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Androgenetic alopecia (AGA) is a major problem that can happen to people of all ages, leading to psychological problems, such as anxiety and depression. Topical Shen Bai hair growing decoction (TSBHGD) is based on the pathogenesis of AGA, combined with Traditional Chinese Medicine theory, improved by the Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital according to its clinical treatment experience. This study was designed to demonstrate the therapeutic efficacy of TSBHGD against AGA, analyze the chemical components of TSBHGD as well as the skin-retained and blood-retained components in mice after topical administration of TSBHGD, and clarify the mechanism of its therapeutic efficacy. It was demonstrated that TSBHGD could suppress TNF-α and IL-6 levels and improve pathological phenomena such as hair loss, reduced follicle density, and dermal thickness caused by testosterone solution. Totally 35 components were identified in TSBHGD extracts, 12 skin-retained components were identified in drug-containing skin, and 7 blood-retained components were identified in drug-containing plasma, according to ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. Transcriptomic sequencing revealed that some of the genes in AGA mice had altered expression patterns, which could be reversed by TSBHGD. Through network pharmacology analysis, it was found that TSBHGD mainly regulated eight signaling pathways, among which the apoptosis signaling pathway ranked first with a significance of 0.00149. Finally, both Bcl-2 and Caspase family proteins in the apoptosis signaling pathway were examined by Western blot. It was confirmed that TSBHGD could inhibit the apoptosis level in AGA mice's skin tissue to exert an anti-AGA effect. This will facilitate the development of new-generation herbal compound formulas with precise efficacy and provide novel ideas for AGA therapy.
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OBJECTIVE: This study aimed to validate the mechanism of triptolide in treating ankylosing spondylitis (AS) through network pharmacology, molecular docking, and in vitro experiments. METHODS: We gathered AS-related genes using databases including DrugBank, OMIM, GeneCards, TTD and DisGeNET. TCMSP database was used to collect Tripterygium wilfordii (TWHF)-related data. Additionally, the potential targets of TWHF in treating AS were predicted by consulting databases such as Venny, String, Cytoscape, and Cytohubba. Subsequently, a protein-protein interaction network was created and the gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed by metascape database. After selecting the most active ingredient of TWHF, molecular docking was performed to confirm the predicted results. Furthermore, we explore the potential mechanism of the most active ingredient of TWHF in the treatment of AS in vitro. RESULT: By integrating the results of network pharmacological analysis, 62 genes were found to be strongly associated with AS, such as STAT3, TNF, MMP9, VEGFA, CXCL8, PTGS2, etc. Triptolide (TP) is one of the most active ingredients in TWHF. The enrichment analysis indicated that 292 biological processes and 132 signaling pathways were involved, with the T helper 17 cells cell differentiation pathway as the key pathway. TP was selected for molecular docking and in vitro experiments. The molecular docking results indicated that TP had excellent affinity with 6 key targets. Further, flow cytometry, cell counting assay, and ELISA demonstrated that the serum level of IL-17 was higher in AS patients compared to XXX, and 25 µg/mL TP was the optimal intervention concentration. RT-qPCR and Western blotting further verified that TP could inhibit the activation of RORγt and the JAK2/STAT3 signaling pathway. CONCLUSION: In conclusion, based on network pharmacology, molecular docking, and experimental verification in vitro, we proposed that the TP can inhibit the activation of RORγt and the JAK2/STAT3 signaling pathway and inhibit the differentiation of T helper 17 cells cells. The article provide a theoretical basis for further development and utilization of TWHF in AS management.
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Medicamentos Herbarios Chinos , Espondilitis Anquilosante , Humanos , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Tripterygium , Simulación del Acoplamiento Molecular , Farmacología en Red , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Selenium (Se) is an essential trace element found in the body. Se deficiency and M1/M2 imbalance are closely related to inflammation. Heat stress can decrease immune function and cause inflammation. In order to investigate whether Se deficiency can aggravate pneumonia caused by heat stress and the role of M1/M2 imbalance in the occurrence of pneumonia, 100 AA broilers were divided into two groups and fed the conventional diet (0.2 mg/kg Se) and the Se-deficient diet (0.03 mg/kg Se). After 40 days of feeding, the normal feeding group was randomly divided into a control group and a heat stress group. At the same time, the Se-deficient diet feeding group was randomly divided into a low Se group and a low Se heat stress group, with 25 chickens in each group. The model was established by exposure at 40â. Six hours later, broilers were euthanized, and their lung tissues were collected. Hematoxylin and eosin staining, immunofluorescence, quantitative real-time PCR, and western blotting were used to detect lung histopathological changes and the expression of M1/M2 markers, nuclear receptor-κB (NF-κB) pathway genes, and heat shock proteins. Meanwhile, the activity and content of oxidative stress-related indices were also detected. We found that the expression of interleukin-1ß, interleukin-6, interleukin-12, and tumor necrosis factor-α was upregulated and the expression of interleukin-2, interleukin-10, and interferon-γ was downregulated. Immunofluorescence showed that the expression of CD16 was increased, the expression of CD163 was weakened, and the M1/M2 imbalance was present. In addition, the NF-κB pathway was activated by the increased expressions of heat shock proteins and oxidative stress. There was an increase in malondialdehyde, nitric oxide, and inducible nitric oxide synthase content, while the activity of total antioxidant capacity, glutathione peroxidase, catalase, and superoxide dismutase decreased, and the expression of NF-κB and cyclooxygenase-2 increased. These results suggest that low Se induces M1/M2 imbalance through oxidative stress activation of the NF-κB pathway and aggravates lung tissue inflammation caused by heat stress. This study offers a theoretical basis for exploring the pathogenesis of various kinds of inflammation induced by Se deficiency from the perspective of M1/M2 and provides a reference for the prevention of such diseases.
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Trastornos de Estrés por Calor , Neumonía , Selenio , Animales , Pollos/metabolismo , Proteínas de Choque Térmico/metabolismo , Respuesta al Choque Térmico , Inflamación/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Selenio/farmacologíaRESUMEN
BACKGROUND: The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of traditional Chinese medicine (TCM) in the treatment of rheumatoid arthritis with interstitial lung disease (RA-ILD). And provides clinicians with evidence on which to base their clinical decision making. METHODS: This review will include all studies comparing clinical efficacy of TCM in the treatment of RA-ILD. The search strategy will be performed in 9 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is lung function, number of swelling joints, number of painful joints, duration of morning stiffness, VAS score, adverse effects, quality of life, ESR, CRP, rheumatoid factor and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software. RESULTS: This study will summarize current evidence to assess the efficacy and safety of TCM in the treatment of RA-ILD. CONCLUSION: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of TCM. REGISTRATION NUMBER: INPLASY202080108 (DOI number: 10.37766/inplasy2020.8.0108).