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Integrated Network Pharmacology Analysis and Experimental Validation to Reveal the Mechanism of Anti-Insulin Resistance Effects of Moringa oleifera Seeds.
Huang, Q, Liu, R, Liu, J, Huang, Q, Liu, S, Jiang, Y
Drug design, development and therapy. 2020;:4069-4084
Abstract
BACKGROUND AND PURPOSE Insulin resistance (IR) is one of the factors that results in metabolic syndrome, type 2 diabetes mellitus and different aspects of cardiovascular diseases. Moringa oleifera seeds (MOS), traditionally used as an antidiabetic food and traditional medicine in tropical Asia and Africa, have exhibited potential effects in improving IR. To systematically explore the pharmacological mechanism of the anti-IR effects of MOS, we adopted a network pharmacology approach at the molecular level. METHODS By incorporating compound screening and target prediction, a feasible compound-target-pathway network pharmacology model was established to systematically predict the potential active components and mechanisms of the anti-IR effects of MOS. Biological methods were then used to verify the results of the network pharmacology analysis. RESULTS Our comprehensive systematic approach successfully identified 32 bioactive compounds in MOS and 44 potential targets of these compounds related to IR, as well as 37 potential pathways related to IR. Moreover, the network pharmacology analysis revealed that glycosidic isothiocyanates and glycosidic benzylamines were the major active components that improved IR by acting on key targets, such as SRC, PTPN1, and CASP3, which were involved in inflammatory responses and insulin-related pathways. Further biological research demonstrated that the anti-IR effects of MOS were mediated by increasing glucose uptake and modulating the expression of SRC and PTPN1. CONCLUSION Our study successfully predicts the active ingredients and potential targets of MOS for improving IR and helps to illustrate mechanism of action at a systemic level. This study not only provides new insights into the chemical basis and pharmacology of MOS but also demonstrates a feasible method for discovering potential drugs from traditional medicines.
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β-Glucan Metabolic and Immunomodulatory Properties and Potential for Clinical Application.
Murphy, EJ, Rezoagli, E, Major, I, Rowan, NJ, Laffey, JG
Journal of fungi (Basel, Switzerland). 2020;(4)
Abstract
β-glucans are complex polysaccharides that are found in several plants and foods, including mushrooms. β-glucans display an array of potentially therapeutic properties. β-glucans have metabolic and gastro-intestinal effects, modulating the gut microbiome, altering lipid and glucose metabolism, reducing cholesterol, leading to their investigation as potential therapies for metabolic syndrome, obesity and diet regulation, gastrointestinal conditions such as irritable bowel, and to reduce cardiovascular and diabetes risk. β-glucans also have immune-modulating effects, leading to their investigation as adjuvant agents for cancers (solid and haematological malignancies), for immune-mediated conditions (e.g., allergic rhinitis, respiratory infections), and to enhance wound healing. The therapeutic potential of β-glucans is evidenced by the fact that two glucan isolates were licensed as drugs in Japan as immune-adjuvant therapy for cancer in 1980. Significant challenges exist to further clinical testing and translation of β-glucans. The diverse range of conditions for which β-glucans are in clinical testing underlines the incomplete understanding of the diverse mechanisms of action of β-glucans, a key knowledge gap. Furthermore, important differences appear to exist in the effects of apparently similar β-glucan preparations, which may be due to differences in sources and extraction procedures, another poorly understood issue. This review will describe the biology, potential mechanisms of action and key therapeutic targets being investigated in clinical trials of β-glucans and identify and discuss the key challenges to successful translation of this intriguing potential therapeutic.
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Ramadan intermittent fasting and immunity: An important topic in the era of COVID-19.
Faris, MAE, Salem, ML, Jahrami, HA, Madkour, MI, BaHammam, AS
Annals of thoracic medicine. 2020;(3):125-133
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Abstract
WITH the growing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) infection, a parallel growing interest arose concerning potential preventive and adjunct therapies, dietary and lifestyle modifications, and remedies that may boost the immunity against SARS-CoV-2 infection. Furthermore, as Ramadan intermittent religious fasting that is practiced by about one and a half billion Muslims throughout the globe is coincide this year with COVID-19 pandemic, a growing debate rose concerning the expected impact of fasting during Ramadan month and the associated dietary and lifestyle behaviors on the body's immunity against the pandemic infection. Published literature was searched to find out how intermittent fasting (IF) and its model of Ramadan affect the various aspects related to the body's immunity against microbial infections. IF was found to impact immunity by changing different related elements, including oxidative stress and inflammation, metabolism, body weight, and body composition. Dietary and lifestyle modifications during Ramadan month and their impact on immunity, such as water intake and hydration status, sleep duration and timing, caloric intake and mealtime, and social and spirtual activities, were addressed. Further research is warranted to figure out how IF during ramadan affects immunity against SARS-CoV-2 infection.
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Rationale and study design for lifestyle intervention in preparation for pregnancy (LIPP): A randomized controlled trial.
Erickson, ML, Mey, JT, Axelrod, CL, Paul, D, Gordesky, L, Russell, K, Barkoukis, H, O'Tierney-Ginn, P, Fielding, RA, Kirwan, JP, et al
Contemporary clinical trials. 2020;:106024
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Abstract
INTRODUCTION Maternal obesity increases neonatal risk for obesity and metabolic syndrome later in life. Prior attempts to break this intergenerational obesity cycle by limiting excessive gestational weight gain have failed to reduce neonatal adiposity. Alternatively, pre-conception lifestyle interventions may improve the in utero metabolic milieu during early pregnancy leading to improved fetal outcomes. This randomized controlled trial (RCT) is evaluating whether a lifestyle intervention to reduce weight and improve maternal metabolism in preparation for pregnancy (LIPP) attenuates neonatal adiposity, compared to standard medical advice. MATERIAL AND METHODS Overweight/class 1 obese women after a previous pregnancy, ~12 weeks postpartum, preparing for a subsequent pregnancy, will be block randomized (1:1) to either LIPP or standard of care in a parallel design. Randomization is stratified by lactation status and overweight vs. class 1 obesity. The LIPP program consists of intensive short-term weight loss followed by weight maintenance until conception using supervised exercise and a low glycemic Mediterranean diet. PRIMARY OUTCOMES Group differences in neonatal adiposity at birth assessed by PEA POD and placental mitochondrial lipid metabolism. SECONDARY OUTCOMES Group differences in maternal pregravid and gestational body composition, insulin sensitivity, β-cell function, fasting metabolic and inflammatory biomarkers, and overall quality of life. Exploratory outcomes include umbilical cord blood insulin resistance, lipid profile and inflammation. DISCUSSION This RCT will determine the efficacy of maternal weight loss prior to pregnancy on reducing neonatal adiposity. Findings may change standard obstetrical care by providing Level 1 evidence on lifestyle interventions improving neonatal outcomes for women planning for pregnancy. CLINICAL TRIAL REGISTRATION NCT03146156.
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What about glucocorticoids in primary Sjögren's syndrome?
Priori, R, Mastromanno, L, Izzo, R
Clinical and experimental rheumatology. 2020;(4):237-244
Abstract
Glucocorticoids (GCs) are involved in several physiological processes such as metabolism, water and electrolyte balance, growth, cardiovascular and cognitive functions, reproduction. Furthermore, they exert different effects on innate and adaptive immune cells. Due to their anti-inflammatory and immunosuppressive functions, these drugs are largely used for the treatment of inflammatory and autoimmune diseases. In comparison to other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to date no reliable evidence is available for the use of systemic GCs in Sjögren's syndrome (SS), which is still based on case reports, case studies, retrospective or prospective studies and a small number of randomised controlled trials (RCTs). Despite this gap in our knowledge, GCs are commonly used in SS for glandular, joint, cutaneous, lung, haematological, renal, neurological involvement. More recently, some sets of recommendations for the management of SS have provided a few pieces of advice regarding the use of GCs in this condition. Future studies should not neglect the role of GCs, as this traditional therapeutic weapon can still have a role in the management of SS. Accordingly, this review will address and discuss the use of systemic GCs in isolated or primary SS.
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Mindfulnes-Based Stress Reduction for Older Couples with Metabolic Syndrome: a Pilot Randomized Controlled Trial.
Monin, JK, Sperduto, CM, Manigault, AW, Dutton, A, Ali, A, Clark, MS, Jastreboff, AM
Mindfulness. 2020;(4):917-927
Abstract
OBJECTIVE We examined the feasibility and explored the physical, psychological, relational, and biological effects of Mindfulness-Based Stress Reduction (MBSR), an 8-week standardized mindfulness program, involving older married couples (60 years or older) with metabolic syndrome (one or both partners had metabolic syndrome). We also explored gender differences. METHODS A pilot randomized controlled trial (RCT) compared MBSR to a Wait List Control (WLC) arm at baseline, post-intervention, and 3-month follow-up clinic visits. Twenty-two spouses (11 couples) self-reported stress, physical and mental functioning, mindfulness, and relationship satisfaction at each time point. Fasting glucose, cholesterol, triglycerides, blood pressure, weight, and waist circumference were measured. MBSR couples answered questions about partner influences on participation, adherence, and practice at the post-intervention visit. RESULTS In terms of adherence to MBSR sessions, four of the six couples attended all 10 sessions; one couple attended 7; and one wife attended 6 and her husband attended 5 sessions. In terms of efficacy, there were no significant intervention effects; however, there were significant gender by intervention effects. Pre- to post-intervention, MBSR wives displayed greater increases in physical functioning (β = 1.18, t(36) = 3.17, p = .003) and relationship satisfaction (β = .72, t(36) = 2.81, p = .007) than WLC wives. Effects for husbands were not significant. Qualitatively, participants reported encouragement and increased relationship closeness. CONCLUSIONS Engaging in MBSR as a couple to address symptoms of metabolic syndrome was well-received and feasible. Preliminary effects suggest more benefits for wives than husbands in terms of physical functioning and relational well-being.
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Does intestinal dysbiosis contribute to an aberrant inflammatory response to severe acute respiratory syndrome coronavirus 2 in frail patients?
Terruzzi, I, Senesi, P
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110996
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Abstract
In a few months, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become the main health problem worldwide. Epidemiologic studies revealed that populations have different vulnerabilities to SARS-CoV-2. Severe outcomes of the coronavirus disease 2019 (COVID-19) with an increased risk of death are observed in patients with metabolic syndrome, as well as diabetic and heart conditions (frail population). Excessive proinflammatory cytokine storm could be the main cause of increased vulnerability in this frail population. In patients with diabetes and/or heart disease, a low inflammatory state is often associated with gut dysbiosis. The increase amount of microbial metabolites (i.e., trimethylamine N-oxide and lipopolysaccharide), which generate an inflammatory microenvironment, is probably associated with an improved risk of severe illness from COVID-19. Nutritional interventions aimed at restoring the gut microbial balance could represent preventive strategies to protect the frail population from COVID-19. This narrative review presents the possible molecular mechanisms by which intestinal dysbiosis that enhances the inflammatory state could promote the spread of SARS-CoV-2 infection. Some nutritional strategies to counteract inflammation in frail patients are also analyzed.
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Non-linear relationship between sleep duration and metabolic syndrome: A population-based study.
Fan, L, Hao, Z, Gao, L, Qi, M, Feng, S, Zhou, G
Medicine. 2020;(2):e18753
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The aims of this study were to evaluate the prevalence of metabolic syndrome (MetS) and explore the association between sleep duration and MetS. This study enrolled 8 272 adults aged 18 years and older from 6 urban and 8 rural areas during 2013 to 2014in Henan China. Participants were interviewed about demographic characteristics, lifestyle factors and medical history, and physical measurements were performed. The relationships between sleep duration and MetS were evaluated and plotted by Restricted Cubic Spline Regression. The mean age was 51.5 years (SD 14.2) and 4 916 (59.4%) were female. The crude prevalence of MetS was 30.3% and the age-standardized rate was 23.6%. Men were more likely to have MetS than women (P = .01). MetS was positively associated with age, education, smoking, drinking, BMI and sleep duration, and seemed irrelevant to occupation and sedentary behavior. In terms of individual component of MetS, high blood pressure was the most prevalent component for both men and women, while the lowest prevalent was high triglycerides in men and for women was low high-density lipoprotein cholesterol (HDL-C). There was a U-shaped relationship between sleep duration and MetS and its components. Sleep duration <6 hours or >9 hours were associated with higher risk of MetS (OR from 1.10 to 2.15). The MetS was prevalent, and more than half of total adult population was suffering from high blood pressure. Sleep duration may be a determinant of metabolic health. Both short (<6 hours) and long sleep duration (>9 hours) was linked to an increased risk of MetS.
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The potential role of sesquiterpene lactones isolated from medicinal plants in the treatment of the metabolic syndrome - A review.
Salazar-Gómez, A, Ontiveros-Rodríguez, JC, Pablo-Pérez, SS, Vargas-Díaz, ME, Garduño-Siciliano, L
South African journal of botany : official journal of the South African Association of Botanists = Suid-Afrikaanse tydskrif vir plantkunde : amptelike tydskrif van die Suid-Afrikaanse Genootskap van Plantkundiges. 2020;:240-251
Abstract
Metabolic syndrome comprises a cluster of metabolic disorders related to the development of cardiovascular disease and type 2 diabetes mellitus. In latter years, plant secondary metabolites have become of special interest because of their potential role in preventing and managing metabolic syndrome. Sesquiterpene lactones constitute a large and diverse group of biologically active compounds widely distributed in several medicinal plants used for the treatment of metabolic disorders. The structural diversity and the broad spectrum of biological activities of these compounds drew significant interests in the pharmacological applications. This review describes selected sesquiterpene lactones that have been experimentally validated for their biological activities related to risk factors of metabolic syndrome, together with their mechanisms of action. The potential beneficial effects of sesquiterpene lactones discussed in this review demonstrate that these substances represent remarkable compounds with a diversity of molecular structure and high biological activity, providing new insights into the possible role in metabolic syndrome management.
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Beyond the CNS: The many peripheral roles of APOE.
Martínez-Martínez, AB, Torres-Perez, E, Devanney, N, Del Moral, R, Johnson, LA, Arbones-Mainar, JM
Neurobiology of disease. 2020;:104809
Abstract
Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with demonstrated roles across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.