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peptide science.
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Exploring the carcinoid crisis: insights from a cancer-specific centre.
Endocr Oncol
Maribel Del Olmo-García, Grace Kong, HuiLi Wong +5 more
To assess the prevalence, pre-procedure biomarkers, and management of carcinoid crisis (CC) in a cancer-specific hospital.
The neuro-cutaneous axis: the role of nerve cells in wound healing.
Biochem Biophys Res Commun
Yijing Zhou, Jin Yang, Lin Chen +2 more
This narrative review summarizes the primary regulatory function of the neurocutaneous axis in wound healing. Hemostasis, inflammation, proliferation, and remodeling are the four phases of skin wound healing. Neurons release neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) along with neurotrophic factors. They initiate vasodilation and promote platelet aggregation during the hemostasis phase, regulate immune cell recruitment and activity during the inflammatory phase, promote keratinocyte migration, fibroblast activation, and angiogenesis during the proliferation phase, and participate in the ordered arrangement of collagen and neural reinnervation during the remodeling phase. Furthermore, the clearance of apoptotic cells by macrophage-mediated phagocytosis couples the resolution of inflammation with the onset of regeneration, forming a closed-loop mechanism through signal contact between the neuro-immune-skin cell network. Along with offering theoretical references for wound regeneration, this paper also examines focused therapeutic approaches such as neuropeptide delivery, the synergistic use of conductive materials and electrical stimulation, and stem cell and gene therapy.
Effect of Weight-Neutral Treatment With Semaglutide or Tirzepatide on β-Cell Identity in db/db Mice.
Acta Physiol (Oxf)
Zhaobin Deng, Dongxu Zheng, Jinsook Son +4 more
Insulin resistance and pancreatic β-cell failure are key characteristics of type 2 diabetes (T2D). Impaired β-cell function is associated with loss of β-cell identity, resulting in β-cell dedifferentiation or trans-differentiation to other endocrine cells. We have shown that β-cell dedifferentiation can be reversed, restoring insulin secretion. The aim of this study was to investigate whether semaglutide or tirzepatide treatment can reverse early stages of β-cell dedifferentiation in db/db mice independent of their effect on body weight.
GLP-1-based therapies for obesity: Impact on comorbidities or obesity-related diseases.
Med Clin (Barc)
Nuria Vilarrasa, Silvia Pellitero
Agents targeting the glucagon-like peptide-1 receptor (GLP-1R) are effective in managing metabolic conditions associated with obesity, such as obstructive sleep apnea (OSA), metabolic dysfunction-associated steatotic liver disease (MASLD), and chronic kidney disease (CKD). In OSA, studies with first generation GLP-1R agonists (ArGLP-1) and co-agonists (GLP-1/GIP) have demonstrated significant improvements in the apnea-hypopnea index and weight reduction. In MASLD, GLP-1RAs and co-agonists (GLP-1/GIP or GLP-1/glucagon) have shown efficacy in reducing hepatic fat, improving fibrosis, and resolving steatohepatitis, with promising results from trials such as ESSENCE and SYNERGY-NASH. In CKD, semaglutide has been associated with a reduction in renal events and slower disease progression. Beyond their metabolic and cardiovascular benefits, these agents represent a comprehensive approach to treating obesity and its complications, with ongoing research exploring their potential indications in chronic inflammatory diseases such as psoriasis and hidradenitis suppurativa.
Treatment and outcome of a boy with lgG4-related hypophysitis caused by SARS-CoV-2 re-infection.
Front Endocrinol (Lausanne)
Hanming Li, Iatlun Leong, Jianyu He
SARS-CoV-2 infection can directly and indirectly affect the nervous system, including the hypothalamus and pituitary, and potentially cause IgG4-related hypophysitis.
Scalable recombinant production of bioactive human neutrophil peptide-1 in Komagataella phaffii.
AMB Express
Mohd Sadeeq, Chaozhi Wang, Ke Yu +5 more
The escalating crisis of antimicrobial resistance demands novel therapeutics that overcome the limitations of conventional antibiotics. Human α-defensins, such as Human Neutrophil Peptide-1 (HNP-1), represent compelling candidates due to their potent, broad-spectrum antimicrobial activity and membrane-disrupting mechanism. However, clinical translation has been hindered by the absence of scalable production systems capable of delivering high yields of functional peptide. To address this challenge, we developed an efficient expression platform in the yeast Komagataella phaffii. In this system, a codon-optimized HNP-1 sequence was fused to a His6-SUMO tag downstream of the α-factor secretion signal to enhance solubility, folding, and recovery. Initial shake-flask optimization identified pH 6.0 with 96 h of induction as optimal fermentation conditions, yielding 19.75 ± 1.1 mg/L of recombinant protein. Subsequent scale-up to a controlled 5 L bioreactor significantly enhanced production, achieving 122 mg/L of the fusion protein. Following purification and precise cleavage, this process delivered 15.25 mg/L of pure, mature HNP-1 representing, to our knowledge, the highest yield of recombinant HNP-1 reported. The final product demonstrated potent antibacterial activity against Staphylococcus aureus and Escherichia coli while exhibiting excellent hemocompatibility, confirming preservation of native structure and function. This work establishes a scalable production platform for HNP-1 and provides an adaptable framework for expressing other structurally complex antimicrobial peptides with therapeutic potential.
Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon.
J Obes
Riad Mohammed Abdelrahman, Taha Hussein Musa, Ismail Adam Arbab +6 more
Obesity has emerged as a pressing global health challenge, and therapies based on glucagon-like Peptide 1 receptor agonists (GLP-1RAs) have transformed its management. Currently, liraglutide, semaglutide, and tirzepatide are FDA-approved for obesity treatment, while other agents are used off-label. These drugs not only provide unprecedented efficacy and acceptable safety in weight reduction and glycemic control for patients with obesity and Type 2 diabetes but also hold promise in broader indications, including neurodegenerative disorders, fatty liver disease, dyslipidemia, atherosclerosis, and cardiovascular conditions.
Family experience with individuals of different ages and clinical presentations diagnosed with DI: do familial DI cases tolerate polyuria better?
J Pediatr Endocrinol Metab
Hakan Birinci, Emrullah Arslan, Tansu Değirmenci +1 more
Familial neurohypophyseal diabetes insipidus (DI) is a rare genetic disorder caused by vasopressin deficiency due to AVP gene mutations. This case report describes the genetic findings and clinical profiles of three generations within a family affected by hereditary central DI and managed with desmopressin.
An Open-Label, Single-Center Proof of Concept Study Evaluating the Efficacy and Safety of Tirzepatide for Moderate to Severe Hidradenitis Suppurativa.
J Drugs Dermatol
Ana Sofia Acosta-Madiedo, Marcela Gutierrez, Martha Gutierrez +2 more
Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with obesity and metabolic dysregulation. Current therapies yield variable benefits and do not target metabolic drivers. Tirzepatide, a dual GLP-1/GIP receptor agonist, induces weight loss and exerts anti-inflammatory effects, offering a potential novel approach for the treatment of HS.
GLP1 and GIP Receptor Agonists: Effects on the Gastrointestinal Tract and Management Strategies for Primary Care Physicians.
Mayo Clin Proc
Bibek Saha, Vijayvardhan Kamalumpundi, Don C Codipilly
Type 2 diabetes and obesity drive significant morbidity, mortality, and health care costs in the United States. Clinicians increasingly prescribe glucagon-like peptide 1 (GLP1) receptor agonists (GLP1-RAs) and dual GLP1 and glucose-dependent insulinotropic polypeptide receptor agonists to treat these and other conditions. However, 40% to 70% of patients experience gastrointestinal adverse effects, such as nausea, vomiting, diarrhea, constipation, delayed gastric emptying, and biliary disease. High-quality studies have not yet confirmed an increased risk of pancreatitis. Management of gastrointestinal symptoms should start with dietary modifications-smaller, more frequent meals; adequate hydration; and avoidance of high-fat or high-sugar foods. If symptoms persist, patients can trial several medications for symptom relief. For patients undergoing elective endoscopy, clinicians should engage in shared decision-making to weigh the risks of continuing vs temporarily discontinuing incretin-based therapies. For endoscopy, GLP1-RA use is associated with a higher incidence of retained gastric contents but not with increased aspiration risk. Long-acting formulations (eg, semaglutide, dulaglutide, and tirzepatide, among others), high doses, procedures during dose escalation, and gastrointestinal comorbidities that delay gastric emptying raise risk of retained gastric contents. In most cases, clinicians can continue GLP1-RAs periprocedurally, although a 24-hour liquid diet may benefit high-risk patients. For colonoscopy, withholding GLP1-RAs may reduce the risk of inadequate bowel preparation, but further research should clarify the magnitude of this risk.
Outcomes of Patients With Familial Central Precocious Puberty due to Mutations of MKRN3 Gene After Treatment With Gonadotropin-Releasing Hormone Agonist.
Int J Endocrinol
Ziwei Chen, Wenying Li, Junqi Wang +7 more
To assess the therapeutic effects of gonadotropin-releasing hormone agonist (GnRHa) on children with familial central precocious puberty (FCPP) due to Makorin ring finger Protein 3 (MKRN3) gene mutations.
Dileucine-supplemented essential amino acids support whole-body anabolism after resistance exercise and serum-stimulated cell-based anabolism.
J Int Soc Sports Nutr
Jonathan A Aguilera, Cassidy T Tinline-Goodfellow, Matthew J Lees +9 more
Essential (EAA) and branched chain (BCAA) amino acid ingestion support whole-body anabolism after resistance exercise and can attenuate markers of postexercise myofibrillar protein breakdown (i.e. urinary 3-methylhistidine; 3MH). Leucine is often considered a primary anabolic EAA through its ability to activate the mechanistic target of rapamycin complex 1 (mTORC1) and stimulate muscle protein synthesis. The dipeptide leucine (dileucine) has been shown to more effectively stimulate myofibrillar protein synthesis than leucine in young males at rest. Therefore, we aimed to determine the effect of a dileucine-containing essential amino acid formula (DIEAA; 2 g dileucine, 1 g leucine, 9.15 g total EAA) on the anabolic and catabolic responses following resistance exercise in young recreationally active adults when compared with ingesting branched chain amino acids (BCAA; 3 g leucine, 1.5 g isoleucine, 1.5 g valine) or isonitrogenous (to DIEAA) collagen hydrolysate (COL).
Concurrent head and neck paragangliomas and pulmonary carcinoid tumor: A rare clinical entity.
Radiol Case Rep
Faria Nisar, Hoo Jung Rhim, Roman Finocchiaro +1 more
We report the first documented case of a 61-year-old female presenting with concurrent multiple head and neck paragangliomas (HNPGLs) and a pulmonary carcinoid tumor, representing an unprecedented association of synchronous neuroendocrine tumors (NETs). This rare coexistence presented unique diagnostic challenges requiring multimodal imaging, including FDG PET-CT, contrast-enhanced CT, MRI, and Cu-64 DOTATATE PET-CT for comprehensive tumor characterization. Management employed a tailored multidisciplinary approach: surgical resection of the dominant carotid body tumor with excellent local control, stereotactic radiation therapy for remaining cervical lesions (45 Gy), and active surveillance with octreotide therapy for the pulmonary carcinoid. At 24-month follow-up, all lesions remained stable with no evidence of progression or new neurological deficits. Despite declining genetic testing, the patient's multiple paragangliomas strongly suggest hereditary predisposition, emphasizing the critical importance of genetic counseling in such presentations. The successful management approach provides a framework for similar complex presentations and highlights the potential for shared molecular mechanisms underlying synchronous neuroendocrine tumorigenesis.
A Systematic Literature Review Exploring the Efficacy and Safety of Tadalafil and Sildenafil in Pulmonary Arterial Hypertension.
Pulm Circ
Rajan Saggar, Nora Rahhali, Assunta Senatore +7 more
Pulmonary Arterial Hypertension (PAH) is a rare, chronic and progressive disease affecting the heart and lungs. Endothelin receptor antagonist (ERA) + phosphodiesterase type 5 inhibitor (PDE5i) treatment is recommended for all PAH patients. The two approved PDE5is are tadalafil and sildenafil. To determine the efficacy and safety outcomes for tadalafil and sildenafil as monotherapies or in combination with ERAs for treating PAH, from randomized controlled trials (RCTs) and real-world evidence studies (RWEs) identified by a systematic literature review (SLR). MEDLINE, Embase and Cochrane Libraries were searched in May 2024. Relevant outcomes included 6-min walk distance (6MWD), pulmonary vascular resistance (PVR) and safety. This report includes studies where patients were treated with either sildenafil or tadalafil. Fifteen RCTs and three RWEs investigated tadalafil (tadalafil 40 mg or 20 mg once daily) or sildenafil (20 mg three times a day). Mean 6MWD change from baseline (CFB) in patients receiving tadalafil or sildenafil monotherapy were comparable, however, in combination with an ERA, tadalafil may be more effective. Generally, there was more data for tadalafil + ERAs, showing marked improvement in mean PVR CFB, compared with patients receiving sildenafil. Conclusions on safety were limited. Risk of bias in RCTs was generally low but moderate in RWEs. Two studies reported patients who switched from sildenafil to tadalafil treatment, treatment transition was feasible. Although comparable when used as monotherapy, this qualitative analysis suggests that tadalafil + ERA combination therapy may have more favorable 6MWD improvements than sildenafil + ERA combination therapy.
Oxytocin: a neglected hormone in pituitary disease - From function to the diagnosis of a deficiency, resulting clinical relevance, and potential treatment options in endocrinology.
Arch Endocrinol Metab
Svenja Leibnitz, Mirjam Christ-Crain, Cihan Atila
Oxytocin (OXT) is a neuropeptide hormone that plays a central role in numerous physiological and socio-emotional processes. Similar to arginine vasopressin (AVP), it is synthesized in the supraoptic and paraventricular hypothalamic nuclei and released both centrally and peripherally. Peripherally, OXT regulates uterine contractions during childbirth and milk ejection during lactation, metabolism, bone health, and cardiovascular functions. Centrally, it modulates social behavior, influencing trust, empathy, stress regulation, and emotional processing. Despite its close connection to AVP, the clinical significance of OXTDeficiency has only recently gained attention, particularly in patients with hypothalamic or pituitary damage with concomitant AVP-Deficiency. OXT-Deficiency may contribute to various neuropsychological symptoms seen in these patients, including social dysfunction, anxiety disorders, and reduced quality of life. However, a major challenge lies in accurately measuring OXT and thereby diagnosing a potential OXT-Deficiency. Basal plasma levels are unreliable, and most studied provocation tests only stimulate to a limited degree; hence, stronger provocation tests (e.g., using MDMA) and new surrogate parameters such as neurophysin I (NP-I) are gaining traction. Preliminary evidence from case reports and one small study suggests that intranasal OXT administration in patients with hypothalamic disorders may have beneficial effects on social behavior and emotion recognition. However, there is a clear need for larger, well-designed clinical trials, and several trials are currently underway to investigate the therapeutic potential of OXT in patients with AVP-Deficiency. OXT is also being explored as a possible treatment option in psychiatric conditions such as autism spectrum disorder, borderline personality disorder, and social anxiety disorder, with controversial results so far.
The Clinical Application of GLP-1RAs and GLP-1/GIP Dual Receptor Agonists Based on Pharmacological Mechanisms: A Review.
Drug Des Devel Ther
Zhao Liu, Shanshan Yu, Xinyan Jin +5 more
This review provides a comprehensive examination of the clinical pharmacological mechanisms and broad therapeutic applications of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual receptor agonists targeting both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. GLP-1RAs exert their effects by stimulating insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite through the activation of the GLP-1 receptor. These agents have demonstrated significant efficacy in the management of type 2 diabetes mellitus (T2DM) and obesity. Moreover, emerging evidence suggests that GLP-1RAs may confer cardiovascular protection, neuroprotective benefits, and positive effects on mental health. Dual GLP-1/GIP receptor agonists, such as tirzepatide, simultaneously activate both receptors, thereby potentiating glycemic control, promoting weight loss, and ameliorating metabolic dysfunction. This review also addresses recent advances in the development of other dual and triple receptor agonists. Distinct from prior reviews that predominantly focus on a single drug class or limited clinical indications, this article systematically contrasts the mechanistic pathways, therapeutic efficacy, and safety profiles of GLP-1RAs versus GLP-1/GIP dual receptor agonists. Notably, it integrates the most current evidence pertaining to novel domains, such as perioperative management, neuropsychiatric outcomes, and the innovation of multi-receptor agonists. This synthesis offers a timely and practical resource to inform clinical precision medicine and to guide future investigative efforts.
The Sustained Effects of Bioactive Collagen Peptides on Skin Health: A Randomized, Double-Blind, Placebo-Controlled Clinical Study.
J Cosmet Dermatol
Yu Wang, Weixing Zhu, Wenyu Luo +2 more
Collagen is a fundamental component of the skin's extracellular matrix, yet its low oral bioavailability raises questions about its efficacy in improving skin health. Bioactive collagen peptides (BCP), as hydrolyzed forms of collagen, offer enhanced absorption and functionality. However, evidence regarding their sustained effects and the impact of molecular weight distribution is still limited.
Efficacy and Safety of PRaG Therapy in Elderly Patients with Advanced Malignant Tumors: A Prospective, Multicenter Clinical Study Protocol (PRaG 9.0 Study).
Technol Cancer Res Treat
Xiangrong Zhao, MengMeng Yang, Junjun Zhang +8 more
Background: Current evidence from evidence-based medicine is limited regarding the efficacy and safety of immunotherapy in elderly patients aged 75 years and older with malignant solid tumors. PRaG therapy, which combines PD-1/PD-L1 inhibitors, radiotherapy, and granulocyte-macrophage colony-stimulating factor (GM-CSF), aims to treat patients with advanced, refractory tumors. Preliminary findings indicate that patients aged 75 years and older can benefit from this treatment and can tolerate it well. Objective: This study aims to evaluate the efficacy and safety of the PRaG regimen in elderly patients with advanced malignant solid tumors to provide evidence-based support for immunotherapy in this population. Methods and Analysis: This study involves a multicenter, prospective, single-arm phase II clinical trial designed to enroll 29 patients aged 75 years and older with either newly diagnosed or recurrent metastatic advanced solid tumors that are histologically confirmed. All of the eligible patients will have had to receive at least two cycles of PRaG therapy until disease progression or intolerable adverse effects occurred. The study protocol was approved on September 12, 2023, by the Ethics Committee of the Second Affiliated Hospital of Soochow University (JD-LK-2023-082-I01) and by the ethics committees of all of the participating centers (Trial Registration Number: NCT06112041).
Dietary Copper on the Onset of Puberty in Rats: Possible Mechanism.
Nutrients
Rui Sun, Zhongshen Wang, Cheng Li +3 more
Background/Objectives: Copper is an essential trace element for physiological processes related to reproduction, but its impact on the hypothalamic-pituitary-ovarian (HPOA) axis and its specific mechanism remain unclear. Methods: In vivo study: 21-day-old female Sprague Dawley (SD) rats were randomly assigned to five groups (n = 10 per group), with all groups fed a basal diet and supplemented with CuSO4·5H2O to achieve copper ion concentrations of 0, 15, 30, 45, or 60 mg/kg in the diet. During the second phase of proestrus, blood samples, hypothalamic tissues, pituitary tissues, and ovarian tissues were collected. In vitro study: Primary mixed hypothalamic neurons were isolated and cultured from fetal SD rats on embryonic day 17. After identification by NSE immunofluorescence staining, six copper ion concentration groups (0, 15.6, 31.2, 46.8, 62.4, and 78 μmol/L) were established. The optimal copper concentration for cell viability and GnRH secretion was screened using CCK-8 assay (Sangon, Shanghai, China) and ELISA (Mlbio, Shanghai, China). On this basis, the cells were treated with different concentrations of PKC agonist (PMA) and PKC inhibitor (chelerythrine). Cell viability was evaluated by CCK-8 assay, the expression level of PKC was detected by Western blot, and the optimal concentration with no obvious toxicity was selected for subsequent mechanism research. Results: Dietary copper dose-dependently regulated rat puberty onset; the 45 mg/kg copper group had the earliest onset, and showed significantly increased levels of reproduction-related hormones (GnRH, FSH, LH, E2) in serum and HPOA axis. Hypothalamic transcriptomics revealed significantly enriched GnRH signaling pathways and GABAergic synaptic pathways. Mechanistically, this copper dose upregulated hypothalamic KISS-1, GPR54, and PKC (mRNA/protein), and downregulated GABA/GABA-R. Adding 46.8 μmol/L copper (as Cu2+, equivalent to optimal in vivo level) could activate the KISS-1/GPR54-GnRH system in hypothalamic neurons; regulating PKC activity could synchronously affect the expression of KISS-1, GPR54, GnRH, and GABA/GABA-R, with additional copper enhancing this effect in vitro experiments. Conclusions: This study demonstrates for the first time that dietary copper at 45 mg/kg promotes puberty onset in SD rats. The mechanism involves activation of the hypothalamic PKC pathway, which inhibits GABAergic neurotransmission while activating the KISS-1/GPR54-GnRH system, thereby enhancing HPOA axis activity and gonadotropin secretion.
Nutritional Supplements for Muscle Hypertrophy: Mechanisms and Morphology-Focused Evidence.
Nutrients
Andreea Maria Mănescu, Simona Ștefania Hangu, Dan Cristian Mănescu
Nutritional supplementation is widely used in resistance training, yet assessment of "hypertrophy" is often confounded by body-composition surrogates. This narrative review, anchored in mechanistic plausibility, integrates trials reporting morphology-direct outcomes (ultrasound/MRI). Across 46 eligible trials, protein/essential amino acids (EAA) showed consistent benefits when daily intake was <1.6 g·kg-1·day-1 or when per-meal leucine provision was <2-3 g; effects plateaued once intakes exceeded ~2.0 g·kg-1·day-1. Creatine monohydrate (3-5 g·day-1, with or without loading) produced measurable increases in muscle thickness or cross-sectional area in interventions lasting ≥8-12 weeks, mediated by enhanced training volume and quality. β-hydroxy-β-methylbutyrate (HMB, 3 g·day-1) demonstrated conditional utility during high training stress or caloric deficit, but was largely neutral in well-fed, resistance-trained cohorts. Adjuncts such as omega-3 fatty acids (1-2 g·day-1), citrulline (6-8 g pre-exercise), and collagen (10-15 g·day-1 plus vitamin C) primarily facilitated training tolerance, recovery, or connective-tissue adaptation, rather than driving hypertrophy directly. A tiered model is proposed: protein/EAA as the foundation, creatine as amplifier, HMB as conditional agent, and adjuncts as facilitators. Methodological heterogeneity, short intervention length, and inconsistent imaging protocols remain limiting factors, underscoring the need for standardized ultrasound/MRI and adequately powered, preregistered trials.