Microbubbles activated by low-frequency ultrasound enhance the anti-tumor effects of curcumin in glioma cells by suppressing the TGF-ß1/Smad/VEGF/NCAM signaling pathway.

This study investigated whether microbubbles activated by low-frequency ultrasound enhanced the anti-tumor effects of curcumin in glioma cells. CCK8 proliferation assay, scratch migration assay, and transwell invasion assay were performed to estimate the proliferation, migration, and invasion rates of the glioma cells in blank control and different treatment groups, respectively. Quantitative RT-PCR (qRT-PCR) analysis was performed to determine the relative expression levels of VEGF and NCAM mRNAs in the various experimental groups. Western blotting was performed to determine the activity status of the TGF-ß1/Smad signaling pathway in various groups of glioma cells by estimating the expression levels of p-SMAD2/3, VEGF, and NCAM proteins. Combined treatment (Cur-Us-MBs) with microbubbles activated by low-frequency ultrasound and curcumin significantly reduced the in vitro proliferation, migration, and invasiveness of glioma cells compared to the control and other treatment groups. Furthermore, Cur-Us-MBs significantly reduced the expression levels of VEGF and NCAM mRNAs and proteins and p-Smad2/3 proteins , including those cells stimulated with rhTGF-ß. These suggested that microbubbles activated by low-frequency ultrasound enhanced the inhibition of TGF-ß1/Smad/VEGF/NCAM signaling pathway by curcumin，and enhanced the antitumor effects of curcumin by significantly reducing in vitro proliferation, migration, and invasiveness of glioma cells through this pathway.

Cholecystokinin Expression in the Development of Myocardial Hypertrophy.

BACKGROUND: Expression of cholecystokinin is found in myocardial tissues as a gastrointestinal hormone and may be involved in cardiovascular regulation. However, it is unclear whether there is an increase in cholecystokinin expression in myocardial hypertrophy progression induced by abdominal aortic constriction. The study is aimed at exploring the relationship between cholecystokinin expression and myocardial hypertrophy. METHODS: We randomly divided the 70 Sprague-Dawley rats into two groups: the sham operation group and the abdominal aortic constriction group. The hearts of rats were measured by echocardiography, and myocardial tissues and blood were collected at 4 weeks, 8 weeks, and 12 weeks after surgery. Morphological changes were assessed by microscopy. The cholecystokinin expression was evaluated by immunochemistry, Western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: The relative protein levels of cholecystokinin were significantly increased in the abdominal aortic constriction groups compared with the corresponding sham operation groups at 8 weeks and 12 weeks. The cholecystokinin mRNA in the abdominal aortic constriction groups was significantly higher than the time-matched sham operation groups. Changes in the left ventricular wall thickness were positively correlated with the relative protein levels of cholecystokinin and the mRNA of cholecystokinin. CONCLUSIONS: The development of myocardial hypertrophy can affect the cholecystokinin expression of myocardial tissues.

Advances in Biological Application of and Research on Low-Frequency Ultrasound.

In recent years, the in-depth study of low-frequency sonophoresis (LFS) has greatly elucidated its biological effects in various therapeutic applications, including drug delivery, enhanced healing, thrombolytic technology, anti-inflammatory effects and tumor treatment. Specifically, numerous studies have reported its use in drug delivery and synergistic antitumor activity, indicating a new treatment direction for cancer. However, there are significant gaps in the understanding of LFS in terms of frequency and sound intensity safety; these issues are becoming increasingly important in understanding the biological effects of LFS ultrasound. This article reviews the treatment mechanism and current applications of LFS technology and discusses and summarizes its safety and application prospects.