Ulcerative colitis (UC) is one of the most refractory digestive diseases in the world. Kui jie tong (KJT) is an effective traditional Chinese medicine used clinically to treat UC. This study observed the regulatory effects of KJT on NIMA-related kinase 7- (NEK7-) activated nod-like receptor protein-3 (NLRP3)/caspase-1 classical pyroptosis pathway and intestinal flora in UC model rats. KJT components were analyzed using an ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). A UC Sprague Dawley (SD) rat model was established using sodium dextran sulfate (DSS). Rats were randomly divided into four groups: control group (CG), UC model group (UG), KJT group (KG), and sulfasalazine (SASP) group (SG). After seven days of intervention, each group’s body weight, disease activity index (DAI) scores, and colon length were recorded. Intestinal mucosal injury to each group was observed using hematoxylin-eosin staining. Additionally, we investigated the expression levels of NEK7, NLRP3, ASC, caspase-1, and GSDMD in intestinal mucosa, as well as serum interleukin- (IL-) 1β, IL-18, and IL-33 proinflammatory factors. Intestinal microflora was analyzed using 16s rRNA sequencing. KJT controlled weight loss; decreased DAI scores; restored colon length; improved pathological injury in the colon; inhibited NEK7, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, and GSDMD-N expression; and decreased IL-1β, IL-18, and IL-33 contents in UG rats’ serum and colon tissue (P <0.001 or P <0.05). KJT also increased Ruminococcaceae, unclassified_f_Ruminococcaceae, and unclassified_g_Ruminococcus_1 levels and decreased Erysipelotrichia, Erysipelotrichales, Erysipelotrichaceae, Turicibacter, and uncultured_bacterium_g_Turicibacter levels. KJT alleviated UC immune-inflammatory responses to NLRP3/caspase-1 by inhibiting the NEK-7-activated classic pyroptosis pathway and improving intestinal microflora.
Osteoarthritis (OA) is an inflammatory and degenerative joint disease with severe effects on individuals, society, and the economy that affects millions of elderly people around the world. To date, there are no effective treatments for OA; however, there are some treatments that slow or prevent its progression. Polyfunctional nanosystems have many advantages, such as controlled release, targeted therapy and high loading rate, and have been widely used in OA treatment. Previous mechanistic studies have revealed that inflammation and ROS are interrelated, and a large number of studies have demonstrated that ROS play an important role in different types of OA development. In this review article, we summarize third-generation ROS-sensitive nanomaterials that scavenge excessive ROS from chondrocytes and osteoclasts in vivo. We only focus on polymer-based nanoparticles (NPs) and do not review the effects of drug-loaded or heavy metal NPs. Mounting evidence suggests that polyfunctional nanosystems will be a promising therapeutic strategy in OA therapy due to their unique characteristics of being sensitive to changes in the internal environment.
Background: Knee osteoarthritis (KOA) has a high clinical prevalence and frequently interferes with patients normal lives. In KOA patients, evidence suggests that intra-articular (IA) injection improves joint function and decreases discomfort. Several IA injection treatments are used in daily practice to improve symptomatic control of knee osteoarthritis, but their efficacy is frequently disputed. Methods: This network meta-analysis compares the efficacy of different IA injections for mild to moderate knee osteoarthritis. Seven databases (PubMed, EMBASE, Web of Science, Cochrane Library, China Biology Medicine disc, WanFang, and China National Knowledge Infrastructure) were searched for randomized controlled trials published up to and including December 20, 2021, and final follow up indicators were used. Visual analogue scale (VAS) score and The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (WOMAC) score change from baseline were the primary outcomes. We used the Cochrane risk of bias tool to assess the quality and risks of biases of papers. We calculated the weighted mean difference (WMD) and 95% confidence interval (CI) for each outcome. State (Version 15.1, Texas, USA) and SPSS (Version 20, Chicago, USA) was used in all statistical analyses, and Review Manager (version 5.4) was used in assessing the risks of biases. Results: Our study included 16 randomized controlled trials with a total of 1652 patients. platelet-rich plasma (PRP) IA injection therapy had the highest likelihood of being the best intervention in reducing WOMAC pain (surface under the cumulative ranking area [SUCRA] 84.7%), stiffness (SUCRA 95.1%), and function (SUCRA 98.5%) scores, according to the SUCRA. The best measures for lowering the WOMAC total and VAS scores were IA injection platelet-rich plasma-derived growth factor (SUCRA 84.9%) and hyaluronic acid and platelet-rich plasma (SUCRA 84.9%). In the VAS score group, PRP outperformed hyaluronic acid (HA) (WMD 1.3, 95% CI 0.55–2.55) and corticosteroids (CS) (WMD 4.85, 95% CI 4.02–5.08), according to the forest map results. PRP also outperformed CS (WMD 14.76, 95% CI 12.11–17.41), ozone (WMD 9.16, 95% CI 6.89–11.43), and PRP + HA (WMD 2.18, 95% CI 0.55–3.81) in the WOMAC total score group. Furthermore, PRP outperforms other drugs in terms of reducing WOMAC function, stiffness, and function score. Conclusion: In patients with mild to moderate KOA, IA injection PRP outperformed IA injection ozone, HA, CS, platelet-rich plasma-derived growth factor, and hyaluronic acid and platelet-rich plasma in terms of pain, stiffness, and dysfunction.
Background: Our aim was to determine the potential pharmacological mechanisms of the Guizhi decoction (GZD) in the treatment of osteoarthritis (OA) through an integrated approach of network pharmacological analyses, RNA sequencing (RNA-seq), and experimental validation.Methods: The quality control and identification of bioactive compounds of the GZD were carried out by using ultra-performance liquid chromatography (UPLC), and their OA-related genes were identified through overlapping traditional Chinese medicine systems pharmacology database (TCMSP), DrugBank and SEA Search Server databases, and GeneCards. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were implemented after constructing the component–target network. RNA-seq was used to screen differentially expressed genes (DEGs) under intervention conditions with and without the GZD in vitro. The crossover signaling pathways between RNA-seq and network pharmacology were then analyzed. Accordingly, protein–protein interaction (PPI) networks, GO, and KEGG analysis were performed using the Cytoscape, STRING, or DAVID database. The OA rat model was established to further verify the pharmacological effects in vivo. Hematoxylin–eosin (H&E) and safranin O/fast green (S-O) staining were used to grade the histopathological features of the cartilage. We verified the mRNA and protein expressions of the key targets related to the TNF signaling pathways in vivo and in vitro by qPCR, Western blotting (WB), and immunofluorescence assay. In addition, we also detected inflammatory cytokines in the rat serum by Luminex liquid suspension chip, which included tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).Results: Eighteen compounds and 373 targets of the GZD were identified. A total of 2,356 OA-related genes were obtained from the GeneCards database. A total of three hub active ingredients of quercetin, kaempferol, and beta-sitosterol were determined, while 166 target genes associated with OA were finally overlapped. The RNA-seq analysis revealed 1,426 DEGs. In the KEGG intersection between network pharmacology and RNA-seq analysis, the closest screening relevant to GZD treatment was the TNF signaling pathway, of which TNF, IL-6, and IL-1β were classified as hub genes. In consistent, H&E and S-O staining of the rat model showed that GZD could attenuate cartilage degradation. When compared with the OA group in vivo and in vitro, the mRNA levels of TNF-α, IL-1β, IL-6, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) were all downregulated in the GZD group (all p < 0.05). The expression levels of anabolic proteins (Col2α1 and SOX9) were all higher in the GZD group than in the OA group (p < 0.05), while the expression levels of the catabolic proteins (MMP9 and COX-2) and TNF-α in the GZD group were significantly lower than those in the OA group (p < 0.05). In addition, the expression levels of TNF, IL-6, and IL-1β were upregulated in the OA group, while the GZD group prevented such aberrations (p < 0.01).Conclusion: The present study reveals that the mechanism of the GZD against OA may be related to the regulation of the TNF signaling pathway and inhibition of inflammatory response.
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