肤色调控系统和美白产品设计

皮肤颜色的深浅主要是由皮肤中的黑色素含量控制,黑色素含量高,皮肤颜色就深;黑色素含量低,皮肤颜色就浅。黑色素是在黑色细胞中以酪氨酸为原料在酪氨酸酶催化作用下合成,通过黑色素细胞树状突起输送给表皮细胞,含黑色素的表皮细胞在表皮屏障结构修护作用推动下不断向皮肤表面移动,最终从皮肤表面脱落,这就是皮肤自身的肤色调控系统。合理的美白护肤品要在充分了解肤色调控系统作用机理的基础上进行设计,做好防晒工作的同时对皮肤自身调控系统进行合理调控,才有可能在健康基础上实现美白。     

天然免疫激活因子多功能抗衰老生物制剂——天来可GL(Tinocare GL)

介绍了由汽巴公司高科技生物技术制备的纯天然高分子多糖类化合物———天来可ＧＬ, 它具有优异的细胞免疫激活作用, 可有效保护并预防紫外线照射引起的光老化, 刺激皮肤细胞活性, 高效修护皮肤, 加强皮肤的自身免疫保护能力。论述了有关天来可ＧＬ的研究结果并对其在护肤品中应用的适应性、添加方法及建议用量作了介绍。     

植物复合舒缓剂（CAP）对外源性皮肤刺激的保护作用（英文）

作为抵御外部环境的第一道防线,皮肤不仅是一种物理屏障,而且是一种具有多种免疫细胞的免疫器官。这些免疫细胞在不同的皮肤层中组织结构良好,并与非免疫结构细胞（如角质形成细胞）建立通信网络,参与先天和适应性免疫反应,以确保皮肤免疫稳态。通过探讨皮肤免疫反应的起始感知、初始传递、初级效应阶段下不同类型细胞所产生的关键调节剂来研究植物复合舒缓剂（CAP）对外源性皮肤刺激的潜在保护作用及机制。同时,利用三维（3D）重建的人类表皮模型（EpiKutis）来模拟弱屏障下的皮肤免疫反应研究CAP在组织层面的作用。结果显示,在外源性刺激时,关键免疫调节因子如胸腺基质淋巴细胞生成素（TSLP）、白细胞介素-8(IL-8)、前列腺素E2(PGE-2)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)在角质形成细胞、3D EpiKutis模型、THP-1衍生细胞和肥大细胞中含量均显著升高,而CAP同步处理下可显著降低这些因子的表达量。此外,CAP剂量依赖性地改善由Poly(I:C)和LPS诱导导致的丝聚蛋白降低。结果表明,CAP通过促进皮肤屏障修复,调控皮肤免疫反应的起始、传递和效应阶段发挥重要作用。     

天然免疫激活因子多功能抗衰老生物制剂

介绍了由汽巴公司高科技生物技术制备的纯天然高分子多糖类化合物－－天来可ＧＬ，它具有优异的细胞免疫激活作用，可有效保护并预防紫外线照射引起的光老化，刺激皮肤细胞活性高效修护皮肤，加强皮肤的自身免疫保护能力。论述了有关天来可ＧＬ的研究结果并对其在护肤品中应用的适应笥、添加方法及建议用量作了介绍。     

高浓度人参皂苷Rg3的制备及其在化妆品中的应用

通过筛选合适的酸催化剂以及酸含量、水解温度和水解时间，制备了一种富含高浓度人参皂苷Rg3的人参提取物。采用细胞功效模型探究富含高浓度人参皂苷Rg3的人参提取物体外功效作用的同时，结合人体功效评价试验来进一步验证其化妆品领域应用的功效表现。结果表明：优选DL-酒石酸作为酸催化剂，当酸含量为5%，水解温度为80℃，水解时间为2 h时，人参皂苷Rg3的转化效率最高，达到64.91 mg/g。高浓度人参皂苷Rg3的人参提取物的细胞模型评价试验显示出其具有修护H₂O₂氧化应激损伤和抑制TNF-α分泌的作用。同时，结合人体功效评价试验结果来看，高浓度人参皂苷Rg3的人参提取物具有较好的修护皮肤屏障、改善皮肤泛红的功效。     

一款模拟皮肤天然保湿系统的精华水改善敏感性皮肤的临床研究

通过搭配内源性保湿、修护成分,模拟皮肤的天然保湿系统制备一款精华水。筛选35例敏感性皮肤的女性使用产品,每日早晚各1次,连续使用28天,通过无创性定量评价该产品对敏感性皮肤的护理效果。于使用前、使用后28天,对面颊角质层含水量、经表皮失水量、皮肤血红细胞浓度、皮肤表面酸碱度进行评估。研究表明,连续使用产品28天后,皮肤角质层含水量显著性升高38.13%(p<0.001),经皮水分流失量显著性降低20.20%(p<0.001),皮肤血红细胞浓度从181.55±38.87降低至171.90±34.34(p<0.01),乳酸刺痛评分从4.43降至2.83(p<0.01)。此实验过程皮肤维持弱酸性环境,且无任何不良反应发生。综上所述,该精华水适用于敏感性皮肤,可改善皮肤干燥、敏感程度,对皮肤屏障有一定的修护效果。     

透明质酸与癌症的研究进展

透明质(HA)是由D-葡萄糖醛酸和N-乙酰-D-葡糖胺两种单糖重复组成的线性多糖。HA在进化上十分保守并在细胞外基质(ECM)、细胞表面甚至细胞内部大量表达。作为一个简单的多糖,HA具有多种生物学功能,HA与各种蛋白质或糖蛋白组织成ECM维持着组织的动态平衡。HA能与细胞表面受体结合,激活不同的信号转导通路,从而控制着肿瘤的发展和转移。从基质的生物学角度阐述了HA的特性,首先引入HA潜在的生物合成和生物降解原则,接着介绍了HA与多种不同蛋白和蛋白多糖的相互作用,然后阐述了HA在癌症中的作用,以期对HA潜在的生物学功能及作用机制有更深的了解。     

透明质酸与癌症的研究进展

透明质(HA)是由D-葡萄糖醛酸和N-乙酰-D-葡糖胺两种单糖重复组成的线性多糖。HA在进化上十分保守并在细胞外基质(ECM)、细胞表面甚至细胞内部大量表达。作为一个简单的多糖,HA具有多种生物学功能,HA与各种蛋白质或糖蛋白组织成ECM维持着组织的动态平衡。HA能与细胞表面受体结合,激活不同的信号转导通路,从而控制着肿瘤的发展和转移。从基质的生物学角度阐述了HA的特性,首先引入HA潜在的生物合成和生物降解原则,接着介绍了HA与多种不同蛋白和蛋白多糖的相互作用,然后阐述了HA在癌症中的作用,以期对HA潜在的生物学功能及作用机制有更深的了解。     

二裂酵母发酵产物溶胞产物复合物的修护功效研究

采用仿生发酵和无损破壁工艺,从青春双歧杆菌中获得一种二裂酵母发酵产物溶胞产物,通过和甘油,1,2-戊二醇混合后得到原料（BF）,分别采用十二烷基硫酸钠（SLS）损伤模型、面部泛红修护模型,通过检测对照组和样品组使用前、使用后皮肤含水量、经表皮失水率（TEWL）、皮肤红度（a*）、皮肤血管密度的变化,对BF修护功效进行研究。结果表明,3%BF处理7天,TEWL值、a*值相比SLS组均呈现显著性下降,且皮下0.2 mm处的血管密度也呈现减少。在面部泛红的受试者人群上,与对照组相比,使用含3%BF的精华乳28天后,皮肤含水量显著上升,TEWL值、a*值均具有显著性下降。因此,BF具有修护功效,且皮肤多光束光学相干性断层扫描系统可从血管密度上辅助评价皮肤红度。     

植物提取物延缓皮肤光老化作用的研究进展

紫外线是导致皮肤光老化的主要因素,寻找和开发能够有效防护皮肤老化的天然产物已被广泛重视。本文从紫外线对皮肤的损伤以及光老化发生的机理入手,通过吸收紫外线、抗皮肤光氧化、调节细胞外基质合成与降解、抑制色素沉着、缓解皮肤炎症、调节细胞自噬等多种途径,对不同来源的植物提取物及其特征化合物延缓皮肤光老化的作用进行了归纳分析,以期为天然产物在功能性化妆品的开发和应用提供参考。     

Cultivation of Keratinocytes and Fibroblasts in a Three-Dimensional Bovine Collagen-Elastin Matrix (Matriderm?) and Application for Full Thickness Wound Coverage in Vivo

New skin substitutes for burn medicine or reconstructive surgery pose an important issue in plastic surgery. Matriderm^® is a clinically approved three-dimensional bovine collagen-elastin matrix which is already used as a dermal substitute of full thickness burn wounds. The drawback of an avital matrix is the limited integration in full thickness skin defects, depending on the defect size. To further optimize this process, Matriderm^® has also been studied as a matrix for tissue engineering of skin albeit long-term cultivation of the matrix with cells has been difficult. Cells have generally been seeded onto the matrix with high cell loss and minimal time-consuming migration. Here we developed a cell seeded skin equivalent after microtransfer of cells directly into the matrix. First, cells were cultured, and microinjected into Matriderm^®. Then, cell viability in the matrix was determined by histology in vitro. As a next step, the skin substitute was applied in vivo into a full thickness rodent wound model. The wound coverage and healing was observed over a period of two weeks followed by histological examination assessing cell viability, proliferation and integration into the host. Viable and proliferating cells could be found throughout the entire matrix. The presented skin substitute resembles healthy skin in morphology and integrity. Based on this study, future investigations are planned to examine behaviour of epidermal stem cells injected into a collagen-elastin matrix under the aspects of establishment of stem cell niches and differentiation.     

Molecular Mechanisms of Changes in Homeostasis of the Dermal Extracellular Matrix: Both Involutional and Mediated by Ultraviolet Radiation

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. With age, an impairment of structures, quality characteristics, and functions of the dermal extracellular matrix (ECM) occurs in the skin, which leads to disrupted functioning of dermal fibroblasts (DFs), the main cells supporting morphofunctional organization of the skin. The DF functioning directly depends on the state of the surrounding collagen matrix (CM). The intact collagen matrix ensures proper adhesion and mechanical tension in DFs, which allows these cells to maintain collagen homeostasis while ECM correctly regulates cellular processes. When the integrity of CM is destroyed, mechanotransduction is disrupted, which is accompanied by impairment of DF functioning and destruction of collagen homeostasis, thereby contributing to the progression of aging processes in skin tissues. This article considers in detail the processes of skin aging and associated changes in the skin layers, as well as the mechanisms of these processes at the molecular level.     

Structural and Functional Changes and Possible Molecular Mechanisms in Aged Skin

Skin aging is a complex process influenced by intrinsic and extrinsic factors. Together, these factors affect the structure and function of the epidermis and dermis. Histologically, aging skin typically shows epidermal atrophy due to decreased cell numbers. The dermis of aged skin shows decreased numbers of mast cells and fibroblasts. Fibroblast senescence contributes to skin aging by secreting a senescence-associated secretory phenotype, which decreases proliferation by impairing the release of essential growth factors and enhancing degradation of the extracellular matrix through activation of matrix metalloproteinases (MMPs). Several molecular mechanisms affect skin aging including telomere shortening, oxidative stress and MMP, cytokines, autophagic control, microRNAs, and the microbiome. Accumulating evidence on the molecular mechanisms of skin aging has provided clinicians with a wide range of therapeutic targets for treating aging skin.     

Simultaneous isolation of keratinocytes and fibroblasts from a human cutaneous biopsy for the production of autologous reconstructed skin

The key step In the reconstruction of skin by the self‐assembly approach is to use fibroblasts capable of secreting a mature extracellular matrix and keratinocytes that can associate with one another to form a stratified, differentiated epidermis. To determine the most efficient way to extract both cell types from a single cutaneous biopsy, five different enzymatic combinations were tested. The yield, viability and morphology of the recuperated cells were compared. The length and temperature of the enzymatic treatments influenced the number and the type of cells recuperated. The cells were then cultured in appropriate media in monolayers and reconstructed skin were produced using the self‐assembly approach. No difference was observed between the different strains of cells.     

新型胶原基人工皮肤模型的建立

根据皮肤的组织结构与生理功能,研制了复合天然三维网络结构胶原组织工程支架材料,并以此为支架材料建立了3层结构的人工皮肤模型:上层是具有良好生物相容性且可降解的聚合物涂层,可以屏蔽细菌并保持人工皮肤良好的透水气性;中间是复合型天然三维网络结构胶原纤维支架材料层,为细胞的增殖提供三维空间和良好的生长环境,起到真皮基质的作用;下层是药物层,具有营养、抗菌消炎、刺激细胞生长的作用。     

Age-Related Changes in the Fibroblastic Differon of the Dermis: Role in Skin Aging

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been revealed that the amount of fibroblasts decreases markedly with age and their functional activity is also reduced. This inevitably leads to a decrease in the regenerative abilities of the skin and the progression of its aging. In this review we consider the mechanisms underlying these processes, mainly the changes observed with age in the stem/progenitor cells that constitute the fibroblastic differon of the dermis and form their microenvironment (niches). These changes lead to the depletion of stem cells, which, in turn, leads to a decrease in the number of differentiated (mature) dermal fibroblasts responsible for the production of the dermal extracellular matrix and its remodeling. We also describe in detail DNA damages, their cellular and systemic consequences, molecular mechanisms of DNA damage response, and also the role of fibroblast senescence in skin aging.     

The Methoxyflavonoid Isosakuranetin Suppresses UV-B-Induced Matrix Metalloproteinase-1 Expression and Collagen Degradation Relevant for Skin Photoaging

Solar ultraviolet (UV) radiation is a main extrinsic factor for skin aging. Chronic exposure of the skin to UV radiation causes the induction of matrix metalloproteinases (MMPs), such as MMP-1, and consequently results in alterations of the extracellular matrix (ECM) and skin photoaging. Flavonoids are considered as potent anti-photoaging agents due to their UV-absorbing and antioxidant properties and inhibitory activity against UV-mediated MMP induction. To identify anti-photoaging agents, in the present study we examined the preventative effect of methoxyflavonoids, such as sakuranetin, isosakuranetin, homoeriodictyol, genkwanin, chrysoeriol and syringetin, on UV-B-induced skin photo-damage. Of the examined methoxyflavonoids, pretreatment with isosakuranetin strongly suppressed the UV-B-mediated induction of MMP-1 in human keratinocytes in a concentration-dependent manner. Isosakuranetin inhibited UV-B-induced phosphorylation of mitogen-activated protein kinase (MAPK) signaling components, ERK1/2, JNK1/2 and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of isosakuranetin on UV-induced MMP-1 production in human keratinocytes. Isosakuranetin also prevented UV-B-induced degradation of type-1 collagen in human dermal fibroblast cells. Taken together, our findings suggest that isosakuranetin has the potential for development as a protective agent for skin photoaging through the inhibition of UV-induced MMP-1 production and collagen degradation.     

Alteration of Skin Properties with Autologous Dermal Fibroblasts

Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.     

A combined chemico-mineralogical and tensiometric approach for evaluation of Euganean Thermal Mud (ETM) quality

The tensiometric vs. skin approach (TVS modelling®) is a non-invasive method based on the permutability principle of tensiometry. TVS modelling® is a technologic model that can evaluate the reproducibility of the matrix of thermal mud, its degree of maturation and consequently its skin affinity, in a non-destructive way. This is an essential pre-condition for defining the objective scientific protocols. The surface energy profile of the matrixes is created by a Tenskinmeter®, a tensiometer modified by us for tensiometric measurements on skin. The development of a chemico-mineralogical index (I _chmi) based on X-ray fluorescence analysis allows the typical chemico-mineralogical constituents of thermal muds to be determined. The combined TVS-I _chmi approach developed here demonstrates the interconnections between the typical chemico-mineralogical components of a Euganean Thermal Mud (ETM) and its energy surface properties. The combined approach also demonstrates the interconnections at the interface between I _chmi and the skin affinity of the mud matrix, revealing their typical functional and therapeutic effects.     

Design,Development, and Delivery of Salbutamol Sulfate from an Adhesive Matrix System

The objective of the present investigation was to design, develop, and evaluate the skin delivery of salbutamol sulfate from a drug-in-adhesive matrix type transdermal patch formulation. Initial formulation design and development experiments were conducted to optimize the formulation parameters before skin delivery in rats. The effects of two different types of pressure sensitive adhesives and permeation enhancers on skin transport of salbutamol sulfate across excised rat skin were investigated methodically. For ex-vivo skin permeation studies, the percutaneous absorption of salbutamol sulfate from a drug-in-adhesive matrix patch across excised rat skin were evaluated using a modified Franz-diffusion cell apparatus at a skin temperature (32°C). Further the fabricated adhesive matrix patches were also characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction study, and differential scanning calorimetry analyses. Drug containing adhesive matrix patches showed sustained release property without showing any incompatibility in adhesive matrix system. This suggests that the transdermal application of salbutamol sulfate in a drug-in-adhesive matrix type transdermal patch may be used for the treatment for asthma patients.