The living record of
peptide science.

Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials.

JAMA Netw Open

Rodolfo J Galindo, Kimberly A Gudzune, Michelle Look +5 more

Given the common use of weight-inducing (WI) medications, it is crucial to understand the potential association of these medications with the effectiveness of obesity treatments.

Not All GLP-1 Receptor Agonists Are Alike: Real-World Evidence of Differential Endocrine and Dermatologic Safety.

Diabetes Metab Res Rev

Nai Lee, Yun Kim

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for metabolic disorders, but emerging safety concerns include alopecia and reproductive or endocrine-related adverse events (AEs). This study investigated the association between specific GLP-1 RAs and these endocrine-related AEs using a large-scale pharmacovigilance database.

New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin.

Expert Opin Pharmacother

Jasmin Barman-Aksözen, Francesca Granata, Sebastian Wäscher +2 more

The erythropoietic protoporphyrias (EPP) are ultra-rare inborn errors of the heme biosynthesis characterized by painful and debilitating phototoxic reactions in the blood vessels upon exposure to visible light. Afamelanotide is the only approved treatment for EPP and effectively prevents pain and prolongs the time patients can spend in sunlight. However, afamelanotide does not address the underlying disease mechanism and is currently only approved for use in adult patients, leaving children and adolescents without a treatment option. The two investigational pharmacotherapies dersimelagon and bitopertin could offer benefits such as treatment options for children and prevention of some of the associated disease complications.

Angiotensin-(1-7) Alleviates Isoproterenol-Induced Cardiac Hypertrophy by Suppressing Autophagy and Apoptosis Through the Synergistic Action of Mas Receptor and Angiotensin II Type 2 Receptor.

Acta Physiol (Oxf)

Xiaomei Wang, Fei Guo, Xiaoqian Wang +4 more

The aim of this study is to determine whether Angiotensin-(1-7) [Ang-(1-7)] alleviates isoproterenol (ISO)-induced cardiac hypertrophy by suppressing excessive autophagy and apoptosis through coordinated Mas receptor (MasR) and angiotensin II type-2 receptor (AT2R) signaling, and to elucidate the underlying mechanisms.

Mid-regional pro-atrial natriuretic peptide in managing cardiovascular and cerebrovascular diseases.

Crit Rev Clin Lab Sci

Xu-Lei Hao, Gjin Ndrepepa, Wen-Qi Zheng +1 more

Mid-regional pro-atrial natriuretic peptide (MR-proANP), along with B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), is a type of natriuretic peptide hormone that is released by atrial muscle cells upon stress. Previous studies have shown that MR-proANP has high diagnostic accuracy for heart failure (HF) in several clinical settings, and it also helps in the risk stratification of patients with HF. In the general population, elevated MR-proANP levels indicate a high risk of cerebrovascular and cardiovascular diseases, including stroke and atrial fibrillation. In patients with established cardiovascular and cerebrovascular diseases, elevated MR-proANP levels are associated with a poor prognosis. This review summarizes the value and the use of MR-proANP in assessing the risk, diagnosis, and prognosis of patients with cardiovascular and cerebrovascular disease(s).

Central Hypothyroidism and Impaired Growth Hormone Secretion Due to Subclinical Cushing's Syndrome: A Case Report.

Intern Med

Masahito Katahira, Taku Tsunekawa, Akira Mizoguchi +4 more

A 34-year-old Chinese woman presenting with general fatigue was found to have central hypothyroidism and low-normal insulin-like growth factor 1 (IGF-1). Although she had no cushingoid features, her adrenocorticotropic hormone levels were suppressed, while her serum cortisol levels were normal. Cortisol secretion was not suppressed following a 1-mg dexamethasone suppression test, and computed tomography revealed a left adrenal tumor. After adrenalectomy, her thyroid function, growth hormone (GH) secretion, and IGF-1 levels were normalized. A histopathological examination confirmed adrenocortical adenoma. This case demonstrates that mild autonomous cortisol secretion can impair GH secretion and cause central hypothyroidism even in the absence of any overt cushingoid features.

Interplay of childhood metabolic dysfunction-associated steatotic liver disease and obesity in the development of youth-onset type 2 diabetes.

World J Clin Pediatr

Razieh Parizad, Juniali Hatwal, Ajit Singh Brar +4 more

The global increase in childhood and adolescent obesity has significantly contributed to the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) - a condition now recognized as a key metabolic complication in youth. MASLD significantly increases the risk of youth-onset type 2 diabetes (T2D), particularly among obese individuals. Its asymptomatic progression presents considerable challenges for timely diagnosis and intervention.

Aldosterone Accelerates Systolic Decline in Volume-Overload Heart Failure.

Biol Pharm Bull

Xin Cao, Luyi Xie, Yoshinobu Nagasawa +2 more

High-output heart failure (HF) occurs with sustained volume overload. Hence, clarifying how compensated high-output states transition to maladaptive HF is essential for developing interventions that preserve cardiac function. Therefore, this study investigated the mechanism by which volume overload induced by aortocaval shunt (AVS) and aldosterone (Ald) affects the progression of myocardial function and structural remodeling. AVS was surgically induced in rats, and osmotic mini-pumps delivering Ald (1.0 μg·h-1) for 4 weeks were intraperitoneally implanted. Cardiac function and structure were serially assessed using echocardiography before surgery and at 4, 12, and 24 weeks under isoflurane. At 23 weeks, atrial natriuretic peptide was analyzed, and at 24 weeks, comprehensive electrophysiological, hemodynamic, morphometric, and histological examinations were performed to characterize cardiopathy. Early diastolic mitral annular velocity (E') remained relatively unchanged after 24 weeks, whereas early diastolic filling wave (E) velocity, atrial contraction wave velocity, and E/E' ratio increased. However, AVS did not markedly reduce systolic function; it was associated with progressive elevation of cardiac output, left ventricular hypertrophy, and dilation. Histological and morphometric analyses confirmed concentric hypertrophy, eccentric remodeling, and focal fibrosis. Ald induced similar diastolic changes and structural remodeling but caused an earlier decline in systolic function at 8 weeks. These findings demonstrate a 2-phase trajectory of high-output stress: an early compensated stage with elevated filling pressure, followed by a decompensated stage with progressive systolic decline. Moreover, Ald accelerates this systolic decline. Therefore, targeting Ald receptors in the early compensation phase may protect against systolic impairment caused by volume overload.

Mahuang decoction targets fluid retention in heart failure with preserved ejection fraction.

Phytomedicine

Xiaoyu Liang, Ziyi Chen, Xiaopeng Hao +7 more

In heart failure with preserved ejection fraction (HFpEF), fluid volume overload constitutes a critical factor driving disease progression. Mahuang decoction (MHD), a traditional Chinese medicine with diaphoretic and diuretic properties, has shown potential in improving HFpEF, yet its mechanisms remain unclear.

Disproportionality analysis of adverse events associated with endothelin receptor antagonists based on the FDA adverse event reporting system (FAERS).

Front Cardiovasc Med

Lizhu Han, Sitian Li, Jianting Liao +5 more

Endothelin receptor antagonists (ERAs), including bosentan, ambrisentan, and macitentan, are recognized as first-line treatments for pulmonary arterial hypertension (PAH). Although their therapeutic efficacy is well established, variations in receptor selectivity and metabolic pathways may lead to distinct adverse drug event (ADE) profiles. Nonetheless, large-scale, real-world comparative safety data remain limited. As part of routine pharmacovigilance activities, we analyzed data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) to identify disproportionate reporting signals.

A prospective cohort study on the association between cervical microenvironmental factors and the efficacy of treating high-risk human papillomavirus infection comorbid with cervical diseases.

Front Cell Infect Microbiol

Lingyun Ji, Jing Wu, Yang Zhou +6 more

Interferon-based local therapy is an intervention for high-risk human papillomavirus (HR-HPV)-associated low-grade squamous intraepithelial lesions (LSIL) or lower-grade cervical abnormalities. This study sought to delineate the differences in clinical outcomes following interferon-based local drug treatment and elucidate the microenvironmental factors driving these disparities.

Assessment of mitochondrial peptide humanin in women with polycystic ovary syndrome: serum and skeletal muscle profile.

J Endocrinol Invest

Irem Sonmezoglu Kutuk, Senay Akin, Haydar Demirel +3 more

Early targets and progressive deterioration in cardiac performance in response to chronically modified cardiac troponin I.

Am J Physiol Heart Circ Physiol

Vani S Ravichandran, Tabea M Schatz, Emily Lavey +9 more

Protein kinase C (PKC) targeted thin filament cardiac troponin I (cTnI) Ser43/45 phosphorylation (p-S43/45) increases during heart failure (HF). Chronic cTnI p-S43/45 causes contractile dysfunction in cardiac myocytes, but the in vivo impact is less clear. To investigate the in vivo impact of this cluster, three lines of transgenic mice were generated with high (HE-), moderate (ME-), and low (LE-) phosphomimetic cTnIS43/45D (SD) replacement of endogenous cTnI within sarcomere thin filament. Each mouse line developed chronic in vivo and/or cellular contractile dysfunction, which initiated structural remodeling and a progressive deterioration in cardiac function. Higher cTnISD replacement levels accelerated the rate of deterioration and progression to end-stage heart failure. In further work, cTnISD initiated sarcomere communication to produce early alterations in mitochondria before the progressive deterioration in cardiac performance. Specifically, early reductions developed in mitochondrial/nuclear DNA, mitochondrial master regulator gene expression, electron transport proteins, and antioxidants along with increased mitochondria-related oxidative stress before extensive remodeling in cTnISD mice. In addition, cTnISD mice developed early differences in mitochondrial ultrastructure and evidence favoring fusion over fission compared with nontransgenic (Ntg) littermates. A second-generation peptide derived from elamipretide improved survival and slowed the progression of remodeling and contractile dysfunction. Overall, the results demonstrate that chronic cTnISD causes cardiac dysfunction and initiates early mitochondrial responses that serve as important drivers of progressive deterioration in cardiac performance to end-stage HF.NEW & NOTEWORTHY Elevated cardiac troponin I (cTnI) Ser43/45 phosphorylation accompanies human heart failure. A mouse model with phosphomimetic substitutions shows that chronic sarcomere replacement with cTnI Ser43/45Asp causes cardiac dysfunction and initiates early downstream changes in mitochondria before the onset of progressive remodeling and progressive deterioration in cardiac performance. These early alterations include differences in mitochondrial architecture and function and oxidative stress. Early mitochondrial targeting improves survival and cardiac function.

Low-Temperature Fabrication of Thymosin β4-Loaded Soluble Microneedles to Promote Wound Healing by Specific Binding to Downregulated Immune Regulators Vsig4 and IL22rɑ2.

Adv Healthc Mater

Shilong He, Mei Yuan, Changkang Feng +2 more

Skin wound treatment is hindered by the poor penetration of large therapeutics and a lack of treatments that effectively regulate immune environments. While microneedles (MNs) can bypass the skin, they destabilize sensitive peptides, including thymosin β4 (Tβ4), whose immunomodulatory targets are not well understood, limiting their clinical use. This study introduces a novel fabrication method for Tβ4-loaded soluble MNs at low temperatures using chitosan and sucrose, avoiding the denaturing conditions of traditional MN production. These MNs exhibit a uniform shape, high drug capacity (248.15 ± 1.37 µg/patch), quick dissolution within an hour, excellent biocompatibility, and significantly enhanced wound healing in mice. This study examines the mechanism by which Tβ4 accelerates wound healing, identifying the downregulated immune regulators Spp1, Vsig4, and IL22rɑ2 through RNA-seq and DEG analysis. In vitro qPCR, western blot, and surface plasmon resonance (SPR) experiments demonstrate that Tβ4 specifically binds to the downregulated immune regulators Vsig4 (KD = 3.56 × 10-6 m) and IL22rɑ2 (KD = 9.69 × 10-6 m). This article explores how Tβ4 influences the wound immune microenvironment to aid healing, identifies its specific molecular targets, and moves beyond its general roles to offer new opportunities for drug development.

Bovine respiratory syncytial virus utilizes the human insulin-like growth factor 1 receptor in the late stages of infection.

J Gen Virol

Sodbayasgalan Amarbayasgalan, Tatsuki Takahashi, Yoshiro Sugiura +4 more

Bovine respiratory syncytial virus (BRSV) is a major viral pathogen associated with the bovine respiratory disease complex, which is a leading cause of morbidity, mortality and economic loss in the cattle industry worldwide. Clinical infection is most severe in young calves, where it commonly causes lower respiratory tract inflammation, bronchopneumonia and predisposition to secondary bacterial infections. In experimental research, BRSV is typically maintained in Vero and MDBK cells. Although reverse genetics systems have been established for BRSV, we developed a bacterial artificial chromosome-based reverse genetics system for the virus. We successfully recovered a recombinant BRSV with the ZsGreen reporter gene inserted between the P and M genes. The recombinant virus displayed comparable growth kinetics to the WT strain, demonstrating the utility of the system for generating reporter viruses. Reporter virus infectivity assessments in mammalian MDBK, VeroE6, HEp-2 and HEK293T cells revealed that HEK293T cells are permissive to BRSV. To investigate the potential role of human insulin-like growth factor 1 receptor (hIGF1R), which human RSV uses for entry, we infected insulin-like growth factor 1 receptor (IGF1R)-knockout (KO) 293 T cells with BRSV-ZsGreen. At 24 h post-infection (hpi), ZsGreen levels were similar between WT and hIGF1R-KO cells; however, by 72 hpi, viral spread was markedly reduced in hIGF1R-KO cells and correlated with IGF1R levels. These findings suggest that IGF1R is dispensable for early BRSV infection but contributes to efficient viral propagation in later stages.

A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review.

J Sports Med Phys Fitness

Luis F D Coutinho, Lucas F DE Oliveira Neves, Rafael P Camilo

The pursuit of pharmacological enhancement in sport has evolved from the widespread use of anabolic-androgenic steroids (AAS) to novel agents such as peptides and peptide analogues. Marketed as more selective and ostensibly safer alternatives, peptides-including growth hormone secretagogues (e.g., Ipamorelin), growth hormone-releasing hormone analogues (e.g., CJC-1295, Sermorelin), and synthetic fragments (e.g., Frag 176-191, KPV)-are promoted for muscle growth, fat metabolism, recovery, and anti-inflammatory effects. Their pharmacological profiles, including enhanced stability and receptor selectivity, have made them attractive in both medical research and bodybuilding communities. Despite their growing popularity, the clinical evidence supporting peptide use in sport is limited. Most published studies examine therapeutic applications under controlled dosing regimens, not the supraphysiological or combined protocols common in bodybuilding. Emerging data highlight potential risks: cardiovascular strain, insulin resistance, dyslipidemia, and psychiatric instability. The largely unregulated supply chain exacerbates these dangers, as products are often mislabeled or contaminated. Regulatory bodies such as the World Anti-Doping Agency (WADA) have responded by expanding detection technologies, yet analytical challenges remain due to peptides' structural similarity to endogenous hormones and short half-lives. Beyond elite sport, the extent of peptide use in the general population is unknown. Anecdotal reports and widespread promotion on social media suggest growing uptake among recreational gym-goers, including younger individuals, but prevalence studies are lacking. This represents a critical gap in current knowledge. In conclusion, peptides represent a new phase in performance enhancement but remain experimental substances with poorly defined long-term risks. Until longitudinal data clarify their safety and prevalence, peptide use in both competitive and recreational settings should be considered high-risk and ethically problematic.

Bispecific GLP-1/GLP-2 agonism in advanced type 2 diabetes: preclinical characterization and a randomized, double-blind, placebo-controlled phase I trial.

Nat Commun

Sang-In Yang, Sae Won Kim, Kyung-Hwa Son +4 more

PG-102 is a potency-optimized bispecific Fc fusion protein targeting GLP-1 and GLP-2 receptors. In db/db mouse models of advanced diabetes characterized by uncontrolled hyperglycemia and catabolic weight loss, PG-102 achieved superior and sustained glycemic control compared with semaglutide or tirzepatide while preserving body weight, uncoupling glycemic control from catabolic weight loss. Mechanistic studies indicated that these effects were not driven by acute insulinotropic activity, but by β-cell preservation and enhanced glucose uptake. These benefits required dual GLP-1R/GLP-2R engagement, as PG-102 outperformed monospecific Fc fusion agonists or their combination and promoted coordinated receptor trafficking with delayed internalization. We conducted a randomized, double-blind, placebo-controlled multiple ascending dose phase 1 study at a single center in the Republic of Korea in adults with overweight (BMI 25-30 kg/m²). Twenty-four participants were randomized within three weekly dose cohorts (15 mg, 30 mg, and 30/60 mg; n = 6 per cohort) in a 6:2 ratio to receive PG-102 (n = 18) or placebo (n = 6). All randomized participants (PG-102 n = 18; placebo n = 6) received at least one dose and were included in the safety analysis. Safety and tolerability were predefined as the primary endpoint and assessed by treatment-emergent adverse events (TEAEs). TEAEs occurred in 5/6 (83.3%) participants in each PG-102 cohort and 4/6 (66.7%) in placebo; treatment-related AEs occurred in 5/6 (83.3%) and 3/6 (50.0%), respectively. No serious adverse events or discontinuations due to adverse events occurred. Gastrointestinal events were mild to moderate. These findings support bispecific GLP-1/GLP-2 agonism as a mechanistically distinct incretin strategy in advanced T2D. ClinicalTrials.gov identifier: NCT06309667.

Lean Mass Changes With Incretin Therapy Versus Lifestyle Intervention: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Diabetes Obes Metab

Naseem Eisa, Omar Barood

To compare lean mass changes between incretin-based therapies (GLP-1 receptor agonists and dual GLP-1/GIP agonists) and intensive lifestyle interventions in adults with overweight or obesity, and to determine whether the proportion of total weight lost as lean mass differs between these treatment modalities.

Diagnostic Value of Serum sCD40L, CCL3, and NT-ProBNP Levels in Detection of Lower Limb Venous Thrombosis among Elderly Patients with Heart Failure.

Arq Bras Cardiol

Xuelian Liu, Lina Mu, Shasha Ma +1 more

The serum levels of soluble CD40 ligand (sCD40L), cytokine ligand 3 (CCL3), and N-terminal pro-brain natriuretic peptide (NT-proBNP) are closely associated with heart failure (HF).

ARD-101, a gut-restricted TAS2R agonist, reduces hunger in adults and promotes weight loss in DIO mice with DPP-4 inhibition.

Mol Metab

Zhenhuan Zheng, Jeremy H Pettus, Alexa Warner +8 more

Obesity management has limited oral pharmacotherapies. Bitter taste receptor (TAS2R) agonists may modulate hunger, satiety, and metabolism via gut-brain signaling. We evaluated denatonium acetate (DA), a gut-restricted TAS2R agonist, across preclinical and clinical settings, and explored its combination with sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor).