Contact sensitization: A new approach to risk assessment

The murine local lymph node assay is a novel predictive test for the identification of skin sensitizing chemicals. The method measures sensitization potential of a chemical in mice as a function of proliferative activity induced in lymph nodes draining the site of topical exposure to that test chemical. Here we describe the use of the local lymph node assay for evaluation of the relative potency of skin sensitizing chemicals via derivation of the concentration required to produce a threshold positive reaction. Subsequently, the development of risk assessments based on comparisons with index contact allergens is outlined.     

镰刀菌所致皮肤感染的文献回顾

镰刀菌主要为植物致病菌,但也可引起严重人类感染。镰刀菌病临床表现形式多样,本文主要综述相关的皮肤感染,分为局限性皮肤感染及播散性感染,诊断多较困难。由于该属真菌对抗真菌药物存在天然耐药,播散性镰刀菌病死亡率可达80%-90%。本文对Medline和中文文献数据库中的相关文献进行了系统查阅和分析,综合归纳了镰刀菌所致皮肤感染的致病种、地域分布、危险因子、临床表现形式、药物敏感性及其诊疗方案等,该综述对全面了解镰刀菌病的特征及对临床医师对本病的诊断具有重要的意义。     

Mesenchymal stromal cell‐derived factors promote the colonization of collagen 3D scaffolds with human skin cells

The development of stem cell technology in combination with advances in biomaterials has opened new ways of producing engineered tissue substitutes. In this study, we investigated whether the therapeutic potential of an acellular porous scaffold made of type I collagen can be improved by the addition of a powerful trophic agent in the form of mesenchymal stromal cells conditioned medium (MSC‐CM) in order to be used as an acellular scaffold for skin wound healing treatment. Our experiments showed that MSC‐CM sustained the adherence of keratinocytes and fibroblasts as well as the proliferation of keratinocytes. Moreover, MSC‐CM had chemoattractant properties for keratinocytes and endothelial cells, attributable to the content of trophic and pro‐angiogenic factors. Also, for the dermal fibroblasts cultured on collagen scaffold in the presence of MSC‐CM versus serum control, the ratio between collagen III and I mRNAs increased by 2‐fold. Furthermore, the gene expression for α‐smooth muscle actin, tissue inhibitor of metalloproteinase‐1 and 2 and matrix metalloproteinase‐14 was significantly increased by approximately 2‐fold. In conclusion, factors existing in MSC‐CM improve the colonization of collagen 3D scaffolds, by sustaining the adherence and proliferation of keratinocytes and by inducing a pro‐healing phenotype in fibroblasts.     

Mouse genetics identifies unique and overlapping functions of fibroblast growth factor receptors in keratinocytes

Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused fibroblast activation and fibrosis in the FGFR1/FGFR2 double‐knockout mice and even more in mice lacking all three FGFRs, revealing functional redundancy of FGFR3 with FGFR1 and FGFR2 for maintaining the epidermal barrier. Taken together, our study demonstrates that FGFR1, FGFR2 and FGFR3 act together to maintain epidermal integrity and cutaneous homeostasis, with FGFR2 being the dominant receptor.     

不同术前皮肤准备方案与手术切口感染的关系研究

目的:研究不同术前皮肤准备方案与手术切口感染(SSI)的关系,为降低临床SSI发生率提供参考。方法:选择自2015年1月～2019年12月在医院行手术治疗的患者1810例为本次研究对象。根据析因设计表,将因素A:是否剃毛(1不剃毛;2剃毛),B:清洁方式(1清水清洁;2肥皂水清洁),C:术前备皮时间(1术前1 d;2术前2 h)配对分为8个组:A1B1C1组226例,A1B2C1组229例,A1B1C2组216例,A1B2C2组232例,A2B1C1组221例,A2B2C1组241例,A2B1C2组221例,A2B2C2组224例,比较各组手术部位及切口类型分布、术后SSI发生率,并采用析因分析法分析术前皮肤准备后各组菌落计数的相关性及交互作用。结果:各组患者的手术部位及切口类型之间的差异不存在统计学意义(P0.05)。A1B1C1组及A2B1C1组的SSI发生率较高,分别为12.83%和14.48%。A1水平的SSI发生率是8.75%,与A2水平的8.27%相比,差异不存在统计学意义(P0.05)。B1、C1水平的SSI发生率分别是11.31%、10.03%,明显高于B2、C2水平的5.83%、6.94%,差异均存在统计学意义(P0.05)。各组术前皮肤准备后的菌落计数差异存在统计学意义(P0.05),析因分析结果显示,B、C单因素分析差异存在统计学意义(P0.05),且A与C,B与C间具有交互作用,而A、B、C间具有二级交互作用(P0.05)。结论:术前皮肤准备对降低SSI发生具有重要作用,实际操作时,建议在较短的时间内利用肥皂水或其他消毒水进行皮肤清洗并完成备皮。     

Neuroendocrinology and neurobiology of sebaceous glands

The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro‐regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α‐melanocyte‐stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro‐autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin‐mediated or facial paresis‐associated reduction of human sebum secretion suggests that cutaneous nerve‐derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.     

Epidermal keratin 5 expression and distribution is under dermal influence

Human skin melanin pigmentation is regulated by systemic and local factors. According to the type of melanin produced by melanocytes, the transfer and degradation of melanosomes differ, thus accounting for most variations between ethnicities. We made the surprising observation that in a drastically changed environment, white and black phenotypes are reversible since Caucasian skin grafted onto nude mice can become black with all black phenotypic characteristics. Black xenografts differed essentially from other grafts by the levels of epidermal FGF‐2 and keratin 5. In vitro analysis confirmed that FGF‐2 directly regulates keratin 5. Interestingly, this phenomenon may be involved in human pathology. Keratin 5 mutations in Dowling–Degos Disease (DDD) have already been associated with the pheomelanosome–eumelanosome transition. In a DDD patient, keratin 5 was expressed in the basal and spinous layers, as observed in black xenografts. Furthermore, in a common age‐related hyperpigmentation disorder like senile lentigo (SL), keratin 5 distribution is also altered. In conclusion, modulation of keratin 5 expression and distribution either due to mutations or factors may account for the development of pigmentary disorders.     

Environmental influences on and antimicrobial activity of the skin microbiota of Proceratophrys boiei (Amphibia,Anura) across forest fragments

The composition of the skin microbiota of amphibians is related to the biology of host species and environmental microbial communities. In this system, the environment serves as a microbial source and can modulate the hosted community. When habitats are fragmented and the environment disturbed, changes in the structure of this microbial community are expected. One important potential consequence of fragmentation is a compromised protective function of the microbiota against pathogenic microorganisms. In this study, the skin microbiota of the amphibian Proceratophrys boiei was characterized, evaluated for relationships with environmental variables and environmental sources of microbial communities, and its diversity evaluated for frog populations from fragmented and continuous forests. In addition, the antimicrobial activity of this skin community was studied in frogs from both forest types. Culture methods and 16S rRNA high‐throughput gene sequencing were used to characterize the microbial community and demonstrated that the skin microbiota of P. boiei is more closely related to the soil microbial communities than those inhabiting water bodies or fragment matrix, the unforested area around the forested fragment. The microbial diversity and abundance of P. boiei skin microbiota are different between continuous forests and fragments. This community is correlated with environmental variables, especially with temperature of microhabitat and distance to human dwelling. All individuals of P. boiei harbored bacteria capable of inhibiting the growth of pathogenic bacteria and different strains of the pathogenic fungus Batrachochytrium dendrobatidis, and a total of 27 bacterial genera were detected. The results of this study indicate that the persistence of populations of this species will need balanced and sustained interactions among host, microorganisms, and environment.