The living record of
peptide science.

Comparison of pharmacotherapies for obesity with sleeve gastrectomy: a network meta-analysis and systematic review.

Expert Rev Endocrinol Metab

Zachary Omeh, Tahira Khan, Olalekan Uthman +1 more

Tirzepatide, a glucagon-like peptide-1 receptor agonist (GLP1RA) and glucose-dependent insulinotropic-peptide (GIP), has shown efficacy regarding weight-loss.

The Roles of Macrophage Lineage Cells (MLCs) in Brain Aging.

CNS Neurosci Ther

Qin Qin, Liubin Zhang, Manning Guo +10 more

Brain aging poses a major public health challenge and is the primary risk factor for neurodegenerative diseases. Macrophage lineage cells (MLCs) have emerged as pivotal mediators of brain aging. While fundamental to central nervous system (CNS) homeostasis through their scavenging, detoxification, and neurotrophic functions, their transition to a senescent state is a primary driver of pathology. This shift is marked by a loss of clearance capacity and the adoption of a pro-inflammatory senescence-associated secretory phenotype (SASP).

A potential multimodal biomarker - cognitive signature associated with the conversion from subjective cognitive decline to mild cognitive impairment.

Alzheimers Dement (N Y)

Mohamed Haddad, Mohamed Raâfet Ben Khedher, Chadi Ouechtati +2 more

The disruption of key mechanisms involved in amyloid beta (Aβ) clearance during the early stages of dementia may contribute to the progression of cognitive decline toward irreversible brain damage. In this study, we investigated multiple immune-related pathways implicated in the management and clearance of Aβ within circulating extracellular vesicles (cEVs) and serum from individuals with subjective cognitive decline (SCD) who later progressed to mild cognitive impairment (MCI).

Oxidative Stress as a Mechanistic Link Between Severe Respiratory Viral Infection and Pulmonary Fibrosis.

Biology (Basel)

Shynggys Sergazy, Alexander Gulyaev, Zarina Shulgau

Post-viral pulmonary fibrosis represents a clinically significant and mechanistically complex consequence of severe respiratory infection. The COVID-19 pandemic has highlighted that a subset of survivors, particularly those with severe pneumonia or acute respiratory distress syndrome, develop persistent fibrosis-like lung abnormalities, including reticulation and traction bronchiectasis, often accompanied by impaired gas transfer. Although the clinical course is heterogeneous and many lesions regress over time, longitudinal studies indicate that structural and functional impairment may persist for years in susceptible individuals. Oxidative stress has emerged as a plausible convergent mechanism linking acute epithelial injury, dysregulated inflammatory resolution, and chronic fibrotic remodeling. Reactive oxygen and nitrogen species amplify inflammatory signaling, promote epithelial cell death and senescence, influence macrophage polarization, and activate canonical profibrotic pathways, notably the TGF-β axis. Redox imbalance is embedded within reinforcing circuits involving NOX4-dependent ROS amplification, mitochondrial dysfunction, endoplasmic reticulum stress, inflammasome activation, and senescence-associated secretory programs. Persistent immune activation and organelle stress may sustain redox dysregulation beyond viral clearance, thereby bridging acute lung injury to maladaptive remodeling. This review integrates epidemiological, clinical, and mechanistic evidence to position oxidative stress as a central mediator of post-viral lung fibrosis and discusses therapeutic and translational implications.

A Multicenter Randomized Clinical Trial of Dapagliflozin in Patients Receiving Chronic Dialysis (The DARE-ESKD-2 Trial).

Kidney Int Rep

Joaquim Barreto, Marilia Paiva Martins, Cleide Aparecida Moreira Silva +18 more

Dapagliflozin reduces heart failure (HF) incidence and hospitalizations in chronic kidney disease (CKD), but its efficacy and safety in patients on maintenance dialysis remain uncertain.

The attenuated incretin effect is associated with glucose intolerance in patients with hepatitis B-related acute-on-chronic liver failure.

Front Physiol

Meichuan Li, Han Hu, Yujuan Liu +6 more

The pathogenesis of glucose homeostasis disturbance in acute-on-chronic liver failure (ACLF) remains poorly defined. This study aimed to investigate the association between incretin effect (IE) and glucose intolerance in patients with hepatitis B virus-related ACLF (HBV-ACLF).

Subarachnoid Hemorrhage Induces mPFC CRF Neuronal Dysfunction Leading to Anxiety and Depression in Male Mice.

Stroke

Jin Yan, Fuming Liang, Na Wu +13 more

Anxiety and depression are common neuropsychiatric sequelae after subarachnoid hemorrhage (SAH), yet the underlying neural mechanisms remain poorly understood. The CRF (corticotropin-releasing factor) system in the medial prefrontal cortex (mPFC) is critical for emotional regulation and stress adaptation; however, its involvement in SAH-induced affective disorders has not been defined.

Challenging the known: unusual case report of acromegaly and subclinical Cushing's disease combination.

AME Case Rep

Xinlian He, Haiyan Li, Tingting Wu +3 more

Pituitary neuroendocrine tumors (PitNETs) are usually characterized by hormone secretion profiles that correspond to lineage-specific transcription factor expression. Growth hormone (GH) and prolactin (PRL) secretion is regulated by pituitary-specific transcription factor-1 (Pit-1), whereas adrenocorticotropic hormone (ACTH) production is classically dependent on T-box transcription factor 19 (T-pit). Accordingly, the concomitant secretion of GH and ACTH from a single pituitary adenoma is exceedingly rare.

Oral Health Considerations and Dental Management Guidelines for Semaglutide Medications.

Can J Diabetes

Karina Kofman, Aviv Ouanounou

Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically meaningful weight loss effects in patients with Type 2 diabetes and high BMI, and dental practitioners and physicians are often encountering patients who take these medications. Semaglutide is known to be associated with several systemic side effects, including delayed gastric emptying, belching, reflux and nausea, nutritional changes, and gastrointestinal discomfort. Systemic effects secondarily manifest in the oral cavity, and as a result, patients taking semaglutide may present with xerostomia (dry mouth), halitosis (bad breath), enamel erosion tied to vomiting, altered taste, among other oral signs and symptoms. It is important for dental professionals and physicians to become informed of possible symptoms and corresponding management strategies, given the multiple potential indirect effects on the oral cavity and relevance to dental treatment planning. This article reviews the pharmacodynamics of semaglutide and dives into the current evidence on oral manifestations of the drug family and implications for dental and oral health. It outlines practical management recommendations for dentists and the broader interdisciplinary healthcare team.

Real-world prescribing patterns and early weight and blood pressure outcomes of GLP-1-based therapies: a retrospective observational study in the United Arab Emirates.

BMC Endocr Disord

Salma Almemari, Nour Almulla, Yasmin Alsarraf +2 more

Preferred GLP-1 Receptor Agonists in Type 2 Diabetes With Established Cardiovascular Disease or High Cardiovascular Risk: A Network Meta-Analysis of Randomized Trials.

Can J Diabetes

Mustafa Abomohsen, Mohamed Rifai, Ahmed Farid Gadelmawla +5 more

The comparative cardiovascular (CV) efficacy and safety of GLP-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.

Nutritional Endocrinology in Dairy Cattle: Roles of the Ghrelin and Glucagon-Like Peptide Axis in Metabolic Adaptation and Developmental Programming.

Anim Sci J

Toshihisa Sugino, Rika Fukumori, Mabrouk Elsabagh +3 more

High-producing dairy cattle experience profound metabolic transitions during the periparturient and periweaning periods that influence health and long-term productivity. In ruminants, feed intake and metabolic adaptation reflect coordinated interactions among rumen fermentation, hepatic oxidative feedback, and gastrointestinal hormones. This review summarizes evidence on ghrelin and the glucagon-like peptide (GLP) axis and organizes recent findings within a hierarchical framework linking rumen-derived substrates, intestinal nutrient sensing, and systemic endocrine responses. Ghrelin increases during negative energy balance in early lactation and appears to support metabolic mobilization, whereas its orexigenic effect is constrained by ruminant-specific intake control. Evidence also indicates that postruminal amino acid supply and fatty acid profile can modulate ghrelin secretion, highlighting the importance of the digestive site and nutrient type. The GLP axis complements this regulation. GLP-1 links postruminal nutrient-related signals with insulin dynamics and satiety, whereas GLP-2 is more closely related to intestinal growth and adaptation during developmental transitions, including weaning. Notably, improvements in intestinal development in early life do not always coincide with large or sustained changes in circulating GLP-2. Overall, viewing dairy nutrition through endocrine responses, alongside nutrient supply, provides a basis to interpret variable outcomes in transition cows and calves and refine feeding strategies across physiological stages.

The plant hormone, 6-benzylaminopurine, ameliorates obesity in male and female mice while on a high-fat diet.

Mol Metab

Calvin V Lieu, Cindy X Zhang, Neruja Loganathan +9 more

Obesity is a global health crisis. Currently available treatments, while effective, show several undesirable side effects that hinder their long-term use. Herein, we investigated the anti-obesity potential of 6-benzylaminopurine (BAP), a plant hormone commonly used in agricultural settings to enhance plant development, in obese mice and mammalian cell models. Orally administered BAP induced significant weight loss in diet induced obese male and female CD-1 mice through sex-specific mechanisms involving appetite suppression, adipose tissue remodeling, and enhanced lipid utilization. Concurrently, BAP improves several metabolic parameters associated with obesity, including glucose tolerance, fasting blood glucose, hyperleptinemia, hyperinsulinemia, white adipose tissue browning, and liver health. In murine- and human-hypothalamic neuronal models, BAP suppresses the expression of feeding stimulating neuropeptide Y (Npy) and increases the anorexigenic pro-opiomelanecortin (Pomc). Using RNA-sequencing, we identified that BAP inhibits EGFR/ErbB2 and MEK/ERK/EGR1 signaling, whereas MEK/ERK inhibition is partially responsible for the in vitro effects of BAP, including Npy downregulation. Moreover, similar MEK/ERK inhibition was also shown to be involved in the induction of thermogenic markers, including uncoupling protein 1 (Ucp1), in 3T3-L1 derived adipocyte, indicating a consistent molecular mechanism of BAP across different cell types. Overall, our data showed that BAP could serve as an efficacious and alternative treatment avenue for obesity with a unique mechanism of action compared to currently available options.

Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.

Sports Med

Christopher L Mendias, Tariq M Awan

Peptides are short chains of amino acids with a unique pharmacological niche between small-molecule drugs and large proteins. Their use in sports medicine is rapidly expanding, driven by patient demand for accelerated injury recovery and performance enhancement. While numerous peptide drugs have undergone a rigorous approval process that evaluates both safety and efficacy, a parallel "gray market" of unapproved compounds has emerged, operating largely outside of regulatory oversight. Our objective is to present the pharmacological mechanisms, safety profiles, and regulatory status of prominent approved and unapproved peptides marketed direct to patients, including AOD-9604 (anti-obesity drug 9604), BPC-157 (body protection compound 157), CJC-1295, FS-344 (follistatin-344), GHK-Cu (glycyl-L-histidyl-L-lysine copper), ipamorelin, MOTS-C (mitochondrial ORF of the 12S rRNA type-c), sermorelin, SS-31 (elamipretide), tesamorelin (Egrifta), Tβ4 (thymosin beta-4), and TB-500 (thymosin beta-4 fragment). Many unapproved peptides demonstrate favorable tissue repair and metabolic outcomes in animal models, but rigorous human safety data are scarce, and there is potential for serious harm to patients. This narrative review focuses on the utilization of peptides in sports medicine, and alternative treatments that may be considered. We provide a framework to navigate patient discussions about peptides to better facilitate evidence-based practices for musculoskeletal healing and athletic performance. We also discuss the placebo effect as a mediator of peptide efficacy, and how social media amplifies this effect.

Decellularized extracellular matrix enhances hydrogel printability for bioprinting functional muscle constructs in a volumetric muscle loss model.

Biomaterials

Shabnam Sabetkish, Yuxuan Luo, Yen-Zhen Lu +3 more

Volumetric muscle loss (VML) remains a major clinical challenge due to the limited regenerative capacity of skeletal muscle. Effective repair requires the use of biomaterials that support cell viability, promote myogenic differentiation and enable vascularisation to allow the formation of structurally aligned, functional muscle. Here, we have integrated a biomimetic bioink based on gelatin methacryloyl (GelMA) and methacryloyl-modified decellularized extracellular matrix (dECM-MA) with a micropost tension-assisted bioprinting strategy to engineer skeletal muscle constructs for VML repair. We synthesized and characterized GelMA and dECM-MA bioinks, demonstrating well-preserved ECM components, reproducible gelation, mechanical properties and rheological properties suitable for extrusion bioprinting. In vitro, printed GelMA + dECM-MA scaffolds supported high cell viability, alignment and robust myogenic differentiation of C2C12 myoblasts, human satellite cells (hSkMSCs) and human umbilical vein endothelial cells (HUVECs). Co-culture of satellite cells with HUVECs enhanced endothelial network formation and improved myotube maturation. Printing around PDMS microposts provided passive mechanical tension, producing aligned fibres and greater contraction velocity and micropost displacement in co-culture constructs under electrical stimulation. To assess regenerative potential, 3-day-matured constructs were implanted in a mouse VML model. Constructs containing both hSkMSCs and HUVECs showed the greatest tissue regeneration, higher myofiber density, improved organization, and enhanced functional recovery compared with acellular or monoculture constructs. No immune response towards the presence of the human cells or porcine ECM was observed, suggesting a protective role for dECM-MA. Together, this integrated bioink-biomechanical platform resulted in the generation of vascularised, aligned, and functional muscle tissue with strong translational potential for VML therapy.

Geriatric Pharmacotherapy Case Series: GLP-1 RA for Weight Management in Older Adults.

Sr Care Pharm

Lauren Toma, Kelsey Buckley, Nicole Early

Background: This case study reviews the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for weight management in older adults. A 69-year-old male patient discusses weight loss goals with his health care provider and seeks pharmacotherapy options in addition to lifestyle modifications. His medical history includes type 2 diabetes mellitus (T2D), coronary artery disease (CAD), prior coronary artery bypass graft, heart failure with reduced ejection fraction (HFrEF), hypertension, hyperlipidemia, and allergic rhinitis. He initiated weight loss efforts following a myocardial infarction; however, dietary and physical activity changes alone have not resulted in substantial weight reduction. Assessment: This patient is an appropriate candidate for GLP-1 RA therapy given his T2D, obesity, CAD, and a recent elevation in serum creatinine (SCr). The patient will initiate semaglutide, a medication approved for weight management with demonstrated cardiovascular benefit. The dose will be titrated to a maintenance dose of 2 mg once weekly, with ongoing monitoring of tolerability and weight loss.Given his age, there is concern for sarcopenia associated with excessive weight loss. The patient will be advised to maintain a balanced diet with an emphasis on protein intake and to engage in regular physical activity to minimize loss of muscle mass. Outcome: The patient experiences weight reduction within the first few weeks of therapy and tolerates treatment well. He has incorporated additional strength training into his exercise routine and increased his intake of vegetables and protein. The patient has insurance coverage for semaglutide due to his comorbid T2D; therefore, medication cost is not a barrier to treatment. Conclusion: When evaluating the use of GLP-1 RA agents in older adults, these agents demonstrate benefits beyond glycemic control and weight loss, including cardiovascular and renal outcomes. However, GLP-1 RA-associated weight loss may contribute to muscle loss, which is of particular concern in older adults who are at risk for frailty or falls. Patients receiving GLP-1 RA therapy should be encouraged to maintain adequate protein intake and engage in regular physical activity, particularly resistance training, to preserve muscle mass. Additionally, the high cost of GLP-1 RA agents may limit access for patients without insurance.

Target-mediated drug disposition modeling of liraglutide in rats: Implications of target engagement for pharmacodynamic predictions.

Biomed Pharmacother

Sungmin Song, Joonhee Kim, Siyeon Kim +2 more

Target-mediated drug disposition (TMDD) is a pharmacokinetic phenomenon in which high-affinity binding to specific receptors leads to nonlinear pharmacokinetics. This study evaluated the pharmacokinetics and pharmacodynamics of the GLP-1 receptor agonist liraglutide in normal and diabetic rats, and developed a TMDD model to mechanistically link receptor dynamics to pharmacological outcomes. Liraglutide was administered intravenously across a wide dose range (0.005-0.8 mg/kg in normal rats; 0.005-0.2 mg/kg in diabetic rats). Plasma concentrations of liraglutide were determined using validated LC-MS/MS methods. Noncompartmental analysis revealed dose-dependent increases in clearance and volume of distribution at lower doses, consistent with TMDD behavior. A TMDD model adequately captured the observed concentration-time profiles across all dose levels. In diabetic rats, the pharmacodynamic response, measured as blood glucose reduction, exhibited a saturating relationship with both dose and plasma exposure (AUC). In contrast, the individually predicted AUC of the drug-receptor complex (AUCD-R complex) showed a linear correlation with the area under the effect curve (AUEC; β = 0.93, 95% CI 0.64-1.21), suggesting that receptor occupancy may serve as a more relevant determinant of pharmacodynamic response than plasma drug concentration. Simulations further revealed dose-dependent receptor depletion and saturable drug-receptor complex formation, providing mechanistic explanations for the prolonged pharmacological effects and nonlinear exposure-response relationship of GLP-1 receptor agonists. These findings support the utility of TMDD modeling for linking receptor dynamics to pharmacodynamic outcomes and provide a translational framework for rational dose optimization of peptide therapeutics.

Activation of neurogenesis improves amyloid-β pathology and cognitive function through AMP kinase signaling in Alzheimer's disease model mice.

Cell Rep

Masahiro Fukui, Takashi Kaise, Taimu Masaki +2 more

Adult hippocampal neurogenesis declines with aging and in neurological disorders, leading to cognitive impairment. We previously showed that inducing Plagl2 and antagonizing Dyrk1a (iPaD) rejuvenates aged neural stem cells (NSCs), enhancing neurogenesis and cognition in aged mice. Here, we found that NSC-specific iPaD treatment activates neurogenesis, reduces amyloid-β deposition, and improves cognition in Alzheimer's disease model mice. Transcriptomic analysis revealed widespread changes in gene expression in the hippocampus after iPaD treatment. The upregulated genes include those associated with astrocyte and microglial activation involved in amyloid-β clearance, while several genes upregulated in Alzheimer's disease are downregulated. Among the latter genes, knockdown of Prkag2 in the hippocampus most effectively enhances neurogenesis and reduces amyloid-β accumulation. Notably, both iPaD treatment and Prkag2 knockdown activate AMP-activated protein kinase signaling, upregulating genes involved in autophagy and cellular homeostasis. These results suggest that Prkag2 may represent a promising therapeutic target for neurodegenerative diseases, including Alzheimer's disease.

Antagonistic Pleiotropy Governing Reproductive Aging: Evolutionary Regulation of Endometrial Receptivity.

Reproduction

Hiroshi Kobayashi, Miki Nishio, Mai Umetani +3 more

This review aims to integrate current knowledge on how mTORC1-centered metabolic and stress-response pathways regulate endometrial decidualization, cellular senescence, and receptivity, with particular emphasis on their impact on implantation in advanced maternal age and metabolic disorders. A literature search was conducted using PubMed and Google Scholar without temporal restrictions, and studies were selected according to predefined inclusion and exclusion criteria focusing on metabolic signaling and reproductive function. Physiological mTORC1 activation during the proliferative phase supports stromal cell proliferation, protein synthesis, and initiation of decidualization, while facilitating formation and clearance of physiological senescent cells. Conversely, sustained mTORC1 activation associated with aging or metabolic dysfunction enhances cellular senescence and the senescence-associated secretory phenotype (SASP) through autophagy suppression, increased oxidative stress, and DNA damage, leading to impaired decidualization and reduced endometrial receptivity. This pattern aligns with the principle of antagonistic pleiotropy, whereby traits advantageous for reproduction in youth become detrimental to tissue function later. Dysregulation of mTORC1 and its related pathways-including AMPK, Tuberous Sclerosis Complex 2 (TSC2), and the p53 axis-is linked to implantation failure, particularly in advanced maternal age, obesity, and insulin resistance. In conclusion, mTORC1-centered metabolic and stress-response networks are fundamental regulators of endometrial maturation and senescence. Incorporating the assessment of mTORC1 activity and aging-associated markers may improve endometrial evaluation and reproductive outcomes, particularly in women of advanced reproductive age. Furthermore, such approaches may also enhance diagnostic precision and potentially increase success rates in assisted reproductive technologies (ART).

Late-onset dyskeratosis congenita due to a TERC (n.269G > C) variant-first reported case from Indonesia: a case report.

J Med Case Rep

Benedreky Leo, Intan Hartandy, Susanna Hilda Hutajulu +4 more

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome caused by defective telomere maintenance. It often presents with mucocutaneous features, cytopenias, and progressive organ involvement, but remains underrecognized in resource-limited settings.