Search

Background: Preconditioning is a promising strategy against ischemic brain injury, and numerous studies in vitro and in vivo have demonstrated its neuroprotective effects. However, at present there is no bibliometric analysis of preconditioning in cerebral ischemia. Therefore, a comprehensive overview of the current status, hot spots, and emerging trends in this research field is necessary. Materials and methods: Studies on preconditioning in cerebral ischemia from January 1999–December 2022 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace was used for data mining and visual analysis. Results: A total of 1738 papers on preconditioning in cerebral ischemia were included in the study. The annual publications showed an upwards and then downwards trend but currently remain high in terms of annual publications. The US was the leading country, followed by China, the most active country in recent years. Capital Medical University published the largest number of articles. Perez-Pinzon, Miguel A contributed the most publications, while KITAGAWA K was the most cited author. The focus of the study covered three areas: (1) relevant diseases and experimental models, (2) types of preconditioning and stimuli, and (3) mechanisms of ischemic tolerance. Remote ischemic preconditioning, preconditioning of mesenchymal stem cells (MSCs), and inflammation are the frontiers of research in this field. Conclusion: Our study provides a visual and scientific overview of research on preconditioning in cerebral ischemia, providing valuable information and new directions for researchers.

Ethnopharmacological relevance: Fructus mume herbs have been used to convergence and antidiarrheal in clinical practice in China for thousands of years. Aim of the study: This study aimed to investigate the molecular mechanism of Fructus mume in the treatment of UC through network pharmacology analysis and experimental validation in vivo. Materials and methods: The main components of Fructus mume were initially identified with the aid of liquid chromatography-mass spectrometry. Using the network pharmacology approach, we predicted the targets of the active components and mapped target genes related to UC. We further evaluated the pharmacodynamic effects of Fructus mume on UC in vivo using a DSS-induced mousemodel of colitis. The degree of pathological damage in mousecolon tissue was examined via hematoxylin-eosin (HE) staining. The results of network pharmacology predictions were further verified measuring the levels of inflammatory and oxidation-related factors in mouse colon tissue via enzyme linked immunosorbent assay method and Western blot analysis. Results: A total of 16 chemical components of Fructus mume were identified, among which 11 active components were screened based on the Ribinski rule and 368 targets predicted. KEGG pathway analysis showed that the predicted targets involved multiple signaling pathways, including PI3K-Akt, AGE-RAGE and HIF-1. In pharmacodynamic experiments, Fructus mume induced a significant increase in colon length and improved the degree of damage to colon tissue. In addition, FM inhibited the increase in TNF-α, IL-1β, NADPH and ROS levels in sera of UC mice, thereby suppressing the occurrence and development of UC. At higher concentrations, Fructus mume inhibited protein expression of downstream related (p38, p-p38, NF-kB and p-NF-kB) through regulation of the AGE/RAGE pathway, further contributing to suppression of UC in mice. Conclusion: Our experiments provide important insights into the pharmacological basis of Fructus mume and its potential multicomponent-multitarget-multipathway pharmacological activities against UC. The therapeutic mechanism of Fructus mume may be associated with suppression of protein expression, p38, p-p38, NF-kB and p-NF-kB, in the AGE/RAGE pathway, partially validating the results from network pharmacology analysis. The collective findings provide a theoretical basis for the further development and clinical application of Fructus mume.

Studies have shown that inhibition of PI3K/AKT signaling is a key strategy for the treatment of tyrosine kinase inhibitor resistance in non-small cell lung cancer (NSCLC). Vasculogenic mimicry (VM) not only accelerates tumor progression but also increases drug-induced resistance. As a tumor suppressor, protein phosphatase 2A (PP2A) is a ubiquitous conserved serine/threonine phosphatase. While its effects and mechanisms on VM formation and invasion in NSCLC remain unclear. The present study aimed to investigate the role of PP2A in VM formation and elucidate the underlying mechanisms. Results showed that PP2A could significantly inhibit VM formation and VM-dependent behavior, including invasion and migration both in vitro and in vivo. Activation of PP2A with FTY720 or Ad-PP2A reduced phosphorylated AKT and inhibited ZEB1 transcription, thereby further downregulating the expression of MMP-2, VE-cadherin, and VEGFR-2, whereas inhibition of PP2A with okadaic acid (OA) or Ad-dn-PP2A exerted the opposite effect. Furthermore, PP2A inhibited tumor growth and VM formation in the xenograft tumor model. PI3K inhibitor BENC-511 could potentiate activation of PP2A, leading to inhibition of p-AKT/ZEB1 and VM formation in vitro and in vivo. This study indicated that PP2A could regulate VM formation in NSCLC through the PI3K/AKT/ZEB1 axis. PP2A reactivation or combination with PI3K inhibitor might be a more effective treatment against advanced NSCLC by inhibiting VM formation.