Safety and efficacy of alectinib versus crizotinib in alk-positive non-small cell lung cancer: An update meta-analysis.

Our study aimed to evaluate the efficacy and toxicity of alectinib compared with crizotinib and provide a reference for clinical use of ALK-TKI, systematically. We searched articles published update till October, 2021 based on the electronic databases, including PubMed, EMBASE and Cochrane Library. All trials analyzed the summary odds ratios (ORs) of the interesting outcomes. Three RCTs, including six studies were included. The pooled hazard ratio (HR) =0.33 (95%CI=0.21-0.51, P<0.00001) shown that the alectinib group achieved significant progress-free survival (PFS) superiority than crizotinib, consistent with those for the with (P=0.001) or without (P<0.00001) measurable CNS lesions at baseline. Also, the regimen of the alectinib did achieved benefit in the ORR (OR=2.07, 95% CI=1.41-3.06, P=0.0002) than crizotinib. Due to the limited data, the pool result of the difference of overall survival (OS) was without statistically significant (P=0.35). With regard to the safety, grade 3 to 5 adverse events were less frequent with alectinib than crizotinib (OR=0.53, 95% CI=0.31-0.90, P=0.02). As compared with crizotinib, alectinib demonstrated better PFS efficacy and comparable safety as a first-line treatment for advanced ALK-positive Non-Small Cell Lung Cancer (NSCLC). OS data remain immature, further trials with long-term survival rate have future to look forward to.

Plumbagin protects H9c2 cardiomyocytes against TBHP-induced cytotoxicity by alleviating ROS-induced apoptosis and modulating autophagy.

Plumbagin (PLB) has been previously reported to alleviate myocardial ischemia/reperfusion injury in vivo. In the present study, the potential of plumbagin to protect against hydrogen peroxide-induced injury in cardiomyocytes was analyzed. Specifically, the cytoprotective effects of PLB were evaluated in H9c2 cardiomyocytes, in which oxidative stress was induced by tertiary butyl hydrogen peroxide (TBHP; 75 µM) treatment. After the cardiomyocytes were treated with different concentrations of PLB, cell viability, creatine kinase (CK) activity and lactate dehydrogenase (LDH) release were determined. The apoptosis rate and reactive oxygen species (ROS) levels were evaluated by flow cytometry. Western blot analyses of cleaved caspase-3, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme 4 (NOX4), and phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK) were performed. PLB pretreatment (5, 10 or 20 µM) restored TBHP-treated H9c2 cell viability (P<0.01). Additionally, PLB significantly decreased CK (P<0.01) and LDH activity (P<0.01). TBHP induced apoptosis and oxidative stress in cardiomyocytes, whereas PLB pretreatment significantly reduced the TBHP-induced apoptosis rate (P<0.01) and ROS levels (P<0.01). Furthermore, PLB resulted in a decrease in the expression of cleaved caspase-3, NOX4, and p-p38 MAPK in TBHP-treated H9c2 cells. The active marker of autophagosomes, LC3-II/LC3-I, was increased following treatment with PLB, indicating the induction of autophagy. The present study revealed the protective role of PLB against TBHP-induced cardiomyocyte injury via the alleviation of ROS-mediated apoptosis and induction of autophagy.

Plumbagin attenuated oxygen-glucose deprivation/reoxygenation-induced injury in human SH-SY5Y cells by inhibiting NOX4-derived ROS-activated NLRP3 inflammasome.

Plumbagin (PLB), an alkaloid obtained from the roots of the plants of Plumbago genus, is an inhibitor of NADPH oxidase 4 (NOX4). This study aimed to investigate the beneficial effect of PLB against oxygen-glucose deprivation/reoxygenation (OGDR)-induced neuroinjury in human SH-SY5Y neuronal cultures. Our results showed that OGD/R stimulated NOX4 protein expression and reactive oxygen species (ROS) production in SH-SY5Y cells, whereas increased 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) production, resulting in the activation of the NLRP3 inflammasome. And PLB pretreatment reduced the ROS production by regulating the expression of NOX4 and downregulated NF-κB signaling which was induced by OGDR. Furthermore, PLB inhibited OGDR induced NLRP3 inflammasome activation but not PARP1. Overall, PLB improved OGDR induced neuroinjury by inhibiting NOX4-derived ROS-activated NLRP3 inflammasome.