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peptide science.

Liraglutide for adults living with obesity.

Cochrane Database Syst Rev

Nicolás Meza, Javier Bracchiglione, Camila Micaela Escobar Liquitay +13 more

Obesity is a complex chronic condition linked to various comorbidities, such as hypertension, diabetes, and dyslipidaemia, with a significant global burden. Standard treatments, such as diet modifications and physical activity, often have limited effects and poor compliance. Pharmacological options, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), show promise for individuals with obesity. This is one of three reviews investigating GLP-1RAs for adults living with obesity.

Cardiovascular Disease and COVID-19: Is There a Place for Mid-Regional Pro-Adrenomedullin? Preliminary Data from a Clinical Cohort.

Int J Mol Sci

Paulina Pietraszko, Marcin Żórawski, Emilia Bielecka-Richter +4 more

Mid-regional pro-adrenomedullin (MR-proADM) has emerged as a promising biomarker reflecting endothelial dysfunction and systemic inflammation. Its prognostic role in cardiovascular complications, particularly in the context of COVID-19 infection, remains under investigation. This study aimed to evaluate MR-proADM concentrations in patients with and without cardiovascular disease and COVID-19 and to assess its association with cardiac complications and biomarkers of myocardial injury. A total of 157 patients (mean age: 72.3 years; 66 men) hospitalized in a tertiary referral center were enrolled. The study population consisted of three groups: patients with cardiovascular disease and COVID-19 (n = 64), patients with cardiovascular disease but no COVID-19 (n = 74), and a control group without cardiovascular disease or COVID-19 (n = 17). Plasma MR-proADM levels were measured, and their relationship with cardiovascular complications (chronic heart failure and myocardial infarction) and standard cardiac biomarkers (troponin T, troponin I, and proBNP) was analyzed. The mean MR-proADM concentration in the overall cohort was 91.48 ± 71.96 pmol/L (median: 77.95; range: 5.81-429.20). Distributions of MR-proADM, troponin T (M = 143.12 ± 733.93 ng/L), troponin I (M = 143.37 ± 749.85 ng/L), and proBNP (M = 2080.29 ± 3632.03 pg/mL) deviated significantly from normality (Shapiro-Wilk, all p < 0.001). No significant differences in MR-proADM concentrations were observed between patients with COVID-19 vs. without (93.78 ± 56.94 vs. 92.08 ± 82.82 pmol/L, p = 0.842) and between active infection vs. past COVID-19 (93.78 ± 56.94 vs. 85.98 ± 50.39 pmol/L, p = 0.869). A trend toward higher MR-proADM concentrations was observed in patients with cardiovascular disease compared to those without, with mean levels of 93.56 ± 74.90 vs. 74.33 ± 37.43 pmol/L, respectively. The frequency of chronic heart failure (55.0% vs. 54.5%, p = 1.000) and myocardial infarction (11.3% vs. 20.8%, p = 0.128) did not differ between patients with low vs. high MR-proADM (cut-off: median). Logistic regression confirmed that MR-proADM did not significantly predict either chronic heart failure (Nagelkerke R2 = 0.002, p = 0.660) or myocardial infarction (Nagelkerke R2 = 0.006, p = 0.465). Correlation analysis showed no significant associations between MR-proADM and proBNP (ρ = 0.09, p = 0.323), troponin T (ρ = 0.22, p = 0.065), or troponin I (ρ = 0.16, p = 0.088). MR-proADM levels did not differ significantly between patients stratified by COVID-19 infection or cardiovascular disease and were not predictive of heart failure or myocardial infarction. Moreover, no correlations were found with standard cardiac biomarkers. These results suggest that, in this cohort, MR-proADM did not provide additional prognostic information for cardiovascular complications.

Trametinib-induced Hyponatremia in a Patient With Craniopharyngioma and Diabetes Insipidus.

J Pediatr Hematol Oncol

Buddhi Gunasekara, Harriet Gunn, Arif H B Jalal +2 more

Adamantinomatous craniopharyngiomas (ACPs) are rare, sellar-suprasellar benign tumors that cause considerable morbidity and mortality due to local invasion and treatment-related damage to surrounding structures, including central diabetes insipidus (CDI). Trametinib is a highly selective inhibitor of MEK1 and MEK2, which has been evaluated in both adult and pediatric cancers/ tumors with activation of the oncogenic mitogen-activated protein kinase (MAPK) pathway. Despite being thought to have fewer side effects than conventional cytotoxic chemotherapy, off-target toxicities such as hyponatremia have been described. The use of MEK inhibitors in ACPs are limited to case reports and a phase II trial is currently underway. We report a pediatric patient with multiply progressive ACP and known brittle CDI who developed severe hyponatremia associated with a significant decrease in desmopressin dosing after starting trametinib and a rapid rebound of desmopressin requirement with its cessation. We recommend close monitoring of serum sodium levels and a review of desmopressin doses in patients with CDI when started on treatment with MEK inhibitors.

Differential hypothalamic regulation of FSH and LH secretion from the fish pituitary by GnRH and CCK.

Reproduction

Naama Mizrahi, Miriam Shulman, Tomer Aiznkot +4 more

The hypothalamus-pituitary-gonad axis integrates environmental and internal signals to tune reproductive functions. We hypothesized that in fish, Gnrh predominantly stimulates luteinizing hormone (LH) secretion, while Cck selectively regulates follicle-stimulating hormone (FSH), thereby uncovering a novel role for Cck as a metabolic gatekeeper that links reproductive activity with nutritional status.

The combination of zalfermin and semaglutide has additive therapeutic effects in a diet-induced obese and biopsy-confirmed mouse model of MASH.

PLoS One

Jenny Norlin, Maria Dermit, Nikos Sidiropoulos +7 more

Fibroblast growth factor 21 (FGF21) analogs have significant therapeutic potential in metabolic dysfunction-associated steatohepatitis (MASH) but limited body weight effects in patients with MASH. This study investigated the effect of combined treatment with the FGF21 analog zalfermin and the glucagon-like peptide-1 receptor agonist semaglutide on body weight and plasma and liver biochemistry and histology in a mouse model of MASH. Amylin liver nonalcoholic steatohepatitis diet-induced obese-MASH mice with biopsy-confirmed MASH and fibrosis were administered (subcutaneous [SC], daily [QD]) vehicle, zalfermin (0.05 or 0.2 mg/kg), semaglutide (3 or 120 µg/kg), or zalfermin 0.05 mg/kg + semaglutide 3 µg/kg for 8 weeks (n = 11-12 per group). Vehicle-dosed (SC, QD) chow-fed mice served as normal controls (n = 10). Pre- to post-liver biopsy histology was compared for within-subject evaluation of changes in non-alcoholic fatty liver disease Activity Score (NAS), fibrosis stage, and quantitative histology. Additional endpoints included plasma/liver biochemistry and liver RNA sequencing. Combined low-dose zalfermin and semaglutide treatment resulted in super-additive body weight loss (-18%) vs. individual low-dose monotherapies (zalfermin, -6%; semaglutide, -4%) and was equally effective as high-dose zalfermin monotherapy (-16%) and semaglutide (-15%). Low-dose combination therapy promoted greater benefits on transaminases, total cholesterol and triglycerides, NAS, steatosis, and inflammation vs. individual low-dose monotherapies and high-dose semaglutide, and high-dose zalfermin was as effective as the low-dose combination therapy on most endpoints. Combination treatment reduced gene expression markers of fibrosis to a greater degree than monotherapies. In conclusion, combined low-dose zalfermin and semaglutide, as well as high-dose zalfermin, resulted in beneficial effects on body weight and biochemical and histological endpoints, supporting the clinical development of zalfermin as therapy for patients with MASH.

The Effects of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists on Polycystic Ovarian Syndrome: A Scoping Review.

Cureus

Mia Hudanich, Shannon N Smith, Amanda Marino +1 more

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in reproductive-aged women worldwide; however, treatment modalities often lack cohesion due to its multifactorial pathophysiology. PCOS is suspected of inducing insulin resistance. Research has explored the use of newly developed incretin mimetics as standard therapy for insulin resistance in insulin-dependent tissues associated with PCOS. The aim of this review was to explore the classes of incretin mimetics, such as glucagon-like peptide-1 (GLP-1) receptor agonists or semaglutide, dual agonists of the GLP-1 receptor and gastric inhibitory peptide (GIP) or tirzepatide, and a new triple agonist, or retatrutide (which is currently seeking Food and Drug Administration (FDA) approval), and their suggested benefits as a treatment for PCOS. A literature review was conducted using EBSCO Medline and PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All three classes of incretin mimetics showed significant improvement in weight loss and insulin sensitivity when compared to traditional pharmacological management with metformin and estradiol-progesterone combination pills in patients with PCOS. The added upregulation of GIP in dual-acting and triple-acting agonists, such as tirzepatide and retatrutide, respectively, resulted in greater reductions in weight loss and insulin sensitivity when compared to medications that acted at the GLP-1 receptor alone. Some research demonstrated symptom improvements specific to PCOS presentation, such as dysmenorrhea and the classic dysmorphic ovarian morphology. Further research is warranted to determine the exact mechanism behind how incretin mimetics may improve the hormonal dysregulation in patients with PCOS, as well as how to best use these medications in conjunction with the current standard of care treatments.

Afamelanotide in managing cutaneous phototoxicity in erythropoietic protoporphyria: a Scottish perspective.

Clin Exp Dermatol

Robert S Dawe, Alastair Kerr, Ewan Eadie +3 more

Emerging Perspectives on Gonadotropin Regulation in Vertebrates Revealed by the Discovery of FSH-RH in Teleosts.

Bioessays

Daichi Kayo, Shun Kenny Uehara, Muhammad Rahmad Royan +1 more

Vertebrate gonadal function is regulated by pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones are considered to be regulated by hypothalamic factor(s). Since the discovery of gonadotropin-releasing hormone (GnRH) in mammals, which stimulates the secretion of both FSH and LH, GnRH had been believed to be the sole gonadotropin-releasing hormone in vertebrates for more than 5 decades. However, recent studies have identified an alternative primary regulator of FSH in teleosts, leading to the hypothesis that FSH and LH are regulated by different factors in teleosts (dual GnRH model). This contrasts with the situation in mammals, where a single GnRH regulates both hormones (solo GnRH model). Importantly, although underlying mechanisms likely differ, both teleosts and mammals reproduce efficiently and have convergently evolved similar phenomena, including steroid feedback regulation. In this review, by comparing these taxa, we summarize mechanistic differences and propose an evolutionary scenario based on current experimental evidence.

Paltusotine versus octreotide: different effects on radioligand uptake in neuroendocrine tumours.

Endocr Oncol

Katharina Wang, Christoph J Auernhammer, Simon Lindner +19 more

Somatostatin receptor analogues are well-established in the treatment of metastatic gastro-enteropancreatic neuroendocrine tumours (GEP-NETs), especially for symptom control in patients with the carcinoid syndrome, and to control tumour growth. However, they need to be discontinued before peptide receptor radionuclide therapy (PRRT) as they may saturate the somatostatin receptor 2 (SSTR2) and prevent binding of the radioactive ligand.

Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: A case series.

SAGE Open Med Case Rep

Grant M Tinsley, Spencer Nadolsky

GLP-1 receptor agonists (e.g., semaglutide) and dual GLP-1/GIP receptor agonists (e.g., tirzepatide) are effective for reducing body weight and fat mass, though lean soft tissue loss comprised 26%-40% of weight loss in recent trials. This case series describes three patients (two female, one male; body mass index: 32.9-51.9 kg m-2) who prioritized lean soft tissue preservation strategies during treatment with semaglutide or tirzepatide. Patients engaged in intentional exercise or structured physical activity 4-7 days·week-1, including resistance training 3-5 days·week-1. Typical protein intakes were 0.7-1.7 g·kg-1·day-1 relative to body mass and 1.6-2.3 g·kg-1·day-1 relative to fat-free mass. Changes in weight, fat mass, and lean soft tissue were: -33.0%, -53.4%, and -6.9% (case 1); -26.8%, -61.6%, and +2.5% (case 2); and -13.2%, -46.9%, and +5.8% (case 3). Accordingly, one patient lost 8.7% of weight as lean soft tissue, while two increased lean soft tissue. These findings highlight the potential for some individuals to preserve or even increase lean soft tissue during treatment with semaglutide or tirzepatide alongside supportive lifestyle strategies.

An overview of opioid peptides: Their sources and molecular sequences.

J Opioid Manag

Vishwadeep Asokan, Ariktha M Koundinya, V Aranganathan

Opioid medications have become increasingly prescribed in recent decades due to their sedative and analgesic properties, making them common treatments for pain management. However, prolonged use of these opioids is associated with serious side effects, including respiratory depression, overdose, dependence, and tolerance. In response, research into safer alternatives has focused on opioid-like compounds, particularly endogenous and exogenous opioid peptides, which are produced in the body or derived from the enzymatic digestion of food proteins. These peptides function as neuromodulators, regulating various physiological processes such as pain, emotion, and attachment behavior by interacting with three major G protein-coupled receptors: µ, κ, and δ. Endogenous opioid peptides, such as endorphins, enkephalins, and dynorphins, are generated from precursor molecules through proteolytic cleavage and play key roles in pain modulation and analgesia. Opioid peptides-including both endogenous and exogenous forms from animal or plant sources, as well as synthetic analogs-exhibit complex pharmacology with diverse effects on living systems, often producing complementary or opposing physiological responses. This review highlights significant discoveries regarding the peptide sequences and structural modifications of opioid peptides, emphasizing the need for continued research to fully elucidate their roles in human behavior and their potential as safer therapeutic alternatives to traditional opioids.

Growth Hormone and IGF-1 Actions in the Brain and Neuropsychiatric Diseases.

Physiology (Bethesda)

Manuel H Aguiar-Oliveira, Margaret C S Boguszewski, Diego L Rovaris +1 more

Growth hormone (GH) is secreted by the anterior pituitary gland under the control of hypothalamic neuroendocrine neurons that express somatostatin or growth hormone-releasing hormone (GHRH). Ghrelin, originating primarily in the stomach, is also an important GH secretagogue. GH stimulates the hepatic secretion of insulin-like growth factor-1 (IGF-1) and the expression of IGF-1 in extrahepatic tissues, including the brain. Many regions of the brain express receptors for GH, IGF-1, and ghrelin. In recent decades, evidence from both human and animal studies has indicated that GH, IGF-1, and ghrelin regulate numerous brain functions. Alterations in the secretion or sensitivity to these hormones may represent risk factors for developing neurodegenerative diseases (e.g., Alzheimer's and Parkinson's) and neuropsychiatric conditions (such as depression, anxiety, posttraumatic stress disorder, schizophrenia, and bipolar disorder). Additionally, classical neurodevelopmental disorders such as autism spectrum and attention-deficit hyperactivity disorders may also be influenced by somatotropic hormones. This review aims to summarize and discuss the emerging role of GH and IGF-1 in influencing brain function and the predisposition to brain diseases and neuropsychiatric disorders.

Electroacupuncture alleviates intestinal ischemia-reperfusion-induced acute lung injury via the vagus-sympathetic nerve pathway.

Int Immunopharmacol

Shihua Lv, Can Ma, Wenchao Fu +6 more

Intestinal ischemia-reperfusion (II/R) injury predominantly causes acute lung injury (ALI), and in severe instances, acute respiratory distress syndrome, both associated with high mortality. Electroacupuncture (EA) excels in regulating autonomic nervous system balance and safeguarding organ function. This study delved into EA's impacts and mechanisms on II/R-induced ALI.

Incorporation of Visible Light-Responsive Push-Pull Azobenzene into Polymer Networks toward the Construction of Photodynamic Hydrogel Scaffolds.

ACS Macro Lett

Itsuki Miyaguni, Kenta Homma, Michiya Matsusaki

Forces play vital roles in regulating cellular behavior, and integrins are prime examples that cells use to sense forces. Designer scaffolds have been developed to trigger integrin-mediated mechanotransduction to control cellular functions. However, current scaffolds lack spatiotemporal control of integrin mechanostimulation in a three-dimensional matrix. In this study, a photoresponsive hydrogel scaffold in which a cell-adhesive push-pull azobenzene was covalently loaded onto the hydrogel was synthesized. The cis-trans photoisomerization of azobenzene is expected to mechanostimulate the interaction of integrins with the cell-adhesive peptides (RGD peptide; arginine-glycine-aspartic acid) bound to azobenzene. The photoresponsive behavior of the synthesized azobenzene exhibited a photoresponse immediately after the on-off switching of blue light. The efficient cross-linking of azobenzene-bearing PEG through a click reaction allowed successful cell encapsulation in the azobenzene-bearing hydrogel. Taken together, the photoresponsive hydrogel scaffold is expected to find applications in controlling cellular behaviors in four dimensions via integrin-mediated mechanotransduction.

Prognostic utility of mid-regional pro-adrenomedullin and growth differentiation factor 15 in patients undergoing transfemoral transcatheter aortic valve implantation.

Clin Res Cardiol

Kerstin Piayda, Stanislav Keranov, Luisa Schulz +11 more

Risk prediction in patients with severe, symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) remains an unsolved issue. In addition to classical risk scoring systems, novel circulating biomarkers like mid-regional pro-adrenomedullin (MR-proADM) and growth differentiation factor 15 (GDF-15) may be of value in assessing risk.

Prospects of late-stage development agents in the treatment of metabolic dysfunction-associated steatohepatitis.

Clin Mol Hepatol

Brian Lee, Ussama Ghumman, Lisa D Pedicone +2 more

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a spectrum of pathology involving fatty liver disease that may progress to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The prevalence of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) continues to increase, mirroring the rise in global prevalence of related comorbidities such as obesity and type 2 diabetes mellitus. Due to the alarming rise of these comorbidities, a greater proportion of the population is at risk for developing MASLD and MASH. As such, there has been a significant effort to develop effective therapies for MASLD and MASH. Recently, the U.S. Food and Drug Administration approved resmetirom, a selective thyroid hormone receptor-beta agonist, as the first treatment for patients with MASH. In India, the Drug Controller General of India approved saroglitazar, a dual peroxisome proliferator-activated receptor (PPAR) α/γ agonist, for the treatment of MASLD. Currently, we have various drug classes, including liver-specific therapies, in Phase 3 development with even more agents earlier in the pipeline. This review will discuss prospective therapies in later stages of development such as thyroid hormone receptor-beta agonists, PPAR agonists, glucagon-like peptide-1 receptor agonists, fibroblast growth factor 21 agonists, and fatty acid synthase inhibitors.

Current and Future Implications of Weight Loss Drugs on Liver Disease.

Clin Liver Dis

Arvind Bussetty, Nishali Shah, Toni Marie Chandler +2 more

The disease burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represents an unmet need for pharmacotherapies to halt progression or reverse fibrosis. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are the first to be approved for chronic obesity management and diabetes to be examined in individuals with MASLD/MASH. Successful phase 2 and phase 3 randomized control trials have shown indirect improvements in liver fat, histology, and biomarkers. Over the last few years, newer agents with glucose-dependent insulinotropic peptide agonism and/or glucagon receptor agonism have shown considerable improvements in liver fat content and histology in phase 2 studies. Based on the mounting evidence, single, dual, and triple incretin receptor agonists are promising agents in the treatment of MASLD. In this narrative review, we evaluate weight loss pharmacotherapy for MASLD and then explore the potential for a "positive" disruption that these agents will bring to the existing management of MASLD in patients with obesity.

Investigating the Impact of GNRH1 Polymorphism rs6185 in Women with Polycystic Ovary Syndrome through Association Study, Meta analysis and In silico Study.

J Hum Reprod Sci

Pallvi Thapar, Mandeep Kaur, Sukhjashanpreet Singh +3 more

Hypothalamic pituitary gonadal axis plays a pivotal role in reproductive physiology, and gonadotropin-releasing hormone 1 (GNRH1) is considered to be the candidate gene in the regulation of the hypothalamic-pituitary-gonadal axis. GNRH1 encodes the pre-proprotein that is processed proteolytically to form the peptide GnRH1. Its polymorphisms may involve in the disruption of the luteinising hormone/follicle-stimulating hormone (LH/FSH) ratio and cause polycystic ovary syndrome (PCOS).

Novel progress in the application of the small molecule drug carnosine for the treatment of several diseases (Review).

Int J Mol Med

Chao Fang, Daihan Xie, Lixin Xie +3 more

Carnosine is a dipeptide composed of β‑alanine and L‑histidine, linked by peptide bonds, and is widely distributed in muscle tissue, the central nervous system (including the brain) and various other organs. As an endogenous bioactive molecule, carnosine plays a crucial role in cellular metabolism and physiological regulation. In recent years, advancements in molecular biology, biochemistry and pharmacology have gradually unveiled the multiple biological functions of carnosine, leading to increased interest in its potential applications for disease therapy. Carnosine exhibits considerable antioxidant and anti‑glycation properties, while also demonstrating unique pharmacological effects related to neuroprotection, anti‑inflammatory responses and immune regulation. These attributes position carnosine as a significant intervention with therapeutic value across various pathophysiological processes associated with different diseases. This review systematically summarizes recent progress on the application of carnosine in disease therapy, focusing on its mechanisms of action and therapeutic roles in neurodegenerative diseases, metabolic disorders, cardiovascular diseases, several types of cancer and ophthalmic conditions. By reviewing existing studies on this topic, this review aims to further explore the diversity of carnosine's roles along with potential mechanisms involved in disease treatment. Ultimately, it aims to provide a theoretical foundation and direction for future research.

A Novel GLP-1 and FGF21 Fusion Protein for the Treatment of Non-alcoholic Steatohepatitis (NASH).

Adv Pharm Bull

Zhipeng Zhang, Yanqin Ma, Cheng Xie +5 more

The objective of this study was to develop and produce a novel fusion protein that combines GLP-1 (glucagon-like peptide-1) and FGF21 (fibroblast growth factor 21), with the aim of achieving synergistic pharmacological effects through the targeting of dual pathways, followed by validation of these effects in a non-alcoholic steatohepatitis (NASH) model.