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1.
Int J Mol Sci ; 23(7)2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1785744

ABSTRACT

Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review has drawn attention to the axis between resveratrol and human microbiota, which plays a key role in maintaining an adequate immune response that can lead to different diseases when compromised. Resveratrol can also be an asset in new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar were searched to find papers that matched our topic dating from 1 January 2017 up to 18 January 2022, with English-language restriction using the following Boolean keywords: ("resveratrol" AND "microbio*"). Eighteen studies were included as relevant papers matching the purpose of our investigation. Immune response, prevention of thrombotic complications, microbiota, gene therapy, and bone regeneration were retrieved as the main topics. The analyzed studies mostly involved resveratrol supplementation and its effects on human microbiota by trials in vitro, in vivo, and ex vivo. The beneficial activity of resveratrol is evident by analyzing the changes in the host's genetic expression and the gastrointestinal microbial community with its administration. The possibility of identifying individual microbial families may allow to tailor therapeutic plans with targeted polyphenolic diets when associated with microbial dysbiosis, such as inflammatory diseases of the gastrointestinal tract, degenerative diseases, tumors, obesity, diabetes, bone tissue regeneration, and metabolic syndrome.


Subject(s)
Dysbiosis , Gastrointestinal Microbiome , Dietary Supplements , Humans , Obesity/drug therapy , Resveratrol/pharmacology , Resveratrol/therapeutic use
2.
Nutr Metab Cardiovasc Dis ; 32(7): 1635-1641, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1778389

ABSTRACT

BACKGROUND AND AIMS: Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on Remdesivir effectiveness among hospitalized COVID-19 patients. METHODS AND RESULTS: We conducted an observational study on patients with SARS-CoV-2-related pneumonia admitted between May 2020 and September 2021 to the COVID-19 Units of Internal Medicine, Pneumology and Intensive Care of Garibaldi Hospital, Catania, Italy, and treated with Remdesivir. The "Ordinal Scale For Clinical Improvement" was used to assess patients' clinical improvement within 28 days of hospitalization. Short-term mortality rate was also evaluated. A total of 142 patients with SARS-CoV-2-related pneumonia were studied. The prevalence of obesity (20.7% vs. 41.9%, p = 0.03), the average BMI (27.1 ± 4.4 vs. 31.1 ± 6.1, p < 0.01) and the mean LDL-C levels (78 ± 19 mg/dl vs. 103 ± 18 mg/dl, p = 0.03) were significantly lower in early-improved (EI) compared to not-improved (NI) individuals. Obesity was negatively associated to clinical improvement after Remdesivir (OR 0.48, 95%CI 0.17-0.97, p = 0.04). Both obesity (OR 2.82, 95% CI 1.05-7.71, p = 0.04) and dyslipidemia (OR 2.78, 95%CI 1.17-7.16, p = 0.03) were significantly related to patients' mortality. Dyslipidemic subjects experienced a slower clinical improvement than non-dyslipidemic ones (Long-Rank p = 0.04). CONCLUSION: Our study showed that unfavorable metabolic conditions such as obesity and dyslipidemia could predict a worse clinical response to Remdesivir as well as the mortality in hospitalized COVID-19 patients. Further prospective and larger-scale studies are needed to confirm these preliminary findings.


Subject(s)
COVID-19 , Dyslipidemias , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Dyslipidemias/diagnosis , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology , Humans , Obesity/diagnosis , Obesity/drug therapy , SARS-CoV-2
3.
Crit Care ; 26(1): 60, 2022 03 14.
Article in English | MEDLINE | ID: covidwho-1741949

ABSTRACT

Obesity is highly prevalent in hospitalized patients admitted with COVID-19. Evidence based guidelines are available for COVID-19-related therapies but dosing information specific to patients with obesity is lacking. Failure to account for the pharmacokinetic alterations that exist in this population can lead to underdosing, and treatment failure, or overdosing, resulting in an adverse effect. The objective of this manuscript is to provide clinicians with guidance for making dosing decisions for medications used in the treatment of patients with COVID-19. A detailed literature search was conducted for medications listed in evidence-based guidelines from the National Institutes of Health with an emphasis on pharmacokinetics, dosing and obesity. Retrieved manuscripts were evaluated and the following prioritization strategy was used to form the decision framework for recommendations: clinical outcome data > pharmacokinetic studies > adverse effects > physicochemical properties. Most randomized controlled studies included a substantial number of patients who were obese but few had large numbers of patients more extreme forms of obesity. Pharmacokinetic data have described alterations with volume of distribution and clearance but this variability does not appear to warrant dosing modifications. Future studies should provide more information on size descriptors and stratification of data according to obesity and body habitus.


Subject(s)
COVID-19 , COVID-19/complications , COVID-19/drug therapy , Decision Making , Humans , Obesity/complications , Obesity/drug therapy , United States
4.
Int J Mol Sci ; 23(5)2022 Feb 23.
Article in English | MEDLINE | ID: covidwho-1715405

ABSTRACT

The abnormal accumulation of methylglyoxal (MG) leading to increased glycation of protein and DNA has emerged as an important metabolic stress, dicarbonyl stress, linked to aging, and disease. Increased MG glycation produces inactivation and misfolding of proteins, cell dysfunction, activation of the unfolded protein response, and related low-grade inflammation. Glycation of DNA and the spliceosome contribute to an antiproliferative and apoptotic response of high, cytotoxic levels of MG. Glyoxalase 1 (Glo1) of the glyoxalase system has a major role in the metabolism of MG. Small molecule inducers of Glo1, Glo1 inducers, have been developed to alleviate dicarbonyl stress as a prospective treatment for the prevention and early-stage reversal of type 2 diabetes and prevention of vascular complications of diabetes. The first clinical trial with the Glo1 inducer, trans-resveratrol and hesperetin combination (tRES-HESP)-a randomized, double-blind, placebo-controlled crossover phase 2A study for correction of insulin resistance in overweight and obese subjects, was completed successfully. tRES-HESP corrected insulin resistance, improved dysglycemia, and low-grade inflammation. Cell permeable Glo1 inhibitor prodrugs have been developed to induce severe dicarbonyl stress as a prospective treatment for cancer-particularly for high Glo1 expressing-related multidrug-resistant tumors. The prototype Glo1 inhibitor is prodrug S-p-bromobenzylglutathione cyclopentyl diester (BBGD). It has antitumor activity in vitro and in tumor-bearing mice in vivo. In the National Cancer Institute human tumor cell line screen, BBGD was most active against the glioblastoma SNB-19 cell line. Recently, potent antitumor activity was found in glioblastoma multiforme tumor-bearing mice. High Glo1 expression is a negative survival factor in chemotherapy of breast cancer where adjunct therapy with a Glo1 inhibitor may improve treatment outcomes. BBGD has not yet been evaluated clinically. Glycation by MG now appears to be a pathogenic process that may be pharmacologically manipulated for therapeutic outcomes of potentially important clinical impact.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glutathione/analogs & derivatives , Hesperidin/therapeutic use , Lactoylglutathione Lyase/metabolism , Neoplasms, Experimental/drug therapy , Resveratrol/therapeutic use , Animals , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Drug Therapy, Combination , Enzyme Induction/drug effects , Glutathione/chemistry , Glutathione/therapeutic use , Glycosylation/drug effects , Hesperidin/chemistry , Humans , Insulin Resistance/physiology , Lactoylglutathione Lyase/antagonists & inhibitors , Mice , Molecular Structure , Neoplasms, Experimental/metabolism , Obesity/drug therapy , Obesity/metabolism , Obesity/physiopathology , Pyruvaldehyde/chemistry , Pyruvaldehyde/metabolism , Resveratrol/chemistry
5.
Int J Mol Sci ; 23(4)2022 Feb 19.
Article in English | MEDLINE | ID: covidwho-1715401

ABSTRACT

Obesity is an increasingly severe public health problem, which brings huge social and economic burdens. Increased body adiposity in obesity is not only tightly associated with type 2 diabetes, but also significantly increases the risks of other chronic diseases including cardiovascular diseases, fatty liver diseases and cancers. Adipogenesis describes the process of the differentiation and maturation of adipocytes, which accumulate in distributed adipose tissue at various sites in the body. The major functions of white adipocytes are to store energy as fat during periods when energy intake exceeds expenditure and to mobilize this stored fuel when energy expenditure exceeds intake. Brown/beige adipocytes contribute to non-shivering thermogenesis upon cold exposure and adrenergic stimulation, and thereby promote energy consumption. The imbalance of energy intake and expenditure causes obesity. Recent interest in epigenetics and signaling pathways has utilized small molecule tools aimed at modifying obesity-specific gene expression. In this review, we discuss compounds with adipogenesis-related signaling pathways and epigenetic modulating properties that have been identified as potential therapeutic agents which cast some light on the future treatment of obesity.


Subject(s)
Adipogenesis/drug effects , Anti-Obesity Agents/pharmacology , Obesity/drug therapy , Adiposity/drug effects , Animals , Energy Metabolism/drug effects , Humans , Obesity/metabolism , Signal Transduction/drug effects , Thermogenesis/drug effects
6.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1686174

ABSTRACT

OBJECTIVE: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatization to estradiol (E2). However, no controlled study has assessed the effects of E2 in the absence of testosterone. DESIGN: Six-month randomized, placebo-controlled trial with the hypothesis that men randomized to E2 would reduce their fat mass. METHODS: Seventy-eight participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel per day, or matched placebo. Dual x-ray absorptiometry body composition was measured at baseline, month 3, and month 6. The primary outcome was total fat mass. RESULTS: Serum E2 increased in the estradiol group over 6 months compared to placebo, and mean-adjusted difference (MAD) was 207 pmol/L (95% CI: 123-292), P < 0.001. E2 treatment changed total fat mass, MAD 1007 g (95% CI: 124-1891), but not significantly, so P = 0.09. There were other consistent non-significant trends toward increased proportional fat mass, MAD 0.8% (95% CI: 0.0-1.6), P= 0.15; gynoid fat, MAD 147 g (95% CI: 2-293), P = 0.08; visceral fat, 53 g (95% CI: 1-105) P = 0.13; and subcutaneous fat, MAD 65 g (95% CI: 5-125), P = 0.11. Android fat increased, MAD 164 g (95% CI: 41-286), P = 0.04. CONCLUSION: Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men. Given the premature closure of clinical trials due to the COVID pandemic, this potentially important observation should encourage additional studies to confirm or refute whether E2 promotes fat expansion in the absence of testosterone.


Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/therapeutic use , Estradiol/pharmacology , Absorptiometry, Photon , Aged , Androgen Antagonists/adverse effects , Australia , Body Composition/drug effects , Double-Blind Method , Humans , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
7.
Diabetes Metab Syndr ; 16(1): 102373, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1587938

ABSTRACT

BACKGROUND AND AIMS: Obesity has been reported to be one of the most frequent comorbidities in COVID-19 patients and associated with higher rates of in-hospital mortality compared to non-obese patients. Acute kidney injury (AKI) is also known to be a complication associated with obesity in critically-ill COVID-19 patients. We aimed to investigate whether obesity was associated with increased risk of in-hospital mortality and AKI among patients with COVID-19 treated with corticosteroids. METHODS: We utilized 9965 hospitalized COVID-19 patient data and divided patients who were treated with corticosteroids into 6 groups by body mass index (BMI) (less than 18.5, 18.5-25, 25-30, 30-35, 35-40, 40 kg/m2 or greater). The association between BMI and in-hospital mortality and between BMI and incidence rate of AKI during admission among COVID-19 patients receiving corticosteroids were retrospectively investigated. RESULTS: There were 4587 study participants receiving corticosteroids (mean age 66.5 ± 15.5 years, men 56.6%, mean BMI 29.0 ± 7.2 kg/m2). The smooth spline curve suggested a J-shape association between BMI and in-hospital mortality. Patients with BMI above 40 kg/m2 exhibited a higher in-hospital mortality and higher incidence rate of AKI during admission compared to patients with BMI between 25 and 30 kg/m2. The differences in in-hospital mortality and the rate of AKI were larger among patients with severe COVID-19. CONCLUSIONS: Class III obesity was associated with high in-hospital mortality and AKI in patients with COVID-19 treated by corticosteroids. Clinicians must stay vigilant on the impact of class III obesity and development of AKI to disease trajectory of COVID-19 patients.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19 , Hospital Mortality , Obesity , Adult , Aged , Aged, 80 and over , Body Mass Index , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , Comorbidity , Critical Illness/mortality , Female , Humans , Incidence , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Obesity/epidemiology , Retrospective Studies , Risk Factors , United States/epidemiology
9.
Front Endocrinol (Lausanne) ; 12: 772865, 2021.
Article in English | MEDLINE | ID: covidwho-1556281

ABSTRACT

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , COVID-19/complications , COVID-19/drug therapy , Diabetes Complications/drug therapy , Diabetes Mellitus/drug therapy , Aged , Animals , Cardiovascular Diseases/complications , Cardiovascular Diseases/drug therapy , Comorbidity , Female , Humans , Hyperglycemia/metabolism , Hypertension , Inflammation , Insulin Resistance , Insulin-Secreting Cells/metabolism , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Risk , Risk Factors , SARS-CoV-2
11.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1484899

ABSTRACT

OBJECTIVE: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatization to estradiol (E2). However, no controlled study has assessed the effects of E2 in the absence of testosterone. DESIGN: Six-month randomized, placebo-controlled trial with the hypothesis that men randomized to E2 would reduce their fat mass. METHODS: Seventy-eight participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel per day, or matched placebo. Dual x-ray absorptiometry body composition was measured at baseline, month 3, and month 6. The primary outcome was total fat mass. RESULTS: Serum E2 increased in the estradiol group over 6 months compared to placebo, and mean-adjusted difference (MAD) was 207 pmol/L (95% CI: 123-292), P < 0.001. E2 treatment changed total fat mass, MAD 1007 g (95% CI: 124-1891), but not significantly, so P = 0.09. There were other consistent non-significant trends toward increased proportional fat mass, MAD 0.8% (95% CI: 0.0-1.6), P= 0.15; gynoid fat, MAD 147 g (95% CI: 2-293), P = 0.08; visceral fat, 53 g (95% CI: 1-105) P = 0.13; and subcutaneous fat, MAD 65 g (95% CI: 5-125), P = 0.11. Android fat increased, MAD 164 g (95% CI: 41-286), P = 0.04. CONCLUSION: Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men. Given the premature closure of clinical trials due to the COVID pandemic, this potentially important observation should encourage additional studies to confirm or refute whether E2 promotes fat expansion in the absence of testosterone.


Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/therapeutic use , Estradiol/pharmacology , Absorptiometry, Photon , Aged , Androgen Antagonists/adverse effects , Australia , Body Composition/drug effects , Double-Blind Method , Humans , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
12.
Phytomedicine ; 92: 153714, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1370665

ABSTRACT

BACKGROUND: As one of traditional Chinese medicine, mulberry leaf is abundant in diverse active ingredients and widely used for the treatment of metabolic disease and its complications. However, there are a few of reports on its application in the prevention and treatment of obesity. And the molecular mechanism on the anti-obesity of mulberry leaf are unknown till now. PURPOSE: The present study aimed to evaluate the potential ingredients and targets of mulberry leaf and uncover the anti-obesity mechanisms by using the network pharmacology tactics and verify its effect by biological experiments. STUDY DESIGN: Active ingredients and key targets of mulberry leaf, genes related to obesity were screened through public database. Based on the results of network pharmacology, the flavonoids-enriched fraction of mulberry leaf (MLF) was extracted and composition of this fraction was identified. After that, HepG2 cells model of lipid accumulation was established for verifying the effect of MLF and related mechanisms. RESULTS: A total of 37 active ingredients in mulberry leaf, 192 predicted biological targets and 8813 obesity-related targets were determined, of which 180 overlapping targets might have obvious curative effects on obesity. The networks showed that mulberry leaf might play a role through key targets, such as AKT, MAPK and IL-6, and regulated PI3K-Akt signaling pathway. Based on HPLC-ESI-QQQ-MS analysis, 13 constituents of MLF were identified, including 9 flavonoids. Furthermore, HepG2 cells model of lipid accumulation was established. The results indicated that MLF treatment could down-regulate the secretion of inflammatory cytokines, as well as clearly inhibited lipid droplets formation and alleviated TC, TG, HDL-C and LDL-C levels. Positive effect was observed on hypolipidemic efficacy due to the regulation of PI3K/Akt/Bcl-xl pathway, as indicated by the amelioration of PI3K, Akt and Bcl-xl gene and protein expression. CONCLUSION: This study firstly systematically disclose the multi-ingredients, multi-targets mechanisms of mulberry leaf on obesity by using network pharmacology approach, and validate in HepG2 cells that the protective effect of MLF against obesity involved both inflammation response and lipid metabolism involving PI3K/Akt/Bcl-xl signaling pathway. It provides indications for further mechanistic research of mulberry leaf and also for the development as a potential candidate for the therapy for obese patients.


Subject(s)
Morus , Humans , Molecular Biology , Obesity/drug therapy , Phosphatidylinositol 3-Kinases , Plant Leaves
13.
Adipocyte ; 10(1): 408-411, 2021 12.
Article in English | MEDLINE | ID: covidwho-1360282

ABSTRACT

Angiotensin converting enzyme-2 (ACE2) is the cell-surface receptor enabling cellular entry of SARS-CoV-2. ACE2 is highly expressed in adipose tissue (AT), rendering AT a potential SARS-CoV-2 reservoir contributing to massive viral spread in COVID-19 patients with obesity. Although rodent and cell studies suggest that the polyphenol resveratrol alters ACE2, human studies are lacking. Here, we investigated the effects of 30-days resveratrol supplementation on RAS components in AT and skeletal muscle in men with obesity in a placebo-controlled cross-over study. Resveratrol markedly decreased ACE2 (~40%) and leptin (~30%), but did neither alter angiotensinogen, ACE and AT1R expression in AT nor skeletal muscle RAS components. These findings demonstrate that resveratrol supplementation reduces ACE2 in AT, which might dampen SARS-CoV-2 spread in COVID-19.


Subject(s)
Adipose Tissue/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Resveratrol/administration & dosage , Adipose Tissue/cytology , Angiotensin-Converting Enzyme 2/genetics , COVID-19/pathology , COVID-19/virology , Cross-Over Studies , Dietary Supplements , Double-Blind Method , Down-Regulation/drug effects , Humans , Leptin/genetics , Leptin/metabolism , Male , Middle Aged , Obesity/drug therapy , Obesity/pathology , Placebo Effect , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Resveratrol/pharmacology , SARS-CoV-2/isolation & purification
14.
Int J Mol Sci ; 22(15)2021 Jul 31.
Article in English | MEDLINE | ID: covidwho-1346501

ABSTRACT

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.


Subject(s)
Anti-Obesity Agents/therapeutic use , Arachidonic Acids/therapeutic use , Benzoates/therapeutic use , Obesity/drug therapy , Phenylurea Compounds/therapeutic use , Adipogenesis , Adipose Tissue, Brown/cytology , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Animals , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/pharmacology , Arachidonic Acids/administration & dosage , Arachidonic Acids/pharmacology , Benzoates/administration & dosage , Benzoates/pharmacology , Blood Glucose/metabolism , Carnitine O-Palmitoyltransferase/metabolism , Diet, High-Fat , Epoxide Hydrolases/antagonists & inhibitors , Fatty Acids/metabolism , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Obesity/etiology , Obesity/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/pharmacology
16.
Front Endocrinol (Lausanne) ; 12: 649405, 2021.
Article in English | MEDLINE | ID: covidwho-1295631

ABSTRACT

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.


Subject(s)
COVID-19/drug therapy , Glucocorticoids/adverse effects , Insulin/therapeutic use , Metabolic Diseases/chemically induced , Metabolic Diseases/prevention & control , COVID-19/complications , Critical Care/methods , Critical Illness/therapy , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Diabetes Complications/diagnosis , Diabetes Complications/drug therapy , Diabetes Complications/mortality , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Glucocorticoids/therapeutic use , Humans , Hyperglycemia/complications , Hyperglycemia/drug therapy , Hyperglycemia/mortality , Metabolic Diseases/etiology , Obesity/complications , Obesity/drug therapy , Obesity/mortality , SARS-CoV-2/physiology , Treatment Outcome
17.
Food Funct ; 12(9): 3799-3819, 2021 May 11.
Article in English | MEDLINE | ID: covidwho-1223115

ABSTRACT

Tea is one of the most consumed beverages around the world and as such, it is constantly the object of novel research. This review focuses on the research performed during the last five years to provide an updated view of the current position of tea regarding human health. According to most authors, tea health benefits can be traced back to its bioactive components, mostly phenolic compounds. Among them, catechins are the most abundant. Tea has an important antioxidant capacity and anti-inflammatory properties, which make this beverage (or its extracts) a potential aid in the fight against several chronic diseases. On the other hand, some studies report the possibility of toxic effects and it is advisable to reduce tea consumption, such as in the last trimester of pregnancy. Additionally, new technologies are increasing researchers' possibilities to study the effect of tea on human gut microbiota and even against SARS CoV-2. This beverage favours some beneficial gut microbes, which could have important repercussions due to the influence of gut microbiota on human health.


Subject(s)
Health Behavior , Plant Extracts/pharmacology , Tea , Antioxidants/analysis , Beverages/analysis , Cardiovascular Diseases/drug therapy , Catechin/analysis , Humans , Hypertension/drug therapy , Obesity/drug therapy , Phenols/analysis , Phytochemicals/pharmacology , Plant Extracts/chemistry
18.
N Engl J Med ; 384(11): 989, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1139778

ABSTRACT

BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).


Subject(s)
Anti-Obesity Agents/administration & dosage , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptides/administration & dosage , Obesity/drug therapy , Adult , Anti-Obesity Agents/adverse effects , Body Composition/drug effects , Body Mass Index , Cholelithiasis/chemically induced , Diarrhea/chemically induced , Double-Blind Method , Female , Glucagon-Like Peptides/adverse effects , Healthy Lifestyle , Humans , Injections, Subcutaneous , Lipids/blood , Male , Middle Aged , Nausea/chemically induced , Obesity/complications , Prediabetic State/complications , Weight Loss/drug effects
19.
PLoS One ; 16(2): e0245394, 2021.
Article in English | MEDLINE | ID: covidwho-1090565

ABSTRACT

BACKGROUND: Due to the wide spread of SARS-CoV2 around the world, the risk of death in individuals with metabolic comorbidities has dangerously increased. Mexico has a high number of infected individuals and deaths by COVID-19 as well as an important burden of metabolic diseases; nevertheless, reports about features of Mexican individuals with COVID-19 are scarce. The aim of this study was to evaluate demographic features, clinical characteristics and the pharmacological treatment of individuals who died by COVID-19 in the south of Mexico. METHODS: We performed an observational study including the information of 185 deceased individuals with confirmed diagnoses of COVID-19. Data were retrieved from medical records. Categorical data were expressed as proportions (%) and numerical data were expressed as mean ± standard deviation. Comorbidities and overlapping symptoms were plotted as Venn diagrams. Drug clusters were plotted as dendrograms. RESULTS: The mean age was 59.53 years. There was a male predominance (60.1%). The mean hospital stay was 4.75 ± 4.43 days. The most frequent symptoms were dyspnea (88.77%), fever (71.42%) and dry cough (64.28%). Present comorbidities included diabetes (60.63%), hypertension (59.57%) and obesity (43.61%). The main drugs used for treating COVID-19 were azithromycin (60.6%), hydroxychloroquine (53.0%) and oseltamivir (27.3%). CONCLUSIONS: Mexican individuals who died of COVID-19 had shorter hospital stays, higher frequency of shortness of breath, and higher prevalence of diabetes than individuals from other countries. Also, there was a high frequency of off-label use of drugs for their treatment.


Subject(s)
Azithromycin/administration & dosage , COVID-19/drug therapy , Diabetes Mellitus, Type 1 , Hospital Mortality , Hydroxychloroquine/administration & dosage , Obesity , Oseltamivir/administration & dosage , SARS-CoV-2 , Adult , Aged , COVID-19/mortality , COVID-19/pathology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/mortality , Diabetes Mellitus, Type 1/pathology , Female , Hospitals , Humans , Length of Stay , Male , Mexico , Middle Aged , Obesity/complications , Obesity/drug therapy , Obesity/mortality , Obesity/pathology , Retrospective Studies , Sex Factors
20.
Eur J Pharmacol ; 898: 173934, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1086916

ABSTRACT

Metformin is the most commonly prescribed oral antidiabetic medication. Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin. Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles. Emerging experimental and clinical evidence suggests that metformin has pleiotropic non-glycemic effects. Metformin appears to have weight stabilising, renoprotective, neuroprotective, cardio-vascular protective, and antineoplastic effects and mitigates polycystic ovarian syndrome. Anti-inflammatory and antioxidant effects of metformin seem to qualify it as an adjunct therapy in treating infectious diseases such as tuberculosis, viral hepatitis, and the current novel Covid-19 infections. So far, metformin is the only prescription medicine relevant to the emerging field of senotherapeutics. Non-glycemic effects of metformin favourable to its repurposing in therapeutic use are hereby discussed.


Subject(s)
Anti-Infective Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Hypoglycemic Agents/therapeutic use , Immunologic Factors/therapeutic use , Metformin/therapeutic use , Protective Agents/therapeutic use , Animals , Anti-Infective Agents/adverse effects , Antineoplastic Agents/adverse effects , COVID-19/drug therapy , COVID-19/epidemiology , Cardiovascular Diseases/prevention & control , Female , Humans , Hypoglycemic Agents/adverse effects , Immunologic Factors/adverse effects , Kidney Diseases/prevention & control , Metabolic Syndrome/drug therapy , Metformin/adverse effects , Obesity/drug therapy , Pandemics , Polycystic Ovary Syndrome/drug therapy , Protective Agents/adverse effects , SARS-CoV-2
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