Emerging roles of lactate in acute and chronic inflammation.

Traditionally, lactate has been considered a 'waste product' of cellular metabolism. Recent findings have shown that lactate is a substance that plays an indispensable role in various physiological cellular functions and contributes to energy metabolism and signal transduction during immune and inflammatory responses. The discovery of lactylation further revealed the role of lactate in regulating inflammatory processes. In this review, we comprehensively summarize the paradoxical characteristics of lactate metabolism in the inflammatory microenvironment and highlight the pivotal roles of lactate homeostasis, the lactate shuttle, and lactylation ('lactate clock') in acute and chronic inflammatory responses from a molecular perspective. We especially focused on lactate and lactate receptors with either proinflammatory or anti-inflammatory effects on complex molecular biological signalling pathways and investigated the dynamic changes in inflammatory immune cells in the lactate-related inflammatory microenvironment. Moreover, we reviewed progress on the use of lactate as a therapeutic target for regulating the inflammatory response, which may provide a new perspective for treating inflammation-related diseases.

Integrated Bioinformatics Analysis and Target Drug Prediction of Inflammatory Bowel Disease Co-existent Diabetes Mellitus.

INTRODUCTION: Inflammatory bowel disease (IBD) has become one of the public problems worldwide and its incidence rate is increasing year by year. Its concomitant disease i.e. diabetes mellitus (DM) has attracted more and more attention due to DM altering the progression of IBD and leading to long periods of intermittent recurrence and deterioration. The common mechanism and potential target drug of IBD with comorbid chronic conditions of DM were explored. METHODS: Gene expression profile data were downloaded from the Gene Expression Omnibus (GEO) public database. The differentially expressed genes (DEGs) were identified by R software. GO annotation and pathway enrichment were performed, a protein-protein interaction (PPI) network was constructed, associated lncRNAs were predicted and drug prediction targeting key genes was made. Additionally, the regulatory network among core genes, associated pathways, and predicted lncRNA in IBD with coexistent DM were visualized. RESULTS: We identified the critical gene MMP3 with lncRNA CDKN2BAS involved in the PPAR pathway, which uncovered the underlying regulatory mechanism of IBD with coexistent DM. We also predicted the potential therapeutic compound ZINC05905909 acting on MMP3. CONCLUSION: Our findings revealed the regulatory mechanism chain of critical gene MMP3, lncRNA CDKN2BAS, and PPAR pathway and provided potential therapeutic compound ZINC05905909 for drug therapy to treat comorbid IBD DM.