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Androgenetic alopecia (AGA) is the most common type of hair loss and features progressive miniaturization of hair follicles. Generally, the occurrence of AGA has long been thought to be driven by genetic and androgen predisposition. However, increasingly, data proposed ageing and AGA are intimately linked. Elevated senescent cell burden and androgen and oxidative stress-induced senescence mechanisms in ageing may be initial targets to improve AGA. This review summarizes the biological links between ageing and AGA, with special focus on cellular senescence. In addition, we discuss the potential therapeutic strategies for improving cellular senescence in AGA, such as inhibiting dermal papilla cells and hair follicle stem cells senescence driven by androgen and reactive oxygen species, removing senescent cell, and reducing senescence-associated secretory phenotype (SASP).
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Alopecia , Androgênios , Humanos , Androgênios/metabolismo , Androgênios/farmacologia , Alopecia/genética , Folículo Piloso , Senescência Celular/genética , Estresse OxidativoRESUMO
The disordered skin microbiome has been reported to contribute to the pathogenesis of acne vulgaris, for which benzoyl peroxide (BPO) has long been recommended as the first-line therapy. However, there are no data regarding the effect of BPO treatment on skin microbiota and the epidermal barrier in young adults with acne vulgaris. Thirty-three patients with acne vulgaris and 19 healthy controls were enrolled in the study. All patients received topical treatment with BPO 5% gel for 12 weeks. The epidermal barrier was analyzed at baseline and after treatment. Microbial diversity was analyzed using a high-throughput sequencing approach targeting the V3-V4 region of 16S rRNA genes. After receiving treatment with BPO, patients had significant improvement in their Global Acne Grading System (GAGS) score, porphyrin, and red areas (p < 0.05), and the presence of sebum, stratum corneum hydration (SCH), and transepidermal water loss (TEWL) increased (p < 0.05). When compared with baseline, microbial diversity was significantly reduced after treatment, as calculated by the goods coverage (p = 0.0017), Shannon (p = 0.0094), and Simpson (p = 0.0017) diversity indices. The prevalence of the genus Cutibacterium (before treatment: 5.64 [3.50, 7.78] vs. after treatment: 2.43 [1.81, 3.05], p = 0.011) was significantly reduced after treatment while Staphylococcus (before treatment: 43.80 [36.62, 50.98] vs. after treatment: 53.38 [44.88, 61.87], p = 0.075) tended to increase. The abundance of Staphylococcus was negatively associated with SCH (p = 0.008, r = -0.286). Despite its contribution to an improved GAGS score, BPO treatment for acne vulgaris may reduce microbial diversity and damage the epidermal barrier.
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Acne Vulgar , Fármacos Dermatológicos , Microbiota , Acne Vulgar/patologia , Peróxido de Benzoíla/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Géis , Humanos , RNA Ribossômico 16S , Resultado do Tratamento , Adulto JovemRESUMO
MOTIVATION: Microbiome-metabolome association studies have experienced exponential growth for an in-depth understanding of the impact of microbiota on human health over the last decade. However, analyzing the resulting multi-omics data and their correlations remains a significant challenge due to the lack of a comprehensive computational tool that can facilitate data integration and interpretation. In this study, an automated microbiome and metabolome integrative analysis pipeline (M2IA) has been developed to meet the urgent needs for tools that can effectively integrate microbiome and metabolome data to derive biological insights. RESULTS: M2IA streamlines the integrative data analysis between metabolome and microbiome, from data preprocessing, univariate and multivariate statistical analyses, advanced functional analysis for biological interpretation, to a summary report. The functionality of M2IA was demonstrated using TwinsUK cohort datasets consisting of 1116 fecal metabolites and 16s rRNA microbiome from 786 individuals. Moreover, two important metabolic pathways, i.e. benzoate degradation and phosphotransferase system, were identified to be closely associated with obesity. AVAILABILITY AND IMPLEMENTATION: M2IA is public available at http://m2ia.met-bioinformatics.cn. CONTACT: yanni617@zju.edu.cn or fjf68@zju.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Metaboloma , Microbiota , Fezes , Humanos , Redes e Vias Metabólicas , RNA Ribossômico 16SRESUMO
BACKGROUND AND OBJECTIVES: The skin microbiota partly determined by epidermal barrier plays an important role in acne vulgaris and intense pulsed light (IPL) has been verified as a safe and effective therapeutic option for this disease. Nevertheless, the exact role of the IPL treatment on the skin microbiota and epidermal barrier for patients with acne vulgaris remains unclear. This article was designed to solve this problem. STUDY DESIGN/MATERIALS AND METHODS: Nineteen healthy controls and 20 patients with mild to moderate acne were enrolled in this study, who received IPL treatment for 12 weeks. The epidermal barrier and skin samples were collected at baseline and after treatment. The microbial diversity was analyzed based on a high-throughput sequencing approach, which targets the V3-V4 region of the bacteria 16S ribosomal RNA genes. RESULTS: After treatment of IPL, the Global Acne Grading System (GAGS) scores, sebum, sclererythrin, and red area of patients were significantly improved by IPL treatment (P < 0.05). Although there was no difference in microbiota diversity before and after IPL treatment, the Nonmetric Multidimension Scaling (NMDS) analysis showed that the samples of the acne patients before and after treatment could be divided into two different sets by skin microbiota (P = 0.011), which could be verified by heatmap analysis. Moreover, we found that the relative abundance of Staphylococcus epidermidis (S. epidermidis) significantly increased, but Cutibacterium acnes (C. acnes) decreased after IPL treatment. The sebum concentration was positively correlated with PH value (R = 0.525, P = 0.017), and the GAGS was positively associated with both sclererythrin (R = 0.477, P = 0.002) and red area (R = -0.503, P = 0.001). CONCLUSIONS: IPL could successfully improve the GAGS scores of acne vulgaris, as well as regulate the equilibrium between C. acnes and S. epidermidis, and inhibit the sebum secretion. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.
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Acne Vulgar , Microbiota , Acne Vulgar/terapia , Epiderme , Humanos , Propionibacterium acnes , PeleRESUMO
Pemphigus vulgaris (PV) is an autoimmune disease characterized by the production of IgG autoantibodies owing to an imbalance in the Th1/Th2 and Th17/Tregs cell pathways. The role of gut microbiota in the development of immune system and autoimmune diseases has been unraveled in the last two decades. However, data pertaining to gut microbiota of PV patients is largely lacking. We aimed to compare the gut microbiota of PV patients and healthy controls and assessed potential correlation with circulating cytokines of Th1/Th2/Th17 cell. Faecal bacterial diversity was analysed in 18 PV patients and 14 age- and gender-matched healthy individuals using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Plasma levels of 20 inflammatory cytokines were assessed using the Luminex screening system. As a result, we identified 10 differentially abundant taxa between patients and controls. At the genera level, Lachnospiracea_incertae_sedis and Coprococcus decreased, while Granulicatella, Flavonifractor enriched in PV. Plasma levels of C5a, interleukin (IL)-2R, IL-6, IL-8, IL-7, IL-1ß, IL17A, IL-5 and IL-21 were significantly increased in PV Flavonifractor exhibited a positive correlation with C5a, IL-6, IL-8, IL-7, IL-1ß, IL17A and IL-21. Lachnospiracea_incertae_sedis and Coprococcus showed a negative correlation with IL-17A. Our results are consistent with the hypothesis that PV patients have gut microbial dysbiosis which might contribute to the immune disorder and the development of PV.
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Doenças Autoimunes/imunologia , Citocinas/imunologia , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Pênfigo/imunologia , Plasma/imunologia , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/microbiologia , Fezes/microbiologia , Feminino , Humanos , Inflamação/microbiologia , Masculino , Pessoa de Meia-Idade , Pênfigo/microbiologia , Plasma/microbiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/microbiologia , Células Th1/imunologia , Células Th1/microbiologia , Células Th17/imunologia , Células Th17/microbiologia , Células Th2/imunologia , Células Th2/microbiologiaRESUMO
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is one of the proteins that contributes to the survival, growth, maintenance of neurons, and plays important roles in the pathophysiology of depression. It has been reported that depression is closely associated with the pathogenesis of acne vulgaris disease. But, there is no report of serum BDNF levels in patients with acne vulgaris. The study aimed to determine the potential association between BDNF and depressive symptoms in young adults with acne vulgaris. METHODS: In this analytical cross-sectional study, the serum BDNF levels were measured in peripheral blood samples of 20 consecutive acne vulgaris patients with depression and 98 consecutive acne vulgaris patients without depression and also compared it with a 59 healthy control group by using a ELISA. The potential correlation between the BDNF levels, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and depressive symptoms such as nine-item patient health questionnaire (PHQ-9) and Athens insomnia scale (AIS) were evaluated with multivariate logistic regression analysis. RESULTS: Our results showed that levels of BDNF expression were lower in consecutive acne vulgaris patients when compared with healthy control (P < 0.05). There was a negative correlation between levels of BDNF and the PHQ-9 scores (r = - 0.486, P < 0.001). Furthermore, acne vulgaris patients with depression showed lower serum BDNF levels (10.96 ± 2.12 ng/ml) compared with acne vulgaris patients without depression (13.85 ± 2.47 ng/ml), as well as with healthy control (14.35 ± 2.70 ng/mg; both P < 0.05). No difference was found in serum BDNF levels between healthy control and acne vulgaris patients without depressive symptoms (z = 0.964, P > 0.05). Similarly, the overall area under the curve of receiver operating characteristic was 0.82, indicating the highly conserving of serum BDNF levels as an biomarker for screening of depression in young adults with acne vulgaris (72% sensitivity and 85% specificity). CONCLUSION: Serum BDNF levels were decreased and negatively associated with depressive symptoms in young Chinese adults with acne vulgaris.
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Acne Vulgar/sangue , Acne Vulgar/epidemiologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Depressão/sangue , Depressão/epidemiologia , Acne Vulgar/diagnóstico , Adolescente , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Depressão/diagnóstico , Feminino , Humanos , Masculino , Questionário de Saúde do Paciente , Adulto JovemRESUMO
PURPOSE: YKL-40 is a chitinase-like protein expressed in multiple tissues including liver and is reported as a fibrosis marker. This study aimed to determine whether YKL-40 could serve as a diagnostic marker for the assessment of liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT. METHODS: Six hundred and eighty-five patients with chronic hepatitis B infection were enrolled in this study from October 2013 to March 2016. All patients underwent liver biopsy and then staged based on Ishak histological system. Serum YKL-40 levels were measured by Human Magnetic Luminex Assays. RESULTS: Among chronic hepatitis B patients with normal and mildly elevated ALT, almost more than 30% of patients have significant liver fibrosis. Serum YKL-40 levels increased significantly in parallel with the progression of fibrosis in patients with ALT less than two times the upper limit of normal range (P < 0.0001). Multivariate analysis revealed that serum YKL-40, hyaluronic acid, PLT, and AST were independently associated with significant fibrosis. We established a novel YKL-40-based fibrosis model for patients with ALT less than two times the upper limit of normal range (ULN). YKL-40 model was superior to APRI, FIB-4, Forns' index, and Hui model for diagnosis of significant fibrosis in patients with ALT < 2ULN, with AUROCs of 0.786 [95% confidence interval (CI) 0.726-0.846] in the training group, 0.831 (95%CI 0.752-0.910) in the validation group and 0.801 (95%CI 0.753-0.849) in the entire cohort. CONCLUSION: Serum YKL-40 is a feasible biomarker of liver fibrosis in chronic hepatitis B patients. YKL-40 model was superior to APRI, FIB-4, Forns' index and Hui model for diagnosis of significant fibrosis in patients with normal and mildly elevated ALT.
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Alanina Transaminase/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Hepatite B Crônica/complicações , Cirrose Hepática/diagnóstico , Adulto , Biomarcadores/sangue , China , Estudos de Coortes , Feminino , Humanos , MasculinoRESUMO
Acne vulgaris has been postulated to have a gastrointestinal mechanism; however, little is known about gut microbiota dysfunction in this condition. The aim of this cross-sectional study was to investigate whether the gut microbiota is altered in acne. Faecal bacterial diversity was analysed in 43 patients with acne and 43 controls, using hypervariable tag sequencing of the V3-V4 region of the 16S rDNA gene. Distinct differences were found in microbial diversity between patients with acne and controls (Shannon diversity index (p = 0.009) and Simpson diversity index (p = 0.01)). At the phylum level, the abundance of Firmicutes was lower in the patient group, but that of Bacteroidiain was higher. The most significantly depleted taxa in acne were Clostridia, Clostridiales, Lachnospiraceae and Ruminococcaceae genera, which are potentially beneficial. In conclusion, patients with acne vulgaris have gut microbial dysbiosis; further study is needed to understand its role in the pathogenesis of acne.
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Acne Vulgar/microbiologia , Bactérias/crescimento & desenvolvimento , Microbioma Gastrointestinal , Intestinos/microbiologia , Acne Vulgar/diagnóstico , Adolescente , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles , Estudos Transversais , Fezes/microbiologia , Feminino , Humanos , Masculino , Ribotipagem , Adulto JovemRESUMO
PURPOSE: To investigate the association between serum complement 5a (C5a) concentration and liver fibrosis and cirrhosis in a large cohort of patients chronically infected with hepatitis B virus (HBV). METHODS: Five hundred and eight patients with chronic HBV infection undergoing liver biopsy were included. Serum concentrations of C5a was measured by Luminex screening system. Ishak histological system was obtained. RESULTS: C5a levels were negatively associated with liver fibrosis stages and significantly declined in patients with severe fibrosis and cirrhosis (P < 0.001). Multiple analysis showed C5a, AST, laminin, Co-IV, platelet count, albumin, HBsAg associated with liver fibrosis independently. Based on the markers above, we created two scores, Fib-model for significant fibrosis and Cirrh-model for earlier cirrhosis. Fib-model was performing better to differentiate from significant fibrosis, with an AUROC of 0.82 (95 % CI 0.78, 0.86), in comparison to existed models APRI, FIB-4 and Forns' index with AUROCs of 0.71 (95 % CI 0.66, 0.76), 0.72 (95 % CI 0.67, 0.77), 0.77 (95 % CI 0.72, 0.81), respectively. Although, Cirrh-model showed AUROC of 0.85 (95 % CI 0.80, 0.91) for evaluation of earlier cirrhosis, superior to APRI, and Forns' index, C5a + FIB-4 performed best with an AUROC of 0.94 (95 % CI 0.90, 0.97). CONCLUSION: In patients with chronic HBV infection, serum C5a concentration significantly decreased in severe fibrosis stages and earlier cirrhosis. Fib-model and C5a + FIB-4 performed better than existed models for assessment of significant fibrosis and earlier cirrhosis, respectively.
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Complemento C5a/análise , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Adulto , Análise de Variância , Biomarcadores/sangue , Estudos de Coortes , Feminino , Vírus da Hepatite B , Hepatite B Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: For hepatitis B patients who do not meet the treatment criteria recommended by guidelines, therapy decisions depend on hepatic histology. Angiopoietin-like protein 2 (Angptl2) is a mediator of chronic inflammation that contributes to extracellular matrix remodeling. The aim of this study was to explore the predictive value of Angptl2 as a novel biomarker of liver histology. METHODS: Hepatitis B patients with normal to minimally raised ALT were recruited. Serum Angptl2 concentrations were detected using commercial ELISA kit. The fibrosis score were assessed according to Ishak criteria. Significant fibrosis was defined as ISHAK score ≥ 3. RESULTS: Of 460 patients, 223 cases served as training cohort and 237 ones as validation cohort. Serum Angptl2 concentration was significantly associated with fibrosis scores in both training and validation group. Angptl2 combined index (ACI) for assessing significant fibrosis was developed from training cohort, based on Angptl2 and conventional variables. ACI showed areas under receiver-operating characteristic curve (AUC) of 0.835 for predicting significant fibrosis, which was superior to APRI (AUC = 0.776, P = 0.049), FIB-4 (AUC = 0.750, P = 0.010), Hui model (AUC = 0.756, P = 0.028), and had a better trend than Forn's index (AUC = 0.796, P = 0.083) in training cohort. Finally, validation cohort revealed its robustness and reliability. CONCLUSION: Higher Angptl2 level represents as a potential biomarker independently associated with fibrosis stages. Compared with APRI, Hui model, FIB-4, Forn's index, ACI did better in diagnosing significant fibrosis in hepatitis B patients. TRIAL REGISTRATION: The complete clinical trials protocol is available by request at clinicaltrials.gov ( NCT01962155 ) and chictr.org ( ChiCTR-DDT-13003724 ).
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Proteínas Semelhantes a Angiopoietina/sangue , Biomarcadores/sangue , Hepatite B Crônica/sangue , Cirrose Hepática/sangue , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Proteína 2 Semelhante a Angiopoietina , Estudos de Coortes , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos TestesAssuntos
Conexinas/genética , Eritroceratodermia Variável/genética , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Sequenciamento do ExomaRESUMO
Objectives:We aimed to explore the potential role of omega-3 (ω-3) fatty acids on acne vulgaris by modulating gut microbiota.Materials and Methods:We randomly divided the untreated acne patients into two groups with or without ω-3 fatty acids intervention for 12 weeks. The Sprague Dawley (SD) rats with acne model were given isotretinoin, ω-3 fatty acids or their combination respectively. Then the colonic contents samples of the drug intervention SD rats were transferred to the pseudo sterile rats with acne model. The severity of the disease was assessed by the Global Acne Grading System (GAGS) score of the patients, and the swelling rate of auricle and the pathological section of the rat with acne model. The 16S rDNA gene sequencing was performed to detect the alteration of the gut microbiota.Results:ω-3 fatty acids could increase the diversity of the gut microbiota and regulate the flora structure positively both in the patients and rats, increase the abundance of butyric acid producing bacteria and GAGS score in the patients, and alleviate the inflammation and comedones of rats.Conclusion:Supplementation of ω-3 fatty acids could alleviate the inflammation of acne vulgaris by increasing the abundance of butyric acid producing bacteria.
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Acne Vulgar , Ácidos Graxos Ômega-3 , Microbioma Gastrointestinal , Animais , Humanos , Ratos , Acne Vulgar/microbiologia , Adjuvantes Imunológicos , Butiratos/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Inflamação/tratamento farmacológico , Ratos Sprague-DawleyRESUMO
Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease, of which the pathogenesis is a complex interplay between genetics and environment. Although the exact mechanisms of the disease pathogenesis remain unclear, the immune dysregulation primarily involving the Th2 inflammatory pathway and accompanied with an imbalance of multiple immune cells is considered as one of the critical etiologies of AD. Tryptophan metabolism has long been firmly established as a key regulator of immune cells and then affect the occurrence and development of many immune and inflammatory diseases. But the relationship between tryptophan metabolism and the pathogenesis of AD has not been profoundly discussed throughout the literatures. Therefore, this review is conducted to discuss the relationship between tryptophan metabolism and the complex network of skin inflammatory response in AD, which is important to elucidate its complex pathophysiological mechanisms, and then lead to the development of new therapeutic strategies and drugs for the treatment of this frequently relapsing disease.
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Dermatite Atópica , Humanos , Triptofano/metabolismo , PeleRESUMO
Background: The depletion of beneficial bacteria in the gut has been found in patients with acne vulgaris, and in previous studies, the supplement of Lactobacillus rhamnosus led to the improvement of adult acne. Nevertheless, the potential mechanism of L. rhamnosus in the amelioration of acne vulgaris has not been elucidated yet. Methods: To mimic the human intestinal environment, a pseudo-germ-free rat model was used, and then gut microbiota from healthy individuals and acne patients were transplanted into rats. The effects of L. rhamnosus and tryptophan (Trp) metabolites on a rat acne model were investigated by gavage. Then, 16S rRNA analysis and targeted measurement of metabolites were performed to discover the differences in gut microbiota and metabolites between groups. Finally, HaCaT cells pretreated with Cutibacterium acnes were employed to validate the effect and mechanism of Trp metabolites on acne. Results: L. rhamnosus significantly improved acne-like symptoms in rats by suppressing the level of inflammatory cytokines such as IL-1ß, IL-6, and TNF-α. L. rhamnosus induced an increase in the production of indole-3-acetic acid (IAA) and indole via targeted Trp metabolic analyses. Furthermore, L. rhamnosus promoted bacterial diversity and also enhanced the Firmicutes/Bacteroidota (F/B) ratio, which was positively related to both IAA and indole. Finally, the roles of IAA and indole in alleviating acne vulgaris were confirmed both in vitro and in vivo, which could be reversed by AhR inhibitors. Conclusion: Our study demonstrated that L. rhamnosus could exert its therapeutic effects on acne vulgaris by modulating the gut microbiota and regulating associated Trp metabolites.
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Acne Vulgar , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Adulto , Humanos , Animais , Ratos , Ratos Sprague-Dawley , RNA Ribossômico 16S , Triptofano , Indóis , Acne Vulgar/terapiaRESUMO
The common causes for melanonychia include melanoma, repetitive trauma, underlying systemic diseases, onychomycosis, pseudomonas infection and drugs. Drug-induced melanonychia usually affects numerous nails and appears as light brown to black pigmentation on the deck or nail bed with longitudinal, transverse or diffuse distribution. In previous cases, a number of chemotherapeutic agents such as azathioprine, bleomycin sulfate, cyclophosphamide, hydroxyurea and methotrexate were usually linked to melanonychia. Citri reticulatae pericarpium (CRP) is a traditional Chinese herb which is widely used in many foods and health care products in China. Up till now, there were no adverse reactions of CRP reported throughout the literature. Herein, we firstly reported a case of melanonychia in a 67-year-old man caused by CRP for external use.
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Signet-ring cell (SRC) is a histologic type in which cells show unique features under the microscope. We mainly found signet-ring cells (SRCs) in gastrointestinal and breast tumors. Cutaneous metastasis from internal carcinomas was an uncommon presentation. The cases of signet-ring cell carcinoma (SRCC) metastasis to the skin were rarely reported. Cutaneous metastasis indicated a poor prognosis for a patient. Here, we report a female who had huge grape-like nodules arising from gastrointestinal SRCC in her trunk and thigh.
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Purpose: Taohong Siwu decoction (THSWD) is traditionally used to treat androgenic alopecia (AGA) in clinical practice of traditional Chinese medicine. This study used a network pharmacology approach to elucidate the molecular mechanism governing the effect of THSWD on AGA. Materials and Methods: The major active components and their corresponding targets of THSWD were screened. AGA-related targets were obtained by analyzing the differentially expressed genes between AGA patients and healthy individuals. The protein-protein interaction networks of putative targets of THSWD and AGA-related targets were visualized and merged to identify the candidate targets for THSWD against AGA. Gene ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for core targets were performed. Finally, the key effective components and core targets screened were verified by molecular docking. Results: In this study, 69 compounds and 202 compound targets of THSWD, as well as 1158 disease targets, were screened. Forty-five interactive targets were identified for constructing the "ingredient-targets" network. The functional annotations of target genes were found to be related to oxidative stress, reactive oxygen species, and hydrogen peroxide. Pathways involved in the treatment of AGA included apoptosis and PI3K-AKT signaling pathways. The luteolin, quercetin, kaempferol, baicalein, and beta-carotene were identified as the vital active compounds, and AKT1, TP53, JUN, CASP3 and MYC were considered as the core targets. Assessment of molecular docking revealed that these active compounds and targets had good-binding interactions. Conclusion: The results indicated that the effects of THSWD against AGA may be related to anti-inflammation and anti-oxidation properties of the compounds through the specific biological processes and the related pathways.
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Acne vulgaris is a chronic inflammatory skin disease in which the influence of gut microbiota has been implicated but without clarification of mechanisms. Gut microbiota may exert such an influence via metabolites, particularly those of tryptophan. End metabolites of tryptophan activate receptors, including aryl hydrocarbon, G protein-coupled, and pregnane X receptors to stabilize the immune microenvironment and intestinal mucosal homeostasis. Any impact on the pathogenesis of acne vulgaris remains unclear. The current review collates recent advances concerning potential roles of tryptophan metabolism in mediating skin inflammation, follicular sebaceous gland function and intestinal permeability, all of which influence the pathogenesis of acne vulgaris. The aim was to improve understanding of the pathogenesis of acne vulgaris and to expose therapeutic opportunities.
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OBJECTIVE: The aim of this research was to systematically investigate the effects of endothelial mesenchymal transition (EndMT) induced by hypoxia on the skin microvascular remodeling of systemic sclerosis (SSc) and the underlying mechanism. METHODS: Skin tissues from SSc patients and controls were collected for isobaric tags for the relative and absolute quantification (iTRAQ)-based proteomics and immunohistochemical test. Human microvascular endothelial cell line-1 (HMEC-1) cultured in hypoxic or normal conditions was treated by tamoxifen or bevacizumab. RESULTS: The iTRAQ-based proteomics indicated a significantly upregulated hypoxia-inducible factor-1 (HIF-1) signal in SSc samples. The immunohistochemical results demonstrated the significant downregulation of CD31, the positive staining of α-smooth muscle actin (α-SMA), HIF-1α, and vascular endothelial growth factor (VEGF-a) in SSc skin tissues, compared with control samples. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside a marked increase in the expression of α-SMA and fibronectin, as well as a distinct upregulation of HIF-1α and VEGF-a, when compared with those under normal conditions. It is noteworthy that the inhibition of HIF-1α by tamoxifen effectively downregulated the hypoxic induction of VEGF-a and α-SMA while rescuing the hypoxic suppression of CD31. In addition, the VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31, as a tamoxifen intervention, but did not reduce HIF-1α. CONCLUSION: These results suggest that the HIF-1α/VEGF signaling pathway can have a critical role in mediating the effect of hypoxia-induced EndMT on the skin microvascular remodeling of SSc.
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Fator A de Crescimento do Endotélio VascularRESUMO
Senile pruritus (SP) is a common skin disease in the elderly. The role of skin dysbacteriosis in the development of various skin diseases has been studied in recent years. However, the research about the skin microbiota of senile pruritus patients is lacking at present. The purpose of this cross-sectional study was to investigate the differences of skin microbiota in senile pruritus patients and their relationship with the epidermal barrier. Thirty patients with senile pruritus and 30 age- and sex-matched healthy controls were enrolled in this study. The skin barrier indexes were recorded by multi-functional skin tester. The skin bacterial diversity was analyzed by using hyper-variable tag sequencing of the V3-V4 region of the 16S rDNA. Compared with the healthy control group, the patients had significantly lower skin hydration (p = 0.014) and higher pH value (p = 0.021). Skin microbial diversity was significantly increased in patients according to the alpha diversity. At the genus level, Acinetobacter (p = 0.002) and Lactobacillus (p = 0.002) increased and Cutibacterium (p = 0.043) decreased. The pH value was positively associated with observed_species diversity (p = 0.026). The transdermal water loss was negatively related to the genus of Lactobacillus (p = 0.036), while the skin hydration was positively associated with the genus of Lactobacillus (p = 0.038). As a result, the damaged skin barrier function and skin dysbacteriosis complemented each other and may be associated with the occurrence of senile pruritus, but their role still needs further study.