The cDNA fragment of human TRAIL (TNF-related apoptosis inducing ligand) was cloned into RevTet-On, a Tetregulated and high-level gene expression system. The gene expression system was constructed in a human leukemic cell line: Jurkat. By using RevTet-On TRAIL gene expression system in Jurkat as a cell model, we studied the influence of TRAIL gene on the changes of cellular apoptosis before and after the TRAIL gene expression, which was induced by adding tetracycline derivative doxycycline (Dox). The results indicated that the cellular apoptosis ratio was largely dependent on the TRAIL gene expression level. Moreover, it was found that the apoptosis-inducing TRAIL could cause significant changes in the biophysical properties of Jurkat cells. The cell surface charge density decreased, the membrane fluidity declined, the elastic coefficients K 1 increased, and the proportion of α-helix in membrane protein secondary structure decreased. Thus, the apoptosis-inducing TRAIL gene caused significant changes on the biomechanic properties of Jurkat cells.
Ovarian cancer (OC) remains the most aggressive and lethal gynecological tumor characterized by massive intraperitoneal dissemination and malignant ascites. The carcinoma cells exfoliated from the primary tumor and were further transformed in the ascites microenvironment. During this suspension process, multi-cellular spheroids are formed and these aggregates represent an invasive and chemoresistant cellular population fundamental to metastatic dissemination. Activation of EGFR signaling is involved in increased cell metastasis and decreased apoptosis of ovarian cancer. The application of EGFR Inhibition in ovarian cancer was hampered for its limited benefit as a solitary therapy. In this work, our results primarily indicated that autophagy was induced in response to EGFR specific inhibitor AG1478 in OC cell lines generated spheres and ascites primary spheroids, characterized by the elevation of LC3-II, Beclin1 and Atg5. Blockage of autophagy with 3MA notably promoted spheroid death in suspension as well as AG1478-induced cell apoptosis, suggesting a protective autophagy contribution during tumor cells in suspension or under EGFR inhibition. Consequently, inhibiting autophagy with 3MA significantly enhanced the inhibitory effect of AG1478 on tumor cell peritoneal propagation in SKOV3 i.p. xenografts model. In addition, elevated EGFR, Beclin1, and Atg5 mRNA levels were associated with decreased ovarian cancer patient survival. Together, our findings suggested that targeting autophagy held the potential to improve EGFR inhibition benefit in the treatment of ovarian cancer cells during detachment from the extra-cellular matrix (ECM), and that this combination strategy might provide a new treatment option in controlling peritoneal metastasis of ovarian cancer.
AIM: To verify the association between retinopathy, nephropathy, and periodontitis in type 2 diabetic (T2D) patients.
METHODS: Several electronic databases were available for our comprehensive search including China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang, Web of Science, ScienceDirect and PubMed and were queried for relevant citations (updated to Mar. 2019). RevMan was utilized to perform Meta analysis and publication bias detection. After evaluation of the methodological quality of included studies, a fixed or random effect model was utilized to analyze data from included studies.
RESULTS: A total of eight articles were finally included in this Meta analysis. In all 3987 subjects, there were 1207 T2D patients accompanying with microvascular complications and 1734 patients with periodontitis as well. The Meta forest plot presented little heterogeneity of the eight studies (P<0.00001, I2=89%). The total effect demonstrated periodontitis was associated with overall microvascular complications (OR: 1.96, 95%CI: 1.67-2.30, Z=8.25, P<0.00001). Subgroup investigations among the studies in Asian (OR: 2.33, 95%CI: 1.91-2.85) and North American (OR: 1.42, 95%CI: 1.08-1.86) populations confirmed the existed association between retinopathy, nephropathy, and periodontitis. While the strength of such associations between periodontitis and diabetic microvascular complications were more obvious in the Asians than North Americans. All the results indicated that periodontitis was associated with diabetic retinopathy (OR: 3.77, 95%CI: 2.71-5.24), diabetic nephropathy (OR: 1.55, 95%CI: 1.24-1.94) in T2D patients.
CONCLUSION: The periodontitis is associated with diabetic retinopathy, diabetic nephropathy among T2D patients and further large sample size clinical trials are in need to confirm the findings.
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