Agent-Based Model of Therapeutic Adipose-Derived Stromal Cell Trafficking during Ischemia Predicts Ability To Roll on P-Selectin

Intravenous delivery of human adipose-derived stromal cells (hASCs) is a promising option for the treatment of ischemia. After delivery, hASCs that reside and persist in the injured extravascular space have been shown to aid recovery of tissue perfusion and function, although low rates of incorporation currently limit the safety and efficacy of these therapies. We submit that a better understanding of the trafficking of therapeutic hASCs through the microcirculation is needed to address this and that selective control over their homing (organ- and injury-specific) may be possible by targeting bottlenecks in the homing process. This process, however, is incredibly complex, which merited the use of computational techniques to speed the rate of discovery. We developed a multicell agent-based model (ABM) of hASC trafficking during acute skeletal muscle ischemia, based on over 150 literature-based rules instituted in Netlogo and MatLab software programs. In silico, trafficking phenomena within cell populations emerged as a result of the dynamic interactions between adhesion molecule expression, chemokine secretion, integrin affinity states, hemodynamics and microvascular network architectures. As verification, the model reasonably reproduced key aspects of ischemia and trafficking behavior including increases in wall shear stress, upregulation of key cellular adhesion molecules expressed on injured endothelium, increased secretion of inflammatory chemokines and cytokines, quantified levels of monocyte extravasation in selectin knockouts, and circulating monocyte rolling distances. Successful ABM verification prompted us to conduct a series of systematic knockouts in silico aimed at identifying the most critical parameters mediating hASC trafficking. Simulations predicted the necessity of an unknown selectin-binding molecule to achieve hASC extravasation, in addition to any rolling behavior mediated by hASC surface expression of CD15s, CD34, CD62e, CD62p, or CD65. In vitro experiments confirmed this prediction; a subpopulation of hASCs slowly rolled on immobilized P-selectin at speeds as low as 2 µm/s. Thus, our work led to a fundamentally new understanding of hASC biology, which may have important therapeutic implications

Atopic dermatitis and vitamin D: facts and controversies

Patients with atopic dermatitis have genetically determined risk factors that affect the barrier function of the skin and immune responses that interact with environmental factors. Clinically, this results in an intensely pruriginous and inflamed skin that allows the penetration of irritants and allergens and predisposes patients to colonization and infection by microorganisms. Among the various etiological factors responsible for the increased prevalence of atopic diseases over the past few decades, the role of vitamin D has been emphasized. As the pathogenesis of AD involves a complex interplay of epidermal barrier dysfunction and dysregulated immune response, and vitamin D is involved in both processes, it is reasonable to expect that vitamin D's status could be associated with atopic dermatitis' risk or severity. Such association is suggested by epidemiological and experimental data. in this review, we will discuss the evidence for and against this controversial relationship, emphasizing the possible etiopathogenic mechanisms involved.Univ Brasilia UNB, Brasilia, DF, BrazilFed Dist Hlth State Dept SES DF, Brasilia, DF, BrazilUniv Brasilia HUB UNB, Brasilia Univ Hosp, Brasilia, DF, BrazilSão Paulo Fed Univ UNIFESP, Brasilia, DF, BrazilSão Paulo Fed Univ UNIFESP, Brasilia, DF, BrazilWeb of Scienc

Yam: a neglected and underutilized crop in Brazil Inhame: uma cultura negligenciada e subutilizada no Brasil

In Brazil current studies and investments on yams are incipient. Similarly, the literature in recent decades lacks adequate information on this group of plants. The existing literature, on its turn, requires more than ever to be revised and organized. Yams have joined the so-called "neglected" group of crops for several reasons, but particularly because they are associated with poor and traditional communities. Many vegetables introduced in Brazil during the colonization period have adapted to different cropping systems, yams being an excellent example. This diversity resulted very widespread, yet poorly recognized in the country. In turn, the gardens using traditional farming systems continue to maintain and enhance yam local varieties. Studies from other countries, with an emphasis on characterization and genetic breeding, brought to light an urgent need for Brazil to invest in yams as a food rich in carbohydrates, even to the point of alterations in food public policy. Reversal of the yam's current stigma is both a challenge to the scientific community and to the population as a whole. This paper aims to raise pertinent questions about Dioscorea species, an important key group for many communities in tropical countries, yet still unrecognized as so in Brazil.<br>No Brasil, estudos e investimentos ao inhame são incipientes. Similarmente, a literatura nas últimas décadas apresenta informações insuficientes para este grupo de plantas. A literatura existente, por sua vez, exige mais que nunca ser revisada e organizada. O inhame tem-se unido ao grupo de culturas ditas "negligenciadas" por diversas razões, mas particularmente devido ao fato de estar associado às comunidades pobres e tradicionais. Muitos vegetais introduzidos no Brasil durante o período da colonização têm-se adaptado a diferentes sistemas de cultivo, sendo o inhame um excelente exemplo. Esta diversidade é resultado de uma ampla dispersão, ainda pouco conhecida no país. Por sua vez, as roças usam o sistema de agricultura tradicional de forma a manter e aumentar as variedades locais de inhame. Estudos de outros países, com ênfase na caracterização e melhoramento genético, trouxeram à luz uma necessidade urgente de o Brasil investir em inhame como uma rica fonte de carboidratos, mesmo apesar das mudanças na política alimentar pública. Reverter o atual estigma do inhame é um duplo desafio para a comunidade científica e população como um todo. Este artigo objetiva-se a trazer questões pertinentes sobre as espécies do gênero Dioscorea, um importante grupo para muitas comunidades em países tropicais, contudo ainda pouco conhecido no Brasil