Skin, as the outermost organ in the human body, continuously confronts the external environment and serves as a primary defense system. The protective functions of skin include UV-protection, anti-oxidant and antimicrobial functions. In addition to these protections, skin also acts as a sensory organ and the primary regulator of body temperature. Within these important functions, the epidermal permeability barrier, which controls the transcutaneous movement of water and other electrolytes, is probably the most important. This permeability barrier resides in the stratum corneum, a resilient layer composed of corneocytes and stratum corneum intercellular lipids. Since the first realization of the structural and biochemical diversities involved in the stratum corneum, a tremendous amount of work has been performed to elucidate its roles and functions in the skin, and in humans in general. The perturbation of the epidermal permeability barrier, previously speculated to be just a symptom involved in skin diseases, is currently considered to be a primary pathophysiologic factor for many skin diseases. In addition, much of the evidence provides support for the idea that various protective functions in the skin are closely related or even co-regulated. In this review, the recent achievements of skin researchers focusing on the functions of the epidermal permeability barrier and their importance in skin disease, such as atopic dermatitis and psoriasis, are introduced.
*Skin Physiology ; Skin Diseases/*metabolism/physiopathology ; Skin/*metabolism ; Permeability ; Humans ; Animals

Skin, as the outermost organ in the human body, continuously confronts the external environment and serves as a primary defense system. The protective functions of skin include UV-protection, anti-oxidant and antimicrobial functions. In addition to these protections, skin also acts as a sensory organ and the primary regulator of body temperature. Within these important functions, the epidermal permeability barrier, which controls the transcutaneous movement of water and other electrolytes, is probably the most important. This permeability barrier resides in the stratum corneum, a resilient layer composed of corneocytes and stratum corneum intercellular lipids. Since the first realization of the structural and biochemical diversities involved in the stratum corneum, a tremendous amount of work has been performed to elucidate its roles and functions in the skin, and in humans in general. The perturbation of the epidermal permeability barrier, previously speculated to be just a symptom involved in skin diseases, is currently considered to be a primary pathophysiologic factor for many skin diseases. In addition, much of the evidence provides support for the idea that various protective functions in the skin are closely related or even co-regulated. In this review, the recent achievements of skin researchers focusing on the functions of the epidermal permeability barrier and their importance in skin disease, such as atopic dermatitis and psoriasis, are introduced.
*Skin Physiology ; Skin Diseases/*metabolism/physiopathology ; Skin/*metabolism ; Permeability ; Humans ; Animals

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.
Humans ; Monoterpenes/metabolism* ; Oils, Volatile/toxicity* ; Sesquiterpenes/metabolism* ; Skin/metabolism* ; Skin Absorption

Animals ; Homeodomain Proteins ; metabolism ; Humans ; Skin ; metabolism ; Wound Healing ; physiology

Impaired wound healing in diabetes is a significant clinical problem which is thought to be associated with neuropathy and angiopathy previously . The present study indicates that accumulation of glucose and glycometabolic products in skin tissue, as the result of glycometabolic disorders, which contributes to cutaneous environmental alterations in diabetes mellitus, and subsequently induces the abnormal cell behaviors, cytokine alteration and matrix modification. Thus, diabetic neuropathy and angiopathy might be regarded as the pathological outcome of cutaneous environmental alterations. In conclusion, glycometabolism disorders could be described as one of the initial events for the alteration involving in the underlying cutaneous disorder which impair healing process. The related research focuses on the initial event of controlling disorders in wound healing and therefore contribute to providing the strategy of treatment as based on these approaches.
Diabetes Mellitus ; metabolism ; physiopathology ; Humans ; Skin ; metabolism ; Wound Healing

Psoriasis is a chronic inflammatory skin disease with significant physical and psychological burdens. The interplay between the innate and adaptive immune systems is thought to contribute to the pathogenesis; however, the details of the pathogenesis remain unclear. In addition, reliable biomarkers for diagnosis, assessment of disease activity, and monitoring of therapeutic response are limited. Metabolomics is an emerging science that can be used to identify and analyze low molecular weight molecules in biological systems. During the past decade, metabolomics has been widely used in psoriasis research, and substantial progress has been made. This review summarizes and discusses studies that applied metabolomics to psoriatic disease. These studies have identified dysregulation of amino acids, carnitines, fatty acids, lipids, and carbohydrates in psoriasis. The results from these studies have advanced our understanding of: (1) the molecular mechanisms of psoriasis pathogenesis; (2) diagnosis of psoriasis and assessment of disease activity; (3) the mechanism of treatment and how to monitor treatment response; and (4) the link between psoriasis and comorbid diseases. We discuss common research strategies and progress in the application of metabolomics to psoriasis, as well as emerging trends and future directions.
Humans ; Psoriasis/drug therapy* ; Skin/metabolism* ; Biomarkers/metabolism* ; Metabolomics/methods*

Impaired regulation of apoptosis is known to be associated with the development of various cancers, and Fas/Fas-ligand (FasL) is known to play an important role in apoptosis. CD40 is a cell surface receptor, which when ligated modulates apoptosis in some cell types. The expressions of CD40 and FasL were examined in 10 normal skins, 7 Bowen's disease skins, 10 squamous cell carcinomas (SCCs) and 12 basal cell carcinomas (BCCs) immunohistochemically. In the normal epidermis, CD40 was more highly expressed in the keratinocytes of the squamous cell and granular layers than in those of the basal layer, and FasL expression was observed in the cell membrane of keratinocytes at the basal and squamous cell layers. CD40 expression was significantly higher in SCCs than in normal or Bowen's disease skin, while FasL expression was significantly higher in Bowen's disease than in SCCs. BCCs expressed the lowest levels of CD40 and FasL. These results suggest that altered CD40 and FasL expression may be related with the progression of SCC, and the marked reduced expression of CD40 and FasL may explain the biologic behavior of BCCs.
Antigens, CD40/*metabolism ; Bowen's Disease/*metabolism ; Carcinoma, Basal Cell/*metabolism ; Carcinoma, Squamous Cell/*metabolism ; Human ; Membrane Glycoproteins/*metabolism ; Reference Values ; Skin/metabolism ; Skin Neoplasms/*metabolism

OBJECTIVETo investigate the possible influence of the impairment of lymph fluid on the metabolism of hyaluronic acid (HA) in the lymphedematous skin tissue.

METHODSTissue fluid was collected in lymphedematous limbs and the contralateral healthy limbs of 39 patients and HA content was measured with radioimmunoassay. The protein contents were also measured.

RESULTSThe HA contents in interstitial fluid of lymphedematous limb were significantly (8 fold) higher than that of normal limb. The protein concentration in the tissue fluid did not show significant differences between lymphedema and those with normal tissue.

CONCLUSIONThe result suggests blockage of regional draining lymphatics may impairs breakdown of HA and the stagnation of HA in the limb may exert a deleterious effect on the interstitium.

Extracellular Fluid ; metabolism ; Forearm ; Humans ; Hyaluronic Acid ; metabolism ; Leg ; Lymphedema ; metabolism ; Radioimmunoassay ; Skin ; metabolism ; pathology

OBJECTIVETo investigate the expression and clinical significance of cyclin H and cyclin-dependent kinase 7 (CDK7) in human hemangiomas.

METHODSImmunohistochemistry technique was used to measure the expression of cyclin H and CDK7 proteins in proliferative, involuting hemangiomas and normal skin tissues. Immunohistochemical technique for factor VIII-related antigen was used to prove that the cells which expressed cyclin H and CDK7 were endothelial cells. Average optical density and positive area of the expression of cyclin H and CDK7 proteins in proliferative, involuting hemangiomas and normal skin tissues were measured by image analysis (HPIAS-1000).

RESULTSThe expression of cyclin H and CDK7 protein in proliferating hemangiomas was significantly higher than that in involuting hemangiomas and normal skin tissues (P < 0.01). But no significant difference was found in the expression of cyclin H and CDK7 protein between involuting hemangiomas and normal skin tissues (P > 0.05).

CONCLUSIONScyclin H and CDK7 may play an important role in the generation and development of human hemangiomas.

Cyclin H ; metabolism ; Cyclin-Dependent Kinases ; metabolism ; Hemangioma ; metabolism ; Humans ; Immunohistochemistry ; Skin Neoplasms ; metabolism

The diabetic ulceration is not uncommon, and becomes refractory, as the skin in a diabetic patient is relatively thin as well as hypoesthetic and less sensitive to temperature. As there are already preexisting histological and cellular derangement in the skin, healing of the skin injury is difficult, thus resulting in an intractable ulceration. When diabetes is not controlled, the skin contents of sugar and advanced glycation end product accumulate, invoking cellular deformation and accumulation of matrix metalloproteinases (MMP), resulting in an imbalance between MMP and its inhibitors, malfunction of growth factors, and inflammatory reaction. These processes lead to obvious skin thinning, denaturation of connective tissues, thickening of vascular basal membrane, and neuropathy, etc. These pathological alterations could be recognized as "covert disorder" of skin in diabetic patients and may be underlying disorders in producing indolent diabetic ulcers.
Animals ; Diabetes Mellitus ; metabolism ; pathology ; Glycation End Products, Advanced ; metabolism ; Rats ; Skin ; metabolism ; pathology ; Skin Ulcer ; pathology ; Wound Healing