Bioavailability and Cardiometabolic Effects of Xanthohumol: Evidence from Animal and Human Studies

Az agyérbetegségek jelentőségét jelzi, hogy a cardiovascularis és tumoros betegségek után a stroke jelenti a harmadik leggyakoribb halálokot világszerte. Mivel stroke során az érintett agyállomány irreverzíbilisen károsodik, az infarktust övező épen maradt, de általában hipoperfundált agyterületek működésének serkentésével lehet a betegek állapotán javítani. Az agyi véráramlás növelése révén várható javulás a stroke-on még át nem esett, de krónikus agyi hipoperfúzióban szenvedő betegek tüneteiben is. Célkitűzés, módszer: Jelen tanulmány célja, hogy áttekintse a vinpocetin akut és krónikus agyérbetegségekben történő alkalmazásának eddig publikált humán vizsgálati eredményeit, és összefoglaló képet adjon a gyógyszer főbb indikációs területeiről, az ott mutatott hatékonyságról. Eredmények: A vinpocetin akut ischaemiás stroke-ban történő alkalmazását vizsgáló tanulmányok száma csekély, eredményeik pedig ellentmondásosak. Krónikus agyérbetegek esetében mind az egyszeri, mind a hosszú távú vinpocetinkezelést követően PET-, SPECT-, TCD- és NIRS-vizsgálatokkal a laesio körüli ép agyterületek perfúziónövekedése, fokozott glükóz- és O 2 -felhasználása igazolódott, és jelentős javulás volt észlelhető a vér reológiai paramétereiben is. A klinikai hatékonyságot értékelő nemzetközi tanulmányok metaanalízise alapján a gyógyszer per os alkalmazásával szignifikáns javulás jelentkezik a kognitív teljesítményben és a napi aktivitásban. Következtetések: A fenti vizsgálatok eredményei alapján kimondható, hogy a vinpocetin sokrétű farmakológiai hatása révén kedvezően befolyásolja az agy ép területeinek perfúzióját és metabolizmusát, a vér áramlási viszonyait, javítva ezzel a krónikus agyérbetegek életminőségét.

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Effects of Probiotics in the Management of Infected Chronic Wounds: From Cell Culture to Human Studies

Current Clinical Pharmacology ◽

10.2174/1574884714666191111130630 ◽

2020 ◽

Vol 15 (3) ◽

pp. 193-206

Author(s):

Brognara Lorenzo ◽

Salmaso Luca ◽

Mazzotti Antonio ◽

Di M. Alberto ◽

Faldini Cesare ◽

...

Keyword(s):

Chronic Wounds ◽

Animal Experiments ◽

Multidrug Resistant ◽

Preliminary Evidence ◽

Human Studies ◽

In Vivo Studies ◽

Resistant Bacteria ◽

Keywords Probiotics

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

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Protective Effect of Isothiocyanates from Cruciferous Vegetables on Breast Cancer: Epidemiological and Preclinical Perspectives

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200924104550 ◽

2020 ◽

Vol 20 ◽

Author(s):

Suong N.T. Ngo ◽

Desmond B. Williams

Keyword(s):

Breast Cancer ◽

Protective Effect ◽

Animal Studies ◽

Cancer Survival ◽

Breast Cancer Survival ◽

Human Studies ◽

In Vitro Studies ◽

Cochrane Library ◽

Cruciferous Vegetables

Background: The effect of cruciferous vegetable intake on breast cancer survival is controversial at present. Glucosinolates are the naturally occurring constituents found across the cruciferous vegetables. Isothiocyanates are produced from the hydrolysis of glucosinolates and this reaction is catalysed by the plant-derived enzyme myrosinase. The main isothiocyanates (ITCs) from cruciferous vegetables are sulforaphane, benzyl ITC, and phenethyl ITC, which had been intensively investigated over the last decade for their antibreast cancer effects. Objective: The aim of this article is to systematically review the evidence from all types of studies, which examined the protective effect of cruciferous vegetables and/or their isothiocyanate constituents on breast cancer. Methods: A systematic review was conducted in Pubmed, EMBASE, and the Cochrane Library from inception to 27 April 2020. Peerreviewed studies of all types (in vitro studies, animal studies, and human studies) were selected. Results: The systematic literature search identified 16 human studies, 4 animal studies, and 65 in vitro studies. The effect of cruciferous vegetables and/or their ITCs intake on breast cancer survival was found to be controversial and varied greatly across human studies. Most of these trials were observational studies conducted in specific regions, mainly in the US and China. Substantial evidence from in vitro and animal studies was obtained, which strongly supported the protective effect of sulforaphane and other ITCs against breast cancer. Evidence from in vitro studies showed sulforaphane and other ITCs reduced cancer cell viability and proliferation via multiple mechanisms and pathways. Isothiocyanates inhibited cell cycle, angiogenesis and epithelial mesenchymal transition, as well as induced apoptosis and altered the expression of phase II carcinogen detoxifying enzymes. These are the essential pathways which promote the growth and metastasis of breast cancer. Noticeably, benzyl ITC showed a significant inhibitory effect on breast cancer stem cells, a new dimension of chemoresistance in breast cancer treatment. Sulforaphane and other ITCs displayed anti-breast cancer effects at variable range of concentrations and benzyl isothiocyanate appeared to have a relatively smallest inhibitory concentration IC50. The mechanisms underlying the cancer protective effect of sulforaphane and other ITCs have also been highlighted in this article. Conclusion: Current preclinical evidence strongly supports the role of sulforaphane and other ITCs as potential therapeutic agents for breast cancer, either as adjunct therapy or combined therapy with current anti-breast cancer drugs, with sulforaphane appeared to display the greatest potential.

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Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

Journal of Diabetes Research ◽

10.1155/2020/8492467 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17 ◽

Cited By ~ 1

Author(s):

Ricardo Pereira-Moreira ◽

Elza Muscelli

Keyword(s):

Glucose Transport ◽

Insulin Action ◽

Current Knowledge ◽

Sglt2 Inhibitor ◽

Proximal Tubules ◽

Human Studies ◽

Glucose Disposal ◽

Diabetic Patients ◽

Insulin Effect ◽

Renal Gluconeogenesis

Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. Method. A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). Summary of Results. Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; in vivo human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with Na+K+ATPase activity impacting on glucose transport. Conclusion. Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.

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Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

Journal of Translational Medicine ◽

10.1186/s12967-021-02878-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Kei Hayashida ◽

Ryosuke Takegawa ◽

Muhammad Shoaib ◽

Tomoaki Aoki ◽

Rishabh C. Choudhary ◽

...

Keyword(s):

Systematic Review ◽

Reperfusion Injury ◽

Animal Studies ◽

Ischemia Reperfusion Injury ◽

Myocardial Dysfunction ◽

Ischemia Reperfusion ◽

Meta Analysis ◽

Relevant Literature ◽

Human Studies ◽

Cochrane Library

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

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Present and Future Prospects for Using Alternatives to Chimpanzees in Research

Alternatives to Laboratory Animals ◽

10.1177/026119299502300515 ◽

1995 ◽

Vol 23 (5) ◽

pp. 634-641

Author(s):

Gill Langley

Keyword(s):

Hepatitis C ◽

Human Studies ◽

Future Prospects ◽

Hepatitis C Infection ◽

Ethical Concerns ◽

Human Volunteers ◽

Different Types

Three chimpanzee studies of hepatitis C infection were found to be duplicative of each other and of research with human volunteers. Research into taste neurophysiology also used chimpanzees, although data which are highly relevant (but less specific) can be obtained from human studies. The use of chimps to study benzene metabolism was found to be poorly planned and unjustifiable. Scientifically, chimps are not always the best “models” for humans, and their use raises insurmountable ethical concerns. Many alternatives are already available, but researchers will need to adjust their perspectives on the usefulness of different types of data.

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Could α-Klotho Unlock the Key Between Depression and Dementia in the Elderly: from Animal to Human Studies

Molecular Neurobiology ◽

10.1007/s12035-021-02313-0 ◽

2021 ◽

Author(s):

Xiang Gao ◽

Yuhong Li ◽

Zuoli Sun ◽

Hong Xu ◽

Guangwei Ma ◽

...

Keyword(s):

The Elderly ◽

Human Studies

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Oxidative stress in phenylketonuria—evidence from human studies and animal models, and possible implications for redox signaling

Metabolic Brain Disease ◽

10.1007/s11011-021-00676-w ◽

2021 ◽

Vol 36 (4) ◽

pp. 523-543

Author(s):

Vanessa Trindade Bortoluzzi ◽

Carlos Severo Dutra Filho ◽

Clovis Milton Duval Wannmacher

Keyword(s):

Oxidative Stress ◽

Animal Models ◽

Redox Signaling ◽

Human Studies

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The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, l-carnitine and related precursors by the human gut microbiota

European Journal of Nutrition ◽

10.1007/s00394-021-02572-6 ◽

2021 ◽

Author(s):

Priscilla Day-Walsh ◽

Emad Shehata ◽

Shikha Saha ◽

George M. Savva ◽

Barbora Nemeckova ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Human Colon ◽

Human Studies ◽

Bacterial Strains ◽

Increased Risk ◽

Carnitine Metabolism ◽

Registration Number ◽

Vitro Model

Abstract Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods TMA production from choline, l-carnitine, betaine and γ-butyrobetaine was studied over 24–48 h using an in-vitro human colon model with metabolite quantification performed using LC–MS. Results Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline–betaine-TMA route, conversion of l-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for l-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. Conclusion The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. Trial registration number NCT02653001 (http://www.clinicaltrials.gov), registered 12 Jan 2016.

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The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies

Cell ◽

10.1016/j.cell.2021.06.002 ◽

2021 ◽

Author(s):

Richard Copin ◽

Alina Baum ◽

Elzbieta Wloga ◽

Kristen E. Pascal ◽

Stephanie Giordano ◽

...

Keyword(s):

Monoclonal Antibody ◽

Human Studies

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