Henan University of Traditional Chinese Medicine

Jinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of human histone deacetylase-2 (HDAC2). However the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear.

To explore the target of Jinwei decoction to enhance the anti-inflammatory effect of GC on COPD through microRNA155-5p (miR-155-5p) by network pharmacology and experimental verification.

The TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-155-5p. COPD-related genes were identified by searching GeneCards, Grugbank and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. A COPD cell model was established by 5% cigarette smoke extract (CSE)- induced bronchial epithelial cell (BEAS-2B), and the results of network pharmacology were verified by in vitro experiments.

Two hundred thirty-one active ingredients, 352 Jinwei decoction drug targets, 5949 miR-155-5p target genes, 8286 COPD target genes, and 127 intersection genes were identified. Twelve core proteins of PPI networks may be involved. GO enrichment analysis showed that regulation of membrane potential， response to steroid hormone, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, and other signaling pathways. The molecular docking results showed that quercetin, luteolin and stigmasterol have higher affinity with PTGS2, HIF1A and AKT1. The results of cell experiments revealed that Jinwei decoction not only enhances the anti- inflammatory effect of GC in the COPD cell model but also reverses the high expression of miR-155-5p、PI3k、Akt, and low expression of HDAC2, thereby inhibiting the inflammatory response of COPD.

Jinwei decoction can regulate HDAC2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-155-5p. Its mechanism of action may be related to its effect on the PI3K-Akt through miR-155-5p.

In this study, the immunomodulatory effects of polysaccharide obtained by hot-compressed steaming of Rehmannia glutinosa Libosch (HRP) were investigated using both in vitro and in vivo methods. It was found that HRP activated the TLR4/NF-κB signaling pathway, up-regulated the intracellular expression of TNF-α, IL-6 and IL-1β, and induced of innate immune memory in macrophages. We then investigated the effect of HRP on immunosuppressed mice induced by cyclophosphamide (CTX). Surprisingly, HRP improved CTX-induced weight loss and increased the splenic index, alleviated intestinal mucosal damage and hematopoietic insufficiency caused by CTX, as demonstrated by H&E staining. In addition, HRP promoted the expression of key proteins in the TLR4/NF-κB and autophagy pathways in intestinal tissues, thereby enhancing intestinal immune function. Bacterial 16S rRNA gene sequences of colon contents suggested that HRP may alleviate gut microbiota disruption by increasing the populations of Lachnospiraceae and Erysipelotrichaceae while inhibiting Lactobacillaceae. The results of this study show the potential use of HRP as an immunomodulator in functional foods or pharmaceuticals.

Numerous cohort studies have explored the association between age-related macular degeneration (AMD) and Parkinson disease (PD). However, a comprehensive meta-analysis on this topic is currently lacking. This study aims to address this gap by conducting a meta-analysis of existing cohort studies to investigate the relationship between AMD and the risk of developing PD.

Relevant studies were systematically identified through thorough searches of the PubMed, Web of Science, Embase, and Cochrane Library databases. Two investigators independently conducted data extraction. Cohort studies meeting the eligibility criteria and providing risk and precision estimates regarding AMD and the risk of PD were included. Pooled hazard ratio (HR) accompanied by 95% confidence interval (CI) were calculated using either a random-effects model or a fixed-effects model. Sensitivity analyses, involving the exclusion of 1 study at a time, were performed to assess the robustness of the findings. Publication bias was evaluated using Egger test.

Five studies were included, encompassing a total of 4,771,416 individuals. Among these, 128,771 individuals had AMD, while 4,642,645 individuals did not. The pooled analysis revealed a significant increase in the risk of developing PD for individuals with age-related macular degeneration (hazard ratio [HR] = 1.44; 95% confidence interval [CI]: 1.22–1.71; I2 = 47.3%). Sensitivity analysis confirmed the robustness of the results. For the exploration of the relationship between nAMD and the risk of developing PD, 2 cohorts were included. The pooled analysis demonstrated a significantly elevated risk of PD for individuals with nAMD (HR = 2.21; 95% CI: 1.55–3.16; I2 = 0%).

This meta-analysis suggests a significant association between AMD and an increased risk of PD. These findings offer fresh perspectives on PD’s etiology and pathogenesis, but should be interpreted with caution given the limitations in establishing causality.