Canadian journal of physiology and pharmacology最新文献_第2页

Is iron therapy indicated for heart failure with reduced ejection fraction patients? 射血分数降低的心力衰竭患者需要铁治疗吗？

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0014

Yamna Jadoon, Marc J Kahn

引用次数: 0

Analysis of the expression of genes encoding the endothelin signaling pathway in fetal, heathy, and diseased adult human heart using single-cell transcriptomics. 利用单细胞转录组学分析内皮素信号通路编码基因在胎儿、健康和患病成人心脏中的表达。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0097

Vincent R Knight-Schrijver, Semih Bayraktar, Rhoda E Kuc, Janet J Maguire, Sanjay Sinha, Anthony P Davenport

{"title":"Analysis of the expression of genes encoding the endothelin signaling pathway in fetal, heathy, and diseased adult human heart using single-cell transcriptomics.","authors":"Vincent R Knight-Schrijver, Semih Bayraktar, Rhoda E Kuc, Janet J Maguire, Sanjay Sinha, Anthony P Davenport","doi":"10.1139/cjpp-2026-0097","DOIUrl":"10.1139/cjpp-2026-0097","url":null,"abstract":"This study maps the cellular landscape of the principal genes (EDN1, EDN2, EDN3, EDNRA, EDNRB, ECE1, and ECE2) in the endothelin signaling pathway using published single cell/nucleus RNA sequencing data, comparing cellular expression in healthy fetal, healthy adult, or diseased adult human hearts. EDN1 was the most abundantly expressed gene, principally localized to endothelial cells from all three conditions. EDN2 and EDN3 expression was only detectable in epicardial mesothelial cells forming the outer layer of the heart, important for cardiac development. EDNRA was expressed in contractile cells (cardiomyocytes and mural cells) with highest levels in pericytes, that are emerging as key regulators of coronary microvascular blood flow. EDNRB localized principally to all endothelial cells, with remarkably the highest expression in fetal Schwann cells of the peripheral nervous system. ECE1 was also present in all endothelial cells from adult and fetal hearts, with detectable levels in pericytes, vascular smooth muscle cells, fibroblasts, and adipocytes, while ECE2 expression was sparse. There was pronounced upregulation of ECE1 in pericytes and other mural cells in myocardial ischemia. Our strategy combining databases highlights conserved and divergent expression patterns, particularly upregulation of ECE1 in ischemic mural cells, thereby uncovering a potential unexploited target for pharmaceutical intervention.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-13"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deferoxamine alleviates brain ischemia/reperfusion injury through decreasing LAG-3 and α-Syn expression. 去铁胺通过降低LAG-3和α-Syn的表达减轻脑缺血再灌注损伤。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0114

Amany Mansour, Mahmoud R Abdel-Fadeil, Ahmed Shoyb Mohamed, Rasha Mohamed Samir Sayed, Asmaa A Muhammed

{"title":"Deferoxamine alleviates brain ischemia/reperfusion injury through decreasing LAG-3 and α-Syn expression.","authors":"Amany Mansour, Mahmoud R Abdel-Fadeil, Ahmed Shoyb Mohamed, Rasha Mohamed Samir Sayed, Asmaa A Muhammed","doi":"10.1139/cjpp-2025-0114","DOIUrl":"10.1139/cjpp-2025-0114","url":null,"abstract":"Ischemic stroke is characterized by brain tissue iron accumulation. Alpha-synuclein (α-Syn) is a neuronal protein, its overexpression in ischemic stroke triggers apoptosis. Lymphocyte activation gene-3 (LAG-3), a receptor for α-Syn, enhances its neurotoxic effects. It is split from the cell membrane forming soluble LAG-3 (sLAG-3) in the bloodstream. The expression of LAG-3 in the brain, its relation to iron and α-Syn, as well as the association between serum sLAG-3 levels, iron, α-Syn, and stroke severity remains poorly understood. A case-control study was generated involving 24 patients with acute ischemic stroke and 24 healthy controls. In addition, an experimental study was designed involving 24 Wistar-albino rats. We randomly assigned rats to three groups: sham-operated, brain ischemia, and deferoxamine-treated ischemic rats. Ischemia decreased serum levels of iron, while increased serum levels of α-Syn and sLAG-3. Significant diagnostic performance of serum α-Syn and sLAG-3 was determined using the ROC curve (AUC = 0.962, 83.33% sensitivity, and 95.83% specificity for α-Syn; AUC = 0.755 with 62.50% sensitivity and 87.50% specificity for LAG-3). In rats, ischemia elevated brain tissue iron, α-Syn, and LAG-3 which were reduced following deferoxamine treatment. In conclusion, brain ischemia is associated with iron accumulation that promotes α-Syn expression and aggregation, potentially through increasing LAG-3 expression which improved after deferoxamine injection. In addition, this study illuminates the future beneficial targeting of LAG-3 in brain ischemia.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-13"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-specific effects of abdominal aortic constriction on renal cytochrome P450 enzymes and arachidonic acid metabolites in male and female rats. 腹主动脉收缩对雌雄大鼠肾细胞色素P450酶和花生四烯酸代谢物的性别特异性影响。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-16 DOI: 10.1139/cjpp-2025-0157

Samar H Gerges, Sara A Helal, Heidi L Silver, Jason R B Dyck, Ayman O S El-Kadi

{"title":"Sex-specific effects of abdominal aortic constriction on renal cytochrome P450 enzymes and arachidonic acid metabolites in male and female rats.","authors":"Samar H Gerges, Sara A Helal, Heidi L Silver, Jason R B Dyck, Ayman O S El-Kadi","doi":"10.1139/cjpp-2025-0157","DOIUrl":"10.1139/cjpp-2025-0157","url":null,"abstract":"We previously showed that male rats develop more severe cardiac hypertrophy than female rats following abdominal aortic constriction (AAC) and highlighted corresponding changes in cardiac cytochrome P450 (CYP) enzymes and their arachidonic acid (AA) metabolites. In this study, we report sex-specific changes in renal CYP enzymes and AA metabolites after AAC. Kidneys were isolated from adult male and female Sprague-Dawley rats 5 weeks after sham or AAC surgeries. Renal CYP, lipoxygenase, and epoxide hydrolase enzyme levels were measured by PCR and Western blot, and renal microsomal formation of hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) was measured by liquid chromatography-tandem mass spectrometry. Protein levels of CYP2E1 and CYP4F were significantly elevated post-AAC only in female rats, paralleled by a significant increase in their respective metabolites, 19(R)-HETE and 20-HETE. On the other hand, CYP2C23 mRNA levels were significantly decreased only in male rats, with no significant decrease in EETs. Our findings indicate that renal CYP-mediated AA metabolism undergoes sex-specific reprogramming in response to cardiac pressure overload, which may contribute to the observed divergent cardiac remodeling. This research highlights the importance of the kidney-heart axis and supports the potential for sex-specific metabolic targets in the treatment of cardiovascular diseases.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-16"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective effects of Melissa officinalis ethanolic extract on doxorubicin-induced cardiotoxicity in a rat model. 梅莉莎乙醇提取物对阿霉素致大鼠心脏毒性的保护作用。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0217

Jelena N Terzic, Lazar Z Veljkovic, Vladimir L J Jakovljevic, Jovana N Novakovic, Jasmina Z Sretenovic, Maja D Muric, Aleksandar G Kocovic, Isidora M Milosavljevic

{"title":"Protective effects of Melissa officinalis ethanolic extract on doxorubicin-induced cardiotoxicity in a rat model.","authors":"Jelena N Terzic, Lazar Z Veljkovic, Vladimir L J Jakovljevic, Jovana N Novakovic, Jasmina Z Sretenovic, Maja D Muric, Aleksandar G Kocovic, Isidora M Milosavljevic","doi":"10.1139/cjpp-2025-0217","DOIUrl":"10.1139/cjpp-2025-0217","url":null,"abstract":"Despite its proven efficacy in cancer treatment, doxorubicin's therapeutic potential is limited by cumulative, dose-dependent cardiotoxicity, primarily associated with oxidative stress. Given the well-documented antioxidant properties of Melissa officinalis L., this study aimed to assess the cardioprotective potential of its ethanolic extract (MOE) against doxorubicin-induced cardiotoxicity (DIC). Twenty-one female Wistar albino rats were randomly divided into three groups: CTRL (healthy, untreated), DOX (doxorubicin-treated), and DOX-MO (treated with both doxorubicin and MOE). Doxorubicin (15 mg/kg, i.p.) was administered on Day 7, while MOE (200 mg/kg, orally) was given daily for 10 days. Cardiac function was evaluated using echocardiography and Langendorff-perfused hearts, followed by analysis of oxidative stress markers and morphometric analysis. MOE improved cardiac function and partially preserved myocardial architecture following DIC, significantly reducing fibrosis compared to the DOX group. Nitrite levels were significantly elevated in MOE-treated rats, suggesting preserved endothelial function and enhanced nitric oxide-mediated vasodilation. These results suggest that MOE may mitigate DIC through antioxidative and vasodilatory mechanisms, as well as by preserving endothelial and myocardial integrity. Histological findings further indicate a possible reduction in inflammatory changes, supporting a modest anti-inflammatory effect. These findings suggest that MOE may have cardioprotective potential against DIC, warranting further investigation in preclinical and clinical settings.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Society of Toxicology of Canada meeting abstracts. 加拿大毒理学学会会议摘要。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0061

引用次数: 0

Editorial Expression of Concern: Metformin attenuates ischemia/reperfusion-induced apoptosis of cardiac cells by downregulation of p53/microRNA-34a via activation of SIRT1. 编辑表达关注：二甲双胍通过激活SIRT1下调p53/microRNA-34a，从而减轻缺血/再灌注诱导的心肌细胞凋亡。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0060

Weiwei Li, Sheng Jin, Jie Hao, Yun Shi, Wenjie Li, Lingling Jiang

引用次数: 0

Coenzyme Q10 ameliorates hepatoprotective effect of metformin in experimentally-induced type 2 diabetes mellitus in rats: a functional and histological study. 辅酶Q10改善二甲双胍对实验性2型糖尿病大鼠的肝保护作用：一项功能和组织学研究

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0244

Heba Rady Salem, Asmaa Eldesouky, Mohamed S Amer, Doaa Z M Shebl, Eman S El-Roghy

{"title":"Coenzyme Q10 ameliorates hepatoprotective effect of metformin in experimentally-induced type 2 diabetes mellitus in rats: a functional and histological study.","authors":"Heba Rady Salem, Asmaa Eldesouky, Mohamed S Amer, Doaa Z M Shebl, Eman S El-Roghy","doi":"10.1139/cjpp-2025-0244","DOIUrl":"10.1139/cjpp-2025-0244","url":null,"abstract":"Management of metabolic dysfunction-associated steatotic liver disease (MASLD) remains a significant clinical challenge. This study evaluated the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant therapy to metformin in the treatment of MASLD using an experimentally induced type 2 diabetes (T2D) rat model. T2D was induced in 18 rats through a high-fat diet combined with a low dose of streptozotocin. The diabetic rats were then randomly allocated into three equal groups: untreated, metformin-treated, and metformin/CoQ10-treated. An additional six rats maintained on a normal chow diet served as the control group. Development of MASLD was confirmed through biochemical assays and histopathological analyses. Liver histology and electron microscopy were performed, along with immunohistochemistry for BAX and CD68 markers. Our results demonstrated that T2D rats exhibited impaired glucose and lipid profiles, elevated liver enzymes, and reduced adiponectin levels. These alterations were accompanied by hepatic oxidative stress, histopathological features of MASLD, fibrosis, and increased expression of BAX and CD68. Treatment with either metformin monotherapy or metformin/CoQ10 combination therapy significantly ameliorated the biochemical and histopathological manifestations of MASLD, as well as reduced the expression of BAX and CD68 in the liver. Importantly, combined metformin/CoQ10 therapy exerted a stronger hepatoprotective effect than metformin alone.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-15"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GLP-1 and diabetic nephropathy share key molecular targets. GLP-1与糖尿病肾病共享关键分子靶点。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0146

Wanderson Gabriel Gomes de Melo, Regina Lúcia Dos Santos Silva, Ianahanna Duarte Santos Soares, Bruno de Sousa Barbosa, Felipe Cardoso de Brito, Napoleão Martins Argôlo Neto, Dayseanny de Oliveira Bezerra

{"title":"GLP-1 and diabetic nephropathy share key molecular targets.","authors":"Wanderson Gabriel Gomes de Melo, Regina Lúcia Dos Santos Silva, Ianahanna Duarte Santos Soares, Bruno de Sousa Barbosa, Felipe Cardoso de Brito, Napoleão Martins Argôlo Neto, Dayseanny de Oliveira Bezerra","doi":"10.1139/cjpp-2025-0146","DOIUrl":"10.1139/cjpp-2025-0146","url":null,"abstract":"Glucagon-like peptide-1 (GLP-1) receptor agonists provide renoprotective benefits in diabetes, yet the molecular mechanisms linking GLP-1 signaling to diabetic nephropathy remain poorly defined. This study aimed to identify shared molecular targets between GLP-1 activity and diabetic kidney disease by integrating protein targets of GLP-1 from UniProt with disease-associated genes from GeneCards. The overlapping gene set was analyzed using STRING and Cytoscape® with MCODE clustering, followed by GO and KEGG enrichment through the clusterProfiler package. Molecular docking with HADDOCK was employed to validate structural interactions between GLP-1 and central network proteins. We identified 17 shared genes, including STAT3, EP300, MAPK1, and INSR, which formed a densely connected cluster enriched in pathways related to insulin response, hypoxia adaptation, apoptosis, and glucose metabolism. Docking analysis demonstrated direct and favorable binding of GLP-1 to STAT3, PIK3R1, and EP300, suggesting noncanonical intracellular mechanisms involving transcriptional regulation and epigenetic modulation. These findings reveal a novel convergence between GLP-1 signaling and diabetic nephropathy pathways, providing mechanistic insights that guide the experimental determination of the underlying molecular interactions. This framework may ultimately contribute to the refinement of renal therapies based on GLP-1 modulation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-10"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cost-effectiveness of incretin therapies: a Canadian lens on diabetes, obesity, and emerging indications. 肠促胰岛素治疗的成本-效果：加拿大对糖尿病、肥胖和新出现适应症的观察。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0248

Luke Awadalla, Siena Iskander, Cherry Chu, Mina Tadrous

引用次数: 0