Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking.

Purpose: Supplemented Erzhi Wan (SEZW) is a Traditional Chinese Medicine commonly used in the treatment of androgenetic alopecia (AGA). This study aims to verify the effectiveness of SEZW for the treatment of AGA in mice and explore the potential molecular mechanisms underlying its function using network pharmacology and molecular docking. Methods: Forty mice were divided into five groups: Control, AGA-model, AGA-Positive, SEZW Low Dose, and SEZW High Dose. Hair regrowth in mice was evaluated by scoring hair on days 0, 14, and 28 post-treatment and weighing mouse hair on day 28 post-treatment. The targets of the active compounds of SEZW were obtained using the Traditional Chinese Medicine Database. AGA-related targets were downloaded from five databases. Then, the overlapping genes were identified. A protein-protein interaction network was constructed using the STRING database. Hub targets were determined through analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Finally, molecular docking of active compounds and hub targets was performed. Results: Hair regrowth in mice in the SEZW treatment groups was significantly enhanced relative to that in the AGA-model mice. A total of 59 potential drug-disease targets were identified. Based on the GO/KEGG analysis results, oxidative stress and gland development were identified as potential mechanisms of action of SEZW in AGA treatment. The PI3K-Akt and AGE-RAGE signaling pathways and seven hub targets were identified as the potential underlying mechanism of SEZW function. Molecular docking results showed that the most active SEZW compounds bind stably to several of the candidate disease targets. Conclusion: SEZW is effective in the treatment of AGA in a mouse model. Combined with network pharmacological analysis, the potential mechanisms, signaling pathways, and hub targets of SEZW in the treatment of AGA were identified, providing new ideas for further studies.

Comprehensive Analysis to Identify Rh Family C Glycoprotein (RHCG) as the Causative Gene for Psoriasis and Search for Alternative Treatment Modalities.

Background: Psoriasis is a complex autoimmune disease. Frequent interactions between epidermal and immune cells are likely to be responsible for the strong heterogeneity of psoriasis. Therefore, our work aims to build on current knowledge and further search for new molecular mechanisms related to psoriasis pathogenesis in order to develop new targeted drugs. Methods: Data from psoriasis samples were obtained from the Gene Expression Omnibus (GEO) database, and batch effects were corrected using the "Combat" algorithm in the "SVA" package. Functional annotation of differential genes in psoriasis was performed by Gene set enrichment analysis (GSEA). Core functional modules were identified using the Multiscale Embedded Gene Co-Expression Network Analysis (MEGENA) algorithm for selection from the differential gene interaction network. The expression and potential function of Rh Family C Glycoprotein (RHCG) was predicted in single cell data by the "Seurat" package and validated in psoriasis samples by multiplex immunofluorescence. In addition, the regulatory function of HOP Homeobox (HOPX) on RHCG in keratinocytes was confirmed using RNA interference. Using immune infiltration analysis, RHCG and DC cells were analyzed for their association. Finally, the molecular mechanisms of treatment of psoriasis using Tripterygii Radix (TR) and Cinnamomi Ramulus (CR) were explored through network pharmacology and experimental validation. Results: Immune response (represented by C1_2) and collagen matrix formation (represented by C1_3) were identified as two important pathogenic factors in psoriasis and helped to define new biological subtypes of psoriasis. One important psoriasis hub gene, RHCG, was obtained and found to be closely associated with keratinocyte differentiation as well as DC cell maturation. And RHCG was regulated by HOPX in keratinocytes. In addition, the mechanism of action of CR and TR in the treatment of psoriasis was tentatively confirmed to be related to TRPV3, NFKB2, and YAP1. Conclusions: Our study identifies a new causal disease gene (RHCG) and offers potential alternatives for the treatment of psoriasis.

Comparison of NB-UVB combination therapy regimens for vitiligo: A systematic review and network meta-analysis.

BACKGROUND: Vitiligo was an autoimmune disease and some guidelines for the management of vitiligo encouraged the use of NB-UVB combination therapies to enhance repigmentation. OBJECTIVES: To compare the effectiveness of current NB-UVB combination regimen at the improvement in repigmentation through a systematic review and network meta-analysis. METHODS: We searched the electronic databases for randomized controlled trials related to NB-UVB combination therapy for vitiligo till October 2022. STATA15.0 software was applied to carrying out data analysis. RESULTS: A total of 28 eligible studies involving 1194 participants were enrolled in the analysis. The NMA results revealed that compared with NB-UVB, carboxytherapy [OR = 32.35, 95% CI (1.79, 586.05)], Er: YAG laser+ topical 5% 5-FU [OR = 10.74, 95% CI (4.05, 28.49)], needling/micro-needling [OR = 3.42, 95% CI (1.18, 9.88)], betamethasone intramuscular injection [OR = 3.08, 95% CI (1.17, 8.13)], topical tacrolimus [OR = 2.54, 95% CI (1.30, 4.94)], and oral Chinese herbal medicine compound [OR = 2.51, 95% CI (1.40, 4.50)] integrated with NB-UVB were more efficacious in excellent to complete repigmentation response rate (≥75%). Besides, NB-UVB+ Er: YAG laser+ topical 5% 5-FU [OR = 0.17, 95% CI (0.04, 0.67)] and NB-UVB+ needling/micro-needling [OR = 0.24, 95% CI (0.06, 0.88)] were less likely evaluated as ineffective repigmentation response (≤25%). CONCLUSIONS: All combination therapies ranked higher than NB-UVB monotherapy in inducing successful repigmentation and avoiding failed treatment in patients with vitiligo. Comprehensive consideration, NB-UVB+ Er: YAG laser+ topical 5% 5-FU and NB-UVB+ needling/microneedling would be the preferred therapeutic approaches.

Green tea polyphenols inhibit malignant melanoma progression via regulating circ_MITF/miR-30e-3p/HDAC2 axis.

Green tea polyphenols (GTPs) are regarded as anticancer substances and have been revealed to play significant roles in the development of malignant melanoma. However, the mechanisms by which GTPs perform anticarcinogenic activity are not well elucidated. Cellular function assays revealed that GTPs inhibited melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro. Circ_MITF expression was elevated in melanoma tissues and cells but was decreased by GTPs in cells. Functional experiments indicated circ_MITF overexpression reversed the anticancer effects of GTPs on melanoma cells. Then the underlying mechanism analysis suggested that circ_MITF served as a sponge for miR-30e-3p to upregulate the level of HDAC2. MiR-30e-3p reexpression attenuated the regulatory effects of circ_MITF on GTPs-treated melanoma cells. Silencing of miR-30e-3p promoted the malignant phenotypes in GTPs-treated melanoma cells, which were reversed by HDAC2 knockdown. Preclinically, administration of GTPs suppressed the expression of downstream target genes and repressed tumorigenesis of xenografts in nude mice. In all, GTPs suppressed melanoma progression by regulating circ_MITF/miR-30e-3p/HDAC2 axis, providing a potential therapeutic strategy for human malignant melanoma intervention.

Clinical Efficacy of Tacrolimus Ointment + 3% Boric Acid Lotion Joint Chinese Angelica Decoction in Chronic Perianal Eczema.

OBJECTIVE: To unearth the clinical efficacy of tacrolimus ointment + 3% boric acid lotion joint Chinese angelica decoction in chronic perianal eczema. METHODS: Patients with chronic perianal eczema admitted to hospital from June 2018 and June 2019 were retrospectively analyzed. Patients in the control group (n = 38) underwent basic therapy with tacrolimus ointment + 3% boric acid lotion, whereas those in the observation group (n = 38) were given oral Chinese angelica decoction on the basis of the above therapy. Patient's baseline information before therapy and clinical symptoms after therapy were observed and compared, including pruritus ani score, anus drainage and damp score, skin lesion score, skin lesion area score, life quality index score, and IL-2, IL-4, and IgE levels in serum. Overall efficacy in the two groups was also evaluated. RESULTS: No significant differences were found in the baseline information between the observation group and control group before therapy. After therapy, pruritus ani score (P = 0.023), anus drainage and damp score (P = 0.041), skin lesion score (P = 0.025), and skin lesion area score (P = 0.035) of patients in the observation group were remarkably lower than those in the control group. Significantly higher release levels of clinical symptoms of patients in the observation group were indicated. With respect to the control group, the life quality score (P = 0.020) and IgE level in serum (P = 0.003) of patients in the observation group were significantly lower, while IL-4 level in serum was significantly higher (P = 0.129). The therapy in the observation group achieved better clinical efficacy. Overall efficacy in the observation group was markedly favorable with respect to the control group. CONCLUSION: With respect to tacrolimus ointment + 3% boric acid lotion, patients with chronic perianal eczema displayed better clinical efficacy after jointly being treated by Chinese angelica decoction.

Our Choice: study protocol for a randomized controlled trial for optimal implementation of psoriasis treatment by the integration of Chinese and western medicine.

BACKGROUND: Plaque psoriasis is a refractory inflammatory skin disease. The common therapies used to treat plaque psoriasis in traditional Chinese medicine (TCM) and western medicine (WM) have distinct characteristics and advantages. Although a combination of TCM and WM therapies, adjusted to the clinical situation, is widely used, there are no systematic studies on the hierarchical selection of this treatment combination based on the severity of skin lesions. We therefore designed a randomized clinical trial to focus on the sequence of internal and external treatments of TCM in patients with mild-to-moderate plaque psoriasis and to optimize the integration of Chinese and western medicine for the treatment of patients with severe plaque psoriasis, thereby achieving high-level clinical evidence and establish treatment norms for the integrated use of Chinese and western medicines. METHODS: In this proposed multicenter, single-blinded, randomized controlled trial, 108 patients with mild-to-moderate plaque psoriasis will be randomly assigned to two groups in a 1:1 ratio to receive either internal or external TCM treatment, and 270 patients with severe plaque psoriasis will be randomly assigned to three groups in a 1:1:1 ratio to receive treatment with TCM or WM, or TCM + WM. All enrolled patients will receive 8 weeks of treatment. Follow-up assessments will be done 8 weeks after the treatment. The primary outcome of this study is the evaluation of efficacy and relapse rate, based on the Psoriasis Area and Severity Index, and the secondary outcome measures include determination of the affected body surface area, physician's global assessment, pruritus scores (determined using a visual analog scale), TCM symptom score, Dermatology Life Quality Index, patient-reported quality of life score and incidence of serious adverse events. DISCUSSION: This study will provide high-level clinical evidence for internal and external TCM treatment optimization and will contribute to establishing norms for the integration of Chinese and western Medicines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03941431. Registered on 8 May 2019.

Oroxylin A inhibits carcinogen-induced skin tumorigenesis through inhibition of inflammation by regulating SHCBP1 in mice.

Accumulating evidence has shown that SHC SH2 domain-binding protein 1 (SHCBP1) functions as an oncogene and participated in the progression of various cancers. Oroxylin A, an active ingredient extracted from Chinese Medicine Scutellaria baicalensis, shows strong anticancer effects on multiple cancers, however, the pharmacological effect of oroxylin A on skin cancer and the regulatory effect of SHCBP1 on this process have never been evaluated. The present study was aimed at elucidating the effect of oroxylin A on carcinogen (DMBA/TPA)-induced skin tumorigenesis, and to further clarify the role of SHCBP1 in oroxylin A induced antitumor effect. Pretreatment with oroxylin A remarkably inhibited DMBA/TPA-induced tumor formation and growth, and significantly reduced tumor incidence and the average number of tumors per mouse. Oroxylin A suppressed DMBA/TPA-induced skin hyperplasia and tumor proliferation. Oroxylin A significantly inhibited the expression of several inflammatory factors in vivo. In vitro experiments found that oroxylin A inhibited TPA-induced cell malignant transformation of skin epidermal JB6 P + cells. Besides, oroxylin A significantly suppressed the levels of TPA-induced inflammatory factors in vitro. Mechanistic studies showed that oroxylin A remarkably inhibited TPA-induced increased expression of SHCBP1. Overexpression of SHCBP1 attenuated the oroxylin A-induced anti-inflammatory effect. In addition, TPA increased the expression of nuclear NF-κB p65, and SHCBP1 siRNA notably decreased the nuclear NF-κB p65 expression in JB6 P + cells. Collectively, the anti-skin cancer effect of oroxylin A may possibly by inhibiting inflammation via suppression of SHCBP1. Oroxylin A might be a potential candidate compound for the treatment of skin cancer.