Alpha-Synuclein Interaction with UBL3 Is Upregulated by Microsomal Glutathione S-Transferase 3, Leading to Increased Extracellular Transport of the Alpha-Synuclein under Oxidative Stress.

Aberrant aggregation of misfolded alpha-synuclein (α-syn), a major pathological hallmark of related neurodegenerative diseases such as Parkinson's disease (PD), can translocate between cells. Ubiquitin-like 3 (UBL3) is a membrane-anchored ubiquitin-fold protein and post-translational modifier. UBL3 promotes protein sorting into small extracellular vesicles (sEVs) and thereby mediates intercellular communication. Our recent studies have shown that α-syn interacts with UBL3 and that this interaction is downregulated after silencing microsomal glutathione S-transferase 3 (MGST3). However, how MGST3 regulates the interaction of α-syn and UBL3 remains unclear. In the present study, we further explored this by overexpressing MGST3. In the split Gaussia luciferase complementation assay, we found that the interaction between α-syn and UBL3 was upregulated by MGST3. While Western blot and RT-qPCR analyses showed that silencing or overexpression of MGST3 did not significantly alter the expression of α-syn and UBL3, the immunocytochemical staining analysis indicated that MGST3 increased the co-localization of α-syn and UBL3. We suggested roles for the anti-oxidative stress function of MGST3 and found that the effect of MGST3 overexpression on the interaction between α-syn with UBL3 was significantly rescued under excess oxidative stress and promoted intracellular α-syn to extracellular transport. In conclusion, our results demonstrate that MGST3 upregulates the interaction between α-syn with UBL3 and promotes the interaction to translocate intracellular α-syn to the extracellular. Overall, our findings provide new insights and ideas for promoting the modulation of UBL3 as a therapeutic agent for the treatment of synucleinopathy-associated neurodegenerative diseases.

Risk factors target in patients with post-thyroidectomy bleeding.

As the highly blood flow of thyroid gland post-thyroidectomy bleeding (PTB) is a serious and life-threatening complication. Our aim was to investigate factors that influenced bleeding after thyroidectomy. Between February 2008 and September 2012, the data of 4449 consecutive patients with thyroid diseases undergoing thyroidectomy were collected and analysed from the department of surgical oncology retrospectively. During the study period, 88 (2.0%) patients were identified to have clinically PTB. 6 risk factors were significantly related to PTB: gender (OR 3.243; 95% CI 2.078-5.061; P < 0.001), age (OR 1.025; 95% CI 1.006-1.043; P = 0.009), tumor size (OR 4.495; 95% CI 2.462-8.208; P < 0.001), postoperative hypertension (OR 2.195; 95% CI 1.006-1.043; P = 0.035), lymph node dissection (OR 3.384; 95% CI 2.146-5.339; P < 0.001) and Graves' disease (OR 3.744; 95% CI 1.920-7.303; P < 0.001). We addressed the most common explicit source of bleeding by reexploration: infrahyoid muscles (30/88), beside the laryngeal recurrent nerve (22/88), subcutaneous tissue (10/88) and superior pole (10/88). In our study, male gender, older age, tumor size > 3 cm, postoperative hypertension (SP > 150 mmHg), lymph node dissection and Graves' disease were independent risk factors for PTB. The sources of bleeding were identified more frequently in the infrahyoid muscles and beside the laryngeal recurrent nerve. It is helpful for surgeons to decide the potential bleeding points during the reexploration of PTB.

Prognostic value of circulating microRNA-21 in digestive system cancers: a meta-analysis.

UNLABELLED: Circulating microRNAs show aberrant expression in patients with cancer. The aim of this study was to investigate the prognostic value of circulating microRNA-21 (miR-21) in digestive system cancers. METHODS: All the eligible studies were searched by Medline and EMBASE. The hazard ratios (HRs) for overall survival (OS), which compared the expression levels of circulating miR-21 in patients with digestive cancer was extracted and estimated. Pooled HRs and 95% confidence intervals (CI) were calculated. Then a meta-analysis was performed to clarify the prognostic value of the miR-21. RESULTS: A total of seven studies involving 907 subjects were included. The results suggested that higher circulating miR-21 could predict worse OS outcome with the pooled HR of 2.19 (95% CI 1.01-4.75, P = 0.05) in digestive system cancers. Subgroup analysis by ethnicity indicated circulating miR-21 was associated with OS in patients with digestive cancer among Asians with the pooled HR of 2.90 (95% CI 1.30-6.45, P = 0.009). However, subgroup analysis by digestive system site revealed that there is no associated with OS in patients with colorectal cancer with the pooled HR of 1.34 (95% CI 0.45-4.00, P = 0.60). CONCLUSION: The present findings suggest that circulating miR-21 is associated with poor survival in patients with digestive cancer and could be a prognostic biomarker for those patients.

Effect and mechanism of the metastasis suppressor gene BRMS1 on the migration of breast cancer cells.

OBJECTIVE: To study the effect of the transfected Breast cancer metastasis suppressor 1 (BRMS1) gene on the migration of breast cancer cells and the possible mechanisms involved. METHODS: MDA-MB-231HM cells which have a high propensity of metastasize to lung was sieved from MDA-MB-231 and its derivative cells stable transfected with BRMS1 were used to study in vitro. Cell migratory ability was observed. The cellular cyclic adenylic acid (cAMP) concentration was tested by radioimmunoassay (RIA). The activity of adenylate cyclase (AC), phosphodiesterase (PDE) and protein kinase A (PKA) were measured by enzyme immunoassay (EIA) and (γ-(32)P) ATP incorporation. The effect of BRMS1 on connexins (Cx) expression was analyzed by by RT-PCR and Western blot. RESULTS: Overexpression of BRMS1 significantly inhibited cell migration in MDA-MB-231HM cells in vitro. However, BRMS1's effect on cell migration could be eliminated after pretreating with pertussis toxin (PTX). BRMS1 overexpression increased cellular cAMP and PKA activity by activating the activity of AC. Furthermore, BRMS1 overexpression up-regulated Cx26 expression, whereas Cx32, Cx43 expressions did not changed. CONCLUSION: The present study indicated G-protein-coupled cAMP signaling pathway was involved in BRMS1 related MDA-MB-231HM cells migration, and BRMS1 could change connexins (Cx) expression profiles through increasing expression of Cx26 in cells.