The living record of
peptide science.

Evaluating sotatercept in the treatment of pulmonary arterial hypertension.

Future Cardiol

William Salibe-Filho, Nathalia Zorze Rossetto, Luiza Sarmento Tatagiba +5 more

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remodeling, right ventricular overload, and premature death. Despite advances achieved through endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin analogs, these agents primarily act as vasodilators and do not reverse underlying vascular pathology. Sotatercept, a first-in-class activin signaling modulator, restores the balance between pro- and antiproliferative signaling within the pulmonary vasculature via the TGF-β/activin-BMPR2 pathway, offering a novel disease-modifying mechanism. Following encouraging preclinical data, a series of clinical trials, PULSAR, SPECTRA, STELLAR, ZENITH, and HYPERION, demonstrated consistent efficacy across diverse PAH populations. Sotatercept significantly reduced pulmonary vascular resistance, improved exercise capacity, and decreased morbidity and mortality, including in patients receiving maximal background therapy. Across studies, adverse events were generally mild to moderate, with epistaxis, telangiectasia, and increased hemoglobin being the most common treatment-related events. Collectively, these findings establish sotatercept as a major advance in PAH therapy, marking a transition from purely vasodilatory approaches toward targeted modulation of vascular remodeling. By improving pulmonary hemodynamics and right ventricular function, sotatercept represents a new therapeutic option for improving clinical outcomes across different stages of PAH.

Targeting Drug-Resistant Tuberculosis with Antimicrobial Peptides: Opportunities and Challenges.

Curr Protein Pept Sci

Asad Ahmad, Rufaida Wasim, Anas Islam +1 more

One of the main causes of infectious disease-related deaths globally is Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB). Novel treatment strategies are now much more urgent due to the emergence of Extensively Drug-Resistant (XDR) and multidrug-resistant (MDR) strains. The purpose of this study is to investigate the potential of antimicrobial peptides (AMPs) as TB adjunctive therapeutic agents, with an emphasis on their immunomodulatory and direct antimycobacterial effects.

Metabolic and Bariatric Surgery vs Glucagon-like peptide-1 Receptor Agonist Therapy: A Head-to-Head Comparison in Improvement of Cardiometabolic Risk Profiles.

Ann Surg

Wissam Ghusn, Robert A Vierkant, Noura Jawhar +11 more

To compare 1-year changes in estimated 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk following metabolic and bariatric surgery (MBS) versus glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy among adults with obesity.

Evaluating the Efficacy, Safety, and Practical Considerations of Semaglutide for Weight Loss in Non-Diabetic Adults: A Narrative Review.

Health Sci Rep

Ayesha Laraib, Uswa Ahmad, Syeda Iman Laraib +4 more

The rising global prevalence of obesity has catalyzed the development of potent glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review evaluates the efficacy, safety, and practical considerations of injectable semaglutide for weight management, specifically in non-diabetic adults, a population where weight loss outcomes often differ from those seen in diabetic cohorts.

Metabolic advances in 2025: from clinical breakthroughs to molecular reprogramming.

Metabol Open

Maria Dalamaga, Junli Liu

The year 2025 represented a turning point in metabolic research, marked by advances that combined unprecedented clinical efficacy with deep mechanistic insight. Landmark obesity trials redefined therapeutic expectations, with head-to-head and combination studies showing that the depth and distribution of weight loss are critical determinants of metabolic benefit across obesity and type 2 diabetes. In parallel, gene-editing studies crossed a translational threshold, showing that durable modification of metabolic pathways in humans is feasible, from bespoke correction of inborn errors to population-scale lipid lowering. Mechanistic investigations challenged long-standing assumptions about metabolic regulation. Experimental work revealed that mitochondrial electron transport functions as a dynamic redox regulator rather than a passive energy conduit, linking coenzyme Q imbalance and reverse electron transport to hepatic steatosis and metabolic dysfunction. Other studies reframed nutrient exposure and endogenous metabolites, demonstrating that non-nutritive sweeteners and cyanide exert context-dependent metabolic effects through regulated endocrine and redox pathways. At the systems level, multi-omics analyses defined reproducible microbiome-metabolome signatures associated with impaired glucose regulation, while artificial intelligence and continuous glucose monitoring exposed dynamic glycemic phenotypes invisible to conventional biomarkers. Precision-nutrition studies further showed that selective manipulation of sulfur amino acid availability can program thermogenic and metabolic responses. Collectively, these studies illustrate how metabolism in 2025 was approached as a modifiable, programmable system, shaped by clinical intervention, molecular control, and data-driven phenotyping, and point toward an era of increasingly precise and integrated metabolic medicine.

Shifts in body mass index category with tirzepatide and associated changes in cardiometabolic risk factors in people with obesity: a post hoc analysis from the SURMOUNT-1 and SURMOUNT-4 trials.

Am J Prev Cardiol

Naveed Sattar, Clare J Lee, Reshmi Srinath +6 more

Obesity is a chronic disease that results in increased morbidity and mortality if left untreated. Tirzepatide is a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist approved in the United States for the treatment of type 2 diabetes, obesity, and obstructive sleep apnea. These post hoc analyses assessed the cardiometabolic risk factors of participants with obesity or overweight treated with tirzepatide who shifted to a lower body mass index (BMI) category.

Tirzepatide as Adjunct to Insulin in Adults With Type 1 Diabetes and Overweight or Obesity: A Systematic Review of Randomized and Real-World Evidence.

Endocrinol Diabetes Metab

Giuseppina Alessia Acucella, Danilo Caponio

Overweight and obesity are increasingly common in adults with type 1 diabetes (T1D), contributing to insulin resistance, higher insulin requirements, and greater cardiometabolic burden. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown major metabolic benefits in type 2 diabetes and obesity, but its role in T1D remains unclear. This systematic review evaluated tirzepatide as adjunctive therapy to insulin in adults with T1D and overweight or obesity.

New Horizons in Metabolic Health: Unveiling the Future of Drug Discovery and Development.

Endocr Metab Immune Disord Drug Targets

Jinshan Zhao, Quanyu Qiu, Jidong Zhang +1 more

Metabolic diseases (diabetes, obesity, NAFLD) pose a severe threat to global health, demanding innovative drug solutions.

Aging disrupts the temporal organization of slow oscillations beyond density reduction.

PNAS Nexus

Lucila Capurro, Michael Radloff, María C González +4 more

Macroscopic and rhythmic brain oscillations have recently been shown to play a crucial role in glymphatic function by promoting cerebrospinal fluid flow and facilitating the clearance of metabolic waste. While age-related reductions in the number and amplitude of slow oscillations (SOs; 0.5-1 Hz) are well documented and associated with impaired clearance, little is known about how aging affects the temporal structure of these oscillations. Here, we propose that the rhythmic dynamics with which SOs occur represent a critical, yet overlooked, feature supporting glymphatic function. We introduce a novel classification of SOs based on their temporal organization, distinguishing isolated SOs from trains of consecutive oscillations according to inter-SO intervals. Using overnight electroencephalographic recordings from 57 young and 51 elderly adults across three independent datasets, we compared the proportions of isolated and consecutive SOs as well as the distribution of train lengths. Elderly adults displayed a significantly higher proportion of isolated SOs and shorter oscillatory trains than young adults, even after controlling for SO density and stage composition. Temporal shuffling procedures and analyses of density-matched epochs further supported that these differences cannot be attributed solely to density but instead reflect a genuine age-related loss of rhythmicity. These findings reveal that natural aging not only reduces the amount and amplitude of SOs but also disrupts their temporal regularity. This alteration may weaken the sustained ionic currents that drive cerebrospinal fluid flow, compromise the efficiency of metabolic clearance during sleep, and thereby contribute to increased vulnerability to age-related neurodegenerative processes.

State-of-the-Art Strategies in Heart Failure Screening.

Curr Cardiol Rev

Mahmoud M Ramadan, Abdelrahman Nouh, Hamza Haj-Mohamed +5 more

Heart Failure (HF) is a major global health concern affecting approximately 64 million individuals. Because early asymptomatic stages are frequently overlooked, many patients are diagnosed late, after preventable morbidity and hospitalization. Screening that identifies high-risk individuals earlier may enable timely intervention and disease modification.

Metoprolol-spironolactone combination for coronary heart disease with concurrent heart failure: impact on cardiac function.

Am J Transl Res

Shujun Zhao, Jiwei Zhang, Yansha Zhao

This study intended to clarify the role of metoprolol-spironolactone combination in treating coronary heart disease (CHD) with concurrent heart failure (HF), focusing on its impact on cardiac function.

Pilot Trial of Vachellia farnesiana Pod Polyphenol Extract: Feasibility, Acute Postprandial Glycemic Response, and Incretin Hormone Modulation in Healthy Adults.

Curr Dev Nutr

Yonatan Y Cariño-Cervantes, Martha Guevara-Cruz, Omar Noel Medina-Campos +9 more

Medicinal plants contain bioactive compounds with potential benefits for metabolic regulation, including glucose homeostasis. Vachellia farnesiana (VF) pods are rich in polyphenols, including quercetin, catechins, methyl gallate, prutin, and hydroxycinnamic acids; however, their clinical effects in humans remain underexplored.

Adrenal Biomarkers of Stress in Transgender and Gender-Diverse Adolescents.

Dev Psychobiol

Simone Coslovich, Stefania Tonetto, Giulia Bragato +7 more

Transgender and gender diverse (TGD) adolescents are frequently exposed to minority stress, which may influence the hypothalamic-pituitary-adrenal (HPA) axis during critical developmental windows. Altered cortisol dynamics have been described in populations facing chronic stress, yet evidence in TGD youth is limited. Understanding adrenal function in this context is essential for clarifying potential biological pathways linking social stressors to developmental and health outcomes. In the present study, identifying as TGD serves as an indirect proxy of exposure to minority stressors, which were not directly measured. We conducted a retrospective, case-control study at a tertiary pediatric center, including 48 TGD adolescents and 298 controls referred for evaluation of premature pubarche with nonclassical congenital adrenal hyperplasia excluded. All participants underwent a standard dose synacthen test (SDST; 250 µg tetracosactide iv, sampling at baseline and 60 min, 8:00 a.m.), which assesses adrenal responsiveness to pharmacological ACTH stimulation. Serum cortisol, DHEAS, ACTH, and 17-hydroxyprogesterone were assayed. Statistical analyses included nonparametric group comparisons, correlations, and multivariable regression adjusting for age and sex assigned at birth. TGD individuals demonstrated significantly higher baseline cortisol levels (293 vs. 214 nmol/L; p < 0.001) and a reduced cortisol response to SDST (Δcortisol: 354 vs. 446 nmol/L; p < 0.001). In the full sample, basal DHEAS levels were higher in TGD youth (231 vs. 142 nmol/L; p = 0.362), whereas the DHEAS-to-cortisol ratio did not differ significantly between groups. In an age-matched subsample (1:2 matching), the DHEAS-to-cortisol ratio was significantly lower in TGD adolescents (0.72 vs. 1.03; p = 0.004). Multivariate analysis confirmed an independent association between TGD status and higher basal cortisol, lower Δcortisol, and a reduced DHEAS-to-cortisol ratio after adjustment for covariates (all p < 0.001). Our findings provide preliminary evidence of altered adrenal responsiveness in TGD adolescents, potentially reflecting the biological embedding of minority stress during development. Although exploratory, these results highlight the need for prospective, longitudinal studies integrating psychosocial and neuroendocrine measures to clarify mechanisms linking stress, HPA axis function, and developmental outcomes in gender-diverse youth.

The mechanism of Longdan Xiegan pills in chronic stress-induced hypertension:a study based on network pharmacology and experimentalvalidation.

In Silico Pharmacol

Huizhuo Jia, Mingyao Lv, Ying Yang +7 more

This study integrated network pharmacology and experimental validation to elucidate the mechanism of Longdan Xiegan Pills (LDXG) in treating chronic stress-induced hypertension. Active components of LDXG were retrieved from the TCMSP database and screened based on oral bioavailability (OB) and drug-likeness (DL). Potential targets were predicted using SwissTargetPrediction. Disease targets related to hypertension were collected from OMIM and GeneCards. A compound-target network was constructed using Cytoscape, and protein-protein interaction (PPI) analysis was performed via the STRING database. Functional enrichment analysis (GO and KEGG) was conducted using DAVID. Molecular docking was performed with LeDock. In vivo, systolic and diastolic blood pressures were measured non-invasively, myocardial histopathology was evaluated by HE staining, the content of target protein in pvn and adrenal gland was measured by western blot, and serum inflammatory markers were quantified via ELISA. A total of 178 active components of LDXG were screened, Gentiana scabra Bunge (Gentian), Gardenia jasminoides Ellis (Gardeniae fructus), Scutellaria baicalensis Georgi (Huangcen), Bupleurum chinense DC (Bupleurum), and Glycyrrhiza uralensis Fisch (Licorice) were identified as the core components.The core targets included SRC, MAPK3, MAPK1, PIK3R1, RELA and STAT3. GO functional enrichment and KEGG pathway enrichment analyses indicated that LDXG primarily modulated protein kinase activity, ATP binding, protein serine/threonine kinase activity and protein kinase binding.These processes involved the PI3K-Akt, HIF-1, VEGF, ErbB and FoXO. Animal experiments demonstrated LDXG can significantly lowered blood pressure level in chronic stress-induced hypertension rats,reduced the contents of src and STAT3 in the PVN and MAPK1 in the adrenal gland and reduced serum levels of angiotensin II (Ang II), cortisol and adrenocorticotropic hormone(ACTH). LDXG can attenuate chronic stress hypertension by regulating JAK/STAT, Src/MAPK and other signaling pathways and reducing the expression of Ang II through a variety of active compounds.

Yttrium-90 Radioembolization Versus Transarterial Embolization for Lung Carcinoid Hepatic Metastasis.

JTO Clin Res Rep

Gavin Yuan, Marios Platon Dimopoulos, Elena N Petre +8 more

To compare the safety and efficacy of transarterial embolization (TAE) and transarterial radioembolization (TARE) in the treatment of lung carcinoid liver metastasis.

GHRH and insulin hypersecretion from a pancreatic neuroendocrine tumor in multiple endocrine neoplasia type 1.

JCEM Case Rep

Elisa Lamback, Daniel Alves Bulzico, Delmar Muniz Lourenço +3 more

Acromegaly caused by ectopic growth hormone-releasing hormone (GHRH)-secreting neuroendocrine tumor (NET) is extremely rare, with cosecreting NETs even more seldom. We report a case of a female patient who presented with primary hyperparathyroidism (pHPT) and a GHRH- and insulin cosecreting pancreatic NET (pNET) and genetically confirmed multiple endocrine neoplasia type 1 (MEN1), within an undiagnosed family with various MEN1-related NETs. Due to the diagnosis of MEN1, screening for pituitary tumor was performed with biochemical evidence of acromegaly. Sellar magnetic resonance imaging revealed a sellar lesion, which was excised and compatible with somatotroph hyperplasia. Postoperatively, the patient developed severe hypoglycemia requiring hospitalization and the pNET was removed. Histopathology confirmed GHRH and insulin secreting pNET. Ectopic acromegaly in MEN1 is exceedingly rare. Patients with MEN1 often present with multiple pNETs, which may exhibit multihormonal secretion and frequently cosecrete GHRH and insulin in MEN1, while hypoglycemia may not be manifested possibly due to GH and insulin's counteractive effects on glucose metabolism.

Leucine supplementation modulates body composition and early weight rebound during GLP-1 receptor agonist therapy in diet-induced obese mice.

J Endocrinol Invest

Ze-Wei Zhao

GLP-1 receptor agonists (GLP-1RAs) like semaglutide are effective for obesity treatment but may cause lean mass loss and post-discontinuation weight rebound. This study aimed to explore whether leucine supplementation alone or combined with semaglutide optimizes body composition in diet-induced obese (DIO) mice.

Reversion to normoglycemia with tirzepatide vs semaglutide in participants with obesity and prediabetes: a post hoc analysis of SURMOUNT-5.

J Endocrinol Invest

Rodolfo J Galindo, Louis J Aronne, Deborah B Horn +8 more

Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study.

J Affect Disord

Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser +1 more

Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability.

Impact of GLP-1 RA plus progestin therapy on fertility-sparing management of endometrial intraepithelial neoplasia and endometrial cancer.

Gynecol Oncol

Tina Yi Jin Hsieh, Ting-Tai Yen, Michele R Hacker +2 more

We examined whether the addition of GLP-1RA to progestin therapy reduced the risk of hysterectomy in patients with endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC) in the U.S. managed with fertility-sparing management.