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Stress and obesity signaling converge on CREB phosphorylation to promote pancreatic cancer.
Mol Cancer Res
December 2024
University of California, Los Angeles, Los Angeles, CA, United States.
One of the deadliest types of cancer is pancreatic ductal adenocarcinoma (PDAC). Chronic stress and obesity are recognized as risk factors for PDAC. We hypothesized that the combination of stress and obesity strongly promotes pancreatic cancer development and growth.
View Article and Find Full Text PDFNeurotensin-expressing lateral hypothalamic neurons alleviate neuropathic and inflammatory pain via neurotensin receptor signaling.
Neurobiol Pain
October 2024
Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
Persistent, severe pain negatively impacts health and wellbeing, but half of patients do not receive adequate relief from current treatments. Understanding signals that modulate central pain processing could point to new strategies to manage severe pain. Administering Neurotensin (Nts) or Nts receptor (NtsR) agonists into the brain provides analgesia comparable to pharmacologic opioids.
View Article and Find Full Text PDFProbiotics modulation of the endotoxemic effect on the gut and liver of the lipopolysaccharide challenged mice.
Drug Chem Toxicol
October 2024
Department of Zoology, University of Allahabad, Prayagraj, India.
The multistrain probiotics' efficacy in ameliorating the endotoxemic effect in Lipopolysaccharide (LPS) challenged mice was evaluated with the agonist of anti-inflammatory peptide, neurotensin (NTS), especially targeting the inflammation of the gut and liver. Swiss Albino Mice (Female, 8 weeks old) were maintained in eight groups: Group I as Control, Group II-Group V were exposed to intraperitoneal (i.p.
View Article and Find Full Text PDFThe neurotensin receptor 1 agonist PD149163 alleviates visceral hypersensitivity and colonic hyperpermeability in rat irritable bowel syndrome model.
Neurogastroenterol Motil
December 2024
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Background: An impaired intestinal barrier with the activation of corticotropin-releasing factor (CRF), Toll-like receptor 4 (TLR4), and proinflammatory cytokine signaling, resulting in visceral hypersensitivity, is a crucial aspect of irritable bowel syndrome (IBS). The gut exhibits abundant expression of neurotensin; however, its role in the pathophysiology of IBS remains uncertain. This study aimed to clarify the effects of PD149163, a specific agonist for neurotensin receptor 1 (NTR1), on visceral sensation and gut barrier in rat IBS models.
View Article and Find Full Text PDFDesign, Synthesis, and Characterization of Proteolytically-Stable Opioid-Neurotensin Hybrid Peptidomimetics.
ACS Pharmacol Transl Sci
September 2024
Research Group of Organic Chemistry, Departments of Chemistry and Bioengineering Sciences, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
Linking an opioid to a nonopioid pharmacophore represents a promising approach for reducing opioid-induced side effects during pain management. Herein, we describe the optimization of the previously reported opioid-neurotensin hybrids (OPNT-hybrids), & , containing the μ-/δ-opioid agonist H-Dmt-d-Arg-Aba-β-Ala-NH and NT(8-13) analogs optimized for NTS2 affinity. In the present work, the constrained dipeptide Aba-β-Ala was modified to investigate the optimal linker length between the two pharmacophores, as well as the effect of expanding the aromatic moiety within constrained dipeptide analogs, via the inclusion of a naphthyl moiety.
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