The role and mechanism of pyroptosis in abdominal aortic aneurysm / 中华胸心血管外科杂志

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with chronic inflammation in the vascular wall while its specific pathogenesis is not fully understood. Recently, a growing number of studies have indicated that pyroptosis, which is a pro-inflammatory kind of programmed cell death might play a vital role in AAA. In this review, we first summarize the role of pyroptosis in AAA progression by not only providing a literature review on the expression changes of NLRP3 inflammasome components and effector mediators in clinical and experimental AAAs, but also discussing the effects of genetic defects or pharmacological inhibition of NLRP3 inflammasome components on experimental AAAs. Next, we introduce the mechanism of canonical and non-canonical pathway of pyroptosis and its activation and execution process. Finally, we discuss several pyroptosis-related drug targets for treating AAA by inhibiting the assembly of NLRP3 inflammasome and its effector mediators. In conclusion, we believe that pyroptosis might be a new treatment target of AAA.

IKKε accelerates abdominal aortic aneurysm formation in mice by increasing VSMCs autophagy / 中华胸心血管外科杂志

Objective:To investigate the effect of IKKε on autophagy during abdominal aortic aneurysm formation in mice.Methods:We stimulated ApoE -/- mice and ApoE -/-IKKε -/- mice with AngⅡ and saline for 28 days. Metaboilic levels and aortic diameter of ApoE -/- mice and ApoE -/-IKKε -/- mice were measured. The arterial fibrosis of mice was detected by Masson staining and HE staining, mitochondrial reactive oxides were detected by fluorescence assay, the expression levels of autophagy factors LC3B and Beclin-1 were detected by immunohistochemistry, and the protein level of LC3B was detected by Western blot. Results:There was no significant difference in metaboilic levels between ApoE -/- mice and ApoE -/- IKKε -/- mice. However, the aortic diameterf ApoE -/-IKKε -/- mice was significantly less than that of ApoE -/- mice. The fibrosis level of ApoE -/-IKKε -/- mice was significantly lower than that of ApoE -/- mice. Furthermore, ROS in ApoE -/-IKKε -/- mice was lower than that in ApoE -/- mice. In addition, immunohistochemical and western blot showed that the expression levels of LC3B and Beclin-1 in ApoE -/-IKKε -/- mice were significantly lower than in ApoE -/- mice. Conclusion:IKKε -/- deficiency can significantly inhibit autophagy, thus reducing the development of abdominal aortic aneurysm in mice.

miR-195/miR-497 Regulate CD274 Expression of Immune Regulatory Ligands in Triple-Negative Breast Cancer / 한국유방암학회지

PURPOSE: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members. METHODS: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target. RESULTS: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274, PDCD1LG2, and NCR3LG1. We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro. Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3′ untranslated region. CONCLUSION: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients.

Advances in the study of the anti-tumor activity of small molecule vascular disrupting agents / 药学学报

Vascular disrupting agents (VDAs) have presented a new kind of anti-cancer drug in recent years. VDAs take advantage of the weakness of established tumor endothelial cells and their supporting structures. In contrast to anti-angiogenic therapy, which inhibits the outgrowth of new blood vessels, vascular targeting treatments selectively attack the existing tumor vasculature. Here we summarized the anti-tumor activities, mechanisms and clinical applications of small molecule VDAs.

Inhibition of berberine on growth of human nasopharyngeal carcinoma cells CNE-2 in vivo and in vitro / 中草药

Objective To study the inhibitory effect of berberine on human nasopharyngeal cancer cell line CNE-2 in vivo and in vitro. Methods CNE-2 cell proliferation was measured by MTT assay and cell cycle was analyzed by flow cytometry. Cell morphology was observed with transmission electron microscopy. The cell cycle relative protein was detected by Western blotting. DNA and protein syntheses were assessed by the cellular incorporation of ~ 3 H-TdR and ~ 3 H-Leu, respectively. Anti-tumor activity of berberine in the experimental transplantation tumor CNE-2 was evaluated by relative tumor growth ratio. Results Berberine inhibited CEN-2 cells growth in a time-and dose-dependent manner. MTT Assay showed that the IC_ 50 values of 48 and 72 h were (49.5?5.8) and (13.3?2.0) ?mol/L, respectively. Cell cycle analyses of 50.0 ?mol/L berberine-treated CNE-2 cells by flow cytometry showed the accumulation of cells in the G_2/M phase while 25.0 ?mol/L berberine treatments for 48 h induced apoptosis with the index of (48.9?10.4)%. The inhibition of CNE-2 cell growth by berberine was associated with suppression of cyclin B1, CDK1, and cdc25c proteins. After the treatment of berberine at dose of 30 mg/kg, the median tumor volume was 317.9 mm~3 which was much lower than that in control group (P