Influencing factors and strategies of enhancing nanoparticles into tumors in vivo

The administration of nanoparticles (NPs) first faces the challenges of evading renal filtration and clearance of reticuloendothelial system (RES). After that, NPs infiltrate through the expanded endothelial space and penetrated the dense stroma of tumor microenvironment to tumor cells. As long as possible to prolong the time of NPs remaining in tumor tissue, NPs release active agent and induce pharmacological action. This review provides a comprehensive summary of the physical and chemical properties of NPs and the influence of various biological factors in tumor microenvironment, and discusses how to improve the final efficacy through adjusting the characteristics and structure of NPs. Perspectives and future directions are also provided.     

服用硝苯地平后牙龈增生以及未增生患者牙龈成纤维细胞生物特性比较

目的：观察服用硝苯地平后牙龈增生和未增生患者牙龈成纤维细胞（nifedipine responders gingival fibro-blasts NIFr-HGF,nifedipine non-responders gingival fibroblasts NIFn-HGF）超微结构、细胞周期变化以及增殖能力的差异性,以探讨该药导致牙龈增生的可能作用机理。方法：采用透射电镜观察NIFr-HGF、NIFn-HGF的超微结构,利用流式细胞仪、MTT法检测和比较2种细胞经硝苯地平诱导后其细胞周期以及增殖能力的差异性。结果：与NIFn-HGF相比较,NIFr-HGF内粗面内质网扩张;受硝苯地平诱导后其增殖明显加强。结论：NIFr-HGF合成蛋白质的能力可能较NIFn-HGF强,且前者对于硝苯地平的反应也明显强于后者,这提示两类细胞的细胞生物学特性以及对钙离子拮抗剂的反应能力存在差异,药物性牙龈增生的发生可能存在细胞异质性。     

苦味药材性状分析

苦味是中药药性理论的重要组成部分。不同的物质组成影响着药材性状,也影响着药材性味。选取《中华本草》所载1 728种寒热药性明确的中药,运用数学统计方法,研究了中药苦味与药材性状的关系,认为药材质地、气味、味道、外观颜色共同影响着中药苦味。药材性状质脆、味苦或味涩越多的中药,药材性味越偏向苦味;药材性状气香、味甘、味咸、味辛和白色越多的中药,药材性味越远离苦味。     

Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture

The dermis can be divided into two morphologically different layers: the papillary and reticular dermis. Fibroblasts isolated from these layers behave differently when cultured in vitro. During skin ageing, the papillary dermis decreases in volume. Based on the functional differences in vitro, it is hypothesized that the loss of papillary fibroblasts contributes to skin ageing. In this study, we aimed to mimic certain aspects of skin ageing by using high‐passage cultures of reticular and papillary fibroblasts and investigated the effect of these cells on skin morphogenesis in reconstructed human skin equivalents. Skin equivalents generated with reticular fibroblasts showed a reduced terminal differentiation and fewer proliferating basal keratinocytes. Aged in vitro papillary fibroblasts had increased expression of biomarkers specific to reticular fibroblasts. The phenotype and morphology of skin equivalents generated with high‐passage papillary fibroblasts resembled that of reticular fibroblasts. This demonstrates that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. Therefore, we hypothesize that papillary fibroblasts represent an undifferentiated phenotype, while reticular fibroblasts represent a more differentiated population. The differentiation process could be a new target for anti‐skin‐ageing strategies.     

Serum levels of interleukin‐1α in patients with systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune systemic connective tissue disorder characterized by sclerotic change of the skin and multiple internal organs. Although the pathogenesis of this disorder is still unknown, overproduction of extracellular matrix proteins, including collagens and fibronectin, and aberrant immune activation may be involved in the mechanism. Interleukin (IL)‐1 is one of the key regulators of inflammatory response. IL‐1 is also involved in regulating connective tissue remodeling and cellular differentiation of epithelial and ectodermal cells. There are three major members of the IL‐1 family: IL‐1α, IL‐1β and IL‐1 receptor antagonist. IL‐1α was first described as a factor derived from keratinocytes that stimulates thymocyte proliferation. IL‐1α plays a crucial role in procollagen production by fibroblasts derived from patients with SSc. The present study was undertaken to investigate the serum levels of IL‐1α in patients with SSc. Serum samples were obtained from 66 Japanese patients with SSc and 19 healthy controls. Levels of serum IL‐1α were measured with a specific enzyme‐linked immunoassay kit. Mean serum levels were significantly higher in SSc patients than in those healthy control subjects. Moreover, contracture of phalanges was found at a significantly lower prevalence in SSc patients with elevated serum IL‐1α levels than those with normal levels. These results suggest that IL‐1α may play a role in the pathogenesis of SSc.     

Microenvironment and tumor cell plasticity: An easy way out

Cancer cells undergo genetic changes allowing their adaptation to environmental changes, thereby obtaining an advantage during the long metastatic route, disseminated of several changes in the surrounding environment. In particular, plasticity in cell motility, mainly due to epigenetic regulation of cancer cells by environmental insults, engage adaptive strategies aimed essentially to survive in hostile milieu, thereby escaping adverse sites. This review is focused on tumor microenvironment as a collection of structural and cellular elements promoting plasticity and adaptive programs. We analyze the role of extracellular matrix stiffness, hypoxia, nutrient deprivation, acidity, as well as different cell populations of tumor microenvironment.     

Generation of full‐thickness skin equivalents using hair follicle‐derived primary human keratinocytes and fibroblasts

Skin equivalents are increasingly used as human‐based test systems for basic and preclinical research. Most of the established skin equivalents are composed of primary keratinocytes and fibroblasts, isolated either from excised human skin or juvenile foreskin following circumcisions. Although the potential of hair follicle‐derived cells for the generation of skin equivalents has been shown, this approach normally requires microdissections from the scalp for which there is limited subject compliance or ethical approval. In the present study, we report a novel method to isolate and cultivate keratinocytes and fibroblasts from plucked hair follicles that were then used to generate skin equivalents. The procedure is non‐invasive, inflicts little‐pain, and may allow easy access to patient‐derived cells without taking punch biopsies. Overall, minor differences in morphology, ultrastructure, expression of important structural proteins, or barrier function were observed between skin equivalents generated from hair follicle‐derived or interfollicular keratinocytes and fibroblasts. Interestingly, improved basal lamina formation was seen in the hair follicle‐derived skin equivalents. The presented method here allows easy and non‐invasive access to keratinocytes and fibroblasts from plucked hair follicles that may be useful particularly for the generation of skin disease equivalents.