Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Synergistic Effects of Cerebrolysin and Aerobic Exercise on 6-hydroxydopamine-induced Model of Parkinson Disease in Adult Male Rats.
Basic Clin Neurosci
Seyed Zanyar Athari, Fereshteh Farajdokht, Daryoush Mohajeri +1 more
Neurotrophic factors and physical activities have beneficial effects on neurodegenerative disorders. This study assessed the impact of physical exercise (EXE) and cerebrolysin (CBL), individually or in combination, in a Parkinson's disease (PD) model caused by 6-hydroxydopamine (6-OHDA).
The effect of growth hormone-releasing hormone on cognition and brain connectivity in adults with cognition ranging from normal to mild cognitive impairment.
eNeurologicalSci
Courtney E Stewart, Kaci P French, Traver J Wright +11 more
Cognitive decline with age and other clinical conditions are linked with reduced hypothalamic-pituitary-adrenal (HPA) axis function. Stimulating the HPA axis with supplemental growth hormone (GH) treatment can improve cognition, however, potential direct effects of stimulation with growth hormone releasing hormone (GHRH) are not established. In a double-blind, placebo-controlled pilot trial, we assessed 22 subjects with baseline cognition ranging from normal cognition to mild cognitive impairment before and after 10 weeks of treatment with low-dose tesamorelin (1 mg; GHRH analog) or placebo. We compared groupwise changes in body composition, fatigue, sleep, physical performance, glucose tolerance, cognitive function, and brain morphometry and functional connectivity. Low-dose GHRH treatment was not directly linked with significant changes in study measures. Using advanced machine learning (ML) models to further examine the data we identified potential treatment-related differences in areas of the brain related to cognitive function including the right anterior cingulate and left superior frontal occipital fasciculus. This pilot study highlights the potential benefits of pairing cognitive tests and neuroimaging with ML tools to achieve greater sensitivity for treatment-related effects. The clinical trial registration number is: NCT02553603.
GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly.
Pituitary
Hirotaka Itoh, Kosuke Mukai, Yuto Mitsui +7 more
Corticotropin-releasing hormone (CRH) induces an increase in growth hormone (GH) secretion in a subset of patients with acromegaly; however, the characteristics of these CRH responders remain poorly defined.
An integrative model of FGF2-induced signaling and muscle cell proliferation.
J Theor Biol
Amine Hanini, Marc Auguet-Lara, Martin Krøyer Rasmussen +2 more
This work is dedicated to a computational framework for predicting FGF2-induced cell proliferation in bovine satellite cells by integrating mechanistic and statistical modeling approaches covering signaling events up to the point of nuclear translocation of key effectors. The model advances previous studies by introducing a third signaling pathway, p38, alongside the established ERK and Akt pathways, to capture a more comprehensive view of signaling dynamics. Sensitivity and stability analyses are performed to assess the system's robustness, specifically its ability to return to equilibrium following perturbations in initial conditions and kinetic parameters, and to identify key regulatory components. At the experimental level, the effects of media additives such as BSA (Bovine Serum Albumin), fetuin, and FGF2 on cell proliferation are explored using linear models, providing statistical insights into their contributions and interactions. To connect intracellular signaling with population-level dynamics, we propose an integrative model that incorporates time-dependent signaling features into a logistic-type population growth formulation. The model predicts cell proliferation based on simulated signaling outputs (area under curves and time-to-peak of pERK, pAkt, and Pp38) alongside experimentally controlled media components. The model's predictive accuracy is assessed using experimental data across multiple cell lines of bovine satellite cells, demonstrating its ability to capture both within cell line variability and overall proliferation trends. This combination of mechanistic and statistical techniques may provide a robust framework for predicting cellular responses while addressing the challenge of modeling biological processes.
Tirzepatide versus conventional GLP-1 receptor agonists for treatment simplification in type 2 diabetes mellitus: a real-world study.
Endocr Pract
Toshitaka Sawamura, Misato Maeno, Yuya Nishimoto +4 more
Polypharmacy and complex insulin regimens increase the treatment burden of type 2 diabetes mellitus, highlighting the need for treatment simplification. Tirzepatide (TZP) is a novel antidiabetic agent that has demonstrated potent glucose-lowering and weight-reducing effects, possibly reducing the use of concomitant antidiabetic medications and insulin dose requirements. However, data regarding its effects on treatment simplification in real-world settings are limited.
Exercise as a regulator of glymphatic function.
Trends Neurosci
James R Broatch, Nicholas J Saner, Melinda L Jackson +3 more
The glymphatic system is a brain-wide perivascular network hypothesized to facilitate the clearance of waste products that accumulate during normal brain activity, including neurotoxic proteins implicated in neurodegenerative diseases. Emerging evidence suggests that exercise may modulate glymphatic function, offering a potential mechanism to help explain the neuroprotective effects of exercise. In this review, we synthesize evidence from animal models and humans on the organization and regulation of the glymphatic system, examine its vulnerability to aging and neurodegenerative pathology, and discuss the potential roles of exercise in enhancing its function. We propose that the convergence between known regulators of glymphatic function and the physiological adaptations to exercise provides a mechanistic framework linking physical activity to glymphatic integrity and brain resilience.
Icariside Ⅱ alleviates heart failure based on Wnt/β-catenin-mitochondrial apoptotic pathway.
Eur J Pharmacol
Jinran Zhu, Wenjing Tang, Dandan Huang +3 more
Heart failure (HF) represents a major global health challenge. This condition is closely linked to the dysregulation of a key signaling mechanism known as the Wnt/β-catenin pathway. Using an isoproterenol (ISO)-induced mice model of HF and H9c2 cells injury, we examined the effects of Icariside II (ICS II) on ventricular remodeling and apoptosis, focusing on the Wnt/β-catenin and mitochondrial apoptotic pathways. ICS II significantly improved cardiac function, reduced left ventricular hypertrophy, and decreased expression of the HF markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). In HF mice treated with ICS II, Western blot analysis revealed reduced levels of both Wnt/β-catenin pathway proteins and apoptotic markers in cardiac tissue. Consistent with these in vivo findings, ICS II also protected H9c2 cells from ISO-induced injury in vitro. This protection was accompanied by a decrease in cell area and apoptosis, as well as a similar suppression of Wnt/β-catenin pathway proteins. GSK-3β inhibitor SB216763 reversed ICS II's protective effects, increasing H9c2 cells apoptosis and restoring Wnt/β-catenin pathway activity (except Wnt3A). These findings demonstrate that ICS II alleviates HF by modulating the Wnt/β-catenin-mitochondrial apoptotic pathway. Given that this compound improves cardiac function while simultaneously addressing pathological remodeling and apoptosis, it holds promise as a new therapeutic approach for HF.
Targeting nuclear receptors in muscular dystrophies and regenerative myogenesis.
Front Cell Dev Biol
Eira Mann, Hoang Vu, Vihang A Narkar +1 more
Skeletal muscle is a highly plastic tissue with a robust capacity for regeneration, largely driven by resident satellite cells. Muscular dystrophies comprise a heterogeneous group of inherited disorders characterized by progressive muscle degeneration, chronic inflammation, and impaired regenerative capacity. Despite well-defined genetic etiologies, effective disease-modifying therapies for these disorders, as well as many acquired myopathies, remain limited. Emerging evidence identifies nuclear receptors (NRs) as key regulators of skeletal muscle homeostasis, integrating hormonal, metabolic, and environmental signals to control transcriptional programs governing mitochondrial function, metabolism, inflammation, and myogenesis. In this review, we summarize the diverse roles and mechanisms of action of NRs in skeletal muscle biology and discuss how their dysregulation contributes to muscle wasting and disease progression. We also highlight emerging NR-targeted therapeutic strategies aimed at enhancing metabolic function, suppressing inflammation and fibrosis, and promoting muscle regeneration. Finally, we outline critical knowledge gaps and future directions to advance the translation of NR-based therapies for muscular dystrophies and related neuromuscular disorders.
Comparative Analysis of Skeletal Muscle Satellite Cells from Hanwoo Steers and Cows for Optimizing Cell-Based Meat Production.
Food Sci Anim Resour
Bosung Kim, Doyeon Kim, Yeongjun Choi +3 more
This study aimed to compare the proliferation, differentiation rates, and related gene expression levels of skeletal muscle satellite cells (SMSCs) isolated from Hanwoo steers and cows to identify a suitable source for cell-based meat production. SMSCs were extracted from three steers and three cows, and their cell growth rates, doubling times, differentiation rates, and genetic differences were determined. Comparative analysis revealed that SMSCs from steers exhibited a higher growth rate than cows. Doubling time was shorter in steers than in cows (p<0.0001). During differentiation, the cell fusion index showed significant differences between steers and cows (p<0.0001). Steers showed differentiation after 24 h, while cows showed differentiation after 72 h. Genetic analysis showed that the expression level of the Pax7 gene was significantly higher in steers than in cows (p<0.001). The expression levels of differentiation-related genes, including MyoG, MRF4, and MHC1 were higher in steers than in cows. Thus, SMSCs isolated from steer muscle exhibit a faster growth rate, and these findings are expected to provide valuable information for determining the optimal cells for cell-based food.
Comparative real-world outcomes of tirzepatide vs semaglutide in patients with obesity and type2 diabetes: A retrospective propensity-matched cohort study.
Diab Vasc Dis Res
Abdul Qadeer, Marwah Bintay Khalid, Ridwan Syed +11 more
BackgroundWith the increasing use of GLP-1 receptor agonists and dual GIP/GLP-1 agonists for managing obesity and type 2 diabetes, understanding their real-world effectiveness and safety is essential. This TriNetX analysis directly compares clinical outcomes among patients treated with tirzepatide vs semaglutide.MethodWe utilized data from the TriNetX Research Network, identifying patients aged > 40 years or with obesity ("BMI ≥ 30 kg/m2") and type 2 diabetes (HbA1c ≥ 6.5% or fasting glucose.≥ 125 mg/dL). Qualifying events were restricted to May 1, 2022, through November 21, 2024. We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists. The index date was defined as the first co-occurrence of the obesity/diabetes criteria and the respective drug prescription. To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort. Outcomes, including all-cause mortality, MACE, heart failure exacerbation, ischemic stroke/TIA, hospitalization/ED use, dementia, UTI, adverse Gastrointestinal (GI) effects, and changes in HbA1c, were assessed within a 1-year window after the index date.ResultsOur matched cohort had a mean age of 75 years, with 45% male patients and 74% identified as white. Patients treated with tirzepatide experienced a significantly lower incidence of MACE at "("3.7% vs 4.1% (RR 0.918, 95% CI 0.862-0.978). All-cause mortality was also lower with tirzepatide (0.2% vs. 0.4%; Risk Ratio 0.436, 95% CI 0.338-0.562). The tirzapetide group achieved better glycemic control with a lower mean HbA1c (6.565% vs. 6.848%; p < 0.001) during the follow-up. There was no significant difference in heart failure exacerbation or UTI incidence. GI side effects were slightly less frequent in the tirzepatide cohort (9.8% vs. 10.2%; Risk Ratio 0.959, 95% CI 0.924-0.997), while hospitalization or emergency visits were comparable between the two groups.ConclusionIn this propensity matched cohort of patients with obesity and type 2 diabetes, tirzepatide demonstrated improved cardiometabolic outcomes compared to semaglutide, including lower all-cause mortality and lower HbA1c. These findings support the cardiovascular safety and efficacy of tirzapetide and highlight the need for further studies to evaluate its effectiveness in broader clinical populations.
Endotypic trait responses to 12-month tirzepatide treatment for an obese patient with obstructive sleep apnea: a case report.
Obes Facts
Yen Hsu, Wan-Ju Cheng, Eysteinn Finnsson +2 more
Obesity is a major risk factor for obstructive sleep apnea (OSA), and weight loss induced by glucagon-like peptide-1 receptor agonists has been associated with reductions in the apnea-hypopnea index (AHI).
Effects of the glucagon-like peptide-1 receptor agonist liraglutide on retinal endothelial function and oxidative stress during sepsis.
Front Pharmacol
Elsa Wilma Böhm, Jenia Kouchek Zadeh, Wael Omran +9 more
To test the hypothesis that the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide improves retinal vascular function in mice with polymicrobial sepsis.
Effects of the GLP-1 receptor agonist liraglutide on bupivacaine-induced sciatic nerve block in a rat model.
J Anesth
Mustafa Büyükcavlak, Mehmet Sarı, Cansu Çiftci +3 more
Glucagon-like peptide-1 receptor agonists exhibit neuroprotective and anti-inflammatory effects; however, their role as perineural adjuvants in peripheral nerve blocks has not been investigated. We evaluated whether perineural liraglutide prolongs bupivacaine-induced sciatic nerve block and attenuates local tissue inflammation in a rat model.
[Errors in the diagnosis of chronic heart failure among outpatient elderly patients with type 2 diabetes mellitus.].
Adv Gerontol
N A Pervyshin, O A Shtegman
Objective - to study the incidence of chronic heart failure (CHF), including clinical manifestations, assessment of the concentration of the precursor of the brain natriuretic peptide (Nt-proBNP) in elderly patients with type 2 diabetes (DM2) hospitalized in the department of endocrinology as planned. The single-stage observational study included 83 patients with DM2 aged 60 to 74,9 years who were hospitalized in the Department of endocrinology as planned. All participants underwent standard physical, including clinical assessment of the presence of CHF, laboratory (determination of Nt-proBNP by a semi-quantitative method) and instrumental (echocardiographic) examinations. In elderly patients with DM2, the frequency of outpatient diagnosis of CHF is 43%, while 76% of the study participants had Nt-proBNP levels exceeding 125 pg/ml, and 97,6% retained ejection fraction. In 30% of patients with Nt-proBNP below the diagnostic threshold, stage 1 CHF has already been clinically established. 52,4% (n=33) of patients with Nt-proBNP ≥125 pg/ml had not been diagnosed with CHF before, of which 24,2% (n=8) were in the range of Nt-proBNP 125-449 pg/ml, and 45,5% (n=15) were in the range of 450-899 pg/ml. in the range of 900-1799 pg/ml - 18,2% (n=6) and in the range ≥1800 pg/ml - 12,1% (n=4) of the patient. The erased clinical symptoms of CHF in DM2 hinder timely diagnosis at the outpatient stage and increase the importance of evidence-based laboratory and instrumental methods, which serves as an argument for mandatory determination of Nt-proBNP and echocardiographic examination in elderly patients with DM2 and requires the development of algorithms for the personalization of diagnostic and therapeutic measures based on objective criteria.
Nano-formulated curcumin restores hypothalamic-pituitary-ovarian axis disturbance in cadmium-induced female reproductive toxicity.
Open Vet J
Mohammed Nabeel Abbas Al-Muhja, Jabbar Abbas Ahmed Al-Saaidi
Cadmium (Cd) is a pervasive environmental toxicant associated with female reproductive dysfunction through endocrine disruption and oxidative stress. Strategies that enhance antioxidant bioavailability may improve therapeutic efficacy against heavy metal-induced ovarian damage.
Exploring glucocorticoid receptor signalling in lymphangioleiomyomatosis.
ERJ Open Res
Alexandra Baiges, Lara Ruiz-Auladell, Irene García +51 more
Lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm that causes progressive cystic lung destruction and is often associated with renal angiomyolipomas (AMLs). Given evidence of pleiotropy linking LAM risk to pulmonary traits, we investigated whether glucocorticoid receptor (GR) signalling might influence LAM biology and clinical features.
Comparative analysis of neuropsychological impairments between Cushing's disease and non-functioning pituitary adenoma patients: the roles of HPA axis hormones and inflammatory markers in a prospective cohort study.
Endokrynol Pol
Hao Shen, Xiao Zang, Junpeng Xu +6 more
This prospective cohort study systematically compared neuropsychological impairments in Cushing's disease (CD),non-functioning pituitary adenomas (NFPA), and healthy controls (HCs), and investigated the roles of HPA axis hormones (ACTH, cortisol)and inflammatory markers in cognitive dysfunction.
Physiological, molecular, and histological evaluation of the effects of cobalamin on cardiac function in castrated rabbits.
Open Vet J
Mohammed Hayder Asker, Wassan Mhammed Husain, Hadeel Kamil Khaleel +1 more
Testosterone deficiency is associated with adverse cardiac remodeling, oxidative stress, and inflammation.
Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system.
Can J Physiol Pharmacol
Anthony P Davenport, Majid Anwar, Rhoda E Kuc +6 more
Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ETA and ETB 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 ETB agonist sovateltide (2021) for cerebral ischemic stroke, demonstrating the benefits of ETB activation. More recent antagonist development has shifted toward ETA-selective agents to preserve ETB function. Clazosentan (ETA) for cerebral vasospasm and aprocitentan (ETA/ETB) for resistant hypertension extended endothelin-targeted therapy into more common diseases. In kidney disease, sparsentan (AT1/ETA) and atrasentan (ETA) 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 ETA-selective diosuxentan and monoclonal antibody getagozumab, and the ETB peptide antagonist vodudeutentan. The review summarizes recent pharmacology and clinical data and highlights emerging strategies for next-generation endothelin-pathway therapeutics.
Neuropsychiatric association of tirzepatide and semaglutide in obesity with and without type 2 diabetes.
Commun Med (Lond)
Yu-Nan Huang, Kai-Wen Liu, Pin-Hung Li +4 more
Neuropsychiatric outcomes after starting newer anti-obesity medicines remain uncertain in routine care. We evaluate associations between initiation of tirzepatide or semaglutide and incident neuropsychiatric diagnoses in people with obesity, stratified by type 2 diabetes (T2D).