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Topical Applications of Thiosulfinate-Enriched Allium sativum Extract Accelerates Acute Cutaneous Wound Healing in Murine Model

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Chinese Journal of Integrative Medicine 2020年第11期26卷 812-818页

作者： Juan Luis Santiago eva maria galan-moya Jose Ramon Munoz-Rodriguez Miguel Angel de la Cruz-Morcillo Francisco Javier Redondo-Calvo Ignacio Gracia-Fernandez Peter M.Elias Jose Manuel Perez-Ortiz Mao-Qiang Man Dermatology Service Hospital General Universitario de Ciudad RealCiudad Real(13004)Spain Translational Research Unit Hospital General Universitario de Ciudad RealCiudad Real(13004)Spain Translational Oncology Laboratory Centro Regional de Investigaciones BiomedicasUniversidad de Castilla-La ManchaAlbacete(02008)Spain Instituto de Tecnologia Quimica y Medioambiental Universidad de Castilla-La ManchaCiudad Real(13004)Spain Dermatology Service Vetera ns Affairs Medical Centerand Department of DermatologyUniversity of CaliforniaSan FranciscoCA(94121)USA Dermatology Hospital Southern Medical UniversityGuangzhou(510091)China

Objective To determine whether topical applications of thiosulfinate-enriched Allium sativum extract(TASE)can accelerate acute cutaneous wound healing(WH)in a murine *** Keratinocyte viability and in vitro wound closure were assessed in keratinocyte *** of topical TASE(0.5μg/mL of allicin in 97%ethanol)on acute cutaneous WH were determined in a murine model of acute cutaneous *** mice were alternately assigned to the vehicle-and TASE-treated groups(n=6 per group).Expression levels of mRNA for keratinocyte differentiation marker-related proteins(filaggrin,loricrin and involucrin)and lipid synthetic enzymes(elongation of very long chain fatty acids protein 4(ELOVL4),fatty acid synthase(FA2H),3-hydroxy-3-methyl-glutaryl-coenzyme A reductase(HMGCoA),and serine palmitoyltransferase(SPT))were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding,while transepidermal water loss(TEWL)rates were measured in wounded *** TASE accelerated WH both in vivo(40%vs.22%reduction in wound area,P<0.01)and in vitro(90%vs.65%reduction in wound area,P<0.01).Moreover,topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4,HMGCoA,SPT,filaggrin,loricrin and involucrin(P<0.05 ***-treated controls)on day 3 after ***,TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8(33.06±2.09 g/(m^2·h)vs.24.60±2.04 g/(m^2·h),P<0.01).Conclusions Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function,leading to acceleration of acute cutaneous *** products containing TASE could be used to manage acute cutaneous WH.

关键词： Allium sativum thiosulfinate wound healing permeability barrier keratinocytes proliferation

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PKR and PP1C Polymorphisms in Alzheimer’s Disease Risk

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Neuroscience & Medicine 2011年第3期2卷 226-231页

作者： Ernest Palomer Gerard ILL-Raga Marta Tajes eva Ramos-Fernández Mònica Bosch-Morató Biuse Guivernau Jose J.galan Jordi Clarimon Carmen Antunez Merce Boada Luis M.Real César Fandos Francisco J.Munoz Laboratory of Molecular Physiology and Channelopathies Department of Experimental and Health SciencesPompeu Fabra University(UPF)BarcelonaSpain NeoCodex SevillaSpain Alzheimer Laboratory Neurology DepartmentSanta Creu and Sant Pau HospitalBiomedical Research Center on Neurodegenerative Diseases(CIBERNED)BarcelonaSpain Fundacion Alzheimur Dementia UnitVirgen de la Arrixaca HospitalMurciaSpain Memory Clinic of ACE Foundation Catalan Institute of Applied NeurosciencesBarcelonaSpain Neurology Department Vall d’Hebron Universitary HospitalBarcelonaSpain

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by senile plaques and neurofibrillary tangles. Senile plaques are deposits of amyloid ?-peptide (A?) produced by the cleavage of a transmembrane protein termed Amyloid Precursor Protein (APP). The amyloidogenic cleavage of APP is performed by γ-secretase complex and ?-site APP cleaving enzyme 1 (BACE1), a key enzyme in AD that can be activated by different noxious stimuli. Interestingly, some viruses could activate double-stranded RNA-activated protein kinase (PKR), which phosphorylates Eukaryotic Initiation Factor 2 alpha (eIF2α). This phosphorylation stops global translation to avoid any synthesis of viral infective proteins, but paradoxically up-regulates BACE1 translation. One of the viral mechanisms to circumvent eIF2α phosphorylation is the recruitment of protein phosphatase 1 (PP1), to fully dephosphorylate eIF2α and allow viral protein synthesis. Due to the functional relationship between BACE1, PKR, PP1 and AD we have performed a large (1122 cases and 1191 control individuals) case-control genetic analysis using two biallelic polymorphisms rs2254958 and rs7480390, located within the genes coding for PKR and the catalytic unit A of PP1, respectively. Although a trend to association of the rs2254958 TT genotype with AD risk was found, our results show that neither rs7480390 nor rs2254958 are associated with AD susceptibility.

关键词： Alzheimer’s Disease BACE1 PKR PP1 eIF2α

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