forrás: https://pubmed.ncbi.nlm.nih.gov/32550253/
2021-01-06 09:52:44
The COVID-19 pandemic demands the rapid identification of drug-repurpusing candidates. In the past decade, network medicine had developed a framework consisting of a series of quantitative approaches and predictive tools to study host-pathogen interactions, unveil the molecular mechanisms of the infection, identify comorbidities as well as rapidly detect drug repurpusing candidates. Here, we adapt the network-based toolset to COVID-19, recovering the primary pulmonary manifestations of the virus in the lung as well as observed comorbidities associated with cardiovascular diseases. We predict that the virus can manifest itself in other tissues, such as the reproductive system, and brain regions, moreover we predict neurological comorbidities. We build on these findings to deploy three network-based drug repurposing strategies, relying on network proximity, diffusion, and AI-based metrics, allowing to rank all approved drugs based on their likely efficacy for COVID-19 patients, aggregate all predictions, and, thereby to arrive at 81 promising repurposing candidates. We validate the accuracy of our predictions using drugs currently in clinical trials, and an expression-based validation of selected candidates suggests that these drugs, with known toxicities and side effects, could be moved to clinical trials rapidly.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/23639291
2015-02-17 16:34:43
Myocardial ischemia (MI) remains one of the leading causes of death worldwide. Angiogenic therapy with the vascular endothelial growth factor (VEGF) is a promising strategy to overcome hypoxia and its consequences. However, from the clinical data it is clear that fulfillment of the potential of VEGF warrants a better delivery strategy. On the other hand, the compelling evidences of the role of oxidative stress in diseases like MI encourage the use of antioxidant agents. Coenzyme Q10 (CoQ10) due to its role in the electron transport chain in the mitochondria seems to be a good candidate to manage MI but is associated with poor biopharmaceutical properties seeking better delivery approaches. The female Sprague Dawley rats were induced MI and were followed up with VEGF microparticles intramyocardially and CoQ10 nanoparticles orally or their combination with appropriate controls. Cardiac function was assessed by measuring ejection fraction before and after three months of therapy. Results demonstrate significant improvement in the ejection fraction after three months with both treatment forms individually; however the combination therapy failed to offer any synergism. In conclusion, VEGF microparticles and CoQ10 nanoparticles can be considered as promising strategies for managing MI.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/24461311
2015-02-17 14:32:03
Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease-associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor-κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management.
Copyright © 2014 Elsevier Inc. All rights reserved.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/16507316
2014-10-28 13:42:48
Prevention of cardiovascular disease through nutritional supplements is growing in popularity throughout the world. Multiple epidemiologic studies found that moderate consumption of alcohol, particularly red wine, lowers mortality rates from coronary heart diseases (CHD). Chronic inflammation and atherosclerosis associated with CHD culminate in aberrant intravascular expression of tissue factor (TF), which triggers blood coagulation leading to thrombosis, a major cause for heart attack. We showed earlier that two red wine phenolics, resveratrol and quercetin, suppressed TF induction in endothelial cells. In the present study, we investigated efficacy of seven resveratrol derivatives, which were shown to be effective in regulating cancer cell growth in vitro at much lower concentrations than the parent compound resveratrol, in inhibiting TF induction in peripheral blood mononuclear cells (PBMCs). We also tested possible synergistic effects of resveratrol and quercetin with the other major red wine phenolics in suppression of lipopolysaccharide-induced TF expression in human PBMCs. We found that several resveratrol derivatives were 2- to 10-fold more efficient than resveratrol in inhibiting TF induction. Our study found no evidence for synergism among red wine polyphenolics. These data suggest that structural alterations of resveratrol can be effective in producing potent antithrombotic agents that will have therapeutic potential in the improvement of cardiovascular health and prevention of CHD. Among major red wine phenolics, quercetin appears to be the predominant suppressor of TF induction.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/23639291
2015-02-17 16:34:43
Simón-Yarza T1, Tamayo E, Benavides C, Lana H, Formiga FR, Grama CN, Ortiz-de-Solorzano C, Kumar MNProsper FBlanco-Prieto MJ
Információk a szerzőről
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1Gyógyszerészeti és Gyógyszerészeti Technológiai Szak, Gyógyszerészeti Iskola, Navarrai Egyetem, Pamplona, Spanyolország.
Kivonat
Világszerte a szívizomzati ischemia (MI) marad a vezető halálok. Az angiogén (ér eredetű) terápia vaszkuláris (véredény-) belhám növekedési faktor (VEGF) egy ígéretes stratégia, hogy le lehessen győzni a hypoxiát (oxigénhiány) és annak következményeit. A klinikai adatokból azonban világos, hogy a lehetséges VEGF elvégzése jobb kivitelezési stratégiát tud biztosítani. Másrészt az oxidatív stressz kényszerítő bizonyítékai az olyan betegségekben, mint az MI, arra bátorítanak, hogy antioxidáns hatóanyagokat használjunk. A Coenzyme Q10 (CoQ10) szerepénél fogva, mellyel részt vesz az elektrontovábbító láncban a mitokondriumban, jó jelöltnek tűnik, hogy felügyelje az MI-t, bár gyenge bio-gyógyszerészeti tulajdonságokkal bír, és jobb közvetítői megközelítést kell keresni hozzá. A Sprague Dawley nőstény patkányoknál MI-t indítottak be, amit VEGF mikrorészecskés kezelés követett miokardiálisan (a szívizomba adva), majd CoQ10 nano-részecskéket kaptak szájon keresztül, vagy pedig ezek kombinációját a megfelelő kontroll alatt. Szívfunkciójukat begyűjtötték a kivetési frakció mérésével, három hónappal a terápia előtt és után. Az eredmények azt mutatják, hogy jelentős javulás mutatkozott a frakció kidobásában három hónappal mindkét fajta kezelés után három hónappal, egyénileg; ám a kombinált gyógymód sikertelen volt bármiféle szinergikus (kölcsönös) lehetőség nyújtásában. Következésképpen a VEGF mikro-részecskéket és a CoQ10 nano-részecskéket ígéretes stratégiának lehet tekinteni az MI kezelésében.
