Canadian journal of physiology and pharmacology
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Can. J. Physiol. Pharmacol. · Feb 2021
ReviewAfter the storm: an objective appraisal of the efficacy of c-kit+ cardiac progenitor cells in preclinical models of heart disease.
The falsification of data related to c-kit+ cardiac progenitor cells (CPCs) by a Harvard laboratory has been a veritable tragedy. Does this fraud mean that CPCs are not beneficial in models of ischemic cardiomyopathy? At least 50 studies from 26 laboratories independent of the Harvard group have reported beneficial effects of CPCs in mice, rats, pigs, and cats. The mechanism of action remains unclear. ⋯ In the retraction notice, the Lancet editors stated: "Although we do not have any reservations about the clinical work in Louisville that used the preparations from Anversa's laboratory in good faith, the lack of reliability regarding the laboratory work at Harvard means that we are now retracting this paper". We must be careful not to dismiss all work on CPCs because of one laboratory's misconduct. An unbiased review of the literature supports the therapeutic potential of CPCs for heart failure at the preclinical level.
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Can. J. Physiol. Pharmacol. · Sep 2020
Single-center prognostic validation of the risk assessment of the 2015 ESC/ERS guidelines in patients with pulmonary arterial hypertension in Japan.
The 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension include a multidimensional risk assessment for patients with pulmonary arterial hypertension (PAH). However, prognostic validations of this risk assessment are limited, especially outside Europe. Here, we validated the risk assessment strategy in PAH patients in our institution in Japan. ⋯ The high-risk group showed significantly higher mortality than the low- or intermediate-risk group at baseline (P < 0.001 for both comparisons), and the mortalities in the intermediate- and low-risk groups were both low (P = 0.989). At follow-up, patients who improved to or maintained a low-risk status showed better survival than those who did not (P = 0.041). Our data suggest that this risk assessment can predict higher mortality risk and long-term survival in PAH patients in Japan.
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Can. J. Physiol. Pharmacol. · Apr 2020
Long noncoding RNA MALAT1 participates in the pathological angiogenesis of diabetic retinopathy in an oxygen-induced retinopathy mouse model by sponging miR-203a-3p.
Diabetic retinopathy (DR) is a devastating complication of diabetes. The aim of the present study is to investigate the exact role and mechanism of long noncoding RNA MALAT1 (MALAT1) in the progress of DR. An oxygen-induced retinopathy (OIR) mouse model and high glucose (HG) stimulated human retinal microvascular endothelial cells (HRMECs) were employed to mimic the pathological statues of DR. ⋯ A dual-luciferase reporter assay showed that miR-203a-3p could bind to the predicted seed regions of MALAT1 as evidenced by the reduced luciferase activity. Furthermore, enforced downregulation of miR-203a-3p abolished the suppressive effect of MALAT1 silencing on HRMEC cell migration and tube formation. In conclusion, these data demonstrated that MALAT1 may affect angiogenesis by sponging miR-203a-3p in DR, suggesting that MALAT1 may act as a novel therapeutic target for the treatment of DR.
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Can. J. Physiol. Pharmacol. · May 2019
Klotho protein inhibits H2O2-induced oxidative injury in endothelial cells via regulation of PI3K/AKT/Nrf2/HO-1 pathways.
Klotho protein secreted in the blood could act as a hormone to regulate various target organs and have a protective effect on the cardiovascular system. Numerous studies had shown that Klotho protein had antioxidative stress, anti-inflammatory, and antiapoptotic effects on vascular endothelial cells. The purpose of this study was to investigate the protective mechanism of Klotho protein on oxidative damage of vascular endothelial cells induced by H2O2. ⋯ Klotho protein activated nuclear translocation of Nrf2 and increased HO-1 expression. Klotho protein also activated phosphorylation of protein kinase B (AKT), whereas the addition of LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), blocked Klotho-protein-induced Nrf2/HO-1 activation and cytoprotection. Klotho protein enhanced the antioxidant defense ability of the cells by activating the PI3K/AKT pathway, which upregulated the expression of Nrf2/HO-1, thereby inhibiting H2O2-induced oxidative damage.
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Can. J. Physiol. Pharmacol. · Apr 2019
Medical education dilemma: How can we best accommodate basic sciences in a curriculum for 21st century medical students? 1.
Over the years, the medical curriculum has been changed to accommodate a variety of evolving disciplines and an exploding scientific knowledge of the basic sciences to prepare "a competent physician" of the 21st century. Therefore, we must be innovative in our approach of curricular development if we wish to continue to incorporate new basic sciences knowledge in the face of decreasing contact hours to satisfy the buzz word, "integration". Certainly, the challenges are phenomenal. ⋯ The purpose of this review is to evaluate different curricular models for their basic sciences content and address their strengths and weaknesses. In addition, we will introduce a spiral design to integrate basic sciences for senior students. Finally, we will provide some insight as to how learning and retention of basic science content can be sustained.