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Clinical outcomes of glucagon-like peptide-1 receptor agonist therapy in kidney transplant recipients: a systematic review and meta-analysis.
Clin Kidney J
Mehmet Kanbay, Sama Mahmoud Abdel-Rahman, Mustafa Guldan +5 more
Metabolic complications after kidney transplantation (KT) significantly affect graft and patient survival. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardio-renal benefits in the general population, but evidence in KT recipients remains limited.
Non-invasive MRI of choroid plexus vascular function.
Imaging Neurosci (Camb)
Peiying Liu, Lori Donaldson, Beini Hu +2 more
Choroid plexus (ChP) is a highly vascularized tissue in the ventricles of the brain, and it plays an important role in the production of cerebrospinal fluid (CSF) and formation of the blood-CSF barrier. The function of ChP vessels has been implicated in waste clearance efficiency during aging and neurodegenerative diseases. At present, postmortem studies are the main method to assess choroid plexus vascular integrity, with a few tools to measure ChP function in living humans. Here, we proposed a non-invasive MRI approach to assess ChP vascular elasticity based on the detection of MRI signal changes in response to vasoactive challenges. The mechanism of the signal is hypothesized to be due to reciprocal blood and stroma volume alterations during vessel expansion. We demonstrated that ChP vascular elasticity can be evaluated with BOLD MRI using a hypercapnia challenge of CO2 inhalation. This effect is specifically located in the brain ventricles where ChP is abundant. We revealed the ability of the technique in detecting age-related reduction in ChP vascular elasticity. We further showed that this effect can be assessed with gas-free methods, including intermittent breath modulation and resting-state BOLD fMRI. We characterized the image contrast requirement under which this effect can be detected. This technique may provide a clinically feasible tool for assessing ChP vascular function in health and disease.
A profile of heart failure in the James and Hudson's Bay region of Ontario: A retrospective cohort study.
Can J Public Health
Sabastian M B Koprich, Samuel J Petrie, Robert P Gagnon +5 more
The James and Hudson Bay (JHB) region in Northern Ontario is home to an estimated 12,000 people; the majority are Mushkegowuk Cree. To better respond to cardiovascular needs in the region and leverage existing partnerships between the Weeneebayko Area Health Authority's Minomathowin Department, ICES, and University Health Network, this study aimed to profile confirmed and possible heart failure (HF) prevalence among community members.
[Clinical and genetic characteristics of 165 children with salt-wasting 21-hydroxylase deficiency in Henan Province].
Zhongguo Dang Dai Er Ke Za Zhi
Hai-Hua Yang, Ai Huang, Yuan Li +2 more
To explore the clinical and genetic characteristics of children with salt-wasting (SW) 21-hydroxylase deficiency (21-OHD) in Henan Province.
Fetal gastric maturation in a rat model: gestational changes in glucose transporter-1, glucose transporter-4, and insulin-like growth factor-1 receptor expression.
Am J Vet Res
Pelin Coştur Filiz, Emin Türkay Korgun
To investigate the relationship between histological maturation of the fetal rat stomach and gestational stage-dependent expression patterns of glucose transporter (GLUT)-1, GLUT-4, and IGF-1 receptor (IGF-1R).
HuR-mediated regulation of mTOR mRNA stability promotes the commitment of satellite cells towards myogenesis.
Cell Death Dis
Anne-Marie K Tremblay, Brenda Janice Sánchez, Bianca Colalillo +6 more
The RNA-binding protein HuR has been shown to promote the differentiation of cultured muscle cells into muscle fibers. HuR mediates this process by differentially regulating, at different stages of this process, mRNA targets encoding pro-myogenic factors. Despite these advancements, the role of HuR, in vivo, at various stages of the myogenic process and its impact on muscle formation and function remain elusive. Towards this end, we used the Myf5-Cre loxP system to knock out HuR at a stage where muscle precursor cells (satellite cells, SCs) commit to myogenesis. Using these mice, we found that the muscle-specific depletion of HuR impairs, physiologically, its formation during embryogenesis and in response to injury. These mice exhibited smaller skeletal muscles and reduced exercise endurance. We demonstrate, using these mice, that this effect is due, in part, to the HuR-mediated regulation of mTOR (mechanistic target of rapamycin) mRNA expression. Using primary and cultured muscle cells, we show that HuR associates with this message, regulating its stability. In doing so, HuR facilitates the commitment of satellite cells toward myogenesis, thus preventing their transdifferentiation toward adipogenesis. These findings thus identify HuR as a master regulator of SCs' commitment to myogenesis and uncover a potential target for manipulating muscle myogenic capacity in both normal and pathological conditions.
Cost-Effectiveness of Incretin Therapies: A Canadian Lens on Diabetes, Obesity, and Emerging Indications.
Can J Physiol Pharmacol
Luke Awadalla, Siena Iskander, Cherry Chu +1 more
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, specifically glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists (e.g., semaglutide, tirzepatide) in patients with type 2 diabetes mellitus (T2DM) 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 (HTA) frameworks. Implications for Canadian reimbursement are highlighted, with attention to price, patient selection, and outcome considerations.
GLP-1 Receptor Agonist Use and Wound Outcomes After Free Flap Breast Reconstruction.
J Reconstr Microsurg
Joy Ha, Ethan Lester, Henning De May +4 more
Background Glucagon-like peptide-1 receptor agonists (GLP-1s) are increasingly used for glycemic control and weight loss, but their impact on surgical wound complications remains unclear. Some studies suggest GLP-1s reduce complications such as infection and dehiscence, though others report increased risk in certain procedures. This study evaluates whether preoperative GLP-1 use is associated with postoperative wound complications in free flap breast reconstruction. Methods We conducted a retrospective cohort study using the TriNetX Research Network, a global database of de-identified health records. Adults (≥18 years) undergoing free flap breast reconstruction (2012-2025) were identified with CPT codes. Patients were stratified into cohorts by GLP-1 use within one year before surgery. Prescriptions for semaglutide, liraglutide, dulaglutide, exenatide, or tirzepatide defined GLP-1 users. Cohorts underwent 1:1 propensity score matching, and matched groups were analyzed for wound outcomes. Subgroup analyses were performed by diabetes status. Results In the pooled cohort, GLP-1 users had significantly lower composite wound complication rates compared with non-users (9.0% vs. 17.1%, p = 0.002), including reduced surgical site infections (4.1% vs. 8.1%, p = 0.026) and wound dehiscence (3.8% vs. 7.8%, p = 0.023). No differences were observed in debridement, seroma, or hematoma rates. In subgroup analyses, GLP-1 use was associated with significantly lower composite wound complications in the non-diabetic subgroup (7.9 vs. 18.6%, p = 0.007), while overall complication rates in the diabetic subgroup were comparable between users and non-users. Conclusion Preoperative GLP-1 use was not linked to increased wound complications and may confer benefit, supporting safety when used perioperatively.
The effects of GLP-1 receptor agonists on Alzheimer's pathophysiology: A systematic review.
Mol Cell Neurosci
Eve Corcoran, Michael Kettlety, Urwa Mogul +2 more
The incidence of Alzheimer's disease (AD) is increasing globally but there are limited effective therapies available. Recently, evidence has demonstrated a role of GLP-1 receptor (GLP-1R) agonists, commonly used in the treatment of type 2 diabetes, may have therapeutic potential in AD. GLP-1R agonists have exhibited their neuroprotective role by targeting tau hyperphosphorylation and the accumulation of beta-amyloid (Aβ) plaques. This systematic review aims to evaluate the effectiveness of liraglutide, semaglutide, exenatide and dulaglutide on AD pathology with a focus on the key biomarkers: hyperphosphorylated tau and Aβ.
Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1-dependent antioxidant pathway.
Phytomedicine
Shiyun Long, Jiaxin Sun, Yaguang Wu +7 more
Sepsis-induced cardiomyopathy (SICM) is characterized by mitochondrial dysfunction, impaired mitophagic flux, and overwhelming oxidative stress. Spermidine (SPD), a natural polyamine known to enhance autophagy and preserve cardiac function in aging and metabolic disorders, has not been systematically evaluated in the context of septic cardiomyopathy.
The critical role of gut-brain signalling in eating behaviour and obesity.
Nat Rev Gastroenterol Hepatol
Guillaume de Lartigue, Daniel I Brierley, Hyung Jin Choi
The process of eating can be divided into three distinct phases of behaviour: food seeking, food consumption and non-prandial activities. The durations of, and transitions between, these behavioural phases are driven by underlying interoceptive phenomena of hunger, satiation and satiety. The gut-brain axis regulates all eating phases, with the vagus nerve a primary conduit for interoceptive feedback about gut-derived mechanical and chemical cues. This Review explores the mechanisms governing each phase, focusing on how gut-derived signals are peripherally and centrally integrated to shape hunger, satiation and satiety, food preferences, and food-related learning. Chronic exposure to high-fat, high-sugar diets disrupts these mechanisms, driving a maladaptive state characterized by hyperphagia, food choice biases and habitual overeating. We examine the mechanisms underlying this maladaptive state, including vagal fibre remodelling, altered gene expression and leptin resistance, which can impair gut-brain communication, diminishing the brain's capacity to appropriately control eating behaviour and maintain energy balance. Emerging therapies, including glucagon-like peptide 1 receptor agonists, are effective in promoting weight loss but typically do not reverse the underlying causes of gut-brain axis dysfunction. By examining the mechanisms of gut-brain signalling, this Review highlights the vagus nerve as a key, yet underappreciated, target for obesity treatment.
Blood Pressure and Adrenocortical Hormone Profiles in 84 Ill Dogs with Normal Post-ACTH Cortisol Concentrations.
J Am Anim Hosp Assoc
Robert L J Runde, Sharon A Center, Ronald Lyman +1 more
Relationship between systolic blood pressure (SBP) and adrenocortical hormones in 10 normotensive (NT) control dogs and 84 ill dogs with clinical features of hypercortisolism but normal post-adrenocorticotropic hormone (ACTH) cortisol was studied. Doppler blood pressure classified dogs as NT (<140 mm Hg), prehypertensive (PHT; 140-159 mm Hg), or hypertensive (HT; ≥160 mm Hg). Serum cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, and aldosterone were measured before and 1-hr after intramuscular (IM) ACTH (250 μg/dog). Ill dogs (40 NT, 29 PHT, and 15 HT) were significantly (P ≤ .04) older, smaller, and received higher ACTH dose/kg versus controls. ACTH dose/kg was not significantly associated with post-ACTH hormone concentrations. Compared to controls, baseline hormones were significantly (P ≤ .05) higher in ill dogs, except progesterone and 17-hydroxyprogesterone in HT and aldosterone in PHT dogs; significantly higher post-ACTH 17-hydroxyprogesterone and androstenedione (P ≤ .01) in NT and PHT dogs, and aldosterone (P = .03) in HT dogs occurred. No significant differences in baseline or post-ACTH hormones existed between SBP groups. Only 3/10 controls had all hormones within reference limits. Findings suggest risk for PHT and HT in ill dogs with increased noncortisol adrenocortical hormones, and show inexplicably increased adrenocortical sex hormones in NT healthy dogs.
Optimization of automated radiosynthesis method for [18F]AlF-NOTA-Octreotide and PET/CT imaging in neuroendocrine neoplasms.
EJNMMI Radiopharm Chem
Xiaoting Wan, Jiangyue Yan, Jieting Hu +11 more
Neuroendocrine neoplasms (NENs) represent heterogeneous tumors with increasing occurrence rate. Somatostatin receptor (SSTR) imaging using 68Ga-labeled analogs is crucial but limited by the relatively short half-life of this radionuclide along with its reliance on generator supply. To overcome these limitations, this study aimed to establish an automated synthesis platform compliant with Good Manufacturing Practice (GMP) standards for the preparation of a novel SSTR-targeting probe, [18F]AlF-NOTA-octreotide. Its diagnostic efficacy in neuroendocrine neoplasms was evaluated through comparison with existing 68Ga-labeled and [18F]FDG probes.
Appetite regulation following energy restriction with almond-enriched vs. nut-free diets - a randomised controlled trial.
Obes Res Clin Pract
Sharayah Carter, Alison M Hill, Jonathan D Buckley +3 more
This study assessed the impact of almonds (AL) or carbohydrate-rich snack bars (SB) on appetite and energy intake. Participants (25-65 yrs, BMI 27.5-34.9 kg/m2) were randomised to consume AL (n = 68) or SB (n = 72) during weight loss (WL) and weight maintenance (WM) diets. Fasting and postprandial appetite hormones and subjective appetite ratings (over 120 min) were measured at baseline (BL), after WL and after WM. Buffet meal energy intake was recorded at 150 min. Fasting ghrelin decreased in AL and increased in SB (group x time, p = 0.011), while leptin had a greater increase in AL versus SB post-WM (group x time, p = 0.001). Fasting glucagon and pancreatic polypeptide (PP) were consistently higher in AL compared to SB at each time point (group, p < 0.001). Fasting cholecystokinin (CCK), glucagon and leptin decreased (p < 0.001), while glucose-dependent insulinotropic polypeptide (GIP) (p = 0.004), glucagon-like peptide-1 (GLP-1), PP, peptide YY (PYY), and subjective hunger (p < 0.001) increased over time for all participants, Postprandial AUCs were consistently higher in AL than SB for glucagon and PP (p < 0.001), and GIP and GLP-1 (p < 0.05). Over time CCK and leptin AUCs decreased (WL -11% and -2%, WM -9% and -2%, p < 0.05), GIP and subjective hunger AUC increased over time (WL +17%,WM +12%, p < 0.05). Total and discretionary buffet energy intake declined over time (WL -16%, WM -25%,p < 0.05). Both groups experienced increased subjective hunger post-WL but demonstrated reduced energy intake at the buffet, suggesting effective behavioural adaptations. AL led to more favourable hormonal changes than SB, highlighting its potential appetite-regulating benefits in long-term WM strategies.
Satellite glial GLRX3 drives ageing-biased neuropathic pain via HMGB1.
Brain
Yang Yang, Bing Zhao, Xinyu Liu +6 more
Chronic neuropathic pain disproportionately affects older individuals, particularly in the context of persistent oxaliplatin-induced peripheral neuropathy (OIPN); however, the molecular mechanisms sustaining this ageing-biased chronicity remain elusive. In this study, we integrated age-stratified murine models and a multicentre longitudinal cohort of patients receiving oxaliplatin-based chemotherapy for colorectal cancer to investigate a glia-to-neuron redox circuit in the dorsal root ganglion. Using single-nucleus RNA sequencing and redox proteomics, we identified selective upregulation of the deglutathionylase glutaredoxin-3 (GLRX3) in satellite glial cells in aged mice during the chronic phase of OIPN. This upregulation leads to a pronounced loss of protein S-glutathionylation (PSSG) within the dorsal root ganglion, a pattern absent in young mice and during acute stages. Mechanistically, GLRX3, via its catalytic Cys148 residue, catalyses the deglutathionylation of high-mobility group box 1 (HMGB1) at the Cys106 site. This modification converts HMGB1 into a potent agonist for the toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, triggering neuronal nuclear factor-κB signalling and the subsequent upregulation of transient receptor potential ankyrin 1 and vanilloid 2 channels in PACAP-positive (C1 subtype) peptidergic nociceptors, thereby sustaining long-term mechanical and cold hypersensitivity. Satellite glial cell-targeted knockdown of GLRX3 restored HMGB1 glutathionylation and reversed the pain phenotype specifically in aged mice. In the clinical cohort, advanced age was significantly associated with a higher incidence of chronic neuropathy. Longitudinal serum analysis revealed that systemic levels of PSSG and glutathionylated HMGB1 declined progressively and correlated inversely with pain duration, particularly among older individuals. Furthermore, oral γ-glutamylcysteine or pharmacologic TLR4 blockade (TAK-242) effectively alleviated refractory hypersensitivity in aged models. These findings define the satellite glial GLRX3-HMGB1-TLR4 redox axis as a critical driver of age-biased neuropathic pain. Circulating PSSG represents a novel age-stratified clinical biomarker, and targeting this redox-sensitive pathway offers a promising therapeutic strategy for geriatric and chemotherapy-related neuropathies.
Single Fiber Isolation Assay for the Assessment of Oxidative Myofiber Behavior.
J Vis Exp
Huascar Pedro Ortuste Quiroga, Yoshitaka Mita, Yasuko Manabe +2 more
Skeletal muscle is composed of multinucleated myofibers whose integrity and function are essential for movement and overall health. In neuromuscular disorders, muscle groups can be affected differentially across disease types and stages, making it important to isolate viable single fibers from representative muscles for mechanistic studies. The objective of this protocol is to provide a reliable method for isolating a high yield of intact single myofibers from the murine soleus (SOL) muscle, which is challenging to dissociate due to fiber length and fragility. By optimizing collagenase concentration and digestion time, the protocol minimizes fiber loss and preserves viability during dissociation. The optimized workflow markedly reduces residual tissue attachment to isolated fibers, thereby limiting carryover of non-fiber cells and minimizing cross-cell contamination. This technique is suitable for single-fiber analyses as well as satellite cell isolation and subsequent expansion under conditions with minimal contamination. Using this optimized workflow, we routinely obtain ~300-500 intact SOL-derived single myofibers that can be immunolabelled with high efficiency and also yield a high-quality satellite cell population with minimal fibroblasts contamination. Using comparative analyses with Extensor Digitorum Longus (EDL) muscle we underscore the value of a tailored, muscle-specific approach to evaluating therapies in neuromuscular disease research, enabling candidate pharmaceutical interventions to be tested within small, tunable experimental windows.
[Mechanisms underlying the antimicrobial and immunomodulatory activities of porcine antimicrobial peptides].
Sheng Wu Gong Cheng Xue Bao
Tingting Zhang, Yandi Pan, Rendong Fang +1 more
Porcine antimicrobial peptides (AMPs) possess excellent antimicrobial activities and multiple biological functions, playing an essential role in the host's innate immune defense against pathogen infections. With the growing limitations of antibiotics, AMPs have been extensively studied due to their mild drug resistance and potent immunomodulatory activities. Porcine AMPs as vital components in the host defense against pathogen infections have the potential to be developed as anti-infective drugs. This review focused on the research progress in porcine AMPs regarding the structure-activity relationships and the antimicrobial and immunomodulatory activities, and discussed the potential application prospects, providing a basis for the development of anti-infective drugs in veterinary medicine.
Antimicrobial Peptides and Systemic Inflammation: A Network Analysis.
Immun Inflamm Dis
Fabiano Pinheiro da Silva, Francisco Garcia Soriano, Ludhmila Abrahão Hajjar
Antimicrobial peptides (AMPs) are essential components of the innate immune system, exhibiting diverse mechanisms of action.
Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial.
J Med Econ
Erin Johansson, John P H Wilding, Navneet Upadhyay +6 more
This study evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity. The analysis focused on individuals with obesity (body mass index [BMI] ≥ 30 kg/m2), or overweight (BMI ≥27 to <30 kg/m2 + ≥1 obesity-related complication), using data from the head-to-head Phase-3 SURMOUNT-5 trial (patients without type 2 diabetes [T2D]).
Dynamics of Body Composition and Metabolic Risk in Adolescents With Obesity Under GLP-1 Receptor Agonist Therapy.
Acta Paediatr
Adar Lopez, Liat Perl, Eyal Cohen-Sela +9 more
To explore changes in body composition in adolescents with obesity treated with glucagon-like peptide-1 receptor agonist (GLP-1 RA) and their association with metabolic syndrome (MetS) components.