The primary aim of this study is to explore the protective mechanisms of glial-derived neurotrophic factor (GDNF) during excitotoxicity by kainate in the hippocampus. After a 15-min microinjection with kainate, excitotoxicity was induced in the rat hippocampus. The protective effect of GDNF in the hippocampus was evaluated by administering GDNF 14 min after injection of kainate. The resulting hydroxyl free radicals were quantified by microdialysis of the hippocampus. The results show that GDNF can effectively suppress the production of kainate-induced hydroxyl free radical production. In addition, histological observation indicated the ability of GDNF to decrease the damage level of pyramidal neurons in the CA3 and CA4 areas of the hippocampus. Superoxide dismutase (SOD) activity in the hippocampus was elevated significantly at 30 min and 7 days after kainate induction, while glutathione peroxidase (cGPx) activity did not increase significantly until the seventh day. With GDNF treatment, SOD and cGPx activity in the hippocampus was elevated significantly 7 days after kainate induction. We suggest that mechanisms including a decrease in free radical generation and scavenging of free radicals might be involved in GDNF protection against kainate-induced excitotoxicity.
Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determine the optimum vehicle for salvianolic acid B, investigate its therapeutic effect on psoriatic-like skin conditions, and explore its underlying mechanisms of action. BALB/c mice were administered topical imiquimod to induce psoriasis-like skin and were then randomly assigned to control, vehicle control, salvianolic acid B in vehicles, and 0.25% desoximetasone ointment treatment groups. Barrier function, cytokine expression, histology assessment, and disease severity were evaluated. The results showed that salvianolic acid B-containing microemulsion alleviated disease severity, reduced acanthosis, and inhibited interleukin-23/interleukin-17 (IL-23/IL-17) cytokines, epidermal proliferation, and increased skin hydration. Our study suggests that salvianolic acid B represents a possible new therapeutic drug for the treatment of psoriasis. In addition, such formulation could obtain high therapeutic efficacy in addition to providing sufficient hydration for dry skin.
Human pluripotent stem cells have the potential assist in the identification of genes involved in mammalian development. The human placenta is considered a repository of stem cells, termed placenta-derived multipotent cells (PDMCs), which are able to differentiate into cells with an osteoblastic phenotype. This plasticity of PDMCs maybe applied clinically to the understanding of osteogenesis and osteoporosis. In the presentstudy, osteoblasts were generated by culturing PDMCs in osteogenic medium. Reverse transcription quantitative polymerase chain reactionand the degree of osteoblast calcification were used to evaluate the efficacy of osteogenesis. The results suggestedthat the expression of mothers against decapentaplegic homolog 3 (SMAD3) increased in the initial stages of osteogenic differentiation but decreased in the later stages. However, osteogenesis was inhibitedwhen the PDMCs overexpressed SMAD3 throughout the differentiation period. In addition, the rate of osteogenic differentiation was decreased when SMAD3 signaling was impaired. In conclusion, SMAD3 serves an important role in osteoblast differentiation and bone formation in a time-dependent manner. The data from the present study indicate that arapid increase in SMAD3 expression is crucial for osteogenesis and suggest a role for PDMCs in the treatment of patients with osteoporosis.
The objective of this study was to investigate the effect of sebum on drug transport across the human stratum corneum (SC) in vivo for two model compounds, 4-cyanophenol (CP) and cimetidine (CM), of different lipophilicity and molecular size by utilizing noninvasive tape-stripping techniques, in conjunction with an unsteady-state diffusion model for data analysis. The results demonstrated that the SC permeability of the relatively hydrophilic CM on the forehead may be as much as four times the permeability on the forearm. The administration of sebum supplementation to the forearm increased the SC permeability of CM more than threefold, but did not have the same effect with regard to CP. Removal of sebum from the forehead demonstrated a small but significant effect (-22%) on the SC permeability of CM. The presence of sebum on the forehead or forearm increased the diffusion of both molecules, but the effect on partition varied between sites and drugs. The change in the SC permeability of the relatively hydrophilic drug using sebum treatment may be attributable to the altered barrier function of the SC due to the disordering structures of the intercellular lipid molecules.
Skin barrier functions, environmental insults, and genetic backgrounds are intricately linked and form the basis of common inflammatory skin disorders, such as atopic dermatitis, psoriasis, and seborrheic dermatitis, which may seriously affect one’s quality of life. Topical therapy is usually the first line of management. It is believed that successful topical treatment requires pharmaceutical formulation from a sufficient dosage to exert therapeutic effects by penetrating the stratum corneum and then diffusing to the target area. However, many factors can affect this process including the physicochemical properties of the active compound, the composition of the formulation base, and the limitations and conditions of the skin barrier, especially in inflammatory skin. This article briefly reviews the available data on these issues and provides opinions on strategies to develop a suitable formulation for inflammatory skin disease treatment.
<b><i>Introduction:</i></b> Wound healing is a process in which damaged cutaneous tissues are repaired and is a dynamic physiological interaction involving several types of cells, tissues, and proteins. Compared with typical treatments, specifically in terms of multifunctional properties, bioactive drug-loaded wound dressing in a controlled and sustained delivery system is an advanced tool that significantly improves wound healing. Curcumin substantially enhances wound healing and prevents oxidative damage. However, the effects of this compound on improving wound healing are limited by its aqueous solubility, poor tissue absorption, and rapid metabolism. Hence, the current study aimed to investigate the therapeutic effect of curcumin-loaded self-microemulsifying gel on wound healing. <b><i>Methods:</i></b> Ex vivo permeation studies of the skin of BALB/c mice were performed using a diffusion cell sampling system. The in vivo therapeutic effect was investigated with a full-thickness wound model. Two 6-mm full-thickness circular wounds were created on the back of the mice via punch biopsy. Then, they received different topical gels for 12 days to enhance wound closure. <b><i>Results:</i></b> The curcumin-loaded self-microemulsifying gel had higher skin flux, cumulative amount, and permeability coefficient than the commercial gels. In addition, it enhanced wound healing. <b><i>Conclusions:</i></b> This is the first study that utilized self-microemulsifying gel loaded with curcumin as a delivery system for wound healing. However, the effect of this delivery system on wound healing or skin disease treatment should be further investigated.
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