Metabolism-related biomarkers, molecular classification, and immune infiltration in diabetic ulcers with validation.

Diabetes mellitus (DM) can lead to diabetic ulcers (DUs), which are the most severe complications. Due to the need for more accurate patient classifications and diagnostic models, treatment and management strategies for DU patients still need improvement. The difficulty of diabetic wound healing is caused closely related to biological metabolism and immune chemotaxis reaction dysfunction. Therefore, the purpose of our study is to identify metabolic biomarkers in patients with DU and construct a molecular subtype-specific prognostic model that is highly accurate and robust. RNA-sequencing data for DU samples were obtained from the Gene Expression Omnibus (GEO) database. DU patients and normal individuals were compared regarding the expression of metabolism-related genes (MRGs). Then, a novel diagnostic model based on MRGs was constructed with the random forest algorithm, and classification performance was evaluated utilizing receiver operating characteristic (ROC) analysis. The biological functions of MRGs-based subtypes were investigated using consensus clustering analysis. A principal component analysis (PCA) was conducted to determine whether MRGs could distinguish between subtypes. We also examined the correlation between MRGs and immune infiltration. Lastly, qRT-PCR was utilized to validate the expression of the hub MRGs with clinical validations and animal experimentations. Firstly, 8 metabolism-related hub genes were obtained by random forest algorithm, which could distinguish the DUs from normal samples validated by the ROC curves. Secondly, DU samples could be consensus clustered into three molecular classifications by MRGs, verified by PCA analysis. Thirdly, associations between MRGs and immune infiltration were confirmed, with LYN and Type 1 helper cell significantly positively correlated; RHOH and TGF-ß family remarkably negatively correlated. Finally, clinical validations and animal experiments of DU skin tissue samples showed that the expressions of metabolic hub genes in the DU groups were considerably upregulated, including GLDC, GALNT6, RHOH, XDH, MMP12, KLK6, LYN, and CFB. The current study proposed an auxiliary MRGs-based DUs model while proposing MRGs-based molecular clustering and confirmed the association with immune infiltration, facilitating the diagnosis and management of DU patients and designing individualized treatment plans.

Meteorology and ethnicity as critical factors in HRIPT: Comparing responses between Chinese and Indian ethnicities.

BACKGROUND: Human repeated insult patch test (HRIPT) is regarded as one of the confirmatory test in determining the safety of skin sensitizers. A number of important factors should be considered when conducting and interpreting the results of the HRIPT. OBJECTIVE: To investigate for probable critical factors that influence the results of HRIPT with the same protocol in Shanghai and Mumbai. METHODS: Two HRIPTs were carried out in Shanghai and Mumbai in 2011. Six identical products and 1% sodium lauryl sulfate were tested. Two Chinese dermatologists performed the grading in the two cities. Climate conditions of Shanghai and Mumbai were also recorded. RESULTS: For four lower reaction ratio products, cumulative irritation scores in the induction phase were higher in individuals whose ethnicity was Indian rather than Chinese. Reaction ratio of the same four products was highly correlated to the climatic parameters. The other two higher reaction ratio products and the positive control had no difference between the two ethnicities. CONCLUSION: Greater attention ought to be paid to the impact of climate on the results of HRIPT, especially for the mild irritation cosmetics when giving the interpretation. Greater emphasis also needs to be placed on the ethnicity of the subjects.

The role and safety of UVA and UVB in UV-induced skin erythema.

Background: Different wavelengths of ultraviolet (UV) light cause skin damage through different mechanisms. Minimal erythema dose (MED) is usually used to clinically evaluate skin sensitivity to ultraviolet radiation by inducing skin erythema using ultraviolet B (UVB) or ultraviolet A (UVA) + UVB. Aims: In this study, we detected changes in the blood flow at the MED erythema caused by UVB and UVA + UVB radiation through optical coherence tomography (OCT) to explain the role of different bands of ultraviolet rays in erythema induction. Methods: Two MED irradiation areas on the subjects' back were irradiated with UVB alone or UVA + UVB (UVA: UVB = 8:1). The absolute energy of UVB remained the same in UVB and UVA+UVB. At 24 h after the irradiation, the changes in the blood flow in the MED area were detected using OCT. Results: Compared with the blank control, the maximum blood flow depth, blood flow peak, and total blood flow of UVB-MED and UVA+UVB-MED were significantly increased. Notably, the maximum blood flow depth and blood flow peak of UVB-MED were higher than UVA+UVB-MED. There was no significant difference in total blood perfusion between UVA+UVB-MED and UVB-MED. Under the same UVB energy, the skin erythema caused by UVA + UVB was weaker than UVB alone. Conclusions: The analysis of local blood flow by OCT showed that the peak and maximum depth of local blood flow caused by UVB alone were significantly higher than UVA + UVB.

Sheng-ji Hua-yu ointment ameliorates cutaneous wound healing in diabetes via up-regulating CCN1.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers (DUs) are one of the most severe complications of diabetes, and efficacious therapeutic means are currently lacking. Sheng-ji Hua-yu (SJHY) ointment is a classical Chinese traditional prescription that can significantly attenuate DU defects, but the specific mechanism remains to be fully elucidated. AIM OF THE STUDY: In order to verify the underlying mechanism of SJHY ointment in accelerating the closure of DUs. MATERIALS AND METHODS: Modular pharmacology and molecular docking were utilized to predict the therapeutic targets of SJHY ointment against DUs. Male db/db diabetic mice and HaCaT cell models induced by methylglyoxal were used to validate the findings. RESULTS: CCN1 was proven to be the core target of SJHY ointment involved in DUs treatment. CCN1 up-regulated by SJHY treatment (0.5 g/cm2/day) at the mRNA and protein levels was detected on Day9 after wounding. With CCN1 knockdown, accelerated cell proliferation, migration, and anti-inflammatory effect of SJHY treatment (10 mg/L) were reversed. CONCLUSIONS: SJHY ointment ameliorates cutaneous wound healing by up-regulating CCN1.

Impact of solar ultraviolet radiation on daily outpatient visits of atopic dermatitis in Shanghai, China.

The potential roles of solar ultraviolet radiation (UVR) as an environmental risk factor in inducing atopic dermatitis (AD) have not been well quantified. To determine the short-term associations between UVR and AD outpatient visits, we obtained daily outpatient visits of AD in Shanghai Skin Disease Hospital from 2013 to 2018. Data of hourly ground UVR were collected. We applied overdispersed generalized additive model to explore its associations. We found that daily exposure to UVR-A rather than UVR-B was positively associated with AD outpatient visits. The visits increased on the present day (lag 0 days) and decreased appreciably with longer lags and became insignificant at lag 4 days. For 10 w/m2 increase in daytime mean and noontime mean exposure to overall UVR and UVR-A from lag 0 to 6 days, the cumulative relative risk of AD was 1.12/1.13 and 1.08/1.08, respectively. Stronger effects of UVR exposure on AD occurred in patients aged 0-7 and > 45 years and in the cold seasons. This study contributed to the few epidemiological evidences that acute exposure to solar UVR may elevate the risks of AD.

N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: results of a randomized, double-blind, controlled study in 60 patients.

BACKGROUND: Asteatotic eczema (AE) is characterized by itchy, dry, rough, and scaling skin. The treatments for AE are mainly emollients, usually containing urea, lactic acid, or a lactate salt. N-palmitoylethanolamine (PEA) and N-acetylethanolamine (AEA) are both endogenous lipids used as novel therapeutic tools in the treatment of many skin diseases. The purpose of this study was to compare a PEA/AEA emollient with a traditional emollient in the treatment of AE. METHODS: A monocentric, randomized, double-blind, comparative trial was conducted in 60 AE patients to evaluate and compare the efficacy of the two emollients. The level of skin dryness among the subjects ranged from mild to moderate. The subjects' skin barrier function and the current perception threshold were tested for 28 days by clinical scoring and bioengineering technology. RESULTS: The results showed that, although some aspects were improved in both groups, the group using the emollient containing PEA/AEA presented a better skin surface change in capacitance. However, the most impressive finding was the ability of the PEA/AEA emollient to increase the 5 Hz current perception threshold to a normal level after 7 days, with a significant difference between values at baseline and after 14 days. A current perception threshold of 5 Hz was positively and significantly correlated with skin surface hydration and negatively correlated with transepidermal water loss in the PEA/AEA emollient group. CONCLUSION: Compared with traditional emollients, regular application of a topical PEA/AEA emollient could improve both passive and active skin functions simultaneously.

Evaluation of 5-aminolevulinic acid-mediated photorejuvenation of neck skin.

OBJECTIVE: To evaluate the outcomes of the combination of red light or intense pulsed laser (IPL) with 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) in the treatment of photodamaged neck skin. METHODS: The anterior of the neck was divided into four 2 cm × 2 cm sections and randomly assigned to red-light, red-light-PDT, IPL or IPL-PDT group. ALA cream of 5% was applied to PDT regions for 2h prior to light irradiation. Treatment was repeated once. The stratum corneum (SC) hydration, transepidermal water loss (TEWL), L(*), a(*), b(*) values, melanin index (MI), erythema index (EI), skin elasticity and skin thickness were examined by a blinded investigator. The function and volume of thyroid were also measured. RESULTS: After red-light-PDT, IPL-PDT and IPL treatment, the appearance of photoaging lesion was improved. The SC hydration, L(*) value, elasticity and thickness increased, whereas the TEWL and MI value decreased. These changes in red-light-PDT and IPL-PDT group were more obvious than IPL group. The a(*) and EI value increased in red-light-PDT group. No significant change was noticed in red-light group. Partial irradiation of the thyroid did not affect the function and volume of the thyroid. CONCLUSION: IPL-PDT and red-light-PDT showed better rejuvenation effect than IPL or red light alone on the neck skin.

Effects of sunscreen on human skin's ultraviolet radiation tolerance.

PURPOSE: To observe the alteration ultraviolet radiation (UVR) of skin's tolerance after its exposure to the small dose of UVR under the protection of sunscreen. METHODS: Eleven subjects who applied sunscreen were exposed to 0.75 dose minimal persistent pigment darkening (MPPD) and minimal erythema dose (MED) by the Phototherapy Unit for 4 weeks. Each week their MPPDs and MEDs were measured by solar simulator. Meanwhile, SPECTCOLOMETER® and VISIOSCAN VC98® were used to detect the test areas and control areas. RESULTS: The values of MPPD and MED increased significantly after the exposure to UVR. But there were no visible changes on the surface of skin's texture. CONCLUSION: With the protection of sunscreen, the UVR tolerance of skin was greatly increased after the skin's exposure to the small dose UV.