ABSTRACT
p53 represents one of the most important tumor suppressors in mammalian cells, and the posttranslational modifications (PTMs) serve as a major strategy for fine-tuning of the functions of p53 in cells. Particularly, the acetylation regulates either the overall transactivity of p53 or the p53-dependent transcriptional selectivity, which plays key roles in modulating a variety of biological processes including cell cycle arrest, apoptosis, senescence, autophagy, and metabolism. This review, starting with the timeline of the researches on p53 acetylation, firstly summarizes how the site-specific acetylation of p53 is built up, including the acetyltransferases that catalyze p53 acetylation and their regulatory mechanism that influencing p53 functions. Secondly, this review summarizes pivotal deacetylases that erase p53 acetylation, and their contributions in modulating p53 cellular activities. Additionally, this review summarizes the reader proteins that specifically recognize and bind to acetylated/ unacetylated residues of p53, and their intimate interactions with p53 in manipulating downstream targets transcriptions. Meanwhile, this review sums up the crosstalk mechanisms between the acetylation and other PTMs in regulating p53 biological functions. Lastly, this review proposes a perspective on the studies of p53 acetylation in the field of molecular biomedicine in future.
ABSTRACT
Immune checkpoints represent a group of inhibitory receptor molecules that are expresses in the surface of immune cells and play a pivotal role in maintaining immune homeostasis. In recent years, several key immune checkpoint molecules such as CTLA-4 and PD-1, has been found to exist in some kinds of tumor cells. These ectopic expressed checkpoint molecules are named as “cancer cell-intrinsic immune checkpoint molecules”. Although our understanding on cancer cell-intrinsic immune checkpoint molecules is quite limited, emerging evidence suggests that the expression and the biological functions of such molecules in different types of cancer cells are heterozygous and diverse. In particular, the discovery of “adaptive immune-independent” regulation on cancer cell behaviors would potentially benefit to design a customized cancer immune therapy, as well as to develop new therapeutic strategies for cancer. In this review, we will briefly describe the timeline of the studies, deeply discuss the complicated biological functions and the regulatory mechanisms (CTLA-4 and PD-1 as representative examples). And finally we put forward a research perspective on cancer cell-intrinsic immune checkpoint molecules. This review aims to present and promote the studies of cancer cell-intrinsic immune checkpoint molecules to the broad scientific community.
ABSTRACT
To compare the clinical application in the percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. One hundred forty three elderly patients with Osteoporotic vertebral compression fractures [OVCFs] underwent percutaneous vertebroplasty under the guidance of one or two C-arm fluoroscopes. The number of pulsed imagings, the time of operation and the incidence of cement leakage were recorded. The average number of pulsed imagings was 16.00 +/- 1.58 vs 13.07 +/- 2.00 per patient under the guidance of one vs two C-arm fluoroscopes. The average time of operation was 48.42 +/- 5.00 minutes vs 39.70 +/- 7.42 minutes per patient under the guidance of one vs two C-arm fluoroscopes. The incidence of cement leakage was 20% vs 15.7% of the patients under the guidance of one vs two C-arm fluoroscopes. The differences in the number of pulsed imagings and the time of operation were statistically significant. The difference in incidence of cement leakage was not statistically significant. The two-fluoroscopic technique reduce the labor cost, the radiation, the time of operation and the operation risk