Canadian journal of physiology and pharmacology最新文献_第3页

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

Retraction: Vitamin D3 potentiates the nephroprotective effects of metformin in a rat model of metabolic syndrome: role of AMPK/SIRT1 activation and DPP-4 inhibition. 撤回：维生素D3增强二甲双胍在代谢综合征大鼠模型中的肾保护作用：AMPK/SIRT1激活和DPP-4抑制的作用。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0317

引用次数: 0

Sixty-minute inhalation of molecular hydrogen decreases blood oxygen saturation but does not alter autonomic cardiac regulation at rest in healthy females: a randomized, double-blind, placebo-controlled crossover study. 一项随机、双盲、安慰剂对照的交叉研究：吸入60分钟氢分子可降低健康女性静息时血氧饱和度，但不改变心脏自主调节。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0228

Pavel Grepl, Jakub Krejčí, Andrew McKune, Michal Botek

{"title":"Sixty-minute inhalation of molecular hydrogen decreases blood oxygen saturation but does not alter autonomic cardiac regulation at rest in healthy females: a randomized, double-blind, placebo-controlled crossover study.","authors":"Pavel Grepl, Jakub Krejčí, Andrew McKune, Michal Botek","doi":"10.1139/cjpp-2025-0228","DOIUrl":"10.1139/cjpp-2025-0228","url":null,"abstract":"Molecular hydrogen has gained attention for its potential antioxidant, anti-inflammatory, and ergogenic effects. However, its impact on blood oxygen saturation and autonomic cardiac regulation under resting conditions remains unclear. This randomized, double-blind, placebo-controlled crossover study investigated the effects of a 60 min molecular hydrogen inhalation on oxygen saturation and heart rate variability in healthy females. Twenty physically active participants (22.1 ± 1.6 years) completed two inhalation sessions with either molecular hydrogen or placebo (ambient air), separated by a 7-day washout period. Oxygen saturation and heart rate variability were continuously monitored during the 60 min of inhalation. The results using 60 min averages showed a statistically significant (p ≤ 0.007) decrease in oxygen saturation during molecular hydrogen inhalation (95.9 ± 1.0%) compared to placebo (96.7 ± 0.7%), but this decrease should not be considered clinically significant. No significant changes (all p ≥ 0.32) were observed in time-domain or frequency-domain heart rate variability indices. These findings suggest that, under resting conditions, molecular hydrogen inhalation does not induce functional changes in autonomic cardiac regulation, and the observed reduction in blood oxygen saturation does not compromise homeostatic stability.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767269","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

5 weeks of online resistance training with blood flow restriction increases sit-to-stand oxygen consumption in healthy older adults. 5周限制血流的在线阻力训练可以增加健康老年人坐立变耗氧量。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0270

Daniela Presta, Andreas Bergdahl

引用次数: 0

Sex-specific vascular effects of menthol: TRPM8- and TRPA1-dependent relaxation in female mouse aorta and pudendal arteries. 薄荷醇对雌性小鼠主动脉和阴部动脉TRPM8和trpa1依赖性松弛的性别特异性血管效应。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0101

Fênix Alexandra Araujo, Raiana Anjos Moraes, Rinaldo Rodrigues Dos Passos, Milene Tavares Fontes, Camilla Ferreira Wenceslau, R Clinton Webb, Fernanda Priviero, Cameron G McCarthy, Darízy Flávia Silva

{"title":"Sex-specific vascular effects of menthol: TRPM8- and TRPA1-dependent relaxation in female mouse aorta and pudendal arteries.","authors":"Fênix Alexandra Araujo, Raiana Anjos Moraes, Rinaldo Rodrigues Dos Passos, Milene Tavares Fontes, Camilla Ferreira Wenceslau, R Clinton Webb, Fernanda Priviero, Cameron G McCarthy, Darízy Flávia Silva","doi":"10.1139/cjpp-2025-0101","DOIUrl":"10.1139/cjpp-2025-0101","url":null,"abstract":"Sexual dysfunction affects the quality of life for both men and women. Menthol, a TRPM8 agonist, is widely used in products to enhance sexual performance due to its cooling effect. Beyond this, menthol also induces vascular effects in male arteries. To explore its effects on female vasculature, we studied male and female C57BL/6 mice, along with female TRPM8 knockout (KO) mice. We isolated the internal pudendal artery and aorta to assess isometric contractile force. Menthol-induced relaxation of the pudendal artery was reduced in both female TRPM8 KO and male mice compared to female controls. Acetylcholine-induced relaxation was not affected in females, but in males, it was attenuated by menthol and enhanced by M8-B, a TRPM8 inhibitor. Menthol did not alter responses to norepinephrine, serotonin, or histamine in either sex. Notably, menthol-induced relaxation was also reduced in the aortas of female TRPM8 KO mice. In both the aorta and pudendal arteries of female mice, the TRPA1 inhibitor HC030031 significantly diminished menthol-induced relaxation. These findings suggest that TRPM8 modulation plays a role in acetylcholine-induced relaxation in male, but not female, pudendal arteries. Moreover, the menthol vascular effect in female arteries relies on TRPM8 and TRPA1 activation.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917077","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

Cerebral edema and brain death following intravenous N-acetylcysteine overdose: a case report. 静脉注射过量n -乙酰半胱氨酸后脑水肿和脑死亡1例报告。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0341

Riley J Hartmann, Sunil Pradhan, Diana Bylyku, Kristine Markieta, James Scozzafava, Scott Lucyk, Mark Yarema

{"title":"Cerebral edema and brain death following intravenous N-acetylcysteine overdose: a case report.","authors":"Riley J Hartmann, Sunil Pradhan, Diana Bylyku, Kristine Markieta, James Scozzafava, Scott Lucyk, Mark Yarema","doi":"10.1139/cjpp-2025-0341","DOIUrl":"10.1139/cjpp-2025-0341","url":null,"abstract":"N-acetylcysteine (NAC) infusions are rarely associated with cerebral edema. We present a patient that received 1242.2 mg/kg intravenous NAC over 8.3 h who developed seizures, cerebral edema, and died. A 17-24-year-old female (48.3 kg) presented after an acute acetaminophen ingestion. Their initial presumed 5 h acetaminophen concentration was 591.7 μmol/L. Initial alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 16 and 21 IU/L, respectively. Due to inconsistencies in the time of ingestion, IV NAC was initiated as a two-step protocol of 150 mg/kg over 1 h followed by 15 mg/kg/h for 20 h. During treatment, the patient developed vomiting, flushing, and a maculopapular rash. It was discovered that NAC had been administered continuously at 150 mg/kg/h for 8.3 h and was stopped. The patient became confused and agitated and subsequently developed seizures. They were treated with lorazepam, phenytoin, intubation, and propofol. Neuroimaging demonstrated cerebral edema with cerebellar tonsillar herniation. Despite neurocritical care, the patient died 86 h post-ingestion. The patient's ALT and AST remained normal. Investigations including lumbar puncture and post-mortem toxicology analysis were unremarkable. Clinicians must be aware of the clinical features of supratherapeutic IV NAC dosing errors and potential adverse effects.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-5"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763334","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

Impact of inhalational anesthetics on neurodegeneration in Alzheimer's disease: current evidence and potential implications. 吸入麻醉剂对阿尔茨海默病神经退行性变的影响：目前的证据和潜在的影响

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0192

Austin Dosanjh, Sanarya Al-Jaf, Emily Ye, Khaled S Abd-Elrahman

{"title":"Impact of inhalational anesthetics on neurodegeneration in Alzheimer's disease: current evidence and potential implications.","authors":"Austin Dosanjh, Sanarya Al-Jaf, Emily Ye, Khaled S Abd-Elrahman","doi":"10.1139/cjpp-2025-0192","DOIUrl":"10.1139/cjpp-2025-0192","url":null,"abstract":"Alzheimer's disease (AD) is the most common form of dementia, primarily affecting the elderly population. It is a progressive neurodegenerative disease with key pathogenesis hallmarks being amyloid-beta plaque accumulation, and neurofibrillary tangles of tau protein. With an increasingly aging population and rising numbers of surgical procedures, growing interest has been directed toward the potential impact of inhalational anesthetics, particularly isoflurane, sevoflurane, and desflurane, in contributing to the neurodegenerative process. Evidence supporting anesthetic-related modulation of AD pathways is derived predominantly from in vitro and animal models, with comparatively limited and heterogeneous human biomarker and clinical data. This review will explore the various mechanisms by which these volatile anesthetics may contribute to the pathogenesis of neurodegeneration in the context of AD. This includes upregulation of beta-secretase 1 resulting in the formation of amyloid-beta oligomers and inhibition of tau dephosphorylation. While certain studies point toward a neuroprotective effect of these anesthetics, the evidence remains inconsistent. Collectively, these findings support perioperative strategies focused on maintenance of normothermia, optimization of oxygenation, and judicious anesthetic exposure as practical measures to mitigate vulnerability in at-risk populations.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403671","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

The transplacental transfer of NHC, the active metabolite of molnupiravir, in the ex vivo human placental perfusion model. 莫那匹拉韦活性代谢物NHC在离体人胎盘灌注模型中的经胎盘转移。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0363

Magdalene Zabek, Eddie Chan, Yong Jin Lim, Bradley L Urquhart, Facundo Garcia-Bournissen, Janine R Hutson

{"title":"The transplacental transfer of NHC, the active metabolite of molnupiravir, in the ex vivo human placental perfusion model.","authors":"Magdalene Zabek, Eddie Chan, Yong Jin Lim, Bradley L Urquhart, Facundo Garcia-Bournissen, Janine R Hutson","doi":"10.1139/cjpp-2025-0363","DOIUrl":"10.1139/cjpp-2025-0363","url":null,"abstract":"Pregnant patients with COVID-19 have an increased risk for negative birthing outcomes such as preterm birth and low birth weight. Molnupiravir, an antiviral used to treat COVID-19, has limited data in pregnancy. Animal studies suggest embryotoxic and mutagenic potential, therefore placental transfer must be characterized to assess fetal risk. This medication may be necessary if the pregnant patient is critically ill. The objective of this study is to determine the rate and extent of placental transfer of molnupiravir. The transplacental pharmacokinetics of the active metabolite of molnupiravir, β-d-N4-hydroxycytidine (NHC), were determined using the ex vivo human placental perfusion model. NHC was introduced into the maternal circuit at therapeutic concentrations (2.97 µg/mL) (n = 4) or 10-times therapeutic concentrations (29.7 µg/mL) (n = 4) and transfer was observed over 3 h and then quantified by liquid chromatography mass spectrometry. NHC was detectable on the fetal side within 10 min. The average fetal:maternal concentration ratio was 0.48 for placentas perfused with 2.97 µg/mL, and 0.57 for those perfused with 29.7 µg/mL. These results suggest that significant concentrations of molnupiravir will reach the fetus and given the risk for teratogenicity, this therapeutic should be avoided in pregnancy unless maternal morbidity is severe and no safer alternatives exist.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629466","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

The association of arterial stiffness with the high incidence of cardiac arrhythmias in patients with peripheral arterial disease. 外周动脉疾病患者动脉僵硬度与心律失常高发的关系

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0161

Delfin Rodriguez-Leyva, Ayelen Rodriguez-Portelles, Randy Guzman, Wendy Weighell, Broderick C Hirst, Susan D Hirst, Grant N Pierce

{"title":"The association of arterial stiffness with the high incidence of cardiac arrhythmias in patients with peripheral arterial disease.","authors":"Delfin Rodriguez-Leyva, Ayelen Rodriguez-Portelles, Randy Guzman, Wendy Weighell, Broderick C Hirst, Susan D Hirst, Grant N Pierce","doi":"10.1139/cjpp-2026-0161","DOIUrl":"10.1139/cjpp-2026-0161","url":null,"abstract":"The purpose of the study was to identify the incidence and type of arrhythmias and their relationship to the vascular abnormalities in a cross-sectional study of 110 patients with peripheral artery disease (PAD). Cardiac arrhythmias were found in 37% of the PAD subjects. Frequent premature ventricular and supraventricular contractions were the most common arrhythmias (78%), and most (65%) were observed at rest. PR segment duration, QRS complex duration, and QTc interval were significantly longer in patients with arrhythmias. QTc differences were significant only for males. Both initial and absolute claudication distances were greater in patients with arrhythmias, but ankle/brachial index values were not. For comparison, arrhythmias were monitored in patients (n = 111) with coronary artery disease (CAD) but without PAD. Cardiac arrhythmias were observed in 29% of this population. Age (>60 years), pre-existing CAD, and greater arterial stiffness (as determined by significantly higher augmentation index values during pulse wave analysis (PWA)) were identified as predictors of arrhythmias in PAD patients. In conclusion, patients with PAD have a high incidence of cardiac arrhythmias at rest. Older age, concomitant CAD, and greater arterial stiffness may pre-dispose PAD patients to arrhythmias. A simple, noninvasive technique like PWA may allow for risk stratification.","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":"148700785","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