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Article ; Online: Cellular and Mitochondrial Pathways Contribute to SGLT2 Inhibitors-mediated Tissue Protection: Experimental and Clinical Data.

Sanz, Raúl Lelio / García Menéndez, Sebastián / Inserra, Felipe / Ferder, León / Manucha, Walter

2024

Abstract: In metabolic syndrome and diabetes, compromised mitochondrial function emerges as a critical driver of cardiovascular disease, fueling its development and persistence, culminating in cardiac remodeling and adverse events. In this context, angiotensin II - ...

Abstract	In metabolic syndrome and diabetes, compromised mitochondrial function emerges as a critical driver of cardiovascular disease, fueling its development and persistence, culminating in cardiac remodeling and adverse events. In this context, angiotensin II - the main interlocutor of the renin-angiotensin-aldosterone system - promotes local and systemic oxidative inflammatory processes. To highlight, the low activity/expression of proteins called sirtuins negatively participates in these processes, allowing more significant oxidative imbalance, which impacts cellular and tissue responses, causing tissue damage, inflammation, and cardiac and vascular remodeling. The reduction in energy production of mitochondria has been widely described as a significant element in all types of metabolic disorders. Additionally, high sirtuin levels and AMPK signaling stimulate hypoxia- inducible factor 1 beta and promote ketonemia. Consequently, enhanced autophagy and mitophagy advance through cardiac cells, sweeping away debris and silencing the orchestra of oxidative stress and inflammation, ultimately protecting vulnerable tissue from damage. To highlight and of particular interest, SGLT2 inhibitors (SGLT2i) profoundly influence all these mechanisms. Randomized clinical trials have evidenced a compelling picture of SGLT2i emerging as game-changers, wielding their power to demonstrably improve cardiac function and slash the rates of cardiovascular and renal events. Furthermore, driven by recent evidence, SGLT2i emerge as cellular supermolecules, exerting their beneficial actions to increase mitochondrial efficiency, alleviate oxidative stress, and curb severe inflammation. Its actions strengthen tissues and create a resilient defense against disease. In conclusion, like a treasure chest brimming with untold riches, the influence of SGLT2i on mitochondrial function holds untold potential for cardiovascular health. Unlocking these secrets, like a map guiding adventurers to hidden riches, promises to pave the way for even more potent therapeutic strategies.
Language	English
Publishing date	2024-03-27
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/0113816128289350240320063045
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Article ; Online: Epigenetic Mechanisms Involved in Inflammaging-Associated Hypertension.

Simão, Vinícius Augusto / Ferder, León / Manucha, Walter / Chuffa, Luiz Gustavo A

Current hypertension reports

2022 Volume 24, Issue 11, Page(s) 547–562

Abstract: Purpose of review: This review summarizes the involvement of inflammaging in vascular damage with focus on the epigenetic mechanisms by which inflammaging-induced hypertension is triggered.: Recent findings: Inflammaging in hypertension is a complex ... ...

Abstract	Purpose of review: This review summarizes the involvement of inflammaging in vascular damage with focus on the epigenetic mechanisms by which inflammaging-induced hypertension is triggered. Recent findings: Inflammaging in hypertension is a complex condition associated with the production of inflammatory mediators by the immune cells, enhancement of oxidative stress, and tissue remodeling in vascular smooth muscle cells and endothelial cells. Cellular processes are numerous, including inflammasome assembly and cell senescence which may involve mitochondrial dysfunction, autophagy, DNA damage response, dysbiosis, and many others. More recently, a series of noncoding RNAs, mainly microRNAs, have been described as possessing epigenetic actions on the regulation of inflammasome-related hypertension, emerging as a promising therapeutic strategy. Although there are a variety of pharmacological agents that effectively regulate inflammaging-related hypertension, a deeper understanding of the epigenetic events behind the control of vessel deterioration is needed for the treatment or even to prevent the disease onset.
MeSH term(s)	Aging ; Endothelial Cells ; Epigenesis, Genetic ; Humans ; Hypertension/genetics ; Inflammasomes ; Inflammation ; Inflammation Mediators ; MicroRNAs/genetics
Chemical Substances	Inflammasomes ; Inflammation Mediators ; MicroRNAs
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-022-01214-4
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Zs.A 5522: Show issues

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Article ; Online: Metabolic Syndrome and Cardiac Remodeling Due to Mitochondrial Oxidative Stress Involving Gliflozins and Sirtuins.

Sanz, Raúl Lelio / Inserra, Felipe / García Menéndez, Sebastián / Mazzei, Luciana / Ferder, León / Manucha, Walter

Current hypertension reports

2023 Volume 25, Issue 6, Page(s) 91–106

Abstract: Purpose of review: To address the mechanistic pathways focusing on mitochondria dysfunction, oxidative stress, sirtuins imbalance, and other contributors in patient with metabolic syndrome and cardiovascular disease. Sodium glucose co-transporter type 2 ...

Abstract	Purpose of review: To address the mechanistic pathways focusing on mitochondria dysfunction, oxidative stress, sirtuins imbalance, and other contributors in patient with metabolic syndrome and cardiovascular disease. Sodium glucose co-transporter type 2 (SGLT-2) inhibitors deeply influence these mechanisms. Recent randomized clinical trials have shown impressive results in improving cardiac function and reducing cardiovascular and renal events. These unexpected results generate the need to deepen our understanding of the molecular mechanisms able to generate these effects to help explain such significant clinical outcomes. Recent findings: Cardiovascular disease is highly prevalent among individuals with metabolic syndrome and diabetes. Furthermore, mitochondrial dysfunction is a principal player in its development and persistence, including the consequent cardiac remodeling and events. Another central protagonist is the renin-angiotensin system; the high angiotensin II (Ang II) activity fuel oxidative stress and local inflammatory responses. Additionally, sirtuins decline plays a pivotal role in the process; they enhance oxidative stress by regulating adaptive responses to the cellular environment and interacting with Ang II in many circumstances, including cardiac and vascular remodeling, inflammation, and fibrosis. Fasting and lower mitochondrial energy generation are conditions that substantially reduce most of the mentioned cardiometabolic syndrome disarrangements. In addition, it increases sirtuins levels, and adenosine monophosphate-activated protein kinase (AMPK) signaling stimulates hypoxia-inducible factor-1β (HIF-1 beta) and favors ketosis. All these effects favor autophagy and mitophagy, clean the cardiac cells with damaged organelles, and reduce oxidative stress and inflammatory response, giving cardiac tissue protection. In this sense, SGLT-2 inhibitors enhance the level of at least four sirtuins, some located in the mitochondria. Moreover, late evidence shows that SLGT-2 inhibitors mimic this protective process, improving mitochondria function, oxidative stress, and inflammation. Considering the previously described protection at the cardiovascular level is necessary to go deeper in the knowledge of the effects of SGLT-2 inhibitors on the mitochondria function. Various of the protective effects these drugs clearly had shown in the trials, and we briefly describe it could depend on sirtuins enhance activity, oxidative stress reduction, inflammatory process attenuation, less interstitial fibrosis, and a consequent better cardiac function. This information could encourage investigating new therapeutic strategies for metabolic syndrome, diabetes, heart and renal failure, and other diseases.
MeSH term(s)	Humans ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Metabolic Syndrome/drug therapy ; Sirtuins/metabolism ; Sirtuins/pharmacology ; Cardiovascular Diseases/drug therapy ; Ventricular Remodeling ; Hypertension/drug therapy ; Diabetes Mellitus ; Oxidative Stress/physiology ; Angiotensin II/metabolism ; Fibrosis
Chemical Substances	Sodium-Glucose Transporter 2 Inhibitors ; Sirtuins (EC 3.5.1.-) ; Angiotensin II (11128-99-7)
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-023-01240-w
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Article ; Online: Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin.

Mocayar Marón, Feres José / Ferder, León / Reiter, Russel J / Manucha, Walter

The Journal of steroid biochemistry and molecular biology

2020 Volume 199, Page(s) 105595

Abstract: From an evolutionary point of view, vitamin D and melatonin appeared very early and share functions related to defense mechanisms. In the current clinical setting, vitamin D is exclusively associated with phosphocalcic metabolism. Meanwhile, melatonin ... ...

Abstract	From an evolutionary point of view, vitamin D and melatonin appeared very early and share functions related to defense mechanisms. In the current clinical setting, vitamin D is exclusively associated with phosphocalcic metabolism. Meanwhile, melatonin has chronobiological effects and influences the sleep-wake cycle. Scientific evidence, however, has identified new actions of both molecules in different physiological and pathological settings. The biosynthetic pathways of vitamin D and melatonin are inversely related relative to sun exposure. A deficiency of these molecules has been associated with the pathogenesis of cardiovascular diseases, including arterial hypertension, neurodegenerative diseases, sleep disorders, kidney diseases, cancer, psychiatric disorders, bone diseases, metabolic syndrome, and diabetes, among others. During aging, the intake and cutaneous synthesis of vitamin D, as well as the endogenous synthesis of melatonin are remarkably depleted, therefore, producing a state characterized by an increase of oxidative stress, inflammation, and mitochondrial dysfunction. Both molecules are involved in the homeostatic functioning of the mitochondria. Given the presence of specific receptors in the organelle, the antagonism of the renin-angiotensin-aldosterone system (RAAS), the decrease of reactive species of oxygen (ROS), in conjunction with modifications in autophagy and apoptosis, anti-inflammatory properties inter alia, mitochondria emerge as the final common target for melatonin and vitamin D. The primary purpose of this review is to elucidate the common molecular mechanisms by which vitamin D and melatonin might share a synergistic effect in the protection of proper mitochondrial functioning.
MeSH term(s)	Animals ; Apoptosis/genetics ; Humans ; Melatonin/genetics ; Melatonin/metabolism ; Mitochondria/genetics ; Mitochondria/metabolism ; Oxidative Stress/genetics ; Reactive Oxygen Species/metabolism ; Renin-Angiotensin System/genetics ; Seasons ; Sleep Disorders, Circadian Rhythm/genetics ; Sleep Disorders, Circadian Rhythm/metabolism ; Sleep Disorders, Circadian Rhythm/pathology ; Vitamin D/genetics ; Vitamin D/metabolism
Chemical Substances	Reactive Oxygen Species ; Vitamin D (1406-16-2) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2020-01-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2020.105595
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Article ; Online: Vitamin D supplementation: An alternative to enhance the effectiveness of vaccines against SARS-CoV-2?

Inserra, Felipe / Tajer, Carlos / Antonietti, Laura / Mariani, Javier / Ferder, León / Manucha, Walter

Vaccine

2021 Volume 39, Issue 35, Page(s) 4930–4931

MeSH term(s)	COVID-19 ; COVID-19 Vaccines ; Dietary Supplements ; Humans ; SARS-CoV-2 ; Vaccines ; Vitamin D
Chemical Substances	COVID-19 Vaccines ; Vaccines ; Vitamin D (1406-16-2)
Language	English
Publishing date	2021-07-16
Publishing country	Netherlands
Document type	Letter
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2021.07.031
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Zs.A 1930: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The little-explored therapeutic potential of nanoformulations of 1,25-dihydroxyvitamin D

Martín Giménez, Virna Margarita / Lahore, Henry / Ferder, León / Holick, Michael F / Manucha, Walter

Nanomedicine (London, England)

2021 Volume 16, Issue 26, Page(s) 2327–2330

MeSH term(s)	Oxidation-Reduction ; Oxidative Stress ; Vitamin D/analogs & derivatives
Chemical Substances	Vitamin D (1406-16-2) ; 1,25-dihydroxyvitamin D (66772-14-3)
Language	English
Publishing date	2021-10-06
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2277839-1
ISSN	1748-6963 ; 1743-5889
ISSN (online)	1748-6963
ISSN	1743-5889
DOI	10.2217/nnm-2021-0284
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Article ; Online: High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial (CARED-TRIAL).

Mariani, Javier / Tajer, Carlos / Antonietti, Laura / Inserra, Felipe / Ferder, León / Manucha, Walter

Trials

2021 Volume 22, Issue 1, Page(s) 111

Abstract: Objectives: To evaluate whether a single high dose of oral cholecalciferol improves the respiratory outcomes as compared with placebo among adults COVID-19 patients at moderate risk of clinical complications.: Trial design: The CARED trial is an ... ...

Abstract	Objectives: To evaluate whether a single high dose of oral cholecalciferol improves the respiratory outcomes as compared with placebo among adults COVID-19 patients at moderate risk of clinical complications. Trial design: The CARED trial is an investigator-initiated, multicentre, randomized, parallel, two-arm, sequential, double-blind and placebo-controlled clinical trial. It was planned as a pragmatic trial since the inclusion criteria are broad and the study procedures are as simple as possible, in order to be implemented in the routine clinical practice in general wards in the pandemic setting and a middle-income country context. The sequential design involves two stages. The first stage will assess the effects of vitamin D supplementation on blood oxygenation (physiological effects). The second stage will assess the effects on clinical outcomes. Participants: Participants of either gender admitted to general adult wards in 21 hospital sites located in four provinces of Argentina are invited to participate in the study if they meet the following inclusion criteria and none of the exclusion criteria: Inclusion criteria SARS-CoV-2 confirmed infection by RT-PCR; Hospital admission at least 24 hours before; Expected hospitalization in the same site ≥24 hours; Oxygen saturation ≥90% (measured by pulse oximetry) breathing ambient air; Age ≥45 years or at least one of the following conditions: ○ Hypertension; ○ Diabetes; ○ At least moderate COPD or asthma; ○ Cardiovascular disease (history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or valve replacement surgery); ○ Body mass index ≥30; Willingness to sign informed consent (online supplementary material 1 and 2). Exclusion criteria: Age <18 years; Women in childbearing age; >= 72 hs since current admission; Requirement for a high dose of oxygen (>5 litres/minute) or mechanical ventilation (non-invasive or invasive); History of chronic kidney disease requiring haemodialysis or chronic liver failure; Inability for oral intake. Chronic supplementation with pharmacological vitamin D; Current treatment with anticonvulsants; History of: ○ Sarcoidosis; ○ Malabsorption syndrome; ○ Known hypercalcemia or serum calcium >10.5 mg/dL; Life expectancy <6 months; Known allergy to study medication; Any condition at discretion of investigator impeding to understand the study and give informed consent. Intervention and comparator: The intervention consists in a single oral dose of 500.000 IU of commercially available cholecalciferol soft gel capsules (5 capsules of 100.000 IU) or matching placebo MAIN OUTCOMES: The primary outcome for the first stage is the change in the respiratory Sepsis-related Organ Failure Assessment (SOFAr) score between pre-treatment value and the worst value recorded during the first 7 seven days of hospitalization, the death or discharge, whichever occurs first. The SOFAr score measured as the ratio between the pulse oximetry saturation (SpO Randomisation: A computer-generated random sequence and the treatment assignment is performed through the web-based randomization module available in the electronic data capture system (Castor®). A randomization ratio 1:1, stratified and with permuted blocks was used. Stratification variables were diabetes (yes/no), age (≤60/>60 years) and the site. Blinding (masking): Double-blind was achieved by using placebo soft gel capsules with the same organoleptic properties as the active medication. Central management of the medication is carried out by a pharmacist in charge of packaging the study drug in unblinded fashion, who have no contact with on-site investigators. Medication is packaged in opaque white bottles, each containing five soft gel capsules of the active drug or matching placebo, corresponding to complete individual treatment. Treatment codes are kept under the pharmacist responsibility, and all researchers are unaware of them. Numbers to be randomised (sample size): The first stage is planned to include 200 patients (100 per group), the second stage is planned to include 1064 additional patients. The total sample size is 1264 patients. Trial status: Currently the protocol version is the number 1.4 (from October 13 Trial registration: The study protocol is registered in ClinicalTrials.gov (identifier number NCT04411446 ) on June 2, 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
MeSH term(s)	Aged ; Aged, 80 and over ; Argentina/epidemiology ; COVID-19/complications ; COVID-19/diet therapy ; COVID-19/epidemiology ; COVID-19/virology ; Cholecalciferol/administration & dosage ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Pandemics ; Patient Admission ; Pragmatic Clinical Trials as Topic ; Reverse Transcriptase Polymerase Chain Reaction ; SARS-CoV-2/genetics ; Treatment Outcome ; Vitamins/administration & dosage
Chemical Substances	Vitamins ; Cholecalciferol (1C6V77QF41)
Language	English
Publishing date	2021-02-01
Publishing country	England
Document type	Clinical Trial Protocol ; Letter
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1745-6215
ISSN (online)	1745-6215
ISSN	1468-6694 ; 1745-6215
DOI	10.1186/s13063-021-05073-3
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Article ; Online: High-dose vitamin D versus placebo to prevent complications in COVID-19 patients

Javier Mariani / Carlos Tajer / Laura Antonietti / Felipe Inserra / León Ferder / Walter Manucha

Trials, Vol 22, Iss 1, Pp 1-

A structured summary of a study protocol for a randomised controlled trial (CARED-TRIAL)

2021 Volume 3

Abstract: Abstract Objectives To evaluate whether a single high dose of oral cholecalciferol improves the respiratory outcomes as compared with placebo among adults COVID-19 patients at moderate risk of clinical complications. Trial design The CARED trial is an ... ...

Abstract	Abstract Objectives To evaluate whether a single high dose of oral cholecalciferol improves the respiratory outcomes as compared with placebo among adults COVID-19 patients at moderate risk of clinical complications. Trial design The CARED trial is an investigator-initiated, multicentre, randomized, parallel, two-arm, sequential, double-blind and placebo-controlled clinical trial. It was planned as a pragmatic trial since the inclusion criteria are broad and the study procedures are as simple as possible, in order to be implemented in the routine clinical practice in general wards in the pandemic setting and a middle-income country context. The sequential design involves two stages. The first stage will assess the effects of vitamin D supplementation on blood oxygenation (physiological effects). The second stage will assess the effects on clinical outcomes. Participants Participants of either gender admitted to general adult wards in 21 hospital sites located in four provinces of Argentina are invited to participate in the study if they meet the following inclusion criteria and none of the exclusion criteria: Inclusion criteria SARS-CoV-2 confirmed infection by RT-PCR; Hospital admission at least 24 hours before; Expected hospitalization in the same site ≥24 hours; Oxygen saturation ≥90% (measured by pulse oximetry) breathing ambient air; Age ≥45 years or at least one of the following conditions: ○ Hypertension; ○ Diabetes; ○ At least moderate COPD or asthma; ○ Cardiovascular disease (history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or valve replacement surgery); ○ Body mass index ≥30; Willingness to sign informed consent (online supplementary material 1 and 2). Exclusion criteria: Age <18 years; Women in childbearing age; >= 72 hs since current admission; Requirement for a high dose of oxygen (>5 litres/minute) or mechanical ventilation (non-invasive or invasive); History of chronic kidney disease requiring haemodialysis or chronic liver ...
Keywords	COVID-19 ; Randomised controlled trial ; protocol ; and vitamin D ; SARS-CoV-2 ; mechanical ventilation ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Vitamin D deficiency in African Americans is associated with a high risk of severe disease and mortality by SARS-CoV-2.

Martín Giménez, Virna Margarita / Inserra, Felipe / Ferder, León / García, Joxel / Manucha, Walter

Journal of human hypertension

2020 Volume 35, Issue 4, Page(s) 378–380

MeSH term(s)	Black or African American ; COVID-19 ; Dietary Supplements ; Humans ; Influenza, Human ; SARS-CoV-2 ; Vitamin D ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/epidemiology
Chemical Substances	Vitamin D (1406-16-2)
Keywords	covid19
Language	English
Publishing date	2020-08-13
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	639472-3
ISSN	1476-5527 ; 0950-9240
ISSN (online)	1476-5527
ISSN	0950-9240
DOI	10.1038/s41371-020-00398-z
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Article: Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D.

de Las Heras, Natalia / Martín Giménez, Virna Margarita / Ferder, León / Manucha, Walter / Lahera, Vicente

Antioxidants (Basel, Switzerland)

2020 Volume 9, Issue 9

Abstract: Due to its high degree of contagiousness and like almost no other virus, SARS-CoV-2 has put the health of the world population on alert. COVID-19 can provoke an acute inflammatory process and uncontrolled oxidative stress, which predisposes one to ... ...

Abstract	Due to its high degree of contagiousness and like almost no other virus, SARS-CoV-2 has put the health of the world population on alert. COVID-19 can provoke an acute inflammatory process and uncontrolled oxidative stress, which predisposes one to respiratory syndrome, and in the worst case, death. Recent evidence suggests the mechanistic role of mitochondria and vitamin D in the development of COVID-19. Indeed, mitochondrial dynamics contribute to the maintenance of cellular homeostasis, and its uncoupling involves pathological situations. SARS-CoV-2 infection is associated with altered mitochondrial dynamics with consequent oxidative stress, pro-inflammatory state, cytokine production, and cell death. Furthermore, vitamin D deficiency seems to be associated with increased COVID-19 risk. In contrast, vitamin D can normalize mitochondrial dynamics, which would improve oxidative stress, pro-inflammatory state, and cytokine production. Furthermore, vitamin D reduces renin-angiotensin-aldosterone system activation and, consequently, decreases ROS generation and improves the prognosis of SARS-CoV-2 infection. Thus, the purpose of this review is to deepen the knowledge about the role of mitochondria and vitamin D directly involved in the regulation of oxidative stress and the inflammatory state in SARS-CoV-2 infection. As future prospects, evidence suggests enhancing the vitamin D levels of the world population, especially of those individuals with additional risk factors that predispose to the lethal consequences of SARS-CoV-2 infection.
Keywords	covid19
Language	English
Publishing date	2020-09-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox9090897
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