Shaofeng Shui

Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke

Background/Aims: LncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be highly expressed in an in vitro mimic of ischemic stroke conditions. However, the exact biological role of MALAT1 and its underlying mechanism in ischemic stroke remain to be elucidated. Methods: The roles of MALAT1 and miR-30a on cell death and infarct volume and autophagy were evaluated in experimental ischemic stroke. The relationships between miR-30a and MALAT1, Beclin1 were confirmed by luciferase reporter assay. The autophagy inhibitor 3-methyadenine (3-MA) was used to examine the impact of autophagy on ischemic injury. Results: We found that MALAT1, along with the levels of conversion from autophagy-related protein microtubule-associated protein light chain 3-I (LC3-I) to LC3-phosphatidylethanolamine conjugate (LC3-II), as well as Beclin1 were up-regulated and miR-30a was down-regulated in cerebral cortex neurons after oxygen-glucose deprivation (OGD) and mouse brain cortex after middle cerebral artery occlusion-reperfusion (MCAO). Down-regulation of MALAT1 suppressed ischemic injury and autophagy in vitro and in vivo. Furthermore, MALAT1 may serve as a molecular sponge for miR-30a and negatively regulate its expression. In addition, MALAT1 overturned the inhibitory effect of miR-30a on ischemic injury and autophagy in vitro and in vivo, which might be involved in the derepression of Beclin1, a direct target of miR-30a. Mechanistic analyses further revealed that autophagy inhibitor 3-methyadenine (3-MA) markedly suppressed OGD-induced neuronal cell death and MCAO-induced ischemic brain infarction. Conclusion: Taken together, our study first revealed that down-regulation of MALAT1 attenuated neuronal cell death through suppressing Beclin1-dependent autophagy by regulating miR-30a expression in cerebral ischemic stroke. Besides, our study demonstrated a novel lncRNA-miRNA-mRNA regulatory network that is MALAT1-miR-30a-Beclin1 in ischemic stroke, contributing to a better understanding the pathogenesis and progression of ischemic stroke.

Outcome of a retrieval stent filter and 30 mm balloon dilator for patients with Budd–Chiari syndrome and chronic inferior vena cava thrombosis: a prospective pilot study

AIM To evaluate the mid-term safety and efficacy of a retrieval stent filter and 30mm balloon dilator in the treatment of Budd-Chiari syndrome (BCS) patients with chronic inferior vena cava (IVC) thrombosis. MATERIALS AND METHODS Twenty-three consecutive patients with BCS and chronic IVC thrombosis were treated with a retrieval stent filter and a 30mm balloon dilator, and subsequently underwent color Doppler ultrasound follow-up at our hospital. Data relating to the technical success, angiographic and ultrasound results, mortality, morbidity, and final clinical outcome were collected retrospectively and follow-ups were performed 1, 3, 6, and 12 months after placement of the stent, and annually thereafter. RESULTS Stent filter placement and balloon dilation were technically successful in all patients, with no procedure-related complications. Removal of the stent filter was technically successful in 22 of 23 attempts, yielding a technical successful rate of 95.7% (95% confidence intervals (CI): 87%, 105%). Inferior vena cavagrams performed immediately before stent removal demonstrated that the IVC thrombus had completely resolved in all patients without pulmonary embolism. The mean primary patency rate 3, 6, 12, and 24 months after venoplasty was 0.91 (95% CI: 0.79-1.04), 0.87 (95% CI: 0.72-1.02), 0.87 (95% CI: 0.72-1.02), and 0.87 (95% CI: 0.72-1.02), respectively. The secondary patency rates were 1.00 throughout the follow-up period. All patients are alive with resolution of the symptoms at the time of this report. CONCLUSIONS The preliminary results indicate that the retrieval stent filter and 30mm balloon dilator are a safe and effective treatment for BCS patients with chronic IVC thrombosis.

microRNA-200a silencing protects neural stem cells against cerebral ischemia/reperfusion injury

Neural stem cells (NSCs) play major roles in neurological recovery after cerebral infarction (CI). This study was trying to investigate whether miR-200a, a vital regulator in cell proliferation, migration and apoptosis, also has a role in oxygen-glucose deprivation/reperfusion (OGD/R) injured NSCs. In this study, primary NSCs were subjected to OGD/R conditions to mimic an in vitro CI model. Before OGD/R induction, NSCs were transfected with vector or shRNA against miR-200a to overexpress or suppress miR-200a expression. The changes in cell viability, apoptosis, migration, the expression of c-Myc, and the phosphorylation of STAT1, STAT3 and MAPK were respectively assessed. Inhibitors of STAT1/3 and MAPK, i.e., Nifuroxazide and BIRB 796, were used to administrate miR-200a-silenced NSCs, and the expressions of above mentioned proteins were detected. After OGD/R exposure, miR-200a was up-regulated in NSCs (P < 0.001). miR-200a silencing alleviated OGD/R-induced the decrease of cell viability and migration (P < 0.01); meanwhile, alleviated OGD/R-induced apoptosis via reducing Bax/Bcl-2 ratio and down-regulating p53 and cytochrome c (P < 0.01 or P < 0.001). c-Myc, p-STAT1, p-STAT3, p-MAPK were all negatively regulated by miR-200a (P < 0.01 or P < 0.001); more important, the increase of c-Myc induced by miR-200a silencing was abolished by Nifuroxazide or BIRB 796 (P < 0.01 or P < 0.001). These data indicate miR-200a silencing protects NSCs from OGD/R-induced injury, possibly via regulating the STATs/c-Myc and MAPK/c-Myc signalings.

Balloon dilatation and thrombus extraction for the treatment of cerebral venous sinus thrombosis

BACKGROUND AND PURPOSE This study aimed to investigate the efficacy and safety of balloon dilatation and thrombus extraction for the treatment of cerebral venous sinus thrombosis (CVST). MATERIALS AND METHODS Twenty-six cases of digital subtraction angiography-confirmed CVST were treated with balloon dilatation and thrombus extraction. Active treatment of primary disease was carried out after cerebral venous sinus recanalization, and the subsequent anticoagulant therapy lasted for 6 months. RESULTS Recanalization of the cerebral venous sinus was achieved in all 26 patients, and no endovascular treatment-related complications occurred during or after the procedure. At discharge, the Glasgow Coma Scale (GCS) of the patients had improved from an average of 12.3 points to 15 points, and clinical symptoms were improved in 100% of the patients. Follow-up times ranged from 12-62 months (mean follow-up time of 42.3 months) and no thrombus re-formation or new neurological deficits occurred during that time. CONCLUSION Based on our small study population, balloon dilatation and thrombus extraction appears to be a safe and effective treatment for cerebral venous sinus thrombosis. However, further research is needed to confirm this.

MicroRNA-29a inhibits proliferation and motility of schwannoma cells by targeting CDK6

MicroRNA‐29 (miR‐29) family is involved in various types of cancer regulation. Although miR‐29 family was shown to play an inhibitory role in tumorigenesis, the effect of miR‐29a expression on schwannoma cells still remains unclear. In this study, we aimed to explore the role of miR‐29 family in schwannoma. The expressions of miR‐29a, miR‐29b, and miR‐29c were detected in the Schwann tissues and cell lines using qRT‐PCR. The effect of miR‐29a, miR‐29b, and miR‐29c on cell viability, migration, invasion, and apoptosis was tested. Then, the regulatory relationship between miR‐29a and CKD6 was detected using qRT‐PCR, Western blot, and luciferase assay. Finally, the phosphorylation levels of mainly factors in JNK and p38MAPK/ERK pathways were analyzed by Western blot. The expression of miR‐29a, miR‐29b, and miR‐29c was downregulated in Schwann tissues and cell lines. Cell viability, migration, invasion were decreased, while apoptosis was increased when miR‐29a, miR‐29b, and miR‐29c overexpression. We further found that miR‐29a negatively regulated expression of CDK6. Then, knockdown of miR‐29a promoted cell viability, migration, invasion, and inhibited apoptosis in schwannoma cells by upregulating CDK6 expression. In addition, the overexpression of miR‐29a downregulated CDK6 expression by deactivation of JNK and p38MAPK/ERK pathways. Our data suggested that miR‐29a could play an important role in inhibiting proliferation and motility of cancerous Schwann cells, and may suppress tumor growth through upregulation of CDK6.

Value of percutaneous transhepatic cholangiobiopsy for pathologic diagnosis of obstructive jaundice: analysis of 826 cases.

Background Obstructive jaundice (OJ) is insensitive to radiation and chemotherapy, and a pathologic diagnosis is difficult to make clinically. Percutaneous transhepatic cholangiobiopsy (PTCB) is simple to perform and minimally invasive, and clinical practice has shown it to be an accurate and reliable new method for bile duct histopathologic diagnosis. Purpose To investigate the value of PTCB for pathologic diagnosis of causes of OJ. Material and Methods From April 2001 to December 2011, PTCB was performed in 826 consecutive patients. Data on pathologic diagnosis, true positive rate, and complications were analyzed retrospectively. Patients with negative pathologic findings were diagnosed using clinical, imaging, laboratory, and prognostic data. The feasibility and safety of PTCB for OJ were evaluated and true positive rates for biliary carcinoma and non-biliary carcinoma compared. Results PTCB was successful in all cases. Of 740 patients clinically diagnosed with malignant biliary stricture and 86 with benign biliary stricture, 727 received a positive pathologic diagnosis; in 99, the pathologic findings were considered false negative. The true positive rate for PTCB was 88.01% overall, differing significantly for biliary and non-biliary carcinoma (χ2 = 12.87, P < 0.05). Malignancy accounted for 89.59% of OJ cases; well, moderately, and poorly differentiated carcinoma represented 57.88%, 19.97%, and 22.15%. Biliary adenocarcinoma was the predominant malignant pathologic type (96.41%). Transient bilemia, bile leakage, and temporary hemobilia occurred in 47, 11, and 28 cases, respectively, with no serious complications. Conclusion PTCB is safe, feasible, and simple, with a high true positive rate for definitive diagnosis of OJ causes. Well differentiated adenocarcinoma was the predominant pathologic type.

Mechanical thrombectomy with Solitaire AB stents for the treatment of intracranial venous sinus thrombosis.

Background Cerebral venous sinus thrombosis (CVST) is a rare clinicopathological entity with substantial diagnostic and therapeutic dilemmas. The appropriate management of CVST remains to be defined. Purpose To evaluate the efficiency and safety of mechanical thrombectomy with Solitaire AB stents for the treatment of intracranial venous sinus thrombosis. Material and Methods Twenty-three consecutive patients with CVST who were treated with mechanical thrombectomy using Solitaire AB stents between January 2013 and October 2014 were retrospectively analyzed. The headache intensity was evaluated according to the visual analogue scale (VAS), and neurological function was assessed using the National Institute of Health Stroke Scale (NIHSS). Follow-up data were available for all patients for 6–14 months. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) were performed at 3 and 6 months after neurointervention, and telephone interviews were performed monthly thereafter. The Wilcoxon signed-rank test was used to compare the evaluation data (VAS and NIHSS) at admission and discharge. Results Twenty-six Solitaire AB stents were used. No neurointervention-related complications were noted. The symptoms were significantly improved after neurointervention in all patients. The comparisons between the VAS and NIHSS evaluations at admission and discharge were significantly different (P < 0.05). No recurrence was observed during the follow-up period. Conclusion Mechanical thrombectomy with Solitaire AB stents is safe and effective for the treatment of CVST and can significantly improve clinical symptoms. The occurrence of complications is low, and the prognosis is favorable.

MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1

Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively. The direct interaction between miR-320 and FoxM1 was detected by luciferase assay. The protein levels of FoxM1, Sirt1 and γH2AX were measured by western blot assay. We found that miR-320 expression was down-regulated and FoxM1 expression was up-regulated in radioresistant glioma tissues and IR-treated glioma cells. miR-320 overexpression dramatically enhanced radiosensitivity, promoted apoptosis, and improved γH2AX expression and caspase 3 activity in glioma cells. Luciferase reporter assay and western blot assay further validated that miR-320 suppressed FoxM1 expression by directly targeting 3’ UTR region of FoxM1. Moreover, miR-320 inhibited Sirt1 expression via targeting FoxM1 in glioma cells. Furthermore, overexpression of FoxM1 and Sirt1 strikingly attenuated miR-320-induced increase of radiosensitivity, apoptosis and γH2AX expression in glioma cells. In conclusion, miR-320 enhanced radiosensitivity of glioma cells through down-regulation of Sirt1 by directly targeting FoxM1.

One-stage endovascular embolization for multiple intracranial aneurysms.

AIM Clinical treatment of multiple intracranial aneurysms remains challenging due its higher rate of rupture compared to a single aneurysm. We aimed to assess the efficacy of one-stage endovascular embolization for treatment of multiple intracranial aneurysms. MATERIAL AND METHODS We treated 72 aneurysms from 33 patients with one-stage endovascular embolization from September 2010 to October 2015. Of these, 60 aneurysms were treated with coils, while 12 wide-neck aneurysms were embolized with the assistance of intracranial stents. Follow-up studies ranged from 3 to 28 months, and patient outcomes were assessed using the modified Rankin Scale (mRS) and digital subtraction angiography (DSA). RESULTS All aneurysms were embolized successfully and no complications occurred. DSA immediately after procedure revealed that complete occlusion was achieved in 39 cases, neck remnant was observed in 27 cases, and a residual aneurysm remnant was observed in six cases. All patients achieved excellent clinical outcomes following embolization (27 patients with a mRS score of 0 and 6 with a mRS score of 1). Six months after the procedure, DSA was performed on 28 patients, revealing one case with a neck remnant, and two cases with completely occluded aneurysms. Despite these outcomes, there was no rupture or hemorrhage of these aneurysms throughout the six months. CONCLUSION One-stage endovascular embolization is a safe and effective treatment for multiple intracranial aneurysms, but long-term outcomes should be further evaluated.

miR-106b regulates the 5-fluorouracil resistance by targeting Zbtb7a in cholangiocarcinoma

BACKGROUND Cholangiocarcinoma (CCA) is highly resistant to chemo-therapy, including 5-fluorouracil (5-FU) treatment. MicroRNAs are endogenous and short non-coding RNAs that can regulate multiple genes expression. Many microRNAs have shown functional roles in the chemo-resistance of tumors. Here, we examined the relationship between microRNAs expression and the sensitivity of CCA cells to 5-FU. METHODS Microarray analysis was used to determine the aberrantly expressed microRNAs in two 5-FU resistant CCA cell lines, KKU-M139 and KKU-M214 cells. To determine the effect of candidate microRNAs on 5-FU sensitivity, expression of candidate was modified via either transfection of a microRNA mimic or transfection of an antagonist. Ontology-based programs were also used to investigate the potential targets of microRNAs that were confirmed to affect the 5-FU sensitivity of CCA cells. RESULTS The microRNA-106b (miR-106b) was significantly down-regulated in 5-FU resistant CCA cells. Instead, over-expression of miR-106b could re-sensitize resistant CCA cells to 5-FU through down-regulation of Zbtb7a. Moreover, decreased expression of miR-106b is related to poor prognosis in patients with CCA, suggesting its potential role as a new prognostic marker in CCA. CONCLUSION Our study demonstrates that miR-106b can reverse 5-FU resistance via Zbtb7a suppression, thus offer a novel and powerful strategy for CCA chemotherapy.Background Cholangiocarcinoma (CCA) is highly resistant to chemo-therapy, including 5-fluorouracil (5-FU) treatment. MicroRNAs are endogenous and short non-coding RNAs that can regulate multiple genes expression. Many microRNAs have shown functional roles in the chemo-resistance of tumors. Here, we examined the relationship between microRNAs expression and the sensitivity of CCA cells to 5-FU. Methods Microarray analysis was used to determine the aberrantly expressed microRNAs in two 5-FU resistant CCA cell lines, KKU-M139 and KKU-M214 cells. To determine the effect of candidate microRNAs on 5-FU sensitivity, expression of candidate was modified via either transfection of a microRNA mimic or transfection of an antagonist. Ontology-based programs were also used to investigate the potential targets of microRNAs that were confirmed to affect the 5-FU sensitivity of CCA cells. Results The microRNA-106b (miR-106b) was significantly down-regulated in 5-FU resistant CCA cells. Instead, over-expression of miR-106b could re-sensitize resistant CCA cells to 5-FU through down-regulation of Zbtb7a. Moreover, decreased expression of miR-106b is related to poor prognosis in patients with CCA, suggesting its potential role as a new prognostic marker in CCA. Conclusion Our study demonstrates that miR-106b can reverse 5-FU resistance via Zbtb7a suppression, thus offer a novel and powerful strategy for CCA chemotherapy.