Chemotherapeutic failure and metastasis are the main causes of high mortality rate in lung cancer. Alteration of cellular redox status in response to endogenous stimuli or exogenous compounds has a significant impact on cell signaling and behavior. Herein we divulge for the first time that lung cancer cells exposed to α-lipoic acid (LA) resulted in a higher level of cellular superoxide anion (O2·-) and hydrogen peroxide (H2O2), and such an increase of the specific reactive oxygen species (ROS) downregulated integrin β1 and β3, the integrins known for potentiating aggressive behavior and metastasis. The LA-treated cells exhibited significant decrease in their abilities to survive in detached condition and grow in anchorage-independent soft agar assay. Furthermore, LA sensitized the cells to cisplatin, etoposide and paclitaxel-induced apoptosis. For underlying mechanism, we found that the treatment of the cells with LA significantly decreased integrin β1 and β3, while had no effect on integrin α5 and αv. Interestingly, survival protein p-AKT and anti-apoptotic protein Bcl-2 were reduced in an association to such integrin modulations. Using ROS probes and selective anti-oxidants, we have shown that H2O2 and O2·- induced by LA are key players for the decrease of β1 and β3 integrins, respectively. These findings indicate a novel effect of LA as well as specific ROS, O2·- and H2O2 in integrin regulation, anoikis and chemotherapeutic sensitizations.

Aims To grade the evidence from published meta‐analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes. Methods MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta‐analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach. Results From 9308 publications, 149 full‐text articles were evaluated for eligibility, and 24 studies with 85 unique meta‐analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta‐analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta‐analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta‐analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta‐analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3 mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all‐cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure. Conclusion This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.

Background. Long-acting injectable (LAI) antipsychotics are used as a monotherapy in patients with schizophrenia. However, the combination of LAI and oral antipsychotics is commonly used in clinical practice, despite there being very limited studies investigating the efficacy and safety of this combination compared with LAI antipsychotic monotherapy. Objective. To study the efficacy and safety of LAI antipsychotic monotherapy compared with the combination of LAI and oral antipsychotics in patients with schizophrenia. Methods. This study was a retrospective cohort study, which classified eligible patients into two groups: the LAI antipsychotic monotherapy group and the combination of LAI and oral antipsychotic group. The primary outcome was hospitalization between groups. The duration of the study was 2 years. Results. In total, 86 patients completed the study and were analysed (LAI antipsychotic monotherapy group: n = 25 ; combination of LAI and oral antipsychotic group: n = 61 ). There was no significant difference in hospitalization between the two groups ( P = 1.000 ). For other outcomes, there were also no significant differences in both all-cause discontinuation ( P = 0.667 ) and adverse drug reactions ( P = 0.732 ) between the two groups. Conclusion. The efficacy and safety of LAI antipsychotic monotherapy appeared similar to the combination of LAI and oral antipsychotics in patients with schizophrenia. Therefore, the combination of LAI and oral antipsychotics, which is commonly used in clinical practice, may not be necessary.

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