Functional Genomics Unique to Week 20 Post Wounding in the Deep Cone/Fat Dome of the Duroc/Yorkshire Porcine Model of Fibroproliferative Scarring

Background: Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete.Methodology/Principal Findings: We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc( pigmented fibroproliferative)/Yorkshire( non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model.Conclusions/Significance: 1) the scars are still thick at forty-six weeks post wounding further validating the model. 2) the differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) the findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. in the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.The National Institute on Disability and Rehabilitation ResearchThe National Institutes of HealthThe Washington State Council of Fire Fighters Burn FoundationThe Northwest Burn FoundationUniv Washington, Dept Surg, Div Plast Surg, Seattle, WA 98195 USAIowa State Univ, Dept Anim Sci, Ames, IA USAUniv Washington, Dept Biostat, Seattle, WA 98195 USAMahidol Univ, Ramathibodi Hosp, Dept Surg, Bangkok 10700, ThailandUniv Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USAUniversidade Federal de São Paulo, Div Plast Surg, Dept Surg, São Paulo, BrazilUniversidade Federal de São Paulo, Div Plast Surg, Dept Surg, São Paulo, BrazilThe National Institute on Disability and Rehabilitation Research: H133G050022The National Institutes of Health: 1R21GM074673The National Institutes of Health: 5U54GM062119-09Web of Scienc

Mulberry leaves and their potential effects against cardiometabolic risks: a review of chemical compositions, biological properties and clinical efficacy

Context: Cardiometabolic risks are regarded as the crucial factors associated with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an increased attention to medicinal plants in the current healthcare system, the effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have been consecutively considered in scientific research. Objective: The present review compiles and summarizes the chemical compositions, biological properties and clinical efficacy of mulberry leaves that are related to the amelioration of cardiometabolic risks. Methods: Published English literature from the PubMed, Science Direct and Google Scholar databases was searched by using ‘mulberry leaves’ ‘Morus spp.’, ‘hyperglycemia’, ‘hyperlipidemia’, ‘obesity’, ‘hypertension’, ‘oxidative stress’, ‘atherosclerosis’ and ‘cardiovascular diseases’ as the keywords. The relevant articles published over the past two decades were identified and reviewed. Results: Mulberry leaves contain numerous chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the prominent functional compounds. Preclinical and clinical studies showed that mulberry leaves possessed various beneficial effects against cardiometabolic risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity, antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and cardioprotective effects. Conclusions: Mulberry leaves could be a promising therapeutic option for modulating cardiometabolic risks. However, further investigations should be performed to substantiate the potential of mulberry leaves in practical uses