Redox Homeostasis Alteration Is Restored through Melatonin Treatment in COVID-19 Patients: A Preliminary Study.

Type II pneumocytes are the target of the SARS-CoV-2 virus, which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. In this study, we evaluated whether treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), lipid peroxidation (LPO), and thiol groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There were significant increases in LPO and carbonyl quantities (p ≤ 0.03) and decreases in TAC and the quantities of NO2-, thiols, and GSH (p < 0.001) in COVID-19 patients. The activities of the antioxidant enzymes such as ecSOD, TrxR, GPx, GST, GR, and peroxidases were decreased (p ≤ 0.04) after the MT treatment. The treatment with MT favored the activity of the antioxidant enzymes that contributed to an increase in TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis, functioning as a glycolytic agent, and inhibited the Warburg effect. Thus, MT restores the redox homeostasis that is altered in COVID-19 patients and can be used as adjuvant therapy in SARS-CoV-2 infection.

Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects.

Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1ß, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFß), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.

Garlic prevents the oxidizing and inflammatory effects of sepsis induced by bacterial lipopolysaccharide at the systemic and aortic level in the rat. Role of trpv1.

Garlic (Allium sativum) possesses healing properties for diseases like systemic arterial hypertension, cancer and diabetes, among others. Its main component, allicin, binds to the Transient Receptor Potential Vanilloid Type 1 (TRPV1). In this study, we investigated TRPV1's involvement in the regulation of various molecules at the systemic and aortic levels in Wistar rats treated with bacterial lipopolysaccharide (LPS) and garlic to activate the receptor. The experimental groups were as follows: 1) Control, 2) LPS, 3) Garlic, and 4) LPS + Garlic. Using Uv-visible spectrophotometry and capillary zone electrophoresis, we measured the levels of nitric oxide (NO), biopterins BH2 and BH4, total antioxidant capacity (TAC) and oxidizing capacity (OXCA). We also analyzed molecules related to vascular homeostasis such as angiotensin Ang 1-7 and Ang II, as well as endothelin ET-1. In addition, we assessed the inflammatory response by determining the levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and galectin-3 (GTN-3). For cell damage assessment, we measured levels of malondialdehyde (MDA), malonate (MTO) and 8-hydroxy-2-deoxyguanosine (8HO2dG). The results showed that LPS influenced the NO pathway at both systemic and aortic levels by increasing OXCA and reducing TAC. It also disrupted vascular homeostasis by increasing Ang-II and ET-1, while decreasing Ang1-7 levels. IL-6, TNFα, GTN-3, as well as MDA, MTO, and 8HO2dG were significantly elevated compared to the control group. The expression of iNOS was increased, but TRPV1 remained unaffected by LPS. However, garlic treatment effectively mitigated the effects of LPS and significantly increased TRPV1 expression. Furthermore, LPS caused a significant decrease in calcitonin gene-related peptide (CGRP) in the aorta, which was counteracted by garlic treatment. Overall, TRPV1 appears to play a crucial role in regulating oxidative stress and the molecules involved in damage and inflammation induced by LPS. Thus, studying TRPV1, CGRP, and allicin may offer a potential strategy for mitigating inflammatory and oxidative stress in sepsis.

Hepatoprotective Mechanisms Induced by Spinach Methanolic Extract in Rats with Hyperglycemia-An Immunohistochemical Analysis.

Spinach methanolic extract (SME) has a hepatoprotective effect due to its polyphenolic antioxidants; however, its action in parenchymal (PQ) and non-parenchymal (nPQ) cells remains unknown. This study investigates the hepatoprotective effect of SME on streptozotocin-induced hyperglycemic rats (STZ), focusing on immunohistochemical analyses. Methods: The extract was prepared, and the total polyphenols and antioxidant activity were quantified. Adult male Wistar rats were divided into four groups (n = 8): normoglycemic rats (NG), STZ-induced hyperglycemic (STZ), STZ treated with 400 mg/kg SME (STZ-SME), and NG treated with SME (SME) for 12 weeks. Serum liver transaminases and lipid peroxidation levels in tissue were determined. The distribution pattern and relative levels of markers related to oxidative stress [reactive oxygen species (ROS), superoxide dismutase-1, catalase, and glutathione peroxidase-1], of cytoprotective molecules [nuclear NRF2 and heme oxygenase-1 (HO-1)], of inflammatory mediators [nuclear NF-κB, TNF-α], proliferation (PCNA), and of fibrogenesis markers [TGF-ß, Smad2/3, MMP-9, and TIMP1] were evaluated. Results: SME had antioxidant capacity, and it lowered serum transaminase levels in STZ-SME compared to STZ. It reduced NOX4 staining, and lipid peroxidation levels were related to low formation of ROS. In STZ-SME, the immunostaining for antioxidant enzymes increased in nPQ cells compared to STZ. However, enzymes were also localized in extra and intracellular vesicles in STZ. Nuclear NRF2 staining and HO-1 expression in PQ and nPQ were higher in STZ-SME than in STZ. Inflammatory factors were decreased in STZ-SME and were related to the percentage decrease in NF-κB nuclear staining in nPQ cells. Similarly, TGF-ß (in the sinusoids) and MMP-9 (in nPQ) were increased in the STZ-SME group compared to the other groups; however, staining for CTGF, TIMP1, and Smad2/3 was lower. Conclusions: SME treatment in hyperglycemic rats induced by STZ may have hepatoprotective properties due to its scavenger capacity and the regulation of differential expression of antioxidant enzymes between the PQ and nPQ cells, reducing inflammatory and fibrogenic biomarkers in liver tissue.

Alteration of the aortic vascular reactivity associated to excessive consumption of Hibiscus sabdariffa Linnaeus: Preliminary findings.

The moderate production of reactive oxidative species (ROS) is important because ROS act as second messengers. However, their depletion through the over-activity of the antioxidant system may lead to reductive stress (RS) which is characterized by an increase in reducing equivalents and an elevation of some components of the antioxidant system disturbing redox homeostasis. Hibiscus sabdariffa Linnaeus (HSL) is a plant with antioxidant properties that provides compounds that favor the antioxidant system. However, excess chronic consumption could lead to the over expression of the antioxidant enzymatic system, and this could contribute to decrease ROS. Therefore, the objective of this study was to evaluate the alteration of the vascular reactivity associated to excessive and chronic consumption of HSL infusions at different percentages. 40 male Wistar rats were divided into 4 groups. Group 1 control (drinking tap water), group 2, 3 and 4, drinking water supplemented with 15, 30 and 60 g/L of HSL calyxes respectively. The systolic blood pressure (SBP), vascular reactivity, morphological changes, and different components of the enzymatic antioxidant system were evaluated in the thoracic aorta by spectrophotometry. We also determined glucose-6-phosphate dehydrogenase (G6PD), glutathione-S-transferase (GST), thioredoxin-reductase (TrxR), glutathione peroxidase (GPx) and glutathione reductase (GR) and some markers of the non-enzimatic system such as the NO3-/NO2-ratio, glutathione (GSH), selenium, thiols, lipoperoxidation (LPO), and 3-nitrityrosine (3-NT). Vasoconstriction was increased and vasorelaxation was decreased. These alterations were reversed by O2- and H2O2. There was an increase in the wall thickness and elastic fibers (p = 0.004 and p = 0.02, respectively) and in G6PD, GPX, TrxR (p = 0.02, p = 0.03, and p = 0.01 respectively). LPO, GSH (p = 0.01), and selenium (p = 0.04) were decreased. There was a decrease in thiols (p < 0.001), 3-NT (p = 0.04) and GST (p = 0.0005) in rats that received the infusion at 3 and 6%. The excess antioxidants provided by the HSL infusions at 3% and 6% modified vascular reactivity, increasing the enzymatic antioxidant system, and depleting ROS.

Effect of Hibiscus sabdariffa L. on the Metabolism of Arachidonic Acid in the Isolated Kidney of a Rat Model of Metabolic Syndrome.

The renal system is engaged in metabolic syndrome (MS) and metabolites of arachidonic acid (AA) participate in renal homeostasis and disruption of functionality. Hibiscus sabdariffa L (HSL) is used as a diuretic and could improve renal function. The aim of this study was to assess if treatment with HSL at 2% improves renal function in MS through the metabolites of AA. A total of 24 male Wistar rats were divided into four groups: Group 1, control (C); Group 2, MS with 30% sucrose in drinking water, Group 3, MS plus HSL infusion at 2% (MS+HSL); and Group 4, C+HSL. We evaluated the perfusion pressure changes (∆-PP), the activities of cyclooxygenases (COXs), the percentage of AA, the expressions of PLA2, COX2, COX1, 5-LOX, TAXS and CYP450, and the concentrations of prostaglandins in the kidney from rats with MS. There was a decrease in the ∆-PP, in the activities of COXs, and the expressions of COX2 and CYP450 (p ≤ 0.03, respectively)as well asPGE2, TxB2, and LKB4 (p ≤ 0.01, respectively). However, the percentage of AA and expressions of PLA2 and PGE1 (p = 0.01, respectively) were increased in C and MS+HSL. The HSL treatment improved the function and anatomical structure of the kidneys in the MS rats, through antioxidant molecules, and inhibited the pathways that metabolize the AA including that of PLA2, COX2, 5-LOX, TAXS, and CYP450 while favoring the COX1 pathway. This improves the vascular resistance of renal arterioles.

Reduced Levels of Selenium and Thioredoxin Reductase in the Thoracic Aorta Could Contribute to Aneurysm Formation in Patients with Marfan Syndrome.

Marfan syndrome (MFS) is an autosomal dominant disorder caused by a heterozygous mutation of the FBN1 gene. MFS patients present oxidative stress that disturbs redox homeostasis. Redox homeostasis depends in part on the enzymatic antioxidant system, which includes thioredoxin reductase (TrxR) and glutathione peroxidases (GPx), both of which require an adequate concentration of selenium (Se). Therefore, the aim of this study was to determine if Se levels are decreased in the TAA of patients with MFS since this could contribute to the formation of an aneurysm in these patients. The results show that interleukins IL-1ß, IL-6 TGF-ß1, and TNF-α (p ≤ 0.03), and carbonylation (p ≤ 0.03) were increased in the TAA of patients with MFS in comparison with control subjects, while Se, thiols (p = 0.02), TrxR, and GPx (p ≤ 0.001) were decreased. TLR4 and NOX1 (p ≤ 0.03), MMP9 and MMP2 (p = 0.04) and NOS2 (p < 0.001) were also increased. Therefore, Se concentrations are decreased in the TAA of MFS, which can contribute to a decrease in the activities of TrxR and GPx, and thiol groups. A decrease in the activities of these enzymes can lead to the loss of redox homeostasis, which can, in turn, lead to an increase in the pro-inflammatory interleukins associated with the overexpression of MMP9 and MMP2.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

N-Acetyl Cysteine Restores the Diminished Activity of the Antioxidant Enzymatic System Caused by SARS-CoV-2 Infection: Preliminary Findings.

SARS-CoV-2 infects type II pneumocytes and disrupts redox homeostasis by overproducing reactive oxygen species (ROS). N-acetyl cysteine (NAC) is a precursor of the synthesis of glutathione (GSH) and it restores the loss of redox homeostasis associated to viral infections. The aim of the study is to evaluate the effect of the treatment with NAC on the enzymatic antioxidant system in serum from patients infected by SARS-CoV-2. We evaluated the enzymatic activities of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), -S-transferase (GST), and reductase (GR) by spectrophotometry and the concentrations of the glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), and lipid peroxidation (LPO) in serum. The activity of the extracellular super oxide dismutase (ecSOD) was determined by native polyacrylamide gels, and 3-nitrotyrosine (3-NT) was measured by ELISA. A decrease in the activities of the ecSOD, TrxR, GPx, GST GR, (p = 0 ≤ 0.1), and the GSH, TAC, thiols, and NO2- (p ≤ 0.001) concentrations and an increase in LPO and 3-NT (p = 0.001) concentrations were found in COVID-19 patients vs. healthy subjects. The treatment with NAC as an adjuvant therapy may contribute to a reduction in the OS associated to the infection by SARS-CoV-2 through the generation of GSH. GSH promotes the metabolic pathways that depend on it, thus contributing to an increase in TAC and to restore redox homeostasis.

Frailty and the Interactions between Skeletal Muscle, Bone, and Adipose Tissue-Impact on Cardiovascular Disease and Possible Therapeutic Measures.

Frailty is a global health problem that impacts clinical practice. It is complex, having a physical and a cognitive component, and it is the result of many contributing factors. Frail patients have oxidative stress and elevated proinflammatory cytokines. Frailty impairs many systems and results in a reduced physiological reserve and increased vulnerability to stress. It is related to aging and to cardiovascular diseases (CVD). There are few studies on the genetic factors of frailty, but epigenetic clocks determine age and frailty. In contrast, there is genetic overlap of frailty with cardiovascular disease and its risk factors. Frailty is not yet considered a risk factor for CVD. It is accompanied by a loss and/or poor functioning of muscle mass, which depends on fiber protein content, resulting from the balance between protein breakdown and synthesis. Bone fragility is also implied, and there is a crosstalk between adipocytes, myocytes, and bone. The identification and assessment of frailty is difficult, without there being a standard instrument to identify or treat it. Measures to prevent its progression include exercises, as well as supplementing the diet with vitamin D and K, calcium, and testosterone. In conclusion, more research is needed to better understand frailty and to avoid complications in CVD.

Tomography and Prognostic Indices in the State of the Art of Evaluation in Hospitalized Patients with COVID-19 Pneumonia.

Evaluation in medical emergencies of COVID-19 patients represents a challenge to regulate preventive and timely management. There are key imaging and laboratory tools to classify the severity. The aim of the study was to evaluate the chest CT score performance and prognostic indices in COVID-19 patients to predict the progression to critical illness. This was a retrospective study between run between April and December 2020, in which 109 patients were included. Patients of any age and gender and who required hospitalization due to a confirmed COVID-19 diagnosis by RT-PCR and chest CT and laboratory were analyzed. In 75% of them, there was at least one comorbidity, and 30% developed critical illness, and the average mortality was 10%. In 49.5%, there was a CORADS-5 on admission, and in 50%, there was a peripheral distribution of the interstitial infiltrate in the left lower lobe. The risk factors were FiO2, CT score > 18, and the NRL index. The combination of the high-risk Quick COVID-19 Severity Index (qCSI) plus CT score > 18 indices was the best prediction index for the development of a critical condition. The combined use of indices in infected COVID-19 patients showed diagnostic accuracy and predicted severity. Imaging and the laboratory tests are key tools independent of the wave of recurrence.

Deodorized Garlic Decreases Oxidative Stress Caused by Lipopolysaccharide in Rat Heart through Hydrogen Sulfide: Preliminary Findings.

Deodorized garlic (DG) may favor the activity of the antioxidant enzymes and promote the synthesis of hydrogen sulfide (H2S). The objective was to test if DG favors an increase in H2S and if it decreases the oxidative stress caused by lipopolysaccharide (LPS) in rat hearts. A total of 24 rats were divided into 4 groups: Group 1 control (C), Group 2 LPS, Group 3 DG, and Group 4 LPS plus DG. The cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and oxidative stress markers, such as total antioxidant capacity (TAC), glutathione (GSH), selenium (Se), lipid peroxidation (LPO), thiols, hydrogen sulfide (H2S), and the activities and expressions of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), cystathionine synthetase (CBS), cystathionine γ-lyase (CTH), iNOS, and eNOS-p, were analyzed in the heart. Infarct zones in the cardiac tissue were present (p = 0.01). The CMP and CVR decreased and increased (p ≤ 0.05), TAC, GSH, H2S, NO, thiols, and GST activity (p ≤ 0.01) decreased, and LPO and iNOS increased (p ≤ 0.05). The activities and expressions of TrxR, GPx, eNOS-p, CTH, and CBS (p ≤ 0.05) decreased with the LPS treatment; however, DG normalized this effect. DG treatment decreases heart damage caused by LPS through the cross-talk between the H2S and NO systems.

Excessive Consumption Hibiscus sabdariffa L. Increases Inflammation and Blood Pressure in Male Wistar Rats via High Antioxidant Capacity: The Preliminary Findings.

Hibiscus sabdariffa L. (HSL) has high amounts of antioxidants and many beneficial effects in several pathologies. However, few studies describe the possible harmful effects of high concentrations of HSL. Here we evaluate the effect of excessive and chronic consumption of infusions with different percentages of HSL on some oxidative stress markers in serum, and the possible association with inflammation and increased systolic blood pressure (SBP), in healthy rats. A total of 32 male Wistar rats were used to form 4 groups with 8 animals each. Group 1 control (drinking tap water), group 2, 3 and 4, drinking water supplemented with 15, 30 and 60 g/L of HSL calyxes respectively. SBP was evaluated and determinations in serum of the NO3-/NO2- ratio, glutathione (GSH), total antioxidant capacity (TAC), selenium (Se), TNF-α, IL-1α/IL-1F1, IL-1ß, IL-10, extracellular superoxide dismutase (EcSOD), thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities, were evaluated. The SBP (p = 0.01), GPx activity, GSH, TAC, Se, TNF-α and EcSOD activities (p ≤ 0.001) and IL-1α/IL-1F1, IL-1ß, TrxR and NO3-/NO2- (p ≤ 0.05), were increased but IL-10 (p < 0.001) was decreased in rats that consumed the 3 and 6% HSL infusions. The excessive and chronic consumption of HSL may increase the TAC that could lead to a proinflammatory state which is associated with hypertension.

Evolutionary cardiology and experimental research / Cardiología evolutiva e investigación experimental

Abstract Evolutionary medicine studies the role of evolution in health problems. Diseases are considered as phenotypes generated by the expression of sets of genes and a complex interplay with the environment. The main mechanisms involved in evolutionary medicine are antagonistic pleiotropy, ecological antagonistic pleiotropy, atavisms and heterochrony. Antagonistic pleiotropism refers to genes that are beneficial during certain stages of development but become detrimental in others. Ecological antagonistic pleiotropy refers to the misadaptation to current lifestyle conditions which are different from those in which humans evolved. These mechanisms participate in the development of congestive heart failure, hypertension and atherosclerosis. Atavistic conditions or genes are expressed in our ancestors but have remained silent during evolution being suddenly expressed without an apparent cause during the appearance of a disease is another mechanism in evolutionary cardiology. The change in the heart metabolism from fatty acid to glucose dependent can be considered as an atavistic condition that appears in the heart after a stroke and may underlie impaired cardiomyocyte regeneration. Heterochrony is the expression of genes that cause the appearance of traits at a different timing during development and is therefore related to atavisms. Evolutionary medicine explains the interactions of pathogens and the host in infectious diseases where the cardiac tissue becomes a target. Mechanisms involved in evolutionary medicine participate in the generation of diseases and may be approached experimentally. Therefore, to better understand health problems and therapeutical approaches, an evolutionary medicine approach in experimental medicine may prove useful.

Resumen La medicina evolutiva estudia el papel de la evolución en los problemas de salud. Las enfermedades son fenotipos generados por la expresión de genes y una interacción compleja con el medio ambiente. Los principales mecanismos implicados son la pleiotropía antagonista, la pleiotropía antagonista ecológica, los atavismos y la heterocronía. El pleiotropismo antagonista se refiere a situaciones donde los genes que son beneficiosos durante ciertas etapas del desarrollo resultan perjudiciales en otras. La pleiotropía antagonista ecológica se refiere a la mala adaptación a las condiciones de vida actuales, que difieren de aquellas en las que los humanos evolucionaron. Estos mecanismos participan en el desarrollo de insuficiencia cardiaca congestiva, hipertensión y aterosclerosis. Las condiciones o genes atávicos fueron características que se expresaron en nuestros antepasados pero han permanecido silenciadas durante la evolución, expresándose repentinamente durante una enfermedad; un ejemplo es el cambio metabólico en el corazón de dependiente de ácidos grasos a dependiente de glucosa en condiciones de hipoxia que aparece después de un infarto y puede subyacer a la dificultad de la regeneración de los cardiomiocitos. La heterocronía es la expresión de genes que provocan la aparición de rasgos en un momento diferente durante el desarrollo. La medicina evolutiva también explica las interacciones entre los patógenos y el huésped en enfermedades infecciosas. Los mecanismos implicados en la medicina evolutiva participan en la generación de enfermedades y pueden abordarse experimentalmente. Por tanto, la medicina experimental puede enriquecer la medicina evolutiva y el origen de muchos problemas de salud.

Bioprosthesis in aortic valve replacement: long-term inflammatory response and functionality.

BACKGROUND: The evaluation of long-term inflammatory response and function in postoperative patients with aortic valve replacement (AVR) deserves special analysis because it is important to try to prevent reoperation and improve durability and functionality of the prostheses. It is our objective METHODS: In this study, we included a cohort of patients with aortic valve damage treated by AVR with mechanical prosthesis, bio prosthesis and we included a control group. RESULTS: We found that IL-4 and osteopontin levels were higher in patients with mechanical vs biological prostheses (p=0.01 and p=0.04, respectively), osteoprotegerin (OPG) levels were decreased (p=0.01), women had lower levels of ET-1 and IL-6, (p=0.02) (p=0.04), respectively. Patients older than 60 years had decreased levels of IL-1ß p<0.001) and a higher concentration of IL-4 p<0.05). IL-1ß, OPG and TNFα were higher in patients with less than 5 years of evolution vs more than 10 years (p=0.004, p=0.02 and p=0.03, respectively). Factors such as age, gender, prosthetic and elevated IL-1B and ET-1 levels are associated with valve dysfunction prosthetic. These results indicate that the inflammatory involvement present prior to valve replacement may be perpetuated by various factors in the long term. CONCLUSIONS: The findings provide us with the opportunity to effectively treat patients with AVR in the postoperative period, which could prolong the functionality of the bio prostheses. TRIAL REGISTRATION NUMBER: NCT04557345.

High Sucrose Ingestion during a Critical Period of Vessel Development Promotes the Synthetic Phenotype of Vascular Smooth Muscle Cells and Modifies Vascular Contractility Leading to Hypertension in Adult Rats.

Cardiometabolic diseases, including hypertension, may result from exposure to high sugar diets during critical periods of development. Here, we studied the effect of sucrose ingestion during a critical period (CP) between postnatal days 12 and 28 of the rat on blood pressure, aortic histology, vascular smooth muscle phenotype, expression of metalloproteinases 2 and 9, and vascular contractility in adult rats and compared it with those of adult rats that received sucrose for 6 months and developed metabolic syndrome (MS). Blood pressure increased to a similar level in CP and MS rats. The diameter of lumen, media, and adventitia of aortas from CP rats was decreased. Muscle fibers were discontinuous. There was a decrease in the expression of alpha-actin in CP and MS rat aortas, suggesting a change to the secretory phenotype in vascular smooth muscle. Metalloproteinases 2 and 9 were decreased in CP and MS rats, suggesting that phenotype remains in an altered steady stationary state with little interchange of the vessel matrix. Aortic contraction to norepinephrine did not change, but aortic relaxation was diminished in CP and MS aortas. In conclusion, high sugar diets during the CP increase predisposition to hypertension in adults.

The Possible Role of Glucose-6-Phosphate Dehydrogenase in the SARS-CoV-2 Infection.

Glucose-6-phosphate dehydrogenase (G6PD) is the second rate-limiting enzyme of the pentose phosphate pathway. This enzyme is present in the cytoplasm of all mammalian cells, and its activity is essential for an adequate functioning of the antioxidant system and for the response of innate immunity. It is responsible for the production of nicotinamide adenine dinucleotide phosphate (NADPH), the first redox equivalent, in the pentose phosphate pathway. Viral infections such as SARS-CoV-2 may induce the Warburg effect with an increase in anaerobic glycolysis and production of lactate. This condition ensures the success of viral replication and production of the virion. Therefore, the activity of G6PD may be increased in COVID-19 patients raising the level of the NADPH, which is needed for the enzymatic and non-enzymatic antioxidant systems that counteract the oxidative stress caused by the cytokine storm. G6PD deficiency affects approximately 350-400 million people worldwide; therefore, it is one of the most prevalent diseases related to enzymatic deficiency worldwide. In G6PD-deficient patients exposed to SARS-CoV-2, the amount of NADPH is reduced, increasing the susceptibility for viral infection. There is loss of the redox homeostasis in them, resulting in severe pneumonia and fatal outcomes.

[Evolutionary cardiology and experimental research]. / Cardiología evolutiva e investigación experimental.

Evolutionary medicine studies the role of evolution in health problems. Diseases are considered as phenotypes generated by the expression of sets of genes and a complex interplay with the environment. The main mechanisms involved in evolutionary medicine are antagonistic pleiotropy, ecological antagonistic pleiotropy, atavisms and heterochrony. Antagonistic pleiotropism refers to genes that are beneficial during certain stages of development but become detrimental in others. Ecological antagonistic pleiotropy refers to the misadaptation to current lifestyle conditions which are different from those in which humans evolved. These mechanisms participate in the development of congestive heart failure, hypertension and atherosclerosis. Atavistic conditions or genes are expressed in our ancestors but have remained silent during evolution being suddenly expressed without an apparent cause during the appearance of a disease is another mechanism in evolutionary cardiology. The change in the heart metabolism from fatty acid to glucose dependent can be considered as an atavistic condition that appears in the heart after a stroke and may underlie impaired cardiomyocyte regeneration. Heterochrony is the expression of genes that cause the appearance of traits at a different timing during development and is therefore related to atavisms. Evolutionary medicine explains the interactions of pathogens and the host in infectious diseases where the cardiac tissue becomes a target. Mechanisms involved in evolutionary medicine participate in the generation of diseases and may be approached experimentally. Therefore, to better understand health problems and therapeutical approaches, an evolutionary medicine approach in experimental medicine may prove useful.

La medicina evolutiva estudia el papel de la evolución en los problemas de salud. Las enfermedades son fenotipos generados por la expresión de genes y una interacción compleja con el medio ambiente. Los principales mecanismos implicados son la pleiotropía antagonista, la pleiotropía antagonista ecológica, los atavismos y la heterocronía. El pleiotropismo antagonista se refiere a situaciones donde los genes que son beneficiosos durante ciertas etapas del desarrollo resultan perjudiciales en otras. La pleiotropía antagonista ecológica se refiere a la mala adaptación a las condiciones de vida actuales, que difieren de aquellas en las que los humanos evolucionaron. Estos mecanismos participan en el desarrollo de insuficiencia cardiaca congestiva, hipertensión y aterosclerosis. Las condiciones o genes atávicos fueron características que se expresaron en nuestros antepasados pero han permanecido silenciadas durante la evolución, expresándose repentinamente durante una enfermedad; un ejemplo es el cambio metabólico en el corazón de dependiente de ácidos grasos a dependiente de glucosa en condiciones de hipoxia que aparece después de un infarto y puede subyacer a la dificultad de la regeneración de los cardiomiocitos. La heterocronía es la expresión de genes que provocan la aparición de rasgos en un momento diferente durante el desarrollo. La medicina evolutiva también explica las interacciones entre los patógenos y el huésped en enfermedades infecciosas. Los mecanismos implicados en la medicina evolutiva participan en la generación de enfermedades y pueden abordarse experimentalmente. Por tanto, la medicina experimental puede enriquecer la medicina evolutiva y el origen de muchos problemas de salud.

Beneficial Effects of Fructooligosaccharides Esterified with Lauric Acid in a Metabolic Syndrome Model Induced by a High-Fat and High-Carbohydrate Diet in Wistar Rats.

Metabolic syndrome (MS) is a group of abnormalities in which obesity, insulin resistance (IR), oxidative stress, and dyslipidemia stand out. This pathology predisposes to the development of cardiovascular diseases and diabetes. The ingestion of linear fructooligosaccharides (FOS) such as inulin reduces conditions such as hyperinsulinemia, increased body fat, and triglyceridemia. When FOS are esterified with fatty acids, they present emulsifying and surfactant properties; however, there are no reports of their function at the biological level. The purpose of this investigation was to evaluate the effect of Agave tequilana Weber's FOS (AtW-FOS) and FOS esterified with lauric acid (FOS-LA) in MS markers in a rat model induced by a HFHC diet. Supplementation with AtW-FOS and FOS-LA decreased IR, improved glucose tolerance, reduced liver weight (19%), plasma triglycerides (24%), and blood pressure (16%) when compared with the untreated MS group. In conclusion, the ingestion of AtW-FOS and FOS-LA has beneficial effects in the prevention of MS alterations, showing a high potential for their application in functional foods.

Hyperglycemia and Loss of Redox Homeostasis in COVID-19 Patients.

The infection with SARS-CoV-2 impairs the glucose−insulin axis and this contributes to oxidative (OS) and nitrosative (NSS) stress. Here, we evaluated changes in glucose metabolism that could promote the loss of redox homeostasis in COVID-19 patients. This was comparative cohort and analytical study that compared COVID-19 patients and healthy subjects. The study population consisted of 61 COVID-19 patients with and without comorbidities and 25 healthy subjects (HS). In all subjects the plasma glucose, insulin, 8-isoprostane, Vitamin D, H2S and 3-nitrotyrosine were determined by ELISA. The nitrites (NO2−), lipid-peroxidation (LPO), total-antioxidant-capacity (TAC), thiols, glutathione (GSH) and selenium (Se) were determined by spectrophotometry. The glucose, insulin and HOMA-IR (p < 0.001), 8-isoprostanes, 3-nitrotyrosine (p < 0.001) and LPO were increased (p = 0.02) while Vitamin D (p = 0.01), H2S, thiols, TAC, GSH and Se (p < 0.001) decreased in COVID-19 patients in comparison to HS. The SARS-CoV-2 infection resulted in alterations in the glucose−insulin axis that led to hyperglycemia, hyperinsulinemia and IR in patients with and without comorbidities. These alterations increase OS and NSS reflected in increases or decreases in some oxidative markers in plasma with major impact or fatal consequences in patients that course with metabolic syndrome. Moreover, subjects without comorbidities could have long-term alterations in the redox homeostasis after infection.