multi-omics-and-integrative-analytics-in-natural-products-discovery

Multi-Omics and Integrative Analytics in Natural Products Discovery

Natural products (NPs) have long been an essential source of new bioactive compounds for drug discovery; however, traditional methods for screening and ...

Deyang People's Hospital of Chengdu University of Traditional Chinese Medicine

Rheumatoid arthritis (RA) is an autoimmune disease with features of synovial inflammation, cartilage erosion, bone destruction, and pain and is currently lacking a satisfactory treatment strategy. Dihydroartemisinin (DHA), the active metabolite of artemisinin, has exhibited outstanding suppressive effects on RA without obvious side effects. However, the underlying mechanisms remain unclear, which limits its further clinical application. The purpose of this study is to reveal the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA sequencing (RNA-seq), proteomics, as well as transcriptomics both in vivo and in vitro. In our results, DHA effectively reduced the degree of redness, swelling, and pain in RA rats and dramatically changed the synovial tissue microenvironment under the pathological state. Within this microenvironment, fibroblasts, macrophages, B cells, and endothelial cells were the major affected cell types, primarily through DHA targeting the extracellular matrix (ECM) structural constituent signaling pathway. In addition, we confirmed that DHA regulated the ECM by modulating matrix metalloproteinase 2 (MMP2) and MMP3 in the synovial tissue of RA rats. Moreover, DHA induced apoptosis in MH7A cells, further validating the bioinformatics data. In conclusion, DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3. Our findings provide a basis for the application of DHA in the treatment of RA.

Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis.

Tissue-resident memory T (T) cells are crucial components of the immune system that provide rapid, localized responses to recurrent pathogens at mucosal and epithelial barriers. Unlike circulating memory T cells, T cells are located within peripheral tissues, and they play vital roles in antiviral, antibacterial, and antitumor immunity. Their unique retention and activation mechanisms, including interactions with local epithelial cells and the expression of adhesion molecules, enable their persistence and immediate functionality in diverse tissues. Recent advances have revealed their important roles in chronic inflammation, autoimmunity, and cancer, illuminating both their protective and their pathogenic potential. This review synthesizes current knowledge on T cells' molecular signatures, maintenance pathways, and functional dynamics across different tissues. We also explore the interactions of T cells with other immune cells, such as B cells, macrophages, and dendritic cells, highlighting the complex network that underpins the efficacy of T cells in immune surveillance and response. Understanding the nuanced regulation of T cells is essential for developing targeted therapeutic strategies, including vaccines and immunotherapies, to enhance their protective roles while mitigating adverse effects. Insights into T cells' biology hold promise for innovative treatments for infectious diseases, cancer, and autoimmune conditions.

Tissue-resident memory T cells in diseases and therapeutic strategies.

Mutations at RNA splicing sites or regulatory elements can alter splicing efficiency or patterns, affecting RNA functionality and tissue-specific expression. Here, we present a protocol to study the impact of mutations near splicing sites on precursor mRNA (pre-mRNA) splicing. We describe steps for constructing plasmids by cloning the target gene into the pEGFP-N1 vector, performing site-directed mutagenesis, and transiently transfecting HEK293 cells. We then detail procedures for conducting mini-gene splicing assays to analyze splicing patterns influenced by mutations. For complete details on the use and execution of this protocol, please refer to Peng et al..

Protocol to study the effects of mutations near splicing sites on pre-mRNA splicing.

Tissue-resident memory T (T) cells are a specialized subset of memory T cells that permanently reside in non-lymphoid tissues, providing localized and long-lasting immune protection. In the urinary tract, T cells play critical roles in defending against infections, mediating tumor immunity, and influencing the pathogenesis of chronic inflammatory diseases. Their therapeutic potential is immense, with promising avenues for vaccine development, enhanced cancer immunotherapy, and targeted treatments for chronic inflammation. However, challenges remain in harnessing their protective roles while minimizing their pathological effects, particularly in immunosuppressive or inflammatory microenvironments. This review explores the diverse roles of T cells in urinary tract diseases, including infections, cancer, and chronic inflammation, and discusses therapeutic strategies and future directions for leveraging T cells to improve clinical outcomes. By advancing our understanding of T cell biology, we can develop innovative interventions that balance their immune-protective and regulatory functions.

Tissue-resident memory T cells in urinary tract diseases.

 The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites-such as SCFAs, bile acids, neurotransmitters, and microbial gases-play critical roles in regulating intestinal function.  We systematically analyzed the current literature on microbial metabolomics in chronic constipation. This review consolidates findings from high-throughput metabolomic techniques (GC-MS, LC-MS, NMR) comparing metabolic profiles of constipated patients with healthy individuals. It also examines diagnostic improvements and personalized treatments, including fecal microbiota transplantation and neuromodulation, guided by these metabolomic insights.  This review shows that reduced SCFA levels impair intestinal motility and promote inflammation. An altered bile acid metabolism-with decreased secondary bile acids like deoxycholic acid-disrupts receptor-mediated signaling, further affecting motility. Additionally, imbalances in amino acid metabolism and neurotransmitter production contribute to neuromuscular dysfunction, while variations in microbial gas production (e.g., methane vs. hydrogen) further modulate gut transit.  Integrating metabolomics with gut microbiota research clarifies how specific microbial metabolites regulate gut function. These insights offer promising directions for precision diagnostics and targeted therapies to restore microbial balance and improve intestinal motility.

Article	Year
Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis. Research (Washington, D.C.)\| PubMed ID: 39257420	2024
Tissue-resident memory T cells in diseases and therapeutic strategies. MedComm\| PubMed ID: 39802636	2025
Protocol to study the effects of mutations near splicing sites on pre-mRNA splicing. STAR protocols\| PubMed ID: 40048423	2025
Tissue-resident memory T cells in urinary tract diseases. Frontiers in immunology\| PubMed ID: 40066439	2025
Metabolomics Insights into Gut Microbiota and Functional Constipation. Metabolites\| PubMed ID: 40278398	2025

Daoyuan Xie

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