The Effect of Gromwell (Lithospermum erythrorhizon) Extract on the Stratum Corneum Hydration and Ceramides Content in Atopic Dermatitis Patients

Background

A disruption of the balance between the water content of the stratum corneum (SC) and skin surface lipids may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis (AD).

Objective

To determine whether supplementation of gromwell (Lithospermum erythrorhizon), one of herbs used in East Asia in remedies for various abnormal skin conditions, may improve the SC level of hydration and ceramides, major lipid in SC in patients with AD.

Methods

A total of 28 subjects with AD were randomly assigned into two groups: either gromwell group received dextrose contained capsules with 1.5 g of gromwell extracts or placebo group received only dextrose contained capsules for 10 weeks.

Results

In contrast to no alteration of SC hydration and ceramides in placebo group, the SC hydration in gromwell group was significantly increased in parallel with an increase of SC ceramides. Furthermore, % increase of SC hydration in gromwell group bore a positive correlation with the clinical severity, which suggests that the increase of SC hydration in gromwell group was more effective as AD was more severe.

Conclusion

Supplementation of gromwell improves SC hydration in parallel with an increase of ceramides in part.     

Defect of insulin signal in peripheral tissues: important role of ceramide

In healthy people,balance between glucose production and its utilization is precisely controlled.When circulating glucose reaches a critical threshold level,pancreaticβcells secrete insulin that has two major actions:to lower circulating glucose levels by facilitating its uptake mainly into skeletal muscle while inhibiting its production by the liver.Interestingly,dietary triglycerides are the main source of fatty acids to fulfill energy needs of oxidative tissues.Normally,the unconsumed fraction of excess of fatty acids is stored in lipid droplets that are localized in adipocytes to provide energy during fasting periods.Thus,adipose tissue acts as a trap for fatty acid excess liberated from plasma triglycerides.When the buffering action of adipose tissue to store fatty acids is impaired,fatty acids that build up in othertissues are metabolized as sphingolipid derivatives such as ceramides.Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway.     

Increased scalp skin lipids in response to antidandruff treatment containing zinc pyrithione

Archives of Dermatological Research -     

Developmental alterations of physical properties and components of neonatal-infantile stratum corneum of upper thighs and diaper-covered buttocks during the 1st year of life

BackgroundAlthough physical properties of neonatal-infantile stratum corneum (SC) change drastically after birth, precise developmental alterations of specific sites have not been fully elucidated.ObjectiveTo determine the longitudinal alterations of neonatal-infantile SC functions and components of upper thighs and diaper-covered buttocks during the first year of life. The data were compared with those of adults.MethodsNineteen full-term neonates and their mothers were subjected to the measurements. Skin hydration, water sorption/retention capacity, TEWL were measured. Superficial SC analyses for NMF, ester binding sebum, and free fatty acids were performed by ATR-FTIR spectrometer. Total amount of ceramides (CERs) and CER subclasses were analyzed by NPLC-ESI-MS.ResultsSC hydration of neonatal thighs was lower than that of their mothers, which rapidly increased during the 1st month. Skin hydration of neonatal buttocks was similar to that of their mothers. This also rapidly increased during the 1st month. The neonatal TEWL was less than those of their mothers indicating more efficient barrier function at both sites, which significantly increased during the 1st year development. This was mostly correlated decreased in the ω-hydroxy fatty acid-esterified CERs. Superficial ester-binding sebum content of neonates was similar to that of their mothers, which significantly decreased during the measurement; the decrease was more marked on buttocks. Neither NMF nor FFA of the superficial SC showed significant alteration during the 1-year development.ConclusionOur results indicate that physical functions and components of neonatal-infantile SC show considerable alterations between diaper-covered buttocks and upper thighs during the 1st year development.     

Ceramide expression in relation to breast cancer molecular subtypes in Saudi women

Background/IntroductionDespite advances in the diagnosis and management of breast cancer (BC), it is still associated with high mortality rates. New biomarkers are being developed for the diagnosis, treatment, and prediction of responses of BC. Ceramide (CER), a bioactive sphingolipid, has emerged recently as a useful diagnostic tool in several types of tumors. In this study, we evaluated CER expression in invasive BC and assessed its relation to the molecular subtypes of BC.Materials and methodsThe clinical data and histopathological slides of 50 patients with invasive ductal carcinoma were retrieved and reviewed. The cases were then stained with a mouse monoclonal anti-ceramide antibody. Pearson correlation was used to assess the correlation between CER percentage and intensity and other clinical and pathological variables.ResultsCER expression showed a direct relationship with estrogen and progesterone receptors Allred scores. However, it showed an inverse relation with tumor grade, HER2/neu status and Ki-67 index.ConclusionsCER expression is likely to be associated with luminal BC molecular subtypes. However, more research is needed to confirm these results and to explore its relation to the different clinical outcomes, including response to treatment and prognosis.     

C2-ceramide influences alveolar epithelial barrier function by downregulating Zo-1, occludin and claudin-4 expression

Noncardiogenic lung edema is a key factor affecting the prognosis of acute lung injury (ALI). Previous studies have been focused on regulatory roles of ceramide on lung vascular endothelial barrier functions and had already identified ceramide as mediator involved in the formation of lung edema. However, the effects of ceramide on lung epithelial barrier were still unknown. This study aimed to investigate the effects of ceramide on the barrier function of alveolar epithelial cells. Primary mouse alveolar type II epithelial cells (AECII) were grown on Transwell polyester membranes to construct monolayer, and stimulated with different concentrations of ceramide. Transepithelial resistance (TER) was measured to assess the epithelial cell permeability. Western blotting and real-time quantitative polymerase chain reaction were used to detect the mRNA and protein levels of tight junction, respectively. After incubation with different concentrations of c2-ceramide, TER of AECII monolayer decreased significantly in a dose-dependent manner. Moreover, expressions of ZO-1, occludin and claudin-4 were significantly reduced by c2-ceramide in the study. This study demonstrated that ceramide could increase alveolar epithelial cell monolayer permeability by downregulation of tight junction proteins. Therefore, modulation of ceramide expression may serve as a new therapeutic approach to treat acute lung injury.     

Self-assembled polymeric nanoparticle of PEGylated chitosan–ceramide conjugate for systemic delivery of paclitaxel

Abstract

Chitosan has been widely explored as one of the most favorable biomaterials for various pharmaceutical applications due to its biodegradability and biocompatibility. Here, we report novel PEGylated–chitosan–ceramide (PEG-CS-CE) that forms stable polymeric nanoparticles capable of functioning as efficient carriers of hydrophobic drug molecules. The chitosan–ceramide conjugate (CS-CE) was linked with amine-polyethyleneglycol (NH₂-PEG₂₀₀₀) by using dicyclohexylcarbodiimide/N-hydroxysuccinimide (DCC-NHS) to obtain PEG-CS-CE that could exhibit steric stabilization in biological environments. The structure of the conjugate was determined by proton (¹H) NMR and FT-IR spectrometry. Under suitable conditions, the PEG-CS-CE self-assembled to form colloidally stable nanoparticles with a mean diameter of ～200?nm. Further, hydrophobic anti-tumor agent paclitaxel (PTX) was incorporated into the polymeric nanoparticle with 90% loading efficiency and 11.3% loading capacity via an emulsion-solvent evaporation method. The PTX-loaded PEG-CS-CE nanoparticle showed sustained release and exhibited higher cellular uptake and a comparable cytotoxic efficacy to that of free PTX on B16F10 melanoma and MCF-7 human breast adenocarcinoma cell lines. The empty nanoparticle showed no toxicity, indicating that the co-polymer is safe to use in drug delivery. The polymeric nanoparticle PEG-CS-CE developed by us represent promising nanocarriers of hydrophobic drug molecules.     

Spinal ceramide and neuronal apoptosis in morphine antinociceptive tolerance

Opiates, like morphine, are the most effective analgesics for treating acute and chronic severe pain, but their use is limited by the development of analgesic tolerance and hypersensitivity to innocuous and noxious stimuli. Because opioids are a mainstay of pain management, restoring their efficacy has great clinical importance. We have recently demonstrated that spinal ceramide, a sphingolipid signaling molecule plays a central role in the development of morphine antinociceptive tolerance. We now report that ceramide upregulation in dorsal horn tissues in response to chronic morphine administration is associated with significant neuronal apoptosis. Inhibition of ceramide biosynthesis attenuated both the increase in neuronal apoptosis and the development of antinociceptive tolerance. These findings indicate that spinal ceramide upregulation is a key pro-apoptotic event that occurs upstream of the development of morphine antinociceptive tolerance and support the rationale for development of inhibitors of ceramide biosynthesis as adjuncts to opiates for the management of chronic pain.     

Ion channels and membrane rafts in apoptosis

Ion channels have been demonstrated to be a central element in the induction and the execution of apoptosis. In particular, mitochondrial ion channels, including not only the permeability transition pore but also a mitochondrial, ATP-sensitive (mK_ATP) channel as well as a mitochondrial calcium-activated potassium channel are involved critically in apoptotic changes in mitochondria. Ion channels in the cell membrane that are altered by induction of apoptosis include potassium, chloride and calcium channels. The Kv1.3 potassium channel belongs to the best-characterized ion channels involved in apoptosis and a genetic model of cells deficient for Kv1.3 has indicated a critical role for Kv1.3, at least in some forms of apoptosis. The mechanisms regulating ion channels during apoptosis are, however, still poorly defined. Recent studies have suggested a function for distinct membrane domains, termed rafts, in the cell membrane for the regulation of ion channels during apoptosis. Small sphingolipid- and cholesterol-enriched membrane domains are modified by many apoptotic stimuli to form large ceramide-enriched membrane platforms. These platforms serve to cluster receptor molecules, to re-organize intracellular signalling molecules including ion channels, to bring ion channels into close contact with their regulators and/or to separate proteins from a specific ion channel. Finally, the lipid composition of the cell membrane might be involved directly in ion channel regulation.     

长期酒精暴露引起小鼠胰岛素抵抗：神经酰胺的可能作用

目的 探讨长期酒精暴露与胰岛素敏感性之间的关系并探讨其相关的分子机制;观察神经酰胺在酒精引起胰岛素抵抗过程中的可能作用。 方法 建立C57BL/6J野生型（WT）小鼠和神经鞘磷脂合成酶2基因敲除（SMS₂^-/-）3月龄小鼠的长期酒精暴露模型,两基因型小鼠又分为对照组、中剂量酒精组和高剂量酒精组,共计90只。建模5个月后,用血糖仪测定小鼠空腹血糖值,用酶学法检测血清胰岛素浓度,并计算胰岛素抵抗指数。利用免疫荧光染色法观察各组小鼠海马CA1区胰岛素受体底物2（IRS2）阳性细胞表达情况,免疫印迹法检测小鼠海马组织IRS2蛋白的相对表达量。 结果 1.长期酒精暴露导致WT和SMS-/-2小鼠空腹血糖值和胰岛素抵抗指数升高,且具有剂量依赖性（P<0.05）;但SMS₂^-/-小鼠随着酒精剂量的增加胰岛素抵抗指数升高幅度较小。 2.免疫组织化学染色显示,酒精暴露诱导WT和SMS₂^-/-小鼠海马IRS2阳性细胞数降低,有剂量依赖性（P<0.05）;与相同处理条件的WT小鼠相比,酒精诱导SMS₂^-/-小鼠海马IRS2阳性细胞数降低增多（P<0.05）。 3.免疫印迹法检测各组间小鼠海马组织IRS2蛋白相对表达量与上述结果一致。 结论 长期酒精暴露可引起胰岛素抵抗,IRS2蛋白表达降低,且存在剂量依赖性,因此酒精导致IRS2表达下降可能是胰岛素抵抗的分子机制之一;神经酰胺可能参与酒精暴露诱导IRS2表达下降的过程,且有促进胰岛素抵抗形成的作用。