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Aging-associated disorders include cardiovascular diseases, type 2 diabetes, Alzheimer′s disease and so on. Recent studies have demonstrated that aging-associated, low-grade inflammation, also termed inflammaging, contributes to the development of these disorders. However, the origin of inflammaging is still unclear. Some studies indicate that epidermal dysfunction may be the cause of inflammaging in the elderly. Compared with the young, the elderly show reduced water content of the stratum corneum, elevated skin surface pH and compromised epidermal permeability barrier homeostasis, which can all provoke cutaneous inflammation. Pruritus commonly occurs in the elderly, and pruritus-induced scratching can further perturb epidermal permeability barrier function and induce cutaneous inflammation. Sustained mild inflammation in the skin may lead to systemic inflammation. Recent studies in aged mice and humans have demonstrated that improvements in epidermal function can decrease inflammatory cytokine levels in peripheral blood, suggesting a pathogenic role of epidermal dysfunction in inflammaging in the elderly. Thus, improvements in epidermal function may be helpful for the prevention and remission of aging-associated disorders.
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Objective To evaluate the reversal effect of a cholinergic receptor agonist on acantholysis in pemphigus,and to investigate its mechanism.Methods Human HaCaT keratinocytes were co-cultured with pemphigus vulgaris immunoglobulin G (PV-IgG) to establish a cell model of pemphigus,then classified into two groups to be incubated with the cholinergic receptor agonist carbachol for 12 hours (test group) or remain untreated (control group).Cell dissociation assay was performed to quantitatively estimate the reversal effect of carbachol on acantholysis,and immunofluorescence assay to qualitatively assess the changes of desmosomal proteins.Radio-immunoprecipitation assay (RIPA) lysis buffer and Triton X-100 were used to lyse HaCaT cells to obtain total proteins and cytoplasmic proteins,and Western blot was conducted to determine the expression levels of adhesion-related proteins desmoglein 3 (Dsg3) and plakoglobin (PG) on the surface of HaCaT cells,as well as the phosphorylation levels of p38 mitogen activated protein kinase (p38 MAPK) and epidermal growth factor receptor (EGFR) at different time points.Quantitative polymerase chain reaction (qPCR) was performed to detect the mRNA expressions of the above surface proteins,and coimmunoprecipitation assay to qualitatively evaluate the interaction between Dsg3 and PG.Results The number of cell debris was significantly lower in the test group than in the control group (18.67 ± 2.52 vs.46.67 ± 2.03,t =11.22,P＜0.01).Immunofluorescence assay showed that carbachol could reverse the internalization of desmosomal molecules induced by PV-IgG.In the pemphigus cell model,the levels of total Dsg3 and PG as well as non-desmosomal Dsg3 were decreased,while the level of non-desmosomal PG increased,and the interaction between Dsg3 and PG was attenuated.When the pemphigus cell model was co-cultured with carbachol,these above changes were reversed.Carbachol also increased the mRNA levels (expressed as 2-△△Ct) of Dsg3 and PG from 1.428 ± 0.215 and 1.563 ± 0.247 in the control group to 4.974 ± 0.948 (t =3.65,P =0.01) and 13.420 ± 1.715 (t =6.85,P ＜ 0.01) in the test group respectively.In phosphorylation assay,carbachol inhibited the phosphorylation of EGFR,but had no significant effect on that of p38 MAPK.Conclusions The cholinergic receptor agonist carbachol can reverse acantholysis in pemphigus,likely by inhibiting the internalization of Dsg3 and PG,enhancing their expressions and interaction,and suppressing the phosphorylation of the key signaling molecule for acantholysis,EGFR.
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Objective To investigate the relationship between disease severity and enzyme-linked immunosorbent assay (ELISA) index values of anti-desmoglein (Dsg) 1 and-Dsg3 antibodies in 56 patients with pemphigus,and to characterize fluctuations in anti-Dsg1 and-Dsg3 antibodies in different forms of pemphigus.Methods Fifty-six patients with pemphigus (including 36 cases of pemphigus vulgaris (PV) and 20 cases of pemphigus foliaceus (PF)) were enrolled in this study.Blood samples were obtained from these patients before treatment and at the following four time points:when the condition was relieved and the taper of glucocorticoids began,the dose of glucocorticoids was tapered to half of their initial dose,the maintenance treatment started,and when the duration of maintenance treatment reached two years.ELISA was performed to determine the levels of anti-Dsg1 and-Dsg3 antibodies in these serum samples.Spearman correlation analysis was carried out to assess the relationship between disease severity and ELISA index values,and independent sample's t test to compare the levels of anti-Dsg antibodies among these time points.Results The severity of pemphigus was correlated with anti-Dsg antibody ELISA index values.Both anti-Dsg1 and anti-Dsg3 ELISA index values were significantly reduced at the remission of pemphigus compared with those before treatment (all P ＜ 0.01).At the end of the two-year maintenance treatment,10 (50％) patients with PF and 7 (19.4％) patients with PV became negative for anti-Dsg1 ELISA,whereas only 1 (2.7％) patient with PV became negative for anti-Dsg3 ELISA.Conclusions Anti-Dsg antibody ELISA index value is correlated with disease severity in patients with pemphigus,which may serve as a useful marker for assessing disease severity and activity as well as evaluating therapeutic efficacy.
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Objective To evaluate the efficacy and safety of centella triterpenes cream(R) for treating crow's feet.Methods A double-blind,randomized,vehicle-controlled 12-week study was conducted.Centella triterpenes cream(R) was applied to the lateral canthus on one side (treatment side) and vehicle-(c)ontrol cream to the lateral canthus on the other side (control side) 3 times daily.Efficacy was evaluated based on an investigator-blinded assessment,subject self-blinded assessment and a quantitative analysis by Visioscan(R)VC98 at the baseline,4,8,12 weeks after the beginning of treatment.Results Thirty-six volunteers were recruited and 35 subjects completed the 12-week trial.The investigator-blinded assessment showed a significant difference in the changes of wrinkle scores between the treatment side and control side after 4 weeks (P ＜ 0.05),and the improvement of wrinkles was more obvious on the treatment side than on the control side at 8 and 12 weeks with a statistical difference in the wrinkle scores (both P ＜ 0.05).Compared with the control side,a significant increase in SEw value,which suggested an improvement in wrinkles,was observed on the treatment side after the application of centella triterpenes cream(R).Subjects' assessments revealed no significant difference in the occurrence of irritation or the improvement of coarse wrinkles,whereas the treatment side was superior to the control side in the improvement of skin texture (P ＜ 0.05) at the lateral canthus.Conclusion Centella triterpenes cream(R) thrice daily is effective for the improvement of crow's feet with no obvious side effects.
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Objective To estimate the prevalence and associated factors of facial wrinkling in females.Methods Questionnaires were designed and delivered to collect related data on volunteers. The subjects were divided into outdoor and indoor groups. Wrinkles were classified into 9 grades based on photos taken by SIA0612 image analyzer and quantification analysis via Visioscan VC 98. SPSS 17.0 software was used to assess the associated factors of wrinkling, including sun-protective measures, skin care and cosmetology, onset age and location of wrinkles in these subjects. Results A total of 246 patients aged 19 - 71 years were recruited in this study. Sun-protective measures were applied in 13.5% of the subjects between 12 and 18 years of age,38.5% of those between 19 and 29 years of age, 39.2% of those between 30 and 39 years of age, 44% of those between 40 and 59 years of age, and in none of those between 60 and 75 years of age, 44.1% of all the subjects in the latest 5 years. Wrinkles were absent in 5.7% of the subjects, and pigmentation macules absent in 21.7%. The first development of wrinkles was mainly observed in subjects aged 30 to 35 years, and that of pigmentation macules in those aged 25 to 30 years. The most common locations of facial wrinkles, in order of decreasing frequency, were infraorbital area, lateral angle of eye, nasolabial fold, glabella in the indoor group,lateral angle of eye, infraorbital area, glabella and nasolabial fold in the outdoor group. Fishtail lines seemed to be the commonest wrinkles with an earliest onset among these wrinkles, and showed a prevalence of 100% in subjects aged 45 years or older in the indoor group, and in those aged 30 years or older in the outdoor group.Conclusions Wrinkles and pigmentation macules are dominate manifestations of skin aging in Chinese females. The onset of pigmentation macules is earlier than that of wrinkles. The main manifestations of skin aging in Chinese females, in order of decreasing frequency, are yellow-grey skin, skin dryness, roughness,leather-like appearance, teleangiectasia, and (or) severe pigmentation macules, increase in skin fragility, etc.The order and age of wrinkle appearance are different between indoor and outdoor females.