Yu-Ping-Feng-San alleviates inflammation in atopic dermatitis mice by TLR4/MyD88/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Yu-Ping-Feng-San (YPF) is a traditional Chinese medicine formula that has therapeutic effects on allergic diseases such as allergic rhinitis and asthma. However, its potential efficacy and mechanism in the treatment of atopic dermatitis (AD) has not been extensively illustrated. AIM OF THE STUDY: The purpose of this study was to investigate the efficacy and possible mechanisms of YPF in AD pathogenesis. METHODS: Network pharmacology and GEO data mining were adopted to firstly identify the potential mechanisms of YPF on AD. Then DNCB induced-AD murine model was established to test the efficacy of YPF and verify its effects on inflammatory cytokines and NF-κB pathway. In addition, molecular docking was performed to detect the binding affinity of YPF's active components with NF-κB pathway related molecules. RESULTS: Network pharmacology and human data mining suggested that YPF may act on the NF-κB pathway in AD pathogenesis. With DNCB mice model, we found that YPF significantly improved AD symptoms, reduced SCORAD scores, and alleviated skin tissue inflammation in mice. At the same time, the expression of inflammatory cytokines, TNF-α, sPLA2-IIA and IL-6, was down-regulated. Moreover, YPF suppressed TLR4/MyD88/NF-κB pathway in situ in a dose-dependent manner. Molecular docking further confirmed that seven compounds in YPF had exceptional binding properties with TNF-α, IL-6 and TLR4. CONCLUSION: YPF may help the recovery of AD by inhibiting the TLR4/MyD88/NF-κB pathway, which provides novel insights for the treatment of AD by YPF.

Qinzhuliangxue mixture ameliorates psoriasis by restraining apoptosis in psoriasis via downregulating the MDA-5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis, which was earliest recorded in the classic Chinese medicine book Xia's Surgery. In our previous clinical studies, QZLX demonstrated 83.33% efficacy with few side effects in the treatment of psoriasis. Furthermore, our published basic research has also proved that the QZLX mixture effectively inhibits the hyperproliferation of keratinocytes, thus exerting therapeutic effects on psoriasis. However, whether QZLX mixture can regulate keratinocytes apoptosis requires further clarification. OBJECTIVE OF THE STUDY: To investigate the mechanism of QZLX in the treatment of psoriasis from the perspective of keratinocyte apoptosis. MATERIALS AND METHODS: First, psoriasis-like mice with imiquimod (IMQ)-induced were given QZLX intragastric administration and Psoriasis Area Severity Index (PASI) scores were recored for 11 consecutive days to appraise the efficacy. Then, tissue samples were collected for transcriptome analysis. The DEseq2 method detected significantly differentially expressed genes (DEGs), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway databases were used to analyze the functions and pathway enrichment of DEGs. After that, the therapeutic mechanisms of QZLX in intervening with psoriasis were explored using TUNEL, immunohistochemical staining, and western blotting. RESULTS: QZLX ameliorated the symptoms and pathological characteristics of IMQ-induced psoriasis in mice. The epidermal cell hyperplasia in the skin was inhibited, in accordance with the suppressed expression of PCNA and Ki67 after treatment. Transcriptome sequencing showed that melanoma differentiation associated gene-5 (MDA-5) was downregulated. GO and KEGG enrichment analysis of the signaling pathways indicated that the differentially expressed genes were significantly enriched in apoptosis pathways. Besides, QZLX treatment decreased the apoptosis of keratinocyte as shown by reduced TUNEL-positive cells. As MDA-5 protein levels decreased, so did the expression of the downstream protein Caspase-8, which indicates that the apoptotic pathway was triggered. Furthermore, QZLX therapy might also help to balance the apoptotic Bcl-2 family expression. CONCLUSION: QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.

Shielded geomagnetic field accelerates glucose consumption in human neuroblastoma cells by promoting anaerobic glycolysis.

A shielded geomagnetic field, also called the hypomagnetic field (HMF), interferes with the metabolic processes of various cells and animals exhibiting diverse effects in different models, however, its underlying mechanism remains largely unknown. In this study, we assessed the effect on the energy metabolism of SH-SY5Y cells in HMF and found that HMF-induced cell proliferation depends on glucose supply. HMF promoted SH-SY5Y cell proliferation by increasing glucose consumption rate via up-regulating anaerobic glycolysis in the cells. Increased activity of LDH, a key member of glycolysis, was possibly a direct response to HMF-induced cell proliferation. Thus, we unveiled a novel subcellular mechanism underlying the HMF-induced cellular response: the up-regulation of anaerobic glycolysis and repression of oxidative stress shifted cellular metabolism more towards the Warburg effect commonly observed in cancer metabolism. We suggest that cellular metabolic profiles of various cell types may determine HMF-induced cellular effects, and a magnetic field can be applied as a non-invasive regulator of cell metabolism.

Prognostic value of derived neutrophil-to-lymphocyte ratio (dNLR) in patients with non-small cell lung cancer receiving immune checkpoint inhibitors: a meta-analysis.

OBJECTIVES: Derived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR in patients with NSCLC treated with immune checkpoint inhibitors (ICIs) remains inconsistent. The objective of this work was to evaluate the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs. DESIGN: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for eligible studies up to 16 October 2020. ELIGIBILITY CRITERIA: (1) Human subjects receiving ICIs therapy and who had been diagnosed with NSCLC; (2) the baseline values of dNLR were obtained; (3) the objective of the study was to investigate the relationships between dNLR and overall survival (OS) or progression-free survival (PFS) in NSCLC and (4) HR and 95% CI were displayed in the original article or could be extracted from Kaplan-Meier curves. DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data independently. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with Cochran's Q test and I2 statistics. Publication bias of studies was assessed by Begg's test and Egger's test. We used V.12.0 of the Stata statistical software. RESULTS: This analysis included eight studies (2456 cases) on the prognostic utility of dNLR in ICI therapy for NSCLC. The results indicate that higher dNLR significantly predicted poor OS (HR=1.65, 95% CI 1.46 to 1.88; p<0.001) and PFS (HR=1.38, 95% CI 1.23 to 1.55; p<0.001). Subgroup analyses of OS-related studies indicated that there were similar results in stratifications by ethnicity, sample size, type of HR and dNLR cut-off value. As for PFS-related studies, subgroup analyses showed no significant difference in Asian populations. Publication biases were not detected using Begg's test and Egger's linear regression test. CONCLUSIONS: This meta-analysis indicated that elevated pretreatment dNLR may be a negative prognostic predictor for patients with NSCLC treated with ICIs. More large-sample and higher-quality studies are warranted to support our findings. PROSPERO REGISTRATION NUMBER: CRD42021214034.

Comparative efficacy and safety of thirteen biologic therapies for patients with moderate or severe psoriasis: A network meta-analysis.

PURPOSE: This network meta-analysis was aimed to enhance the corresponding evidence with respect to the efficacy and safety of biologic treatments. METHODS: PubMed and EMBASE database searches were conducted. Odds ratios were used to evaluate multi-aspect comparisons. SUCRA was used to analyze the ranking of treatments in each endpoint. Psoriasis Area and Severity Index 50%, 75%, 90%, 100%, PGA, dermatology quality of life index were considered as outcomes while adverse events and discontinuation were adopted to evaluate safety. RESULTS: For safety issues, briakinumab was associated with least headache and itolizumab had the lowest risk of infection. Ustekinumab performed best in discontinuation. SUCRA ranked briakinumab, brodalumab, Infliximab and ixekizumab as the favorable efficacy therapies, while briakinumab and brodalumab seemed to have mild side effects. No heterogeneity was observed between these comparisons. CONCLUSIONS: Briakinumab performed relatively stable under efficacy and safety outcome. Infliximab can be a good choice for its lower risk of infection. Brodalumab present very good potential in efficacy outcome like PASI and PGA. More clinical trials are required to supply more data about discontinuation of infliximab and infection of brodalumab and larger RCT for assessment of briakinumab.