miR-1204 Positioning in 8q24.21 Involved in the Tumorigenesis of Colorectal Cancer by Targeting MASPIN.

BACKGROUND: Colorectal cancer remains to be the third leading cause of cancer mortality rates. Despite the diverse effects of the miRNA cluster located in PVT1 of 8q24.21 across various tumors, the specific biological function in colorectal cancer has not been clarified. METHODS: The amplification of the miR-1204 cluster was analyzed with the cBioPortal database, while the expression and survival analysis of the miRNAs in the cluster were obtained from several GEO databases of colorectal cancer. To investigate the functional role of miR-1204 in colorectal cancer, overexpression and silencing experiments were performed by miR-1204 mimic and inhibitor transfection in colorectal cancer cell lines, respectively. Then, the effects of miR-1204 on cell proliferation were assessed through CCK-8, colony formation, and Edu assay. In addition, cell migration was evaluated using wound healing and Transwell assay. Moreover, candidate genes identified through RNA sequencing and predicted databases were identified and validated using PCR and western blot. A Dual-luciferase reporter experiment was conducted to identify MASPIN as the target gene of miR-1204. RESULT: In colorectal cancer, the miR-1204 cluster exhibited high amplification, and the expression levels of several cluster miRNAs were also significantly increased. Furthermore, miR-1204 was found to be significantly associated with disease-specific survival according to the analysis of GSE17536. Functional experiments demonstrated that transfection of miR-1204 mimic or inhibitor could enhance or decrease cancer cell proliferation and migration. MASPIN was identified as a target of miR-1204. Additionally, the overexpression of MASPIN partially rescued the effect of miR-1204 mimics on tumorigenic abilities in LOVO cells. CONCLUSION: miR-1204 positioning in 8q24.21 promotes the proliferation and migration of colorectal cancer cells by targeting MASPIN.

Co-stimulators CD40-CD40L, a potential immune-therapy target for atherosclerosis: A review.

The interaction between CD40 and CD40 ligand (CD40L) a crucial co-stimulatory signal for activating adaptive immune cells, has a noteworthy role in atherosclerosis. It is well-known that atherosclerosis is linked to immune inflammation in blood vessels. In atherosclerotic lesions, there is a multitude of proinflammatory cytokines, adhesion molecules, and collagen, as well as smooth muscle cells, macrophages, and T lymphocytes, particularly the binding of CD40 and CD40L. Therefore, research on inhibiting the CD40-CD40L system to prevent atherosclerosis has been ongoing for more than 30 years. However, it's essential to note that long-term direct suppression of CD40 or CD40L could potentially result in immunosuppression, emphasizing the critical role of the CD40-CD40L system in atherosclerosis. Thus, specifically targeting the CD40-CD40L interaction on particular cell types or their downstream signaling pathways may be a robust strategy for mitigating atherosclerosis, reducing potential side effects. This review aims to summarize the potential utility of the CD40-CD40L system as a viable therapeutic target for atherosclerosis.

In vitro chemical treatment of silk increases the expression of pro-inflammatory factors and facilitates degradation in rats.

OBJECTIVES: Silk fiber is difficult to degrade in vivo, which limits its application in tissue engineering materials such as artificial nerves. Therefore, in this study aim to promote its degradation in vivo by chemical treating silk fibers in vitro. MATERIALS AND METHODS: Sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), scanning electron microscopy (SEM) observations, mechanical test, Fourier transform infrared spectroscopy (FT-IR) measurements were used to investigate the degradation effect of chemicals (hydrochloric acid, phosphoric acid, acetic acid, sodium hydroxide, calcium hydroxide, sodium bicarbonate, and calcium chloride) on silk fiber in vitro. Immunofluorescence staining and transcriptome analysis were used to investigate the effect of inflammatory factors on the degradation of chemically treated silk fiber in rats. RESULTS: (1) Silks were separated into finer fibers in each group. (2) FT-IR absorption peaks of amides I, II, and III overlap in each group. (3) Silk degradation degree in each group was higher than that in an untreated group. The calcium chloride-treated group was completely degraded. (4) Fibronectin, collagen I, collagen III, integrin α and CD68 were immunofluorescence positive in all vegetation section. (5) There were no significant differences in the expressions of collagen I, collagen III, and fibronectin in the vegetations formed on the 14th day of subcutaneous implantation, while integrin α, CD68, TNF-α, IL-1b, and IL-23 express at higher levels with IL-10 at lower levels. CONCLUSIONS: All chemicals could completely degrade silk; however, their degradation products were not the same. The chemicals change the mechanical properties of silk by separating it into finer fibers, which increase the contact surface area between the silk and tissue fluid, accelerating the degradation of monofilaments in vivo by promoting inflammation and macrophage activity through the increased and decreased expressions of pro- and anti-inflammatory factors, respectively.

Costimulatory and coinhibitory molecules of B7-CD28 family in cardiovascular atherosclerosis: A review.

Accumulating evidence supports the active involvement of vascular inflammation in atherosclerosis pathogenesis. Vascular inflammatory events within atherosclerotic plaques are predominated by innate antigen-presenting cells (APCs), including dendritic cells, macrophages, and adaptive immune cells such as T lymphocytes. The interaction between APCs and T cells is essential for the initiation and progression of vascular inflammation during atherosclerosis formation. B7-CD28 family members that provide either costimulatory or coinhibitory signals to T cells are important mediators of the cross-talk between APCs and T cells. The balance of different functional members of the B7-CD28 family shapes T cell responses during inflammation. Recent studies from both mouse and preclinical models have shown that targeting costimulatory molecules on APCs and T cells may be effective in treating vascular inflammatory diseases, especially atherosclerosis. In this review, we summarize recent advances in understanding how APC and T cells are involved in the pathogenesis of atherosclerosis by focusing on B7-CD28 family members and provide insight into the immunotherapeutic potential of targeting B7-CD28 family members in atherosclerosis.