which would increase the risk of reentrant arrhythmias. It is concluded that the viral spike protein, endocytosed by macrophages/pericytes, can induce a myocarditis with the possibility of conduction dysfunction due to abnormal localization of key intercalated disc proteins.
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19
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Nuovo GJ, Suster D, Sawant D, Mishra A, Michaille JJ, Tili E. The amplification of CNS damage in Alzheimer's disease due to SARS-CoV2 infection. Ann Diagn Pathol 2022; 61:152057. [PMID: 36334414 PMCID: PMC9616485 DOI: 10.1016/j.anndiagpath.2022.152057] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 10/26/2022] [Indexed: 11/28/2022]
Abstract
Pre-existing Alzheimer's disease is a risk factor for severe/fatal COVID-19 and infection by SARS-CoV2 virus has been associated with an increased incidence of un-masked Alzheimer's disease. The molecular basis whereby SARS-CoV2 may amplify Alzheimer's disease is not well understood. This study analyzed the molecular changes in autopsy brain tissues from people with pre-existing dementia who died of COVID-19 (n = 5) which was compared to equivalent tissues of people who died of COVID-19 with no history of dementia (n = 8), Alzheimer's disease pre-COVID-19 (n = 10) and aged matched controls (n = 10) in a blinded fashion. Immunohistochemistry analyses for hyperphosphorylated tau protein, α-synuclein, and β-amyloid-42 confirmed the diagnoses of Alzheimer's disease (n = 4), and Lewy body dementia (n = 1) in the COVID-19 group. The brain tissues from patients who died of COVID-19 with no history of dementia showed a diffuse microangiopathy marked by endocytosis of spike subunit S1 and S2 in primarily CD31+ endothelia with strong co-localization with ACE2, Caspase-3, IL6, TNFα, and Complement component 6 that was not associated with SARS-CoV2 RNA. Microglial activation marked by increased TMEM119 and MCP1 protein expression closely paralleled the endocytosed spike protein. The COVID-19 tissues from people with no pre-existing dementia showed, compared to controls, 5-10× fold increases in expression of neuronal NOS and NMDAR2 as well as a marked decrease in the expression of proteins whose loss is associated with worsening Alzheimer's disease: MFSD2a, SHIP1, BCL6, BCL10, and BACH1. In COVID-19 tissues from people with dementia the widespread spike-induced microencephalitis with the concomitant microglial activation co-existed in the same areas where neurons had hyperphosphorylated tau protein suggesting that the already dysfunctional neurons were additionally stressed by the SARS-CoV2 induced microangiopathy. ACE2+ human brain endothelial cells treated with high dose (but not vaccine equivalent low dose) spike S1 protein demonstrated each of the molecular changes noted in the in vivo COVID-19 and COVID-19/Alzheimer's disease brain tissues. It is concluded that fatal COVID-19 induces a diffuse microencephalitis and microglial activation in the brain due to endocytosis of circulating viral spike protein that amplifies pre-existing dementia in at least two ways: 1) modulates the expression of proteins that may worsen Alzheimer's disease and 2) stresses the already dysfunctional neurons by causing an acute proinflammatory/hypercoagulable/hypoxic microenvironment in areas with abundant hyperphosphorylated tau protein and/or βA-42.
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Affiliation(s)
- Gerard J Nuovo
- Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; GnomeDX, Powell, OH, USA.
| | - David Suster
- Rutgers University Hospital Department of Pathology, Newark, NY, USA
| | | | | | - Jean-Jacques Michaille
- Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, College of Medicine, Columbus, OH, USA
| | - Esmerina Tili
- Department of Anesthesiology, The Ohio State University Wexner Medical Center, College of Medicine, Columbus, OH, USA
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20
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Roy B, Runa SA. SARS-CoV-2 infection and diabetes: Pathophysiological mechanism of multi-system organ failure. World J Virol 2022; 11:252-274. [PMID: 36188734 PMCID: PMC9523319 DOI: 10.5501/wjv.v11.i5.252] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/25/2022] [Accepted: 08/01/2022] [Indexed: 02/05/2023] Open
Abstract
Since the discovery of the coronavirus disease 2019 outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ failure, while the co-existence of these two culprits can accelerate the rate of disease progression and magnify the severity of the disease. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidneys, brain, eyes, gastrointestinal system, and bones, and sub-sequent manifestation of multi-system organ failure.
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Affiliation(s)
- Bipradas Roy
- Department of Physiology, Wayne State University, Detroit, MI 48201, United States
- Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, United States
| | - Sadia Afrin Runa
- Department of Biotechnology and Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
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21
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Bo Y, Yuli C, Ye W, Junfeng L, Xiaolin C, Yan B, Zhongyuan W. Immune-inflammatory biomarkers and the risk of cardiac injury in COVID-19 patients with diabetes: a retrospective cohort study. Cardiovasc Diabetol 2022; 21:188. [PMID: 36123740 PMCID: PMC9483899 DOI: 10.1186/s12933-022-01625-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 09/07/2022] [Indexed: 11/20/2022] Open
Abstract
Background To determine the risk-assessment role of the immune-inflammatory biomarkers on myocardial damage in COVID-19 patients with diabetes mellitus (DM). Methods This retrospective study was conducted on 822 COVID-19 inpatients from 1 January to 10 March 2020 at Renmin Hospital of Wuhan University. The demographic data, clinical data, and immune-inflammatory parameters of participants were collected. The predictors of cardiac injury were assessed by Logistics regression analysis. Results A total of 246 COVID-19 inpatients were diagnosed with DM (29.9%). The incidence of cardiac injury was higher in patients with DM than in non-DM cases (28.9% vs 9.0%, p < 0.001), even grouped by age, gender, and the level of fasting plasma glucose (FPG). The mortality in diabetic COVID-19 patients with cardiac injury and without cardiac injury was 42.9% and 3.4%, respectively (p < 0.001). COVID-19 patients with DM and cardiac injury presented a decreased number of immunocyte subsets, lower C3 concentration, and a higher level of interleukin-6 (IL-6) and immunoglobulin A (IgA). The independent risk factors for cardiac injury in COVID-19 patients with DM were CD3+CD4+ T cells counts ≤ 288 cells/μl (adjusted Odds ratio (OR), 2.501; 95% confidence interval (CI) 1.282–4.877; p = 0.007) and IL-6 > 25.68mpg/ml (adjusted OR, 4.345; 95% CI 2.192–10.374; p < 0.001) (all Pinteraction < 0.05). Conclusions For diabetic patients with COVID-19, cardiac injury not only induce severer immune-inflammatory responses, but also increase in-hospital mortality. The decreased number of CD3+CD4+ T cells and increased IL-6 are recommended to distinguish the people who refer to high risk of cardiac injury and mortality from those persons. However, it remains a testable theory whether decision-making strategies based on the risk status of cardiac injury in COVID-19 patients, especially with DM, would be expected to get better outcomes. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-022-01625-2.
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Affiliation(s)
- Yi Bo
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Cai Yuli
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Wang Ye
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Li Junfeng
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Chen Xiaolin
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Bao Yan
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Wen Zhongyuan
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
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22
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Abstract
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a global pandemic impacting 254 million people in 190 countries. Comorbidities, particularly cardiovascular disease, diabetes, and hypertension, increase the risk of infection and poor outcomes. SARS-CoV-2 enters host cells through the angiotensin-converting enzyme-2 receptor, generating inflammation and cytokine storm, often resulting in multiorgan failure. The mechanisms and effects of COVID-19 on patients with high-risk diabetes are not yet completely understood. In this review, we discuss the variety of coronaviruses, structure of SARS-CoV-2, mutations in SARS-CoV-2 spike proteins, receptors associated with viral host entry, and disease progression. Furthermore, we focus on possible mechanisms of SARS-CoV-2 in diabetes, leading to inflammation and heart failure. Finally, we discuss existing therapeutic approaches, unanswered questions, and future directions.
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Affiliation(s)
- Chandrakala Aluganti Narasimhulu
- Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States
| | - Dinender K Singla
- Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States
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23
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Cardiac fibroblast sub-types in vitro reflect pathological cardiac remodeling in vivo. Matrix Biol Plus 2022; 15:100113. [PMID: 35719864 PMCID: PMC9198323 DOI: 10.1016/j.mbplus.2022.100113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 05/26/2022] [Accepted: 06/03/2022] [Indexed: 12/03/2022] Open
Abstract
A panel of 12 fibrosis related genes clearly identified heart failure (HF) patients better than measurement of the collagen-related hydroxyproline content. A subcluster enriched for ischemic HF was recognized, but not for diabetes, obesity, or gender. Single-cell transcriptomic analysis of in vitro differentiated mouse cardiac fibroblasts distinguished 6 subpopulations, including a contractile Acta2high precursor population, and Acta2low subpopulations with high production of extracellular matrix molecules. The 12 gene profile identified in HF patients showed highest similarity to the fibroblast subset with the strongest expression of extracellular matrix molecules. Major features of cardiac fibroblast differentiation in heart failure patients, in murine heart disease models, and in cell culture of primary murine cardiac fibroblast are shared. Many heart diseases are associated with fibrosis, but it is unclear whether different types of heart disease correlate with different subtypes of activated fibroblasts and to which extent such diversity is modeled during in vitro activation of primary cardiac fibroblasts. Analyzing the expression of 82 fibrosis related genes in 65 heart failure (HF) patients, we identified a panel of 12 genes clearly distinguishing HF patients better from healthy controls than measurement of the collagen-related hydroxyproline content. A subcluster enriched in ischemic HF was recognized, but not for diabetes, high BMI, or gender. Single-cell transcriptomic analysis of in vitro activated mouse cardiac fibroblasts distinguished 6 subpopulations, including a contractile Acta2high precursor population, which was predicted by time trajectory analysis to develop into Acta2low subpopulations with high production of extracellular matrix molecules. The 12 gene profile identified in HF patients showed highest similarity to the fibroblast subset with the strongest expression of extracellular matrix molecules. Population markers identified were furthermore able to clearly cluster different disease stages in a murine model for myocardial infarct. These data suggest that major features of cardiac fibroblast activation in heart failure patients, in murine heart disease models, and in cell culture of primary murine cardiac fibroblast are shared.
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24
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Yang WL, Li Q, Sun J, Huat Tan S, Tang YH, Zhao MM, Li YY, Cao X, Zhao JC, Yang JK. Potential drug discovery for COVID-19 treatment targeting Cathepsin L using a deep learning-based strategy. Comput Struct Biotechnol J 2022; 20:2442-2454. [PMID: 35602976 PMCID: PMC9110316 DOI: 10.1016/j.csbj.2022.05.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 05/11/2022] [Accepted: 05/12/2022] [Indexed: 01/06/2023] Open
Abstract
Cathepsin L (CTSL), a cysteine protease that can cleave and activate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, could be a promising therapeutic target for coronavirus disease 2019 (COVID-19). However, there is still no clinically available CTSL inhibitor that can be used. Here, we applied Chemprop, a newly trained directed-message passing deep neural network approach, to identify small molecules and FDA-approved drugs that can block CTSL activity to expand the discovery of CTSL inhibitors for drug development and repurposing for COVID-19. We found 5 molecules (Mg-132, Z-FA-FMK, leupeptin hemisulfate, Mg-101 and calpeptin) that were able to significantly inhibit the activity of CTSL in the nanomolar range and inhibit the infection of both pseudotype and live SARS-CoV-2. Notably, we discovered that daptomycin, an FDA-approved antibiotic, has a prominent CTSL inhibitory effect and can inhibit SARS-CoV-2 pseudovirus infection. Further, molecular docking calculation showed stable and robust binding of these compounds with CTSL. In conclusion, this study suggested for the first time that Chemprop is ideally suited to predict additional inhibitors of enzymes and revealed the noteworthy strategy for screening novel molecules and drugs for the treatment of COVID-19 and other diseases with unmet needs.
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Affiliation(s)
- Wei-Li Yang
- Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Qi Li
- Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Jing Sun
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China
| | - Sia Huat Tan
- Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, China
| | - Yan-Hong Tang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China
| | - Miao-Miao Zhao
- Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Yu-Yang Li
- Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Xi Cao
- Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
| | - Jin-Cun Zhao
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China
- Guangzhou Laboratory, Bio-Island, Guangzhou, Guangdong 510320, China
- Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, China
| | - Jin-Kui Yang
- Beijing Key Laboratory of Diabetes Research and Care, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
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25
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Mandal CC, Panwar MS, Yadav CP, Tripathi V, Bandyopadhayaya S. Combinatorial influence of environmental temperature, obesity and cholesterol on SARS-CoV-2 infectivity. Sci Rep 2022; 12:4796. [PMID: 35314722 PMCID: PMC8935894 DOI: 10.1038/s41598-022-08485-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 03/03/2022] [Indexed: 01/27/2023] Open
Abstract
The continuing evolution of SARS-CoV-2 variants not only causes a long-term global health concerns but also encounters the vaccine/drug effectiveness. The degree of virus infectivity and its clinical outcomes often depend on various biological parameters (e.g., age, genetic factors, diabetes, obesity and other ailments) of an individual along with multiple environmental factors (e.g., air temperature, humidity, seasons). Thus, despite the extensive search for and use of several vaccine/drug candidates, the combinative influence of these various extrinsic and intrinsic risk factors involved in the SARS-CoV-2 virus infectivity has yet to be explored. Previous studies have reported that environment temperature is negatively associated with virus infectivity for SARS-CoV-2. This study elaborates on our previous findings, investigating the link between environmental temperature and other metabolic parameters, such as average total cholesterol and obesity, with the increase in COVID-19 cases. Statistical analysis conducted on a per country basis not only supports the existence of a significant negative correlation between environmental temperature and SARS-CoV-2 infections but also found a strong positive correlation between COVID-19 cases and these metabolic parameters. In addition, a multiphase growth curve model (GCM) was built to predict the contribution of these covariates in SARS-CoV-2 infectivity. These findings, for first time, support the idea that there might be a combinatorial impact of environmental temperature, average total cholesterol, and obesity in the inflation of the SARS-CoV-2 infectivity.
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Affiliation(s)
- Chandi C Mandal
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India.
| | - Mahaveer S Panwar
- Department of Statistics, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Chandra P Yadav
- Department of Statistics, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Vaishnavi Tripathi
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
| | - Shreetama Bandyopadhayaya
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Ajmer, Rajasthan, 305817, India
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26
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Brooks SD, Smith RL, Moreira AS, Ackerman HC. Oral Lisinopril Raises Tissue Levels of ACE2, the SARS-CoV-2 Receptor, in Healthy Male and Female Mice. Front Pharmacol 2022; 13:798349. [PMID: 35359831 PMCID: PMC8961328 DOI: 10.3389/fphar.2022.798349] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 02/03/2022] [Indexed: 12/15/2022] Open
Abstract
Angiotensin-converting enzyme 2 (ACE2) is the established cellular receptor for SARS-CoV-2. However, it is unclear whether ACE1 inhibitors (e.g., lisinopril) or angiotensin receptor blockers (e.g., losartan) alter tissue ACE2 expression. This study sought to determine whether lisinopril or losartan, as monotherapies or in combination, changes tissue levels of ACE2 in healthy male and female mice. Mice received lisinopril (10 mg/kg/day), losartan (10 mg/kg/day), or both for 21 days via drinking water. A control group received water without drug. The ACE2 protein index (ACE2 protein/total protein) was determined on the small intestine, lung, kidney, and brain. Oral lisinopril increased the ACE2 protein index across all tissues (p < 0.0001 vs. control). In contrast, the combination of lisinopril plus losartan did not increase ACE2 levels in any tissue (p = 0.89 vs. control) and even decreased tissue expression of the Ace2 gene (p < 0.001 vs. control). Tissue ACE2 remained elevated in the mice 21 days after cessation of lisinopril (p = 0.02). Plasma ACE2 did not correlate with the ACE2 protein index in any tissue. A sex difference was observed: kidney ACE2 levels were higher in male than in female mice (p < 0.0001). Oral lisinopril increases ACE2, the cellular receptor for SARS-CoV-2, in tissues that are relevant to the transmission and pathogenesis of COVID-19. Remarkably, the addition of losartan prevented lisinopril-induced increases in ACE2 across tissues. These results suggest that ACE inhibitors and angiotensin receptor blockers interact to determine tissue levels of ACE2.
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27
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da Silva Torres MK, Bichara CDA, de Almeida MDNDS, Vallinoto MC, Queiroz MAF, Vallinoto IMVC, dos Santos EJM, de Carvalho CAM, Vallinoto ACR. The Complexity of SARS-CoV-2 Infection and the COVID-19 Pandemic. Front Microbiol 2022; 13:789882. [PMID: 35222327 PMCID: PMC8870622 DOI: 10.3389/fmicb.2022.789882] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the death of millions of people worldwide and thousands more infected individuals developed sequelae due to the disease of the new coronavirus of 2019 (COVID-19). The development of several studies has contributed to the knowledge about the evolution of SARS-CoV2 infection and the disease to more severe forms. Despite this information being debated in the scientific literature, many mechanisms still need to be better understood in order to control the spread of the virus and treat clinical cases of COVID-19. In this article, we carried out an extensive literature review in order to bring together, in a single article, the biological, social, genetic, diagnostic, therapeutic, immunization, and even socioeconomic aspects that impact the SAR-CoV-2 pandemic. This information gathered in this article will enable a broad and consistent reading of the main aspects related to the current pandemic.
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Affiliation(s)
- Maria Karoliny da Silva Torres
- Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
- Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Pará, Belém, Brazil
| | - Carlos David Araújo Bichara
- Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
- Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Pará, Belém, Brazil
| | - Maria de Nazaré do Socorro de Almeida
- Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Pará, Belém, Brazil
- Laboratory of Complex Diseases, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Mariana Cayres Vallinoto
- Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
- University Center of the State of Pará, Belém, Brazil
| | - Maria Alice Freitas Queiroz
- Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
- Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Pará, Belém, Brazil
| | | | - Eduardo José Melo dos Santos
- Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Pará, Belém, Brazil
- Laboratory of Complex Diseases, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | | | - Antonio Carlos R. Vallinoto
- Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
- Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Pará, Belém, Brazil
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28
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Ali Kazem T, Zeylabi F, Filayih Hassan A, Paridar P, Pezeshki SP, Pezeshki SMS. Diabetes mellitus and COVID-19: review of a lethal interaction from the cellular and molecular level to the bedside. Expert Rev Endocrinol Metab 2022; 17:1-19. [PMID: 34781797 DOI: 10.1080/17446651.2022.2002145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/25/2021] [Indexed: 01/08/2023]
Abstract
INTRODUCTION While the main mode of transmission of coronavirus disease 2019 (COVID-19) is close contact with other individuals, the presence of chronic underlying diseases such as Diabetes Mellitus (DM) increases the chance of hospitalization and mortality rate due to infection. AREAS COVERED To investigate the effects of COVID-19 infection in DM patients, we reviewed literature from Google Scholar search engine and PubMed database from '2013 to 2020' using the terms "COVID-19; SARS-CoV-2; Diabetes mellitus; obesity; Angiotensin-converting enzyme 2; ACE2; Insulin and Metformin. Evidence suggests that COVID-19 exacerbates the course of diabetes. Presence of pro-inflammatory conditions, increased expression of receptors, and more difficult control of glucose levels in diabetics COVID-19 patients are some of the problems that diabetic patients may face. Also, psychological problems caused by the COVID-19 epidemic in diabetic patients is one of the most important problems in these patients, which is less covered. EXPERT OPINION DM is a strong and independent risk factor with a poor prognosis, which increases the risk of COVID-19 infection, the need for emergency services, the rate of hospitalization in the intensive care unit and also increases the mortality rate of COVID-19 patients.
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Affiliation(s)
| | - Fatemeh Zeylabi
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Pouria Paridar
- Islamic Azad University, North-Tehran Branch, Tehran, Iran
| | - Seyedeh Pardis Pezeshki
- Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Mohammad Sadegh Pezeshki
- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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29
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Current understanding of the role of microRNAs from adipose-derived extracellular vesicles in obesity. Biochem Soc Trans 2021; 50:447-457. [PMID: 34940800 DOI: 10.1042/bst20211031] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 12/09/2021] [Accepted: 12/13/2021] [Indexed: 11/17/2022]
Abstract
Obesity and its associated metabolic diseases, including diabetes, insulin resistance, and inflammation, are rapidly becoming a global health concern. Moreover, obese individuals are more likely to be infected with COVID-19. New research on adipose tissue is required to help us understand these metabolic diseases and their regulatory processes. Recently, extracellular vesicles (EVs) have been identified as novel intercellular vectors with a wide range of regulatory functions. The miRNAs carried by EVs participate in the regulation of white adipose tissue (WAT) browning, insulin resistance, diabetes, and inflammation. In addition, EV miRNAs demonstrate great potential for helping elucidating the mechanism of metabolic diseases, and for advancing their prevention and treatment. In this review, we focus on the mechanisms underlying the regulation of adipose differentiation and metabolic diseases by adipose-derived EV miRNAs. Understanding the role of these miRNAs should enrich our understanding of the etiology and pathogenesis of metabolic diseases caused by obesity.
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30
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Herman-Edelstein M, Guetta T, Barnea A, Waldman M, Ben-Dor N, Barac YD, Kornowski R, Arad M, Hochhauser E, Aravot D. Correction to: Expression of the SARS‑CoV‑2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system. Cardiovasc Diabetol 2021; 20:216. [PMID: 34711255 PMCID: PMC8553107 DOI: 10.1186/s12933-021-01402-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Michal Herman-Edelstein
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Nephrology Department, Rabin Medical Center, Petach Tikva, Israel
| | - Tali Guetta
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel
| | - Amir Barnea
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel
| | - Maayan Waldman
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel
| | - Naomi Ben-Dor
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Nephrology Department, Rabin Medical Center, Petach Tikva, Israel
| | - Yaron D Barac
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel
| | - Ran Kornowski
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Department of Cardiology, Rabin Medical Center, 49100, Petach Tikva, Israel
| | - Michael Arad
- Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel
| | - Edith Hochhauser
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel. .,Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel. .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Dan Aravot
- Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel.,Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel
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Qu L, Chen C, Yin T, Fang Q, Hong Z, Zhou R, Tang H, Dong H. ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review. Int J Mol Sci 2021; 22:11483. [PMID: 34768911 PMCID: PMC8583933 DOI: 10.3390/ijms222111483] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/21/2021] [Accepted: 10/21/2021] [Indexed: 01/08/2023] Open
Abstract
Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.
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Affiliation(s)
- Lihua Qu
- Department of Pathogenic Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; (L.Q.); (T.Y.); (Q.F.); (Z.H.); (R.Z.)
| | - Chao Chen
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210013, China;
| | - Tong Yin
- Department of Pathogenic Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; (L.Q.); (T.Y.); (Q.F.); (Z.H.); (R.Z.)
| | - Qian Fang
- Department of Pathogenic Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; (L.Q.); (T.Y.); (Q.F.); (Z.H.); (R.Z.)
| | - Zizhan Hong
- Department of Pathogenic Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; (L.Q.); (T.Y.); (Q.F.); (Z.H.); (R.Z.)
| | - Rui Zhou
- Department of Pathogenic Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; (L.Q.); (T.Y.); (Q.F.); (Z.H.); (R.Z.)
| | - Hongbin Tang
- Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China
| | - Huifen Dong
- Department of Pathogenic Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; (L.Q.); (T.Y.); (Q.F.); (Z.H.); (R.Z.)
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Renin-angiotensin system inhibitors and mortality among diabetic patients with STEMI undergoing mechanical reperfusion during the COVID-19 pandemic. DIABETES EPIDEMIOLOGY AND MANAGEMENT 2021; 4:100022. [PMID: 35072135 PMCID: PMC8556094 DOI: 10.1016/j.deman.2021.100022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 10/26/2021] [Indexed: 01/08/2023]
Abstract
Background During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment. Methods The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients. Results Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, p = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, p < 0.0001), consistently both in 2019 and in 2010. Conclusions This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients’ survival during the hospitalization, neither increased the risk of SARS-CoV2 infection. Trial registration number NCT 04412655
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Abstract
The current COVID-19 pandemic, which continues to spread across the globe, is caused by severe acute respiratory syndrome coronavirus (SARS-Cov-2). Soon after the pandemic emerged in China, it became clear that the receptor-binding domain (RBD) of angiotensin-converting enzyme 2 (ACE2) serves as the primary cell surface receptor for SARS-Cov-2. Subsequent work has shown that diabetes and hyperglycemia are major risk factors for morbidity and mortality in COVID-19 patients. However, data on the pattern of expression of ACE2 on human pancreatic β cells remain contradictory. Additionally, there is no consensus on whether the virus can directly infect and damage pancreatic islets and hence exacerbate diabetes. In this mini-review, we highlight the role of ACE2 receptor and summarize the current state of knowledge regarding its expression/co-localization in human pancreatic endocrine cells. We also discuss recent data on the permissiveness of human pancreatic β cells to SARS-Cov-2 infection.
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Affiliation(s)
- Waseem El-Huneidi
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates (UAE)
| | - Mawieh Hamad
- Department of Basic sciences, Sharjah Institute for Medical Research, Sharjah, University of Sharjah, United Arab Emirates (UAE)
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, SharjahUAE
| | - Jalal Taneera
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates (UAE)
- Department of Basic sciences, Sharjah Institute for Medical Research, Sharjah, University of Sharjah, United Arab Emirates (UAE)
- CONTACT Dr. Jalal Taneera Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272 United Arab Emirates (UAE) Tel: +97165057743
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Du X, Guo Z, Fan W, Hai T, Gao F, Li P, Qin Y, Chen C, Han Z, Ren J, Jiao P, Liu W, Bi Y, Yu D, Wu S. Establishment of a humanized swine model for COVID-19. Cell Discov 2021; 7:70. [PMID: 34404772 PMCID: PMC8371120 DOI: 10.1038/s41421-021-00313-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 07/18/2021] [Indexed: 01/08/2023] Open
Affiliation(s)
- Xuguang Du
- State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
- Sanya Institute of China Agricultural University, Sanya, Hainan, China
| | - Zihang Guo
- State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
- Sanya Institute of China Agricultural University, Sanya, Hainan, China
| | - Wenhui Fan
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, China
| | - Tang Hai
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Fei Gao
- State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
- Sanya Institute of China Agricultural University, Sanya, Hainan, China
| | - Pan Li
- State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
- Sanya Institute of China Agricultural University, Sanya, Hainan, China
| | - Yumin Qin
- State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
- Sanya Institute of China Agricultural University, Sanya, Hainan, China
| | - Chaolei Chen
- Beijing Dhelixon Biotechnology Company Limited, Beijing, China
| | - Zhiqiang Han
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, China
| | - Jilong Ren
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, China
| | - Pengtao Jiao
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, China
| | - Wenjun Liu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, China
- Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Yuhai Bi
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, China.
- University of Chinese Academy of Sciences, Beijing, China.
| | - Dawei Yu
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
- Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
| | - Sen Wu
- State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
- Sanya Institute of China Agricultural University, Sanya, Hainan, China.
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