ABSTRACT
Proteolysis targeting chimera (PROTAC) technology, one of the targeted protein degradation technologies, has drawn marked attention from researchers of both academia and industry in recent years. After over two decades of development, the literature on it has proliferated. In order to better grasp the frontiers and hot spots of PROTAC, this bibliometric analysis was carried out. The articles and reviews regarding PROTAC were culled from the Web of Science Core Collection. General information and the trend of publication outputs, countries/regions, authors, journals, influential papers, and keywords in this field were visually analyzed using CtieSpace, VOSviewer, or Excel software. As a result, a total of 808 publications were included. The number of papers regarding PROTAC significantly increased yearly. These papers mainly come from 45 countries/regions led by the USA and China. 3886 authors were identified participating in these studies, among which Craig M. Crews had the most significant number and influential articles. Journal of Medicinal Chemistry and European Journal of Medicinal Chemistry are the two journals with the most papers. After analysis, the most influential papers were identified in the area, including highly cited papers, references with citation burst, and high co-citated papers. The most common keywords including cancer, E3 ligase, drug discovery, epigenetic, resistance, and so on, represent the current and developing areas of study. BRDs, androgen receptor (AR), HDACs, estrogen receptor (ER), EGFR, CDKs, and KRAS are the most common targets. At last, frontiers and challenges of PROTAC were discussed through the bibliometric analysis. This paper will be helpful for better understanding the frontiers and hotspots of PROTAC.
Subject(s)
Proteolysis , BibliometricsABSTRACT
α-carboline (9H-pyrido[2,3-b]indole), contains a pyridine ring fused with an indole backbone, is a promising scaffold for medicinal chemistry. In recent decades, accumulating evidence shows that α-carboline natural products and their derivatives possess diverse bioactivities. However, hitherto, there is no comprehensive review to systematically summarize this important class of alkaloids. In this perspective, this paper represents the first review to provide a comprehensive description of α-carbolines including natural products, updated literature of synthesis, and their diverse biological activities. Their biological activities including antitumor, anti-microbial, anti-Alzheimer's disease, anti-atherosclerosis, and antioxidant activities were hilighted. And the targets and the main structure activity relationships (SARs) will be presented. Finally, challenges and future directions of this class of compounds will be discussed. This review will be helpful in understanding and encouraging further exploration for this group of alkaloids.
ABSTRACT
Deep vein thrombosis (DVT) is a common type of venous thrombosis. Successful resolution of DVT-related thrombi is important in the treatment of DVT. Endothelial progenitor cells (EPCs) have emerged as a promising therapeutic choice for DVT-related thrombus resolution; however, the clinical application of EPCs faces many challenges. In the present study, the expression of miR-582, miR-195 and miR-532 under hypoxic or normoxic conditions was measured using quantitative real-time PCR analysis (qRT-PCR) and the results showed that the increased fold of miR-195 was highest in human EPCs (hEPCs) under hypoxic conditions. Then the role and regulating mechanism of miR-195 in improving the function of EPCs was investigated. To investigate the effect of miR-195 inhibition on the autophagy of hEPCs, the expression of the autophagy-related genes LC3B and beclin1 was examined using western blotting, and the formation of autophagosomes was observed using TEM. The results indicated that the inhibition of miR-195 expression could promote autophagy of hEPCs. In addition, we investigated the role of miR-195 on the proliferation, migration and angiogenesis of hEPCs under hypoxia. The results revealed that miR-195 inhibition promotes cell proliferation, migration and angiogenesis of hEPCs under hypoxia. Furthermore, GABA type A receptor associated protein like 1 (GABARAPL1) was identified as a directed target of miR-195 and GABARAPL1 silencing could decrease the effect of miR-195 knockdown on cell proliferation, migration, angiogenesis and autophagy of hEPCs under hypoxia. Together, these results indicate that miR-195 regulates cell proliferation, migration, angiogenesis and autophagy of hEPCs by targeting GABARAPL1.
