Abstract-Ischemic preconditioning (IPC) is a potent cellular protective mechanism whereby brief periods of sublethal ischemia protect the myocardium from prolonged ischemia-induced injury. We demonstrate the selective role of phosphatidylinositol 3-kinase (PI3K) isoforms in IPC. Hearts from PI3K␥ knockout mice (PI3K␥ Ϫ/Ϫ ) displayed poorer functional recovery and greater tissue injury following IPC compared to wild-type and PI3K␥ ϩ/Ϫ hearts. Examination of the cell-signaling pathways revealed restored phosphorylation levels of Akt and glycogen synthase kinase (GSK)3␤ in wild-type hearts, which were abolished in PI3K␥ Ϫ/Ϫ hearts subjected to IPC. Inhibition of GSK3␤ by LiCl reversed the loss in protection in PI3K␥ Ϫ/Ϫ hearts. In contrast, mice expressing a cardiac-specific kinase-deleted PI3K␣ (PI3K␣DN) were resistant to injury induced by 30 minutes of ischemia followed by 40 minutes of reperfusion. Furthermore, the resistance of PI3K␣DN hearts to ischemia/reperfusion correlated with the persistent expression of p110␥ and was blocked by the PI3K inhibitor wortmannin, suggesting the possible enhanced cell signaling through the PI3K␥ pathway. These results demonstrate the importance of the PI3K␥-Akt-GSK3␤ signaling pathway in IPC. Selective activation of myocardial PI3K␥ may be an attractive target for the treatment of ischemic heart disease. Key Words: heart Ⅲ ischemic preconditioning Ⅲ PI3K Ⅲ Akt Ⅲ GSK3␤, transgenic mice I schemic preconditioning (IPC) is a potent cellular protective mechanism that is initiated by brief periods of sublethal ischemic stress (reviewed elsewhere 1 ). First identified by Murry et al, 2 they observed a reduction in infarct size when canine hearts were subjected to 4 brief episodes of 5 minutes of ischemia and 5 minutes of reperfusion before a period of sustained ischemia. It has been concluded that the heart adapted within minutes to become resistant against ischemiainduced injury. 1 The cellular mechanisms underlying the protection initiated by myocardial IPC have been scrutinized intensively, 1,3 given the potential to identify novel targets for treating ischemic heart disease. Work has focused on identifying the triggers, mediators, and end effectors of IPC. Numerous signal transduction pathways have been demonstrated to be the mediators affording protection by IPC. 3 Phosphatidylinositol 3-kinase (PI3K) is a family of conserved lipid and protein kinases that are ubiquitously expressed in many cells, including the heart (reviewed elsewhere 4,5 ). These enzymes phosphorylate phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 or PIP 2 ] to form phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P 3 or PIP 3 ]. Class IA and IB PI3Ks are heterodimeric enzymes that have a regulatory subunit coupled to a tightly bound catalytic subunit. Class IA PI3Ks are activated through their coupling with tyrosine kinase receptors, whereas class IB activation occurs through G protein-coupled receptors. 6 The class IA family is comprised of PI3K␣, -␤, and -␦, with PI3K␥ constituting class IB. 4...

Background Excess alcohol (ethanol, EtOH) consumption is a significant cause of chronic liver disease, accounting for nearly half of the cirrhosis‐associated deaths in the United States. EtOH‐induced liver toxicity is linked to EtOH metabolism and its associated increase in proinflammatory cytokines, oxidative stress, and the subsequent activation of Kupffer cells. Dihydromyricetin (DHM), a bioflavonoid isolated from Hovenia dulcis , can reduce EtOH intoxication and potentially protect against chemical‐induced liver injuries. But there remains a paucity of information regarding the effects of DHM on EtOH metabolism and liver protection. As such, the current study tests the hypothesis that DHM supplementation enhances EtOH metabolism and reduces EtOH‐mediated lipid dysregulation, thus promoting hepatocellular health. Methods The hepatoprotective effect of DHM (5 and 10 mg/kg; intraperitoneal injection) was evaluated using male C57BL/6J mice and a forced drinking ad libitum EtOH feeding model and HepG2/VL‐17A hepatoblastoma cell models. EtOH‐mediated lipid accumulation and DHM effects against lipid deposits were determined via H&E stains, triglyceride measurements, and intracellular lipid dyes. Protein expression of phosphorylated/total proteins and serum and hepatic cytokines was determined via Western blot and protein array. Total NAD + /NADH Assay of liver homogenates was used to detect NAD + levels. Results DHM reduced liver steatosis, liver triglycerides, and liver injury markers in mice chronically fed EtOH. DHM treatment resulted in increased activation of AMPK and downstream targets, carnitine palmitoyltransferase (CPT)‐1a, and acetyl CoA carboxylase (ACC)‐1. DHM induced expression of EtOH‐metabolizing enzymes and reduced EtOH and acetaldehyde concentrations, effects that may be partly explained by changes in NAD + . Furthermore, DHM reduced the expression of proinflammatory cytokines and chemokines in sera and cell models. Conclusion In total, these findings support the utility of DHM as a dietary supplement to reduce EtOH‐induced liver injury via changes in lipid metabolism, enhancement of EtOH metabolism, and suppressing inflammation responses to promote liver health.

This data article describes the dataset of the International COVID-19 Impact on Parental Engagement Study (ICIPES). ICIPES is a collaborative effort of more than 20 institutions to investigate the ways in which, parents and caregivers built capacity engaged with children's learning during the period of social distancing arising from global COVID-19 pandemic. A series of data were collected using an online survey conducted in 23 countries and had a total sample of 4,658 parents/caregivers. The description of the data contained in this article is divided into two main parts. The first part is a descriptive analysis of all the items included in the survey and was performed using tables and figures. The second part refers to the construction of scales. Three scales were constructed and included in the dataset: ‘parental acceptance and confidence in the use of technology’, ‘parental engagement in children's learning’ and ‘socioeconomic status’. The scales were created using Confirmatory Factor Analysis (CFA) and Multi-Group Confirmatory Analysis (MG-CFA) and were adopted to evaluate their cross-cultural comparability (i.e., measurement invariance) across countries and within sub-groups. This dataset will be relevant for researchers in different fields, particularly for those interested in international comparative education.

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