Davenport A, Anwar M, Kuc R
… +6 more, Brynne L, Mercier A, Åstrand M, Greasley P, Ambery P, Maguire J
Can J Physiol Pharmacol
· 2026 Jan · PMID 42378327
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Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ET and ET receptors in 1990, enabling rapid development of the first endothelin receptor antagonists (bosentan, ambrisentan, and macitentan) for p...Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ET and ET receptors in 1990, enabling rapid development of the first endothelin receptor antagonists (bosentan, ambrisentan, and macitentan) for pulmonary arterial hypertension, a condition marked by elevated ET-1. Nearly a decade later, a new therapeutic wave began with the ET agonist sovateltide (2021) for cerebral ischemic stroke, demonstrating the benefits of ET activation. More recent antagonist development has shifted toward ET-selective agents to preserve ET function. Clazosentan (ET) for cerebral vasospasm and aprocitentan (ET/ET) for resistant hypertension extended endothelin-targeted therapy into more common diseases. In kidney disease, sparsentan (AT/ET) and atrasentan (ET) have both been approved for IgA nephropathy, with atrasentan succeeding after earlier failed trials. Repurposing has become a major strategy in G protein-coupled receptor drug development. This review outlines approaches for identifying legacy endothelin compounds suitable for new indications, using zibotentan, now combined with dapagliflozin to reduce fluid retention as an example. Kidney disease remains a central focus of current trials, which include new ET-selective diosuxentan and monoclonal antibody getagozumab, and the ET peptide antagonist vodudeutentan. The review summarizes recent pharmacology and clinical data and highlights emerging strategies for next-generation endothelin-pathway therapeutics.
Liu J, Tan H, Liu Y
… +3 more, Lu Z, Zhong W, Niu Z
Can J Physiol Pharmacol
· 2026 Jun · PMID 42276014
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Diabetic foot ulcers (DFU) are a major complication of diabetes, often driven by chronic inflammation. The role of specific inflammatory cytokines in DFU development is unclear due to challenges in observational studies....Diabetic foot ulcers (DFU) are a major complication of diabetes, often driven by chronic inflammation. The role of specific inflammatory cytokines in DFU development is unclear due to challenges in observational studies. This study used a two-sample, bidirectional Mendelian randomization (MR) approach to assess the causal effects of 41 circulating inflammatory cytokines on DFU risk. Instrumental variables were selected based on genome-wide significance and linkage disequilibrium criteria. The primary analysis was inverse-variance weighted (IVW), with validation through enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR) in DFU patients and controls. Genetically predicted levels of CTACK (CCL27) and MIG (CXCL9) were linked to reduced DFU risk, with odds ratios of 0.538 for CTACK and 0.501 for MIG. Sensitivity analyses confirmed the robustness of the findings. Reverse MR analysis showed no causal relationship between DFU and these cytokines. Clinical validation revealed lower protein and mRNA levels of CTACK and MIG in DFU patients. This study provides evidence for a protective role of CTACK and MIG in DFU development, suggesting they could serve as biomarkers or therapeutic targets for diabetic wound care.
Can J Physiol Pharmacol
· 2026 Jun · PMID 42276013
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Pain modulation relies on complex molecular interactions among ion channels, G protein-coupled receptors, and intracellular signaling cascades. The Transient Receptor Potential Vanilloid 1 (TRPV1) channel serves as a pol...Pain modulation relies on complex molecular interactions among ion channels, G protein-coupled receptors, and intracellular signaling cascades. The Transient Receptor Potential Vanilloid 1 (TRPV1) channel serves as a polymodal detector and integrator of noxious stimuli, linking sensory transduction with broader neuromodulatory systems. This review delineates the mechanistic crosstalk between TRPV1, endocannabinoid, and opioid pathways in nociceptive regulation. TRPV1 activation by heat, protons, or endogenous lipids induces calcium influx and engages protein kinase C (PKC), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) pathways that modulate channel phosphorylation and neuronal excitability. Endocannabinoids such as anandamide act as dual CB₁ and TRPV1 agonists, establishing feedback loops that adjust nociceptive thresholds, while μ-opioid receptor activation inhibits adenylate cyclase and TRPV1 sensitization through Gi/o-mediated signaling. Given the recent progress in cryo-electron microscopy and molecular modeling, simulation studies have been possible, revealing key structural determinants underlying key receptor interactions. Integrating pharmacophore modeling, molecular docking, and artificial intelligence-based screening enables rational design of multi-target ligands that exploit TRPV1-endocannabinoid-opioid synergy. This mechanistic framework supports the development of next-generation analgesics that achieve potent, sustained, and safe modulation of nociceptive signaling.
Bagchi AK, Liu Y, Dhingra S
… +3 more, Ravandi A, Singal PK, Shah AH
Can J Physiol Pharmacol
· 2026 Jun · PMID 42250285
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BACKGROUND: Despite restoration of systemic and pulmonary circulation and normalized oxygen saturation, patients with Fontan circulation experience frailty, exercise intolerance, and impaired exercise hemodynamics. Alter...BACKGROUND: Despite restoration of systemic and pulmonary circulation and normalized oxygen saturation, patients with Fontan circulation experience frailty, exercise intolerance, and impaired exercise hemodynamics. Altered cytokine-chemokine profiles have been reported, but their relationship with Fontan pathophysiology remains poorly defined. METHODS: Adult Fontan patients and matched controls were assessed for frailty, cardiopulmonary exercise capacity, and resting/exercise-augmented hemodynamics. Plasma cytokine-chemokine concentrations were measured using multiplex ELISA. RESULTS: Twenty Fontan patients (mean age 28.8 ± 9.8 years; 35% female) and 20 controls (29.7 ± 6.0 years; 30% female) were studied. Fontan patients had slower 5× sit-to-stand times (9.6 ± 3.1 vs. 5.7 ± 1.3 sec; p<0.0001), lower VO₂max (% predicted), and reduced stroke index, cardiac index, and cardiac power index. TNF-α, IL-1β, IL-6, IFN-γ, IL-8, IP-10, MCP-1, and SDF-1α were elevated in Fontan patients, while IL-10 and MIP-1α were not different. SDF-1α and IP-10 correlated with frailty, impaired oxygen uptake, and hemodynamic parameters. CONCLUSION: Elevated SDF-1α and IP-10 are associated with frailty and impaired exercise hemodynamics in Fontan patients. These novel findings suggest a role for inflammation in Fontan-associated dysfunction and warrant further investigation.
Min E, Goyette A, Young E
… +3 more, Moon K, Bellini N, Isaacs DM
Can J Physiol Pharmacol
· 2026 Jun · PMID 42250284
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Type 2 diabetes (T2D) is a growing global health challenge. With prevalence projected to rise significantly in the coming decades, T2D is expected to contribute to increased healthcare costs due to associated morbidity a...Type 2 diabetes (T2D) is a growing global health challenge. With prevalence projected to rise significantly in the coming decades, T2D is expected to contribute to increased healthcare costs due to associated morbidity and mortality. Characterized by insulin resistance and impaired pancreatic insulin secretion, T2D could be mediated by the effects of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretin-based therapies have, therefore, emerged as effective treatments for improving glycemic management and weight reduction in people with T2D. Since the approval of the first twice daily GLP-1 RA in 2005, advancements have led to the development of once-daily and once-weekly injectable formulations and an oral formulation. Furthermore, the approval of a dual GLP-1/GIP RA marked a significant milestone in incretin-based therapies. These agents have demonstrated glycemic-lowering benefits, weight loss, and reduced cardiovascular risk in high-risk populations. The most common adverse effects are gastrointestinal and can be partially mitigated with slow dose titration and patient education. Ongoing research into alternative dosing regimens, combination therapies, and strategies to improve access will be important for optimizing the long-term impact of incretin-based therapies in T2D management.
Bajic Z, Sobot T, Stojiljković M
… +2 more, Djuric D, Škrbić R
Can J Physiol Pharmacol
· 2026 Jan · PMID 42132521
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The potential therapeutic applications of glucagon-like peptide-1 (GLP-1) have led to the development of GLP-1 receptor agonists (GLP-1RAs), which replicate GLP-1's effects. The primary use of GLP-1RAs is the management...The potential therapeutic applications of glucagon-like peptide-1 (GLP-1) have led to the development of GLP-1 receptor agonists (GLP-1RAs), which replicate GLP-1's effects. The primary use of GLP-1RAs is the management of type 2 diabetes (T2DM) by stimulation of insulin secretion. In addition to its metabolic functions, GLP-1 exhibits significant anti-inflammatory effects through various molecular pathways, utilizing both direct and indirect mechanisms. Experimental studies have revealed that GLP-1RAs modulate multiple inflammatory pathways, including cytokine production, oxidative stress, glucotoxicity, lipotoxicity, and immune cell recruitment across multiple organs. They interact with their receptors on immune cells, thereby reducing the production of inflammatory cytokines and decreasing the infiltration of immune cells into tissues. There is considerable overlap among the pathways activated by GLP-1R in cardiovascular tissue, which can lead to anti-apoptotic, antioxidative, and anti-inflammatory effects. Clinical studies have confirmed the anti-inflammatory effects of GLP-1RAs in conditions such as acute myocardial infarction, left ventricular dysfunction, coronary artery disease, and ST-segment elevation myocardial infarction. Notably, GLP-1RAs are included in the European Society of Cardiology guidelines for managing cardiovascular disease in patients with T2DM.
Gogic I, Jakovljevic V, Nikolic M
… +2 more, Raicevic S, Stojanovic A
Can J Physiol Pharmacol
· 2026 Jan · PMID 42127161
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The aim of the study was to follow the impact of cystectomy and compare bipolar and laser electrocoagulation on prooxidative stress biomarkers and antioxidative capacity. A total of 60 women with diagnosed endometriosis...The aim of the study was to follow the impact of cystectomy and compare bipolar and laser electrocoagulation on prooxidative stress biomarkers and antioxidative capacity. A total of 60 women with diagnosed endometriosis were included in the study and divided in two groups according to laparoscopy treatment with different energy sources for electrocoagulation. Prooxidative parameters (superoxide anion radical (O), nitrites (NO), hydrogen peroxide (HO), index of lipid peroxidation measured as thiobarbituric acid reactive substances) and antioxidative defence system parameters (reduced glutathione (GSH), activity of superoxide dismutase (SOD), and activity of catalase (CAT)) were determined spectrophotometrically before and after the surgery. The value of HO was decreased in group treated with biporal electrocoagulation, while the value of GSH was increased in both groups. The value of O was significantly decreased in the group treated with laser, while SOD activity was increased in the same group. Both methods had a similar effect on index of lipid peroxidase and reduced glutathione, but when it comes to the decreasing of harmful superoxide anion radical and increasing of SOD activity, laser electrocoagulation showed better outcome. The role of oxidative stress in both understanding the pathogenesis of this disease and as a potential therapeutic target is certainly of great importance.
Can J Physiol Pharmacol
· 2026 Jan · PMID 42096721
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Calcium channel blockers (CCBs), particularly amlodipine, are among the most widely prescribed antihypertensive agents globally. However, no comprehensive disproportionality analysis has quantified this association. This...Calcium channel blockers (CCBs), particularly amlodipine, are among the most widely prescribed antihypertensive agents globally. However, no comprehensive disproportionality analysis has quantified this association. This pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) to evaluate the reporting association between CCBs and pseudolymphoma. The FAERS database was parsed through its 14 104 743 adverse event reports. Five CCBs were evaluated: three dihydropyridines (amlodipine, nifedipine, and felodipine) and two non-dihydropyridines (diltiazem, verapamil). Disproportionality was quantified using reporting odds ratios (RORs). The MedDRA preferred term "pseudolymphoma" was employed for case identification. Among 319 pseudolymphoma reports, 44 were associated with dihydropyridines and 1 with non-dihydropyridines. Amlodipine demonstrated the strongest signal (ROR 38.08, 95% CI 27.60-52.54; = 42), followed by nifedipine (ROR 18.61, 95% CI 4.64-74.74; = 2). Diltiazem showed a non-significant signal (ROR 5.47, 95% CI 0.77-38.93; = 1). Felodipine and verapamil yielded no reports. Dihydropyridines exhibited 7- to 70-fold greater RORs compared with non-dihydropyridines. This analysis establishes a robust, though not causal, class-specific safety signal linking dihydropyridine CCBs, particularly amlodipine, to pseudolymphoma risk. The substantial disproportionality suggests a pharmacologically mediated mechanism requiring heightened clinical surveillance, prompt recognition, and timely drug discontinuation to prevent potential malignant transformation.
Yuan K, Huang Z, Liu R
… +4 more, Liu Z, Lv J, Li C, Xu Q
Can J Physiol Pharmacol
· 2026 Jan · PMID 42091231
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This study analyzed safety data for atorvastatin calcium hydrate (ACH) using real-world adverse event reports from the U.S. FDA Adverse Event Reporting System (FAERS, 2004-2024) and the European Medicines Agency's EudraV...This study analyzed safety data for atorvastatin calcium hydrate (ACH) using real-world adverse event reports from the U.S. FDA Adverse Event Reporting System (FAERS, 2004-2024) and the European Medicines Agency's EudraVigilance (EV, 2002-2024). A total of 104 798 ACH-related reports were included: 67 498 from FAERS and 37 300 from EV. Four signal detection algorithms (ROR, PRR, BCPNN, and MGPS) identified 597 significant positive signals, 356 in FAERS and 241 in EV, covering 27 system organ classes. FAERS signals mainly involved metabolic, cardiac, and nervous system disorders, while EV was dominated by examination abnormalities (66 signals, 27.39%) and musculoskeletal disorders (29 signals, 12.03%). Rhabdomyolysis and drug-induced liver injury were major designated medical events in both databases. EV also identified liver failure, hepatocellular injury, and death (1833 cases, 4.91%) as key serious outcomes. Stratified analyses showed elderly patients in FAERS had higher risks of type 2 diabetes and emotional distress. In EV, patients aged ≥65 years accounted for 34.12%, females 49.83% versus males 37.21%, and severe cases reached 94.50%. The study recommends close clinical monitoring for rhabdomyolysis, liver injury, and fatal outcomes, with special attention to liver function and muscle symptoms in elderly, diabetic, emotionally distressed, and female patients.
Awadalla L, Iskander S, Chu C
… +1 more, Tadrous M
Can J Physiol Pharmacol
· 2026 Jan · PMID 42013575
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Incretin therapies have emerged as key interventions for glycemic control and weight reduction and are now among Canada's costliest outpatient drug classes. This review synthesizes current clinical and economic evidence...Incretin therapies have emerged as key interventions for glycemic control and weight reduction and are now among Canada's costliest outpatient drug classes. This review synthesizes current clinical and economic evidence on the cost-effectiveness of incretin-based therapies. These include glucagon-like peptide-1 receptor agonists (GLP-1RAs; e.g., semaglutide) and dual agonists (e.g., tirzepatide) targeting both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, in patients with type 2 diabetes mellitus or for weight loss. We review data from clinical trials and recent Canadian and international economic models, identify emerging indications, and discuss limitations in current health-technology assessment frameworks. Implications for Canadian reimbursement are highlighted, with attention to price, patient selection, and outcome considerations.
Hartmann R, Pradhan S, Bylyku D
… +4 more, Markieta K, Scozzafava J, Lucyk S, Yarema M
Can J Physiol Pharmacol
· 2026 Jan · PMID 42013574
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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 fe...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.
Selvakumar L, Choy J, Rashkovetsky R
… +3 more, Jeerakathil T, Hill M, Vethanayagam D
Can J Physiol Pharmacol
· 2026 Jan · PMID 41979236
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Intrapulmonary right-to-left shunts (RLSs) are a clinical concern in hereditary hemorrhagic telangiectasia (HHT), contributing to dyspnea, brain abscess, and ischemic stroke. HHT is a genetic disorder characterized by ar...Intrapulmonary right-to-left shunts (RLSs) are a clinical concern in hereditary hemorrhagic telangiectasia (HHT), contributing to dyspnea, brain abscess, and ischemic stroke. HHT is a genetic disorder characterized by arteriovenous malformations (AVMs), with pulmonary AVMs (PAVMs) being a major source of intrapulmonary shunting. Screening for PAVMs is essential to prevent paradoxical embolization, guide management, and mitigate mortality risk. Agitated saline contrast echocardiography ("bubble echo") is the recommended method for detecting and grading RLS, as outlined in International HHT Guidelines. Given Western Canada's large rural population, satellite HHT clinics and affiliated echo labs have been established to improve access to care. This observational cross-sectional study evaluated the written policies governing bubble-echo protocols across Alberta's accredited echocardiography laboratories. With the help of the College of Physicians and Surgeons of Alberta (CPSA), all CPSA-accredited adult echocardiography laboratories were contacted (as of 15 July 2024) to determine whether they perform RLS assessments and to obtain available written bubble-echo protocols. Of the 62 accredited facilities identified, 12 performed bubble-echo studies. Policy review of participating labs revealed notable variations in injection techniques and shunt grading criteria. These findings suggest that considering a standardized protocol could reduce variability and allow for more reliable comparisons over time.
Can J Physiol Pharmacol
· 2026 Jan · PMID 41979228
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The subject of this communication is the kinetic analysis of dynamic processes in the myometrium of rats in a depolarized state, with a focus on their biomechanics and possible implications in obstetrics. Depolarization...The subject of this communication is the kinetic analysis of dynamic processes in the myometrium of rats in a depolarized state, with a focus on their biomechanics and possible implications in obstetrics. Depolarization was achieved by increasing the concentration of K in the organ bath. It is attended by a fast transient increase in muscle tension and the slower establishment of a new resting state in which the phasic component of contractile activity is suppressed. The myometrium remains stimulable by oxytocin and its structural analogues. Time-tonic response profiles indicate participation of several superimposed, time-dependent exponential components whose rate constants reflect transport and distribution routes regulating the intracellular calcium concentration. The initial rapid rise in tension is followed by a slower change to a steady-state level. Its interruption by oil immersion is followed by an exponential tension decline which allows the determination of the affinity constants of OXT peptides in the depolarized state. The average potency ratio polarized-to-depolarized myometrium assessed for 11 OXT peptides is 9.14. There was no evidence of ligand bias between the two states. Kinetic analysis of the response profiles shows a satisfactory consistency with the reported changes in calcium sensitization and transport processes following OXT stimulation.
Can J Physiol Pharmacol
· 2026 Jan · PMID 41975239
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In view of the well-known anti-inflammatory property of roxithromycin, the present study was carried out to evaluate its efficacy in ameliorating prostate inflammation-induced chronic pelvic pain in rat model. Inflammati...In view of the well-known anti-inflammatory property of roxithromycin, the present study was carried out to evaluate its efficacy in ameliorating prostate inflammation-induced chronic pelvic pain in rat model. Inflammation was induced by single intraprostatic injection of carrageenan where a time course study revealed a peak histology score on day 14. The efficacy study was carried out in four sets of rats, each comprising five groups, which included respective normal and experimental controls (NC, EC). The drugs (roxithromycin 5 and 20 mg/kg, diclofenac 5 mg/kg) were given daily orally and pain score and body weight were evaluated at different time intervals. The prostatic index, vascular permeability, tissue levels of TNF-α and PGE, thiobarbituric acid reactive substances, glutathione and superoxide dismutase, histology score, and immunoreactivity of COX-2 and iNOS were evaluated on day 14. Like diclofenac, roxithromycin decreased pain score and the rats gained weight during the study period as compared to the EC group. The beneficial effect of roxithromycin was also evident from the dose-dependent restoration of markers of inflammation and oxidative stress. This study shows that by alleviating pain and suppressing inflammation and oxidative stress, roxithromycin has a potential to provide relief in prostatitis.
Can J Physiol Pharmacol
· 2026 Jan · PMID 41954519
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Human genome- and transcriptome-wide analyses revealed that 56% of heart failure cases have unknown causes. Interestingly, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is one of those causes. P...Human genome- and transcriptome-wide analyses revealed that 56% of heart failure cases have unknown causes. Interestingly, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is one of those causes. Previously, we have shown a robust increase in the degradation of a disintegrin and metalloproteinase (ADAM) and connexin-43 (Cx43) in human end-stage heart failure with reduced ejection fraction (HFrEF). We also observed Cx43 degradation and blood-heart barrier leakage during HFrEF in mice. Although Cx43 coordinates mitochondrial fusion-fission with myocyte contraction-relaxation, respectively, the mechanism is unclear. Interestingly, inhibition of mitochondrial ATP citrate lyase (ACYLi, a lipid-lowering agent) causes HFpEF, but its role in HFrEF is unknown. We hypothesize that during HFrEF, activation of ADAMTS1 degrades Cx43, causing dyssynchronous endothelial-myocyte-mitochondrial contraction coupling, as well as myocyte slippage during contraction and HFrEF. Because HFrEF is more prevalent in males than females, we created chronic cardiopulmonary volume overload by aorta-vena cava fistula (AVF) below the kidney in male wild-type (C57BL/6J) mice aged 12 weeks. By serial echocardiography, we observed HFrEF after 16 weeks. The ADAMTS1 inhibitor (epigallocatechin gallate) or ACYLi (hydroxycitric acid lactone) was administered in drinking water at the same time as AVF. Also, to assess interoceptive inhibition via Piezo channels, we ganglionally denervated the heart prior to AVF. By gel-specific substrate zymography, we measured NGAL, MMP2, MMP9, ADAMTS1, ADAMTS14, and TMPRSS2. The levels of Cx43, ADAMTS1, mitochondrial Drp1 (fission protein), and ACYL were measured by Western blot analysis. The results suggest that ADAMTS1 is activated during HFrEF. Connexin-43 degradation and mitochondrial mitophagy were increased by an increase in Drp1. The therapeutic effects of ADAMTS1 and ACYL inhibitors for systolic HFrEF are suggested.
Gadallah A, Abdelhaffez A, Hussein O
… +3 more, Sayed S, Abdelhakiem M, El-Mottaleb N
Can J Physiol Pharmacol
· 2026 Jan · PMID 41838466
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This study aimed to evaluate ostarine effects on blood glucose, dyslipidemia, and osteoporosis in diabetic rats. Forty-eight adult male rats were divided into six groups (Control, Ostarine: 0.4 mg/kg daily orally, diabet...This study aimed to evaluate ostarine effects on blood glucose, dyslipidemia, and osteoporosis in diabetic rats. Forty-eight adult male rats were divided into six groups (Control, Ostarine: 0.4 mg/kg daily orally, diabetes mellitus (DM), DO: diabetic rats received ostarine, DI: diabetic rats received insulin, DOI: diabetic rats received ostarine and insulin for 8 weeks). Radiographic examination for bone was done. Blood samples, bone, and pancreas were taken for examination. Ostarine significantly increased body weight, muscle weight, bone weight and ashing, lowered blood glucose, TC, low-density lipoprotein-cholesterol (LDL-C), and triglycerides, increased Ca, phosphorus (P), osteocalcin, RUNX2, and positive immunostained osteopontin cells compared to DM, but no significance on CTX-I or RANKL. It improved bone density in X-ray, pancreatic islet cells and bone microarchitecture in histological examinations, being more apparent in ostarine and insulin-treated group. However, insulin alone had no significant effect on TC, LDL-C, Ca, P, OC, CTX-I, RUNX2, RANKL, or osteopontin and downregulated alkaline phosphatase compared to DM, with focal decreased bone radiodensity and minimal improvement in bone and pancreatic sections. In conclusion, ostarine could have beneficial effects on diabetes such as improving glycemic state, dyslipidemia, and mainly diabetic osteoporotic bone. Ostarine should be further evaluated in diabetic osteoporosis or other types of osteoporosis.
Johnson A, O'Sullivan E, Valyasevi P
… +6 more, Metras B, Jang S, Shields-Cutler R, Hendel K, Harindhanavudhi T, Teigen L
Can J Physiol Pharmacol
· 2026 Jan · PMID 41818791
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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications used to treat and manage type 2 diabetes mellitus (T2DM) and obesity. The present narrative review explores potential interactions between...Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications used to treat and manage type 2 diabetes mellitus (T2DM) and obesity. The present narrative review explores potential interactions between the gut microbiome and GLP-1 RAs. Limited research has been conducted at the intersection of the gut microbiome and GLP-1 RA therapy. Therefore, this review focuses on potential relationships among GLP-1 RA, the microbiome, body weight, dietary changes, and gastrointestinal symptoms. The review of the current literature reveals significant gaps, particularly concerning the role of diet in mediating or confounding any impact of GLP-1 RA medications on the gut microbiome. Therefore, the body of the review is structured as a series of proposed directional and causal relationships. The limited available evidence suggests changes in behavior, diet, and weight loss resulting from GLP-1 RA treatment are the primary drivers of microbiome changes observed after GLP-1 RA treatment. The review concludes by proposing directions for future studies to clarify the complex interplay between GLP-1 RAs, the gut microbiome, diet, and obesity management.