ReproCELL (United Kingdom)

Polycystic ovarian syndrome (PCOS) has been recognized as the most prevalent endo-crine-metabolic disorder in women of reproductive age. As it is a polygenic disorder; multiple genes determining PCOS susceptibility have been identified, including the FSHR gene. In this study, the susceptibility of 3 SNPs to PCOS in the FSHR gene was evaluated in a sample of Colombian women. The study included 49 patients and 49 participants in the control group. Allelic discrimination was performed by iPLEX and the MassARRAY system (Agena Bioscience). In addition to the PCOS risk analysis, a genotype-phenotype analysis, and a linkage disequilibrium (LD) analysis were performed in PCOS women. No associations were found between SNPs in FSHR and the risk of PCOS. It was identified that rs2268361 was associated with low FSH levels, high LH, and post-glucose levels. Associations with younger menarche were identified in rs2349415, and associations with high levels of TSH, and low levels of E2 were found in rs11692782. SNPs rs2349415 and rs11692782 showed a strong LD. No differences were observed in the distribution of haplotypes between groups. This exploratory study provides preliminary results that can be used for future research with a larger sample size and adequate statistical power.

㈱ヘミセルロース（神奈川県川崎市）は，樹木・植物の構成成分であるヘミセルロースおよびセルロースを原料に，独自の「抽出～化学合成～混練・ペレット化～成形」の一貫製造技術を駆使して開発した生分解性バイオプラスチック「HEMIXTM」の実用化を進めている。

Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal compartments, which limits their application. We describe advances in the field skin tissue modeling to produce a construct containing sensory-like neurons that is responsive to known noxious stimuli. Through incorporation of mammalian sensory-like neurons, we were able to recapitulate aspects of the neuroinflammatory response including secretion of substance P and a range of pro-inflammatory cytokines in response to a well-characterized neurosensitizing agent: capsaicin. We observed that neuronal cell bodies reside in the upper dermal compartment with neurites extending toward the keratinocytes of the stratum basale where they exist in close proximity to one another. These data suggest that we are able to model aspects of the neuroinflammatory response that occurs during exposure to dermatological stimuli including therapeutics and cosmetics. We propose that this skin construct can be considered a platform technology with a wide range of applications including screening of actives, therapeutics, modeling of inflammatory skin diseases, and fundamental approaches to probe underlying cell and molecular mechanisms.

Human skin ageing is a complex and heterogeneous process, which is influenced by genetically determined intrinsic factors and accelerated by cumulative exposure to extrinsic stressors. In the current world ageing demographic, there is a requirement for a bioengineered ageing skin model, to further the understanding of the intricate molecular mechanisms of skin ageing, and provide a distinct and biologically relevant platform for testing actives and formulations. There have been many recent advances in the development of skin models that recapitulate aspects of the ageing phenotype in vitro. This review encompasses the features of skin ageing, the molecular mechanisms that drive the ageing phenotype, and tissue engineering strategies that have been utilised to bioengineer ageing skin in vitro.

Abstract The calcium-activated chloride channel TMEM16A enables chloride secretion across several transporting epithelia, including in the airway where it represents a therapeutic target for the treatment of cystic fibrosis. Additional roles for TMEM16A have also been proposed, including enhancing goblet cell exocytosis, increasing goblet cell numbers and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, both potentiation and inhibition, could affect any of these proposed biological roles.In vitro, a recently described potent and selective TMEM16A potentiator (ETX001) failed to stimulate mucin release from primary human bronchial epithelial (HBE) cells over a 24h exposure period using both biochemical and imaging endpoints. In addition, treatment of HBE cells with ETX001 or a potent and selective TMEM16A inhibitor (Ani9) for 4 days did not influence mucin release or goblet cell formation. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 driven goblet cell metaplasia model.Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats.Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response.

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