Canadian journal of physiology and pharmacology最新文献

Lysine acetylation of aquaporin-3 does not improve lithium-induced nephrogenic diabetes insipidus. 水通道蛋白-3赖氨酸乙酰化不能改善锂致肾源性尿崩症。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-10-02 DOI: 10.1139/cjpp-2025-0177

Nha V Huynh, Hung Nguyen, Kelly A Hyndman

{"title":"Lysine acetylation of aquaporin-3 does not improve lithium-induced nephrogenic diabetes insipidus.","authors":"Nha V Huynh, Hung Nguyen, Kelly A Hyndman","doi":"10.1139/cjpp-2025-0177","DOIUrl":"https://doi.org/10.1139/cjpp-2025-0177","url":null,"abstract":"Aquaporin-3 (AQP3) is expressed in the basolateral membrane of the renal principal cell contributing to vasopressin-mediated water reabsorption and urine concentration. We reported that post-translational acetylation of lysine 282 of AQP3 promotes water permeability. In this study, we hypothesized that AQP3 acetylation may improve polyuria in a mouse model of lithium-induced nephrogenic diabetes insipidus (Li-NDI). Wild type, AQP3 acetylation (K282Q), and deacetylation (K282R) mimetic mice were fed a lithium-containing diet or a control diet for 14 days. Body masses and spot urines were collected overtime, while urine flow and osmolality, plasma osmolality and kidneys were collected on day 14 of the diets. All Li-NDI mice had greater urine output and water intake compared to control fed mice and unexpectedly, this was exacerbated in female Li-NDI AQP3-acetylation and AQP3-deacetylation mice. After 14 days of lithium diet, acetylated AQP3 was almost undetectable in the kidneys of WT mice, and AQP3 localization in acetylated and deacetylated mice was minimal. In the setting of LI-NDI, the significant loss of AQP3 was not prevented in acetylated-AQP3 mice and in female mice mutation of K282 resulted in a worsened Li-NDI phenotype suggesting this lysine is critical for promoting sex-specific AQP3-water permeability.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211905","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

A review of the common causes of acute coronary syndrome (ACS) in females, and the role of estrogen on its pathologies and risk factors-review article. 综述了女性急性冠脉综合征（ACS）的常见病因，以及雌激素在其病理和危险因素中的作用。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-10-01 Epub Date: 2025-02-07 DOI: 10.1139/cjpp-2023-0425

Jenny Youn Namkoong, Kunal Minhas

{"title":"A review of the common causes of acute coronary syndrome (ACS) in females, and the role of estrogen on its pathologies and risk factors-review article.","authors":"Jenny Youn Namkoong, Kunal Minhas","doi":"10.1139/cjpp-2023-0425","DOIUrl":"10.1139/cjpp-2023-0425","url":null,"abstract":"As our understanding of acute coronary syndromes (ACS) has increased, we have been able to better delineate the unique pathologies that cause ACS. This review article on the common causes of ACS in females explores the atherosclerotic pathologies of plaque rupture and plaque erosion, and non-atherosclerotic pathologies of SCAD, MINOCA, and Takotsubo cardiomyopathy. It reviews the literature on the link between estrogen and its protection against both atherosclerotic risk factors and induction of plaque vulnerability. This review also explores the mechanistic plausibility that estrogen may contribute to the increased risk of SCAD, MINOCA, and Takotsubo cardiomyopathy-although these mechanisms remain under investigation. Whilst there is still much to be researched about these pathologies, an analysis of the biological impact of sex hormones at the molecular level has helped identify links between mechanisms suggesting a possible unifying pathology between plaque erosion, MINOCA, and microvascular spasm. In this way, a new paradigm for ACS as an equilibrium between thrombus-stabilisation and thrombus-dissolution states is also explored in this article. What has become evident is that the attempt to understand the common causes of ACS in females has resulted also in a deeper understanding of atherosclerotic ACS in males, and highlighted areas of exciting further discovery.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"312-324"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370454","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

KCNQ3 activation by the naturally occurring phenol, eugenol. KCNQ3被天然存在的苯酚、丁香酚激活。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-10-01 Epub Date: 2025-07-31 DOI: 10.1139/cjpp-2025-0064

Adrián Rivera-Ruedas, Alejandro R Medina-Vilchis, Juan J Romero-Tovar, Gema R Cristóbal-Mondragón, Victor De la Rosa

{"title":"KCNQ3 activation by the naturally occurring phenol, eugenol.","authors":"Adrián Rivera-Ruedas, Alejandro R Medina-Vilchis, Juan J Romero-Tovar, Gema R Cristóbal-Mondragón, Victor De la Rosa","doi":"10.1139/cjpp-2025-0064","DOIUrl":"10.1139/cjpp-2025-0064","url":null,"abstract":"Pharmacological targeting of ion channels represents a crucial avenue for pain management. The KCNQ family of ion channels plays a significant role in controlling neuronal excitability and the generation and propagation of pain-related nerve impulses, mitigating excessive electrical signaling and limiting the transmission of pain signals. Eugenol has a variety of biological activities, including analgesic and anti-inflammatory properties. When used in conjunction with the anti-inflammatory drug diclofenac, eugenol demonstrates enhanced analgesic efficacy in animal models. We investigated the effects of eugenol on KCNQ ion channels. Eugenol acts as a KCNQ2/3 activator, shifting the voltage dependency to negative potentials, most of the activation can be explained by the effect on the KCNQ3, molecular docking simulation and mutagenesis experiments suggest that the binding pocket of eugenol is located at the top of the voltage-sensing domain. We also show that eugenol is a weak activator of the TRPV1 channel yet inhibits the capsaicin and acidic pH-activated current. Diclofenac also inhibits the TRPV1 channel current. In cells co-expressing KCNQ2/3 and TRPV1, eugenol and diclofenac limit the extent of membrane depolarization. Altogether, we report a new target for eugenol that adds to its wide array of biological activities, including its role in modulating acute pain.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"325-333"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759267","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

Disproportionality analysis of ALK inhibitor-induced hemolytic adverse events: a pharmacovigilance study using the FDA Adverse Event Reporting System Database. ALK抑制剂诱导的溶血不良事件的歧化分析：使用FDA不良事件报告系统数据库的药物警戒研究。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-10-01 Epub Date: 2025-04-30 DOI: 10.1139/cjpp-2025-0065

Connor Frey

{"title":"Disproportionality analysis of ALK inhibitor-induced hemolytic adverse events: a pharmacovigilance study using the FDA Adverse Event Reporting System Database.","authors":"Connor Frey","doi":"10.1139/cjpp-2025-0065","DOIUrl":"10.1139/cjpp-2025-0065","url":null,"abstract":"Anaplastic lymphoma kinase (ALK) inhibitors have transformed treatment for ALK-rearranged malignancies, particularly non-small cell lung cancer, by disrupting oncogenic signalling. However, hematologic adverse effects, including hemolysis, have emerged as concerns, especially with alectinib. This study evaluates the prevalence of hemolytic events associated with ALK inhibitors using FDA Adverse Event Reporting System (FAERS) data. A retrospective pharmacovigilance analysis was conducted using FAERS data (2013-2023). Disproportionality analysis with OpenVigil 2.1 assessed associations between ALK inhibitors and hemolysis-related events. Reporting odds ratios (RORs) were calculated, with statistical significance defined as ROR > 2.00 and a lower 95% confidence interval (CI) bound > 1.00. Alectinib exhibited strong associations with hemolysis (ROR 24.01, 95% CI: 17.88-32.24; 45 reports) and bilirubin increase (ROR 18.86, 95% CI: 15.92-22.34; 138 reports). Crizotinib and ceritinib showed weaker signals, while brigatinib and lorlatinib had no significant associations. The findings highlight alectinibs potential hemolytic risk, necessitating hematologic monitoring. Proposed mechanisms include immune-mediated hemolysis, direct cytotoxicity, and metabolic variability. Routine hemoglobin and bilirubin assessments, along with clinical vigilance, are essential. Further studies are needed to elucidate mechanisms of causality and optimize patient safety.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"334-337"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966364","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

Effects of vitamin B6 on cardiometabolic biomarkers, cardiac oxidative stress and enzymes activities, and cardiovascular histomorphometric parameters in hyperhomocysteinemic rats. 维生素B6对高同型半胱氨酸血症大鼠心脏代谢生物标志物、心脏氧化应激和酶活性以及心血管组织形态计量参数的影响

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-09-26 DOI: 10.1139/cjpp-2025-0073

Dušan Todorović, Marija Stojanović, Jovana Jakovljević Uzelac, Slavica Mutavdžin Krneta, Nina Radisavljevic, Kristina Gopčević, Ana Medić, Milica Labudović Borović, Sanja Stankovic, Dragan Djuric

{"title":"Effects of vitamin B6 on cardiometabolic biomarkers, cardiac oxidative stress and enzymes activities, and cardiovascular histomorphometric parameters in hyperhomocysteinemic rats.","authors":"Dušan Todorović, Marija Stojanović, Jovana Jakovljević Uzelac, Slavica Mutavdžin Krneta, Nina Radisavljevic, Kristina Gopčević, Ana Medić, Milica Labudović Borović, Sanja Stankovic, Dragan Djuric","doi":"10.1139/cjpp-2025-0073","DOIUrl":"https://doi.org/10.1139/cjpp-2025-0073","url":null,"abstract":"Hyperhomocysteinemia can induce significant alterations in the cardiovascular system, and vitamin B6 is one of the primary cofactors of enzymes involved in homocysteine metabolism. The aim of this study was to examine the effects of vitamin B6 in hyperhomocysteinemic conditions on cardiovascular biomarkers in sera, oxidative stress parameters, metabolic enzymes activities, and histological changes in rat heart and aorta. Male Wistar albino rats were divided into four groups (n = 10, per group): C: 0.9% NaCl 0.2 mL/day s.c. + 0.9% NaCl 0.5 mL i.p; H: D, L-homocysteine 0.45 mmol/g b.w./day s.c. + 0.9% NaCl 0.5 mL i.p; CB6: 0.9% NaCl 0.2 mL/day s.c. + vitamin B6 7 mg/kg b.w. i.p.; and H-B6: D, L-homocysteine 0.45 mmol/g b.w./day s.c. + vitamin B6 7 mg/kg b.w. i.p. Substances were applied s.c. for 2 weeks and i.p for 4 weeks. Level of homocysteine, activity of superoxide dismutase, concentration of malondialdehyde, and right ventricle wall thickness were significantly lower in HB6 group compared to H group, while lactate dehydrogenase activity was higher in HB6 group compared to all other groups. These findings suggest the potential beneficial effects of vitamin B6 supplementation on cardiovascular system in patients with hyperhomocysteinemia.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136611","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

Aerobic and/or Resistance Exercise in Restoring Metabolic Dysregulation Induced by Chronic Sleep Restriction in Rats. 有氧和/或阻力运动在恢复大鼠慢性睡眠限制引起的代谢失调中的作用。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-09-25 DOI: 10.1139/cjpp-2025-0019

Gülhan Cansu Şen, Muhammed Ali Aydın, Ozan Öner, Selen Yıldız, Esra Akbaş, Levent Ozturk

{"title":"Aerobic and/or Resistance Exercise in Restoring Metabolic Dysregulation Induced by Chronic Sleep Restriction in Rats.","authors":"Gülhan Cansu Şen, Muhammed Ali Aydın, Ozan Öner, Selen Yıldız, Esra Akbaş, Levent Ozturk","doi":"10.1139/cjpp-2025-0019","DOIUrl":"https://doi.org/10.1139/cjpp-2025-0019","url":null,"abstract":"Chronic sleep restriction disrupts blood glucose regulation, leading to glucose intolerance and insulin resistance. Regular exercises, however, are known to enhance glycemic control. This study aimed to evaluate the regulatory effects of three distinct exercise protocols on blood glucose alterations caused by chronic REM sleep restriction. Thirty-four Sprague-Dawley rats were allocated into five groups: control (CTRL), sleep restriction (SR), SR plus aerobic exercise (SR+ExA), SR plus resistance exercise (SR+ExR), and SR plus combined exercises (SR+ExC). Except for the control group, all rats underwent 18 hours of sleep restriction daily for 8 weeks using a modified multi-platform model. Exercise protocols included 30 minutes of swimming and/or vertical ladder climbing (15 repetitions/day) performed 3 days per week for 8 weeks. Following the intervention, glucose and insulin tolerance tests were conducted. Chronic sleep restriction increased blood glucose levels, while aerobic and/or resistance exercises effectively reduced or prevented this elevation. Glucose tolerance was significantly improved in all exercise groups compared to the sedentary group (ipGTT blood glucose 120 min: SR+ExA = 95±7.7, SR+ExR = 100±7.3, SR+ExC = 90±12.6, SR = 119±14.5 mg/dL; P < 0.05). Regular exercise may mitigate adverse metabolic effects of sleep restriction.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147832","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

Repurposing incretin therapies: a narrative review of emerging indications across cardiometabolic, liver, kidney, neurological, psychiatric, and other systems. 肠促胰岛素治疗的重新定位：对心脏代谢、肝脏、肾脏、神经、精神和其他系统的新适应症的叙述性回顾。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-09-01 Epub Date: 2025-05-14 DOI: 10.1139/cjpp-2025-0038

Ibrahim S Alhomoud, Sarah E Wheeler, Dave L Dixon

引用次数: 0

Celebrating the life and legacy of Dr. Gary D. Lopaschuk (1955-2025). 纪念加里·洛帕恰克博士（1955-2025）的一生和遗产。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-09-01 Epub Date: 2025-08-11 DOI: 10.1139/cjpp-2025-0166

引用次数: 0

The calcium-sensitive receptor in the pathogenesis of sepsis. 钙敏感受体在败血症发病机制中的作用。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-09-01 Epub Date: 2025-04-30 DOI: 10.1139/cjpp-2025-0004

Bin Yu, Xuelian Li, Li Yang, Cheng Han, Jun Tan, Xiaoyan Yu, Min Li, Zhe Xu, Xiongying Chen

{"title":"The calcium-sensitive receptor in the pathogenesis of sepsis.","authors":"Bin Yu, Xuelian Li, Li Yang, Cheng Han, Jun Tan, Xiaoyan Yu, Min Li, Zhe Xu, Xiongying Chen","doi":"10.1139/cjpp-2025-0004","DOIUrl":"10.1139/cjpp-2025-0004","url":null,"abstract":"Sepsis is an organ dysfunction caused by the body's dysfunctional response to infection, which is one of the most important causes of death in critically ill patients. It is characterized by high morbidity, high mortality, and high treatment costs. Currently, the treatment of sepsis relies mainly on supportive therapy, and there is a lack of targeted intervention ways. Studying the pathogenesis of sepsis and exploring new therapeutic targets are of great theoretical and clinical importance. Calcium-sensitive receptor (CaSR) is a cell membrane receptor belonging to the family of G protein-coupled receptors and is widely distributed in various tissues and organs. Research indicates that CaSR plays a role in mitigating sepsis-induced organ dysfunction, exhibiting tissue-specific protective effects in certain tissues while inducing inflammatory responses in others. Elucidating these dual effects and the underlying signaling pathways could facilitate the development of targeted therapies for sepsis-related organ damage. This review summarizes recent literature and evidence on CaSR signaling in sepsis-induced organ dysfunction. In addition, we provide an up-to-date schematic of the most important and likely molecular signaling pathways associated with CaSR in sepsis.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"286-297"},"PeriodicalIF":1.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964292","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

Suppression of protein kinase RNA-like endoplasmic reticulum kinase by probiotics circumvents cardiovascular risk profile in experimentally induced PCOS model. 益生菌抑制蛋白激酶rna样内质网激酶可规避实验性PCOS模型的心血管风险。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-08-19 DOI: 10.1139/cjpp-2025-0095

Stephanie Esosa Areloegbe, Linus Anderson Enye, Kehinde S Olaniyi

{"title":"Suppression of protein kinase RNA-like endoplasmic reticulum kinase by probiotics circumvents cardiovascular risk profile in experimentally induced PCOS model.","authors":"Stephanie Esosa Areloegbe, Linus Anderson Enye, Kehinde S Olaniyi","doi":"10.1139/cjpp-2025-0095","DOIUrl":"10.1139/cjpp-2025-0095","url":null,"abstract":"The present study was designed to investigate the role of PERK in CVD risk associated with polycystic ovarian syndrome (PCOS) in experimental rat model, and the therapeutic benefits of probiotics. Eight-weeks-old female Wistar rats were assigned into four groups (n=6); Control (CTRL), Probiotics (PROB), Letrozole (PCOS), PCOS + PROB. Daily administration of letrozole (1 mg/kg) for 21 days was used to induce PCOS, thereafter, probiotics (3 x 109 CFU) was administered daily for 6 weeks. Biochemical parameters and histological evaluations were performed with appropriate techniques. The present findings revealed that animals with PCOS were characterized with phenotypic features such as hyperandrogenemia and multiple cysts in the ovaries. In addition, PCOS rats manifested insulin resistance and increase in glucose regulatory protein (GRP78), together with increased levels of circulating corticosterone, cardiac triglyceride, inflammatory mediators (NF-κB/TNF-α), TGF-β1, Caspase-6, and HDAC2, while a decrease in HIF-1α and NrF2 was observed when compared with control animals. These were accompanied by elevated level of PERK. However, treatment with probiotics reversed these systemic, endocrine, metabolic and cardiac anomalies. The present study suggests that probiotics attenuates CVD risk profile in experimental PCOS rat model by suppression of PERK/HDAC2-dependent pathway.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882267","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