Objective: To provide evidence that iNOS expression solely in leukocytes plays a role in postoperative ileus.
Summary Background Data: Intestinal handling initiates a molecular and cellular muscularis inflammation that has been associated with iNOS expression and ileus. The specific cellular source of iNOS is a matter of speculation.
Methods: Chimeric mice were constructed that selectively express the iNOS gene only in their leukocytes or only in their parenchymal cells by lethal radiation and reconstitution with reciprocal bone marrow. Mild intestinal manipulation was used to induce postoperative ileus.
Results: Intestinal manipulation caused a significant leukocyte extravasation into the muscularis of all groups. Postoperative iNOS mRNA expression was evident in iNOS and transplanted iNOS mice with iNOS bone marrow but not in iNOS animals. The loss of the iNOS gene in leukocytes of iNOS mice reduced iNOS mRNA expression by 59%. iNOS-deficient mice and iNOS animals with iNOS leukocytes presented with a significant improvement in postoperative intestinal transit and in vitro smooth muscle contractility, whereas the replacement with iNOS bone marrow in iNOS mice completely reversed this improvement.
Conclusion: These results clearly show that iNOS expressed in leukocytes within the intestinal muscularis plays a major role in mediating smooth muscle dysfunction and subsequently postoperative ileus.
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http://dx.doi.org/10.1097/01.sla.0000229963.37544.59 | DOI Listing |
Neuroscience
January 2025
Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address:
Background: The mechanisms underlying esketamine's therapeutic effects remain elusive. The study aimed to explore the impact of single esketamine treatment on LPS-induced adolescent depressive-like behaviors and the role of Nrf2 regulated neuroinflammatory response in esketamine-produced rapid antidepressant efficacy.
Methods: Adolescent male C57BL/6J mice were randomly assigned to three groups: control, LPS, and LPS + esketamine (15 mg/kg, i.
Bioorg Chem
December 2024
Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
Ursolic acid (3-hydroxy-urs-12-ene-28-oic acid, UA) is a pentacyclic triterpene present in numerous plants, fruits and herbs and exhibits various pharmacological effects. However, UA has limited clinical applicability since it is classified as BCS class IV molecule, characterized by low solubility, low oral bioavailability and low permeability. In the present study, UA was isolated from the biomass marc of Lavandula angustifolia and was structurally modified by an induction of indole ring at the C-3 position and amide group at the C-17 position with the aim to enhance its pharmacological potential.
View Article and Find Full Text PDFMar Pollut Bull
January 2025
Molecular Invertebrate Systematics and Ecology Laboratory, Faculty of Science, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan; Tropical Biosphere Research Center, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan. Electronic address:
The coastline of Okinawa Island, Japan, has been affected by human-made alterations for decades, often from land reclamation and coastal defense construction. Here, we use an Imperial Japanese Army map made between 1919 and 1921 to describe the composition of the Okinawan coastline approximately 100 years ago, and by overlapping this old map with a modern-day map of Okinawa (2018), we identified 131 sites where coastlines showed clear human-made alterations. For these sites, we examined what kinds of ecosystems were lost and what has replaced them.
View Article and Find Full Text PDFCytokine
January 2025
College of technical engineering, the Islamic University, Najaf, Iraq; College of technical engineering, The Islamic University of Al Diwaniyah, Diwaniya, Iraq; College of technical engineering, The Islamic University of Babylon, Hillah, Iraq.
Inflammation, driven by various stimuli such as pathogens, cellular damage, or vascular injury, plays a central role in numerous acute and chronic conditions. Current treatments are being re-evaluated, prompting interest in naturally occurring compounds like kaempferol, a flavonoid prevalent in fruits and vegetables, for their anti-inflammatory properties. This study explores the therapeutic potential of kaempferol, focusing on its ability to modulate pro-inflammatory cytokines and its broader effects on inflammatory signaling pathways.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
PCM Consulting, Pathways Connectivity Maps Inc., Mountain View, CA, USA.
Background: High-throughput assays have attracted significant attention in Alzheimer's Disease (AD) research, especially for enabling rapid diagnostics screening for factors at the molecular level contributing to the disease recurrence. With advances in laboratory automation, there is a growing need for quality pre-clinical data. Assays such as Microarrays, Proteomics, or AI are all dependent on high-quality input data that serve as a starting point.
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