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DLC-1 (deleted in liver cancer-1) is a potential tumor suppressor gene, which is inactive in liver carcinogenesis. To observe the effects of DLC-1 gene expression on cell proliferation and migration in the human colon cancer cell line, RNAi Lipo-recombinant of the DLC-1 gene (pGCsil-DLC-1) was constructed and transduced into LoVo cells which are positive for DLC-1 gene expression. Results showed that the RNAi recombinant effectively inhibited the expression of the DLC-1 gene in LoVo cells. Additionally, our data showed decreased DLC-1 gene expression which resulted in the promotion of LoVo cell proliferation. Flow cytometry in cell cycle detection further indicated that the DLC-1 gene induced cell cycle arrest at G2/M and a cell migration assay confirmed that the knocking down of DLC-1 gene expression promotes LoVo cell migration. Our observations suggest that the DLC-1 gene is associated with LoVo cell proliferation, migration and cell cycle distribution. DLC-1 is a potential suppressor gene in the colon cancer LoVo cell line and may play an important role in colon cancer mechanisms.

Objective-Increased cardiac stromal cell-derived factor-1α (SDF-1α) expression promotes neovascularization and myocardial repair after ischemic injury through recruiting stem cells and reducing cardiomyocyte death. Previous studies have shown that heme oxygenase-1 and its reaction byproduct, carbon monoxide (CO), induce SDF-1α expression in ischemic heart. However, the mechanism underlying heme oxygenase-1/CO-induced cardiac SDF-1α expression remains elusive. This study aims to investigate the signaling pathway and the transcriptional factor that mediate CO-induced SDF-1α gene expression and cardioprotection. Approach and Results-CO gas and a CO-releasing compound, tricarbonyldichlororuthenium (II) dimer, dosedependently induced SDF-1α expression in primary neonatal cardiomyocytes and H9C2 cardiomyoblasts. Promoter luciferase-reporter assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation demonstrated that the activator protein 2α (AP-2α) mediated tricarbonyldichlororuthenium (II) dimer-induced SDF-1α gene transcription. Tricarbonyldichlororuthenium (II) dimer induced AP-2α expression via protein kinase B (AKT)-dependent signaling.AKT inhibition or AP-2α knockdown reduced tricarbonyldichlororuthenium (II) dimer-induced SDF-1α expression. Coronary ligation induced transient increases of cardiac AP-2α and SDF-1α expression, which were declined at 1 week postinfarction in mice. Periodic exposure of coronary-ligated mice to CO (250 ppm for 1 hour/day, 6 days) resumed the induction of AP-2α and SDF-1α gene expression in infarcted hearts. Immunohistochemistry and echocardiography performed at 4 weeks after coronary ligation revealed that CO treatment enhanced neovascularization in the myocardium of peri-infarct region and improved cardiac function. CO-mediated SDF-1α expression and cardioprotection was ablated by intramyocardial injection of lentivirus bearing specific short hairpin RNA targeting AP-2α. Conclusions-Our data demonstrate that AKT-dependent upregulation of AP-2α is essential for CO-induced SDF-1α expression and myocardial repair after ischemic injury. (Arterioscler Thromb Vasc Biol. 2013;33:785-794.) Key Words: activator protein 2α ◼ carbon monoxide ◼ heme oxygenase-1 ◼ ischemic heart ◼ stromal cell-derived factor-1α ◼ vascularization Activator Protein-2α Mediates Carbon MonoxideInduced Stromal Cell-Derived Factor-1α Expression and Vascularization in Ischemic HeartHeng-Huei Lin, Yen-Hui Chen, Ming-Tsai Chiang, Pei-Ling Huang, Lee-Young Chau Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results HO-1/CO Induces SDF-1α ExpressionTo confirm our previous finding that HO-1 overexpression promotes SDF-1α gene induction in myocardium in vivo, 14 we performed HO-1 gene transduction experiment in primary neonatal cardiomyocytes and H9C2 cardiomyoblasts. As shown in Figure 1A and 1B, when cells were infected with adenovirus bearing HO-1 gene for 48 hours, SDF-1α gene expression examined by quantitative real-time PCR was significantly higher, as comp...

Off-target effect" is one of the obstacles for targeted prodrugs in chemotherapy. To circumvent this issue, herein we proposed a dual biomarker cascade-activated prodrug strategy based on high levels of reactive oxygen species (ROS) and tyrosinase (TYR) in melanoma cells. A representative prodrug, Coumarin-Quinazolinone-phenylBoronic acid pinacol ester (CQB) was prepared. The prodrug contained coumarinquinazolinone (CQ) as mitochondria targeting and monitoring moiety, and phenylboronic acid pinacol ester as a cascade-activated pro-warhead. After activated by the endogenous ROS and subsequent TYR in melanoma cells, CQB can be converted to the final active reagent Coumarin-Quinazolinone-o-Quinone (CQQ) which

Objective. We investigated combined cognitive and exercise interventions in the literature and summarized their effectiveness in improving poststroke cognitive impairment (PSCI). Data Sources. Electronic databases and trial registries were searched from their inception until July 2020. Study Selection. Trials were collected with the following study inclusion criteria: (1) patients over 18 years of age who were diagnosed with PSCI; (2) combined cognitive-exercise interventions, regardless of the order of the two types of interventions or whether they were administered simultaneously; (3) any control group studied at the same time that was deemed acceptable, including no intervention/routine care, delayed intervention, sham intervention, and passive training; (4) the use of any validated cognitive neuropsychological test to evaluate cognitive function; and (5) clinically administered random trials with controls. Data Extraction. Five randomized controlled trials met the inclusion criteria. Two reviewers independently assessed the eligibility of the full texts and methodological quality of the included studies using the Cochrane risk of bias tool. Inconsistent results were resolved by additional discussion or decided by a third examiner, if necessary. Data Analysis. Meta-analysis demonstrated that the combined interventions had a significant effect on executive function and working memory [Stroop test (time), standardized mean difference SMD = 0.42 , 95% confidence interval (CI): 0.80–0.04, p = 0.02 ; Trail Making Test, SMD = 0.49 , 95% CI: 0.82–0.16, p = 0.004 ; Forward Digit Span Test, SMD = 0.91 , 95% CI: 0.54–1.29, p ≤ 0.001 ]. While it was impossible to conduct a meta-analysis of global cognitive function and other cognitive domains, individual experiments demonstrated that the combined interventions played a significant role in global cognition, reasoning ability, logical thinking, and visual-spatial memory function. Conclusions. Our analyses demonstrated that the combined interventions had a significant effect on the improvement of PSCI, particularly in terms of executive function. However, the moderate risk of bias in the included trials and the small number of relevant studies indicated a need for more uniform diagnostic and evaluation criteria, and larger trials would provide stronger evidence to better understand the effectiveness of the combined interventions. This trial is registered with trial registration number INPLASY202160090.

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