Anti-angiogenic and antitumor effects of anlotinib combined with bevacizumab for colorectal cancer.

BACKGROUND: The progression and metastasis of tumors are typically accompanied by angiogenesis. Crucially, vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a significant role in tumor-associated angiogenesis. In this study, the aim was to investigate the antitumor effect of combining bevacizumab (Bev) with anlotinib (An) on colorectal cancer (CRC). METHODS: The CCK-8 assay, EdU assay, and Annexin V staining were conducted to evaluate the proliferation and apoptosis of CRC cells in vitro. The migration capability of CRC cells and HUVECs was assessed using the Transwell assay. Additionally, the tube formation capability of HUVECs was investigated. Furthermore, the antitumor and antiangiogenic effects were evaluated in the BALB/c mice model using immunohistochemistry, TUNEL staining, and 18F-FDG PET/CT imaging. Finally, we analyzed the inhibitory effect of Bev and/or An on related signaling effectors through western blotting. RESULTS: The in vivo CRC mice model revealed that the combination of Bev + An significantly suppressed tumor formation and angiogenesis. Bev + An inhibited tumor glucose metabolism and increased the median survival period in tumor-bearing mice. Mechanistically, the expressions of VEGF, VEGFR2, PDGFR, and FGFR, as well as the phosphorylation levels of AKT, were inhibited after Bev+An treatment. In conclusion, the dual vertical targeting of VEGF and VEGFR in the CRC mice model strongly inhibited tumor growth and angiogenesis, with the suppression of the AKT signaling pathway playing a partial role.

Different stimuli induce endothelial dysfunction and promote atherosclerosis through the Piezo1/YAP signaling axis.

Vascular endothelial dysfunction is the initial step in atherosclerosis (AS). AS tends to occur at vascular bifurcations and curves, and endothelial cells(ECs) are highly susceptible to injury due to mechanical forces induced by disturbed flow (DF) with inconsistent blood flow directions. However, the pathogenesis of endothelial cell dysfunction in AS remains unclear and needs further study. Here, we found that Piezo1 expression was significantly increased in DF- and oxidized low-density lipoprotein(ox-LDL)-treated HUVECs in vitro and a model of atherosclerotic plaque growth in ApoE-/- mice fed a Western diet. Furthermore, Piezo1 upregulated autophagy levels in the HUVECs model, which was reversed by Piezo1 knockdown with a lentivirus-mediated shRNA system. Mechanistically, the level of Yes-associated protein (YAP), a transcriptional coactivator in the Hippo pathway, was significantly elevated in the DF- and ox-LDL-induced HUVECs model, and this effect was further inhibited by Piezo1 knockdown. Moreover, the Piezo1 agonist Yoda1 inhibited the protein level of microtubule-associated protein 1 light chain 3-II(LC3-II) and increased the protein level of sequestosome1(p62/SQSTM1) in a dose-dependent manner, while significantly promoting the protein expression and nuclear translocation of YAP. The YAP inhibitor CA3 weakened Yoda1-mediated inhibition of autophagy. Our results suggest that Piezo1 may regulate endothelial autophagy by promoting YAP activation and nuclear translocation, thereby contributing to vascular endothelial dysfunction.

Advances in treatment strategies based on scavenging reactive oxygen species of nanoparticles for atherosclerosis.

The development of atherosclerosis (AS) is closely linked to changes in the plaque microenvironment, which consists primarily of the cells that form plaque and the associated factors they secrete. The onset of inflammation, lipid deposition, and various pathological changes in cellular metabolism that accompany the plaque microenvironment will promote the development of AS. Numerous studies have shown that oxidative stress is an important condition that promotes AS. The accumulation of reactive oxygen species (ROS) is oxidative stress's most important pathological change. In turn, the effects of ROS on the plaque microenvironment are complex and varied, and these effects are ultimately reflected in the promotion or inhibition of AS. This article reviews the effects of ROS on the microenvironment of atherosclerotic plaques and their impact on disease progression over the past five years and focuses on the progress of treatment strategies based on scavenging ROS of nanoparticles for AS. Finally, we also discuss the prospects and challenges of AS treatment.

Bibliometrics research on radiomics of lung cancer.

BACKGROUND: Lung cancer is currently the most commonly diagnosed malignant tumor worldwide. Exploring ways to improve the accuracy and timeliness of diagnosis has important clinical significance. Radiomics transforms images into high-dimensional data, and uses deep learning and artificial intelligence to improve the accuracy and efficiency of disease diagnosis. There is an increasing amount of research on radiomics in the diagnosis of lung cancer. This study analyzes the relevant literature in the Science Citation Index Expanded (SCI-E) database to understand the current research status and future development direction of lung cancer radiomics. METHODS: This study is based on the SCI-E database. The first search formula is topic = Lung cancer OR Lung neoplasms (#1), the second search formula is topic = Radiomics (#2), and the third search formula is #1 and #2, that is, literature that meets both the first and second search results. CiteSpace software was used to analyze lung cancer radiomics from the annual distribution of articles, countries, institutions, journals, and authors and keywords. HistCite software was used to visualize the citation chronology of the lung cancer radiomics literature, and Pajek software was used to analyze the main path of the citation chronology. RESULTS: There were a total of 749 publications, of which most were original articles (529, 70.63%) and reviews (109, 14.55%). The citation frequency is 21,676 times, the h-index is 66, and the average number of citations per publication is 28.94. The research mainly comes from the United States of America, China and other countries. The research institutions are mainly medical centers such as Moffitt Cancer Center, Maastricht University and Harvard Medical School. The authors are also mainly from these institutions. The literature was published in many related journals, mainly imaging and oncology journals. Keyword analysis shows that in recent years, research has focused on deep learning and artificial intelligence. CONCLUSIONS: The field of lung cancer radiomics is developing rapidly, and the main focuses of research are deep learning and artificial intelligence.