forrás: http://www.ncbi.nlm.nih.gov/pubmed/24691430
2014-10-28 13:24:22
A kalória korlátozás [caloric restriction – CR] anélkül, hogy alultápláltságot eredményezne, növeli a kilátásokat a hosszú életre és késlelteti az öregedéssel összefüggő rendellenességeket a rövid élettartamú fajoknál, az egysejtű szervezetektől a laboratóriumi egerekig és patkányokig. A kalória korlátozás (CR) – mint az emberi öregedés megértésének eszköze – előnye, hogy a kalória korlátozás főemlősökre gyakorolt hatásainak az alakíthatóságán alapul. Jelen esetben azt mutatjuk be, hogy majmok esetében hosszú távon, fiatal felnőtt kortól alkalmazott ~30%-al csökkentett étrend alkalmazásával a kalória korlátozás jelentős mértékben növeli a korral összefüggő és az egyéb okoknak betudható élethossz növekedését. Ezek az adatok ellentmondanak a NIA [National Institute on Aging - Nemzeti Öregedéskutató Intézet] 2012-es belső tanulmányában szereplő megfigyeléseknek, ahol az élethossz növekedését illetően nem állapítottak meg különbséget a kalória csökkentett táplálkozású majmok és a kontroll csoport majmai között. Egy összehasonlítás - mindkét tanulmányból a kontroll állatok testsúlyának egymással, valamint főemlősök öregedésére vonatkozó multicentrikus* adatbázisokból összegyűjtött adatokkal történő összevetése - azt mutatja, hogy az NIA kontroll majmait ténylegesen kalória korlátozásnak vetették alá. Adataink azt mutatják, hogy a kalória korlátozások az öregedésre gyakorolt jótékony hatásai megőrződnek a főemlősöknél.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/24691430
2014-10-28 13:24:22
Restricţia calorică (CR) fără malnutriţie creşte longevitatea şi întârzie declanşarea afecţiunilor asociate îmbătrânirii, la speciile cu durată scurtă de viaţă, începând cu organismele unicelulare şi până la şoarecii şi şobolanii de laborator. Valoarea lui CR ca instrument pentru a înţelege îmbătrânirea constă în faptul că pot fi translatate la oameni efectele pe care CR le are la primate. Aici noi arătăm că CR îmbunătăţeşte semnificativ supravieţuirea la maimuţe, atât legat de îmbătrânire cât şi de toate celelalte cauze de mortalitate, prin dietă restrictivă de aprox 30%, pe termen lung, începută din etapa de tânăr adult. Aceste date sunt în contradicţie cu observaţiile din raportul studiului intern al NIA din 2012, unde nu s-a detectat nici o diferenţă în ceea ce priveşte rata de supravieţuire între maimuţele hrănite normal pentru control şi cele cu CR. O comparaţie a greutăţii corporale la grupurile de control din ambele studii, pusă faţă în faţă cu datele colectate într-o bază de date aflată în relaţie cu mai multe centre, referitoare la îmbătrânirea primatelor, sugerează că maimuţele din grupa de control a NIA erau de fapt sub incidenţa CR. Datele noastre indicând beneficiile CR asupra îmbătrânirii la primate se păstrează.
forrás: https://app.dimensions.ai/details/publication/pub.1125450507
2021-01-22 10:57:07
In the new millennium, the outbreak of new coronavirus has happened three times: SARS-CoV, MERS-CoV, and 2019-nCoV. Unfortunately, we still have no pharmaceutical weapons against the diseases caused by these viruses. The pandemic of 2019-nCoV reminds us of the urgency to search new drugs with totally different mechanism that may target the weaknesses specific to coronaviruses. Herein, we disclose a new targeted oxidation strategy (TOS II) leveraging non-covalent interactions potentially to oxidize and inhibit the activities of cytosolic thiol proteins via thiol/thiolate oxidation to disulfide (TOD). Quantum mechanical calculations show encouraging results supporting the feasibility to selectively oxidize thiol of targeted proteins via TOS II even in relatively reducing cytosolic microenvironments. Molecular docking against the two thiol proteases Mpro and PLpro of 2019-nCoV provide evidence to support a TOS II mechanism for two experimentally identified anti-2019-nCoV disulfide oxidants: disulfiram and PX-12. Remarkably, disulfiram is an anti-alcoholism drug approved by FDA 70 years ago, thus it can be immediately used in phase III clinical trial for anti-2019-nCoV treatment. Finally, a preliminary list of promising TOS II drug candidates targeting the two thiol proteases of 2019-nCoV are proposed upon virtual screening of 32143 disulfides
forrás: http://medpublics.com/docs/tripartite_combination.pdf
2021-01-21 10:16:25
Abstract: Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (VDR; GATA5; SFTPC; HIF1a) and activators (HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, Biomedicines 2020, 8, 129; doi:10.3390/biomedicines8050129 www.mdpi.com/journal/biomedicines Biomedicines 2020, 8, 129 2 of 26 namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website
forrás: http://medpublics.com/docs/HUchoquenet2008.pdf
2017-07-11 10:33:40
Overexposure to ultraviolet radiation can cause skin damage. This can be immediate and long-term, with effects ranging from sunburn and premature wrinkling to carcinogenesis.
1–3
Sunscreens have been used for many years on exposed areas to protect the skin from the damaging effects of ultraviolet light. Although sunscreens are essential, some have adverse effects such as estrogenic activity
full text: http://medpublics.com/docs/choquenet2008.pdf
