The type-1 parathyroid hormone receptor (PTHR1), which regulates calcium homeostasis and tissue development, has two native agonists, parathyroid hormone (PTH) and PTH-related protein (PTHrP). PTH forms a complex with the PTHR1 that is rapidly internalized and induces prolonged cAMP production from endosomes. In contrast, PTHrP induces only transient cAMP production, which primarily arises from receptors on the cell surface. We show that backbone modification of PTH(1-34)-NH and abaloparatide (a PTHrP derivative) with a single homologous β-amino acid residue can generate biased agonists that induce prolonged cAMP production from receptors at the cell surface. This unique spatiotemporal profile could be useful for distinguishing effects associated with the duration of cAMP production from effects associated with the site of cAMP production.
Introduction: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the progressive degradation of articular cartilage, resulting in pain and reduced mobility. Turmeric ( L.) has been widely recognized for its anti-inflammatory and antioxidant properties, but the molecular mechanisms underlying its therapeutic effects remain inadequately explored.
Secretory diarrhea, a major global health concern, particularly among young children, is often characterized by excessive chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) channel. Nornidulin, a fungus-derived natural product from Aspergillus unguis, has previously been shown to inhibit cAMP-induced Cl- secretion in T84 cells (human intestinal cell lines). However, the cellular mechanism of nornidulin in inhibiting cAMP-induced Cl- secretion and its anti-secretory efficacy is still unknown especially in a human colonoid model, a preclinical model recapitulating intestinal physiology in humans.
Department of Veterinary Anatomy and Pathology, College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, Morogoro, Tanzania.
Background: Brucellosis poses serious public health implications and substantial economic losses in pastoral rural settings in South Sudan. In humans, brucellosis is almost always originating from animals. Current literature provides scant data regarding the seroprevalence of brucellosis in South Sudan.
Department of Breast Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, JXHC Key Laboratory of Tumor Microenvironment and Immunoregulation, Jiangxi Key Laboratory of Tumour Metastasis of Jiangxi Health Commission, Nanchang, China.
Background: Triple-negative breast cancer (TNBC) is a particularly aggressive type of breast cancer, known for its lack of effective treatments and unfavorable prognosis. The G protein-coupled estrogen receptor (GPER), a novel estrogen receptor, is linked to increased malignancy in various cancers. However, its involvement in the metabolic regulation of cancer-associated fibroblasts (CAFs), a key component in the tumour microenvironment, remains largely unexplored.
UCD School of Medicine, UCD Conway Institute, University College Dublin, Dublin 4, Belfield, Ireland; Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin D02 YN77, Ireland. Electronic address:
Hypochlorous acid (HOCl), made by neutrophil-derived myeloperoxidase, has been suggested to inhibit platelets, however, the mechanisms involved have not been described. Here we confirm that HOCl exposure changes platelet morphology and inhibits platelet spreading and aggregation. HOCl effects could be reversed by glutathione suggesting a role for cysteine oxidation.
