Severe acute pancreatitis (SAP) is a common acute abdominal disease. This study was designed to investigate the preventive effects of curcumin on SAP and its possible mechanism of action. We observed increased volume of ascites, serum AMY, IL-6, and TNF-α levels, and expression of TLR-4 and NF-κB mRNA and protein in a rat model of SAP. Application of curcumin resulted in lower ascites volume and serum AMY. The levels of serum cytokines IL-10 and TNF-α were also significantly reduced after curcumin treatment, as evident from ELISA analysis. RT-PCR analysis showed down-regulation of TLR4 and NF-κB expressions as a function of curcumin treatment. Our results demonstrate the protective effect of curcumin in a rat model of SAP via the involvement of TLR-4/NF-κB signaling pathway.
Background: Hirudin has been widely used in the treatment of antifibrosis. Previous studies have shown that hirudin can effectively improve the clinical remission rate of chronic kidney disease. However, the mechanism of its renal protection has not been systematically investigated.Methods: In this study, the reliability of UUO-induced renal interstitial fibrosis was evaluated by histopathological verification. High-throughput transcriptome sequencing was used to elucidate the molecular mechanism of hirudin, differentially expressed mRNAs were identified, and their functions were analyzed by GO analysis and GSEA. In addition, the RNA-seq results were validated by in vitro and vivo experiments.Results: We found 322 identical differential expressed genes (IDEs) in the UUO hirudin-treated group compared with the sham group. Functional enrichment analysis indicated that cellular amino acid metabolic processes were the most obvious enrichment pathways in biological processes. In terms of molecular functional enrichment analysis, IDEs were mainly enriched in coenzyme binding, pyridoxal phosphate binding and other pathways. In addition, microbody is the most obvious pathway for cellular components. A total of 115 signaling pathways were enriched, and AMPK, JAK-STAT, and PI3K-Akt signaling pathways were the important signaling pathways enriched. We found that PI3K, p-Akt, and mTOR expression were significantly reduced by hirudin treatment. In particular, our results showed that hirudin could induce a decrease in the expression of autophagy-related proteins such as P62, LC3, Beclin-1 in TGF-β1-induced NRK-52E cells.Conclusion: Our results suggest that hirudin may protect the kidney by ameliorating renal autophagy impairment through modulating the PI3K/Akt pathway.
Background: Diabetic nephropathy (DN) is one of the common complications of diabetes, it can cause a disproportionate burden. Leeches are widely used to treat DN in China, and hirudin is the main component of leeches. However, its pharmacological mechanisms and molecular targets are unclear. This work aimed to explore new biomarkers of DN and reveal the mechanism of hirudin in DN. Methods: Expression microarray datas between kidney tissues of DN and control individuals were obtained from the GEO database, and differentially expressed genes were identified as DN-related targets using the robust rank aggregation analysis. The SEA, GeneCards and SwissTargetPrediction databases were used to predict targets of hirudin. A protein-protein interaction network of DN-hirudin was conducted by Cytoscape software. GO and KEGG pathway enrichment analyses were carried out to explore the involved pharmacological mechanism of hirudin in treatment of DN. And molecular docking was adopted to predict the hub targets of hirudin. Results: A total of 30 significant DEGs (16 up- and 14 down-regulated) were identified. ATF3, SLC22A8 and TGF-Β1 are likely as new biomarkers of DN. The 42 candidate targets were identifyed in PPI network. GO analysis revealed that these targets were enriched with ubiquitin protein ligase, transcription factor binding and nuclear transport. The KEGG pathways were enriched, including AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, Focal adhesion. The docking results showed that hirudin could easily dock with ITGA4, EGFR and ESR1. Conclusion: Our study demonstrates that hirudin is involved in DN therapy through a multi-targeted, multi-pathway approach. It provides a basis for further research on its mechanism of action.
Encapsulating peritoneal sclerosis (EPS) is an uncommon and harmful complication which may cause destructive outcomes. Matrix metalloproteinase-2 (MMP-2) as a protease can reduce constituents of the extracellular matrix and play a crucial role in the progression of EPS. As a new biomarker, MMP-2 may improve the detection rate of EPS patients in clinical work. In this review, we summarize the recent study of MMP-2 in different etiologies and the assessment of its application value and draw attention to its future directions.
Amydrium sinense has been widely used to treat rheumatism are in ethnic areas. The modern studies have shown that rheumatism is closely related to inflammation, and volatile oil of traditional Chinese medicine has anti-inflammatory activity, but the mechanism is not fully elucidated. In this study, the potential mechanism of anti-inflammatory effect of Amydrium sinense was systematically explored by using the network pharmacology. Firstly, the active chemical ingredients of Amydrium sinense were prescreened according to ADME parameters (OB≥30% and DL≥0.18) and the Pharmacological activity. The potential targets were screened with the databases of TCMSP. Then the “component-target-disease” network was constructed using Cytoscape 3.6.1 software. Finally, GO (gene function) enrichment analysis were carried out by biological information annotation database (DAVID), and signal pathway analysis were executed by KEGG Pathway database. The network analysis revealed that 27 compounds were screened as active compounds; 193 targets were searched, of which 38 potential targets the most were closely related to the prevention and treatment of inflammation. In addition, it suggested that 212 biological processes and 79 signalling pathways were screened. Among them, the signalling pathway most closely related to the relevant regulated of NF-kB, TNF, Toll-like receptor signalling pathway, Hepatitis B and Inflammatory response, etc. Its anti-inflammatory mechanism may coordinate with each other through multiple processes to exert anti-inflammatory biological effects. The above results provide strong support for studying the molecular mechanism of Amydrium sinense in the treatment of inflammation.
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