Yiqi Kaimi prescription regulates protein phosphorylation to promote intestinal motility in slow transit constipation.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical efficacy of the Yiqi Kaimi prescription has been confirmed in slow transit constipation. However, the effects and biological mechanism of Yiqi Kaimi prescription are still unclear. AIMS OF THE STUDY: To identify the effects of Yiqi Kaimi prescription on intestinal motility; To reveal the potential key targets and pathways of Yiqi Kaimi prescription for the treatment of slow transit constipation. MATERIALS AND METHODS: The effects of Yiqi Kaimi prescription on slow transit constipation were investigated in a mouse model. The terminal ink propulsion experiment and fecal indocyanine green imaging was used to measure the intestinal transit time. Protein phosphorylation changes in colon tissues treated with Yiqi Kaimi prescription were detected using a Phospho Explorer antibody microarray. Bioinformatic analyses were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID) and the Search Tool for the Retrieval of Interacting Genes (STRING). Western blot analysis and immunohistochemistry confirmed the observed changes in phosphorylation. RESULT: s: Yiqi Kaimi prescription significantly increased the intestinal transit rate (P < 0.05 vs. model) and reduced the time to first discharge of feces containing fecal indocyanine green imaging in mice (P < 0.05 vs. model). The administration of Yiqi Kaimi prescription induced phosphorylation changes in 41 proteins, with 9 upregulated proteins and 32 downregulated proteins. Functional classification of the phosphorylated proteins with DAVID revealed that the critical biological processes included tyrosine protein kinases, positive regulation of calcium-mediated signaling and response to muscle stretch. The phosphorylation of the spleen tyrosine kinase (SYK) at Tyr348 increased 2.19-fold, which was the most significant change. The phosphorylation level of the transcription factor p65 (RELA) at Thr505 was decreased 0.57-fold. SYK was a hub protein in the protein-protein interaction network and SYK and RELA formed the core of the secondary subnetwork. The key protein phosphorylation after treatment with Yiqi Kaimi prescription were verified by Western blot analysis and immunohistochemistry. CONCLUSION: Yiqi Kaimi prescription significantly enhanced intestinal motility. This effect was attributed to alterations in the phosphorylation levels of various target proteins. The observed changes in protein phosphorylation, including SYK and RELA, may serve as crucial factors in the treatment of slow transit constipation.

Bibliometric insights in fournier's gangrene: Research landscapes, turning points, and global trends.

Study Design: Bibliometric and visualization analysis. Objective: To analyze the research landscapes and hotspots of Fournier's gangrene, and reveal the dynamic changes and development trend of research hotspots for the purpose of providing ideas and a basis for clinical and basic research in this field. Methods: Research datasets were acquired from the Web of Science. The publication years were limited from January 1, 1900 to August 5, 2022. The bibliometric tools CiteSpace (v5.8) and VOSviewer (v1.6) were used to analyze the data and generate visualization knowledge maps. Trends in annual publications, distribution, H-index status, coauthorships status and research hotspots were analyzed. Results: According to the search strategy, we identified and enrolled 688 publications regarding to Fournier's gangrene. The number of published papers showed an overall upwards trend. The USA was the largest contributor, ranking first in total publications, citations and the H-index. The top 10 most productive institutions were all from the USA. De Simone B and Sartelli M were the most productive authors. There was close cooperation among countries, but the cooperation among institutions and authors had little contact and poor interactivity. The research hotspots included the pathogenesis factors and treatment. All the identified keywords were divided into 14 clusters, and the label of the latest cluster was "empagliflozin". Prognosis and risk factors, emerging treatment methods, and pathogenesis were at the forefront of the Fournier's gangrene field and were predicted to be the next hot topics. Conclusion: The research of Fournier's gangrene has made some achievements, but the overall research level is still in the primary stage. The academic cooperation between different institutions and authors needs to be strengthened. At the early stage, the mainstream of research was the infected tissue and site, pathogenesis, and diagnosis of disease, while research on newly discovered sodium-glucose cotransporter 2 inhibitor, adjuvant therapy and prognostic factors may be the main directions in the future.

Caldesmon: Biochemical and Clinical Implications in Cancer.

Caldesmon, an actin-binding protein, can inhibit myosin binding to actin and regulate smooth muscle contraction and relaxation. However, caldesmon has recently attracted attention due to its importance in cancer. The upregulation of caldesmon in several solid cancer tissues has been reported. Caldesmon, as well as its two isoforms, is considered as a biomarker for cancer and a potent suppressor of cancer cell invasion by regulating podosome/invadopodium formation. Therefore, caldesmon may be a promising therapeutic target for diseases such as cancer. Here, we review new studies on the gene transcription, isoform structure, expression, and phosphorylation regulation of caldesmon and discuss its clinical implications in cancer.