urocortin II (NBI-69734) / Renova Therap - LARVOL DELTA

Urocortin2 measurement for heart failure assessment. (PubMed, Sci Rep) - "The assay showed that blood UCN2 values indicated a negative relationship with cardiac ejection fraction in 52 patients with heart failure. Blood UCN2 levels were not correlated with brain natriuretic peptide, a standard marker of heart failure, and were higher in patients with cardiomyopathy than in those with heart failure, suggesting that measuring blood UCN2 levels may be a novel test for assessing the pathophysiology of heart failure."

Biomarker • Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • GPRC6A • NPPB

Carexyankouensis, a new species of Cyperaceae from limestone landform in northern Guangdong, China. (PubMed, PhytoKeys) - "The new species is similar to C.brevicuspis C. B. Clarke, but differs in having shorter culms (10-15 cm vs 20-55 cm) and spikes (1-1.5 cm vs 3.7-7 cm), leaves wider (15-20-35 mm vs 5-10 mm) and lighter colored (pale green or yellow-green vs dark green), nutlet beak oblique (vs erect or slightly curved), and slightly thickened (vs thickened) style base. Following the IUCN Red List Criteria (IUCN 2024), Carexyankouensis is assessed as 'Data Deficient (DD)'."

Journal

Electroacupuncture Improves the Motor Function in Rats with Spinal Cord Injury by Regulating UCN2-Mediated cAMP-PKA Signaling in the Spinal Cord Microenvironment. (PubMed, Cell Mol Neurobiol) - "This process improves the presence of astrocytes and microglia around the injury site, inhibits neuronal apoptosis, and increases the number of myelin sheaths and NF. As a result, hind-limb locomotor ability is restored in rats with SCI."

Journal • Preclinical • CNS Disorders • Orthopedics • MBP

Osmoregulatory contributions of the corticotropin-releasing factor system in the intestine of Atlantic salmon. (PubMed, J Exp Biol) - "Similar increases in UCN2 and CRFR2 were observed following seawater to freshwater transfer of post-smolts. Our results indicate that the intestinal CRF system of Atlantic salmon contributes to osmoregulation during the initial days following changes in environmental salinity and that osmoregulatory actions of the intestinal CRF system are conserved across vertebrates."

Journal

Suppression of luteinizing hormone secretion in female mice by a Urocortin 2 - CRHR2 signaling pathway. (PubMed, Endocrinology) - "Together these data demonstrate that UCN2-CRHR2 signaling disrupts the pulsatile and surge modes of LH secretion via direct suppression of kisspeptin cells. Furthermore, these findings suggest UCN2 cells in the PVN are regulated by metabolic stress and brainstem norepinephrine signaling pathways that convey stress cues to the hypothalamus."

Journal • Preclinical • Hypoglycemia • FOS

Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders. (PubMed, Molecules) - "This review examines 10 antimicrobial neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), ghrelin, adrenomedullin (AM), neuropeptide Y (NPY), urocortin II (UCN II), calcitonin gene-related peptide (CGRP), substance P (SP), and catestatin (CST). Their expression characteristics and the immunomodulatory mechanisms mediated by their specific receptors are summarized, along with potential drugs targeting these receptors. Future studies should focus on further investigating antimicrobial neuropeptides and advancing the development of related drugs in preclinical and/or clinical studies to improve the treatment of immune-related diseases."

Journal • Review • Immunology • ADCYAP1 • ADM

The effects of corticotropin-releasing factor (CRF) and urocortins on the serotonin (hydroxytryptamine, 5HT) released from the raphe nuclei (RN). (PubMed, Neuropeptides) - "Corticotropin-releasing factor (CRF) and urocortins (UCN1, UCN2 and UCN3) belong to the same CRF family of neuropeptides...Our results indicate the existence of two apparently opposing CRF systems in the RN: activation of CRF1 by CRF and UCN1 may inhibit, whereas activation of CRF2 by UCN3 may stimulate the 5HT release. The dysbalance between CRF1 and CRF2 activation and, consequently, alteration of serotoninergic signalling may result in anxiety and depression, associated with hyperactivity of the HPA axis."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Mesoporous NiFe2O4@g-C3N4-based p-n Heterostructures for Boosting Solar-Driven Photocatalytic Dye Degradation and Hydrogen Evolution. (PubMed, Chem Asian J) - "Notably, mp-NiF@uCN-20% with 1.0 wt% of Pt loading achieves the highest H2 evolution rate of 2294 µmolg⁻¹h⁻¹, which is 3.72, 1.52, and 13.49 times higher than that of pure CN, p-uCN, and NiFO, respectively...Further, the magnetic nanocomposite exhibits remarkable stability even after multiple runs, indicating their reusability. The experimental findings emphasize the importance of p-n heterojunctions, interfacial band alignment, and mesoporous architecture in enhancing the photocatalytic efficiency of NiFe2O4@g-C3N4 nanocomposites."

Journal

Regulation and function of the gill corticotropin-releasing factor system during osmoregulatory disturbances in Atlantic salmon. (PubMed, J Exp Biol) - "Most CRF system components were expressed in the gills with CRF receptor 2 (crfr2a), CRF binding protein (crfbp1 and crfbp2), and urocortin 2 (ucn2a) being the most abundant...Indeed, activation of the CRF system in cultured filaments from freshwater-acclimated (but not seawater-acclimated) salmon had transcriptional effects on several physiological systems (e.g., endothelial permeability, angiogenesis, and immune regulation) which involved contributions by both CRF receptor subtypes. Overall, our results indicate that the gill CRF system is more active in hypoosmotic environments and directly contributes to the coordination of physiological responses following osmotic disturbances."

Journal

Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease. (PubMed, Front Immunol) - "This review systematically examines 12 neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), orexin-B (ORXB), ghrelin, substance P (SP), adrenomedullin (AM), calcitonin-gene related peptide (CGRP), urocortin-II (UCN II), neuropeptide Y (NPY), NDA-1, and catestatin (CST), identified for their antimicrobial properties, summarizing their structural features, antimicrobial effectiveness, and action mechanisms...However, the connection between this anti-inflammatory property and the brain's infection defense strategy has rarely been explored. Our review suggests that the combined antimicrobial and anti-inflammatory actions of neuropeptides could be integral to the brain's defense strategy against pathogens, marking an exciting direction for future research."

Journal • Review • Infectious Disease • Inflammation • ADCYAP1 • ADM

A novel Urocortin-2 analog COR-1167 corrects cardiac and renal dysfunction on top of Empagliflozin in a rat model of acute decompensated heart failure (AHA 2024) - "Introduction: Urocortin-2 (UCN-2) is a peptide belonging to the corticotropin-releasing factor family that has cardiovascular, renal, metabolic and anti-inflammatory actions and improves cardiac function in human heart failure (HF) and cardiorenal dysfunction in chronic HF models. In the setting of ADHF, significant cardiorenal benefits and decongestion occurred when COR-1167 was administered on top of an SGLT2 inhibitor."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Single Intranasal Administration of Ucn3 Affects the Development of PTSD Symptoms in an Animal Model. (PubMed, Int J Mol Sci) - "The aim of this work was to investigate how intranasal administration of the CRHR2-specific agonist urocortin 2 (Ucn2) or urocortin 3 (Ucn3) affects manifestations of PTSD in a single prolonged stress (SPS) animal model of PTSD...We demonstrate that Ucn3 has the potential to ameliorate anxiety-like behavior in SPS animals and also to affect the neuroendocrine system in the BNST and PVN. In addition, we confirm the important role of CRHR2 signaling in mediating the stress response."

Journal • Preclinical • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • FKBP5

The effects of corticotropin-releasing factor (CRF) and urocortins on the noradrenaline (NA) released from the locus coeruleus (LC). (PubMed, Peptides) - "In addition, UCN2, but not UCN3, decreased significantly the tritium-labelled NA release from the LC, and this effect was reversed by astressin2B, but not antalarmin. Our results indicate the existence of two apparently opposing CRF systems in the LC, since activation of CRF1 by CRF and UCN1 stimulated, whereas activation of CRF2 by UCN2 inhibited the NA release."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Long-acting CRF2 receptor agonist, COR-1389, improves cardiopulmonary function in the rat model of Sugen plus hypoxia-induced pulmonary hypertension and right heart failure (AHA 2024) - "Introduction: Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors... These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF."

Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

The CRF/Urocortin systems as therapeutic targets for alcohol use disorders. (PubMed, Int Rev Neurobiol) - "The CRF/Ucns system is comprised of a family of peptides (CRF, Ucn 1, Ucn 2, Ucn 3) which act upon two receptor subtypes, CRFR1 and CRFR2, each with different affinity profiles to the endogenous peptides and differential brain distribution...Finally, the limited translational value of CRF/Ucn interventions in stress-related and alcohol use disorders is discussed. So far, CRFR1 antagonists have shown little or no efficacy in human clinical trials, although a range of unexplored conditions and possibilities remain to be explored."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Transcriptomic analysis of embryonic mouse hypothalamic N38 cells exposed to high-energy protons and/or simulated microgravity. (PubMed, Heliyon) - "Notably, the expressions of UCN2 and UGT1A5 genes were upregulated in all three experimental groups, suggesting a shared regulatory mechanism with potential consequences for brain function during space missions...The present study on mHypoE-N38 cells exposed to space environments revealed a complex molecular narrative with disease-oriented implications. The knowledge gained might serve as a cornerstone for developing strategies to mitigate potential health risks associated with extended exposure to space-related stressors."

Journal • Preclinical

Combining HM17321 and Incretins Augments Fat Loss and Preserves Lean Mass in Mouse Model of Obesity (OBESITY WEEK 2024) - "Urocortin-2 (UCN2) is a selective corticotropin-releasing factor receptor 2 (CRFR2) agonist and has been shown to reduce fat mass while simultaneously promoting muscle hypertrophy... C57BL/6 mice fed a HFD were subcutaneously injected with HM17321 alone or in combination with incretin-based drugs including HM15275 (a GLP-1/GIP/GCG triple agonist), semaglutide and tirzepatide for 4 weeks... Combining HM17321 with incretin-based drug led to additional fat reduction while preserving lean mass compared to incretin alone, suggesting improved body composition during weight loss. Thus, HM17321 could be a therapeutic option along with incretin-based drugs for healthy weight loss."

Preclinical • Genetic Disorders • Obesity • GCG

Discovery and Nonclinical Characterization of a Novel CRFR2 Selective and Biased UCN2 Analog, HM17321, for High Quality Weight Management (OBESITY WEEK 2024) - "HM17321, a novel long-acting CRFR2-selective and biased UCN2 analog, is capable of reducing fat mass and increasing lean mass in DIO mice. These data suggest that HM17321 deserves to be developed as stand-alone therapy as well as incretin COMBO for high quality weight management. Human relevance of these findings warrants further research."

Prediction of clear cell renal cell carcinoma prognosis based on an immunogenomic landscape analysis. (PubMed, Heliyon) - "Fifteen IRGs (CCL7, CHGA, CMA1, CRABP2, IFNE, ISG15, NPR3, PDIA2, PGLYRP2, PLA2G2A, SAA1, TEK, TGFA, TNFSF14, and UCN2) were identified as prognostic IRGs associated with overall survival and were used to construct a prognostic model...Additionally, we developed a nomogram containing the model and clinical characteristics with high prognostic potential. By systematically examining the sophisticated regulatory mechanisms, molecular characteristics, and prognostic potential of ccRCC immune interactions, we provided an important framework for understanding the molecular mechanisms of ccRCC and identifying new prognostic markers and therapeutic targets for future research."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CHGA • CRABP2 • NPR3 • PDIA2 • PLA2G2A • SAA1 • TNFSF14

Identification of novel CRHR2 antagonists (ACS-Fall 2024) - "Its endogenous peptide ligands urocortin2 (Ucn2) and urocrtin3 (Ucn3) are known to be involved in chronic heart failure and metabolic disease such as diabetes...We will also present SAR analysis, ADMET profile, and PK profile of the RQ-00490721 analogs. Additionally, we will present advanced compounds towards a preclinical candidate."

Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

A New Method for Low Density Distribution Modeling and Near Threatened Species: The Study Case of Plectrohyla Guatemalensis. (PubMed, Bull Math Biol) - "We address challenges in modeling species that are seldom observed in nature, for example species included in The International Union for Conservation of Nature's Red List of Threatened Species (IUCN 2023)...Drawing inspiration from quantum mechanics, we incorporate quantum Hamiltonians into classical statistical mechanics (i.e. Gibbs measures or Markov random fields). The equilibrium between spreading and attractive/repulsive forces governs the behavior of the species, expressed through a global control problem involving an energy operator."

Journal

Is Urocortin 2 A Mediator Of Stress-induced Suppression Of The Luteinizing Hormone Surge? (ENDO 2024) - "The PVN initiates activation of Corticotropin Releasing Hormone (CRH) neurons and, in addition to CRH, the PVN contains a population of neurons expressing Urocortin 2 (UCN2), a CRH-like family member, with high affinity for CRH receptor 2...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO."

Late-breaking abstract • Infertility • Sexual Disorders • FOS • UCN

COR-1167, a new long-acting CRF2 receptor agonist, decreases congestion by improving cardiorenal function in a sheep model of worsening heart failure (WHF) (HEART FAILURE 2024) - "Background: Urocortin-2 (UCN-2) has cardiovascular (CV) protective effects mediated via activation of the corticotrophin releasing factor type 2 (CRF2) receptors. CRF2 agonist COR-1167 on top of furosemide reduced elevated cardiac and venous pressures, increased fluid loss and decreased BW and improved renal function in a HF model, even under conditions of fluid overload and represents a promising new treatment for WHF."

Cardiovascular • Congestive Heart Failure • Heart Failure

Urocortin-2 as a novel biomarker of clinical deterioration in HFpEF: a prospective cohort study (HEART FAILURE 2024) - "In patients with HFpEF, it was observed that serum Ucn2 levels were correlated with left chamber remodeling and adverse prognosis, particularly with clinical signs of congestion. These findings provide evidence for the potential pathophysiological role of this peptide and suggest its usefulness as a circulating biomarker for HFpEF."

Biomarker • Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

Role of CRH in colitis and colitis-associated cancer: a combinative result of central and peripheral effects? (PubMed, Front Endocrinol (Lausanne)) - "Corticotropin-releasing factor family peptides (CRF peptides) comprise corticotropin releasing hormone (CRH), urocortin (UCN1), UCN2 and UCN3...However, up to date, there still exist not many relevant experimental data on this topic, and there seems to be no absolute clearcut between the central and direct peripheral effects of CRH in colitis and colon cancer. Taken together, CRH, as a critical factor in stress and immunity, may participate in colitis and CAC as a centrally active molecule; meanwhile, CRH has direct peripheral effects regulating the development of colitis and CAC, both of which will be summarized in this review."

Journal • Review • Colon Cancer • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Immunology • Oncology • Solid Tumor