Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 148 - 148

Published: Jan. 23, 2025

Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of cannabinoid 1 (CB1) receptor, part endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in murine model dextran sodium sulphate (DSS)-induced Methods: Acute was induced 4% DSS 7 days, followed by 3 days water. Chronic modelled over 24 alternating concentrations. The combination 2.5 mg/kg 20 10 evaluated. Key markers were assessed determine efficacy safety, including activity index (DAI), inflammation, cytokine levels, GLP-1, organ health. Results: DSS-induced resulted increased DAI scores, cytokines, inflammation dysregulation GLP-1 ammonia. at significantly improved but ineffective 5 mg/kg. alone showed transient effects. However, either alleviated markers, restored colon integrity reestablished homeostasis. also maintained favourable haematological biochemical profiles, notable reduction colitis-induced elevated ammonia levels. Conclusions: demonstrates synergistic potential low-dose combined as novel, effective safer therapeutic strategy ulcerative

Language: Английский

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Metabolic Crosstalk between Liver and Brain: From Diseases to Mechanisms

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7621 - 7621

Published: July 11, 2024

Multiple organs and tissues coordinate to respond dietary environmental challenges. It is interorgan crosstalk that contributes systemic metabolic homeostasis. The liver brain, as key organs, have their unique dialogue transmit messages. interconnected pathogenesis of brain implicated in numerous neurodegenerative disorders. Recent insights positioned the not only a central hub but also an endocrine organ, capable secreting hepatokines signals throughout body via bloodstream. Metabolites from or gut microbiota facilitate complex between brain. In parallel humoral factors, neural pathways, particularly hypothalamic nuclei autonomic nervous system, are pivotal modulating bilateral interplay cerebral hepatic compartments. term “liver–brain axis” vividly portrays this interaction. At end review, we summarize cutting-edge technical advancements enabled observation manipulation these signals, including genetic engineering, molecular tracing, delivery technologies. These innovations paving way for deeper understanding liver–brain axis its role

Language: Английский

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Ai-Driven Discovery of Brain-Penetrant Galectin-3 Inhibitors for Alzheimer's Disease Therapy

Published: Jan. 1, 2025

Language: Английский

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Use of machine learning algorithms and NMR metabolomics to identify potential serum biomarkers in patients with amnestic mild cognitive impairment

Journal of Radiation Research and Applied Sciences, Journal Year: 2025, Volume and Issue: 18(1), P. 101278 - 101278

Published: Jan. 13, 2025

Language: Английский

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Association of objective subtle cognitive difficulties with amyloid-β and tau deposition compared to subjective cognitive decline

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Language: Английский

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Association between plasma short-chain fatty acids and inflammation in human immunodeficiency virus-associated neurocognitive disorder: a pilot study

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 21, 2025

Short-chain fatty acids (SCFAs), key metabolites produced by gut microbiota, have neuroprotective effects in neurodegenerative diseases modulating immune responses. However, their role human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains largely unexplored. We recruited HAND patients, HIV Control, and healthy controls (HC). Plasma SCFAs SCFA-producing microbiota were quantified via gas chromatography-mass spectrometry fecal metagenomic analysis. Inflammatory cytokine levels measured using liquid chromatography. Receiver operating characteristic (ROC) curves generated to evaluate the predictive accuracy of for HAND. significantly reduced correlating with a decrease bacteria, such as Prevotella its related species. Reduced positively correlated pro-inflammatory cytokines cognitive impairment, while being negatively anti-inflammatory cytokines. ROC curve analysis demonstrated that several exhibited strong status. may influence function inflammatory responses, identifies plasma potential biomarkers therapeutic targets Further investigation is needed delineate mechanisms pathology.

Language: Английский

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Tau pathology is associated with postsynaptic metabotropic glutamate receptor 5 (mGluR5) in early Alzheimer's disease in a sex‐specific manner

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION To investigate the associations of metabotropic glutamate receptor 5 (mGluR5) with tau deposition and cognitive ability in patients early Alzheimer's disease (AD). METHODS Twenty‐six cognitively impaired (CI) 14 unimpaired (CU) individuals underwent mGluR5 positron emission tomography (PET) ([ 18 F]PSS232), amyloid PET F]florbetapir), F]MK6240), neuropsychological assessment. The relationships among availability, deposition, assessment were analyzed using Spearman's correlation mediation analyses. RESULTS CI had lower hippocampus than CU (standardized uptake value ratio [SUVr]: 2.03 ± 0.25 vs 1.79 0.17, p = 0.003). Hippocampal was negatively associated hippocampal ( r −.46, 0.003) positively performance, but only women. mediated effect on performance. DISCUSSION Reduced is related most cortical regions making it a promising biomarker for AD diagnosis therapy. Highlights Cognitively exhibited availability subjects. widespread cortex. close association cognition performance exists females. Tau pathology relationship between cognition.

Language: Английский

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Targeting the Endocannabinoidome: A Novel Approach to Managing Extraintestinal Complications in Inflammatory Bowel Disease

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 478 - 478

Published: March 27, 2025

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder marked by persistent gastrointestinal inflammation and spectrum of systemic effects, including extraintestinal manifestations (EIMs) that impact the joints, skin, liver, eyes. Conventional therapies primarily target intestinal inflammation, yet they frequently fail to ameliorate these complications. Recent investigations have highlighted complex interplay among immune system, gut, nervous system in IBD pathogenesis, thereby underscoring need for innovative therapeutic approaches. Methods: We conducted comprehensive literature search using databases such as PubMed, Scopus, Web Science, Science Direct, Google Scholar. Keywords “cannabinoids”, “endocannabinoid system”, “endocannabinoidome”, “inflammatory disease”, “extraintestinal manifestations” were used identify peer-reviewed original research review articles explore role endocannabinoidome (eCBome) IBD. Results: Emerging evidence suggests eCBome—a network comprising lipid mediators, receptors (e.g., CB1, CB2, GPR55, GPR35, PPARα, TRPV1), metabolic enzymes—plays critical modulating responses, maintaining gut barrier integrity, regulating inflammation. Targeting eCBome not only improves but also appears mitigate metabolic, neurological, complications arthritis, liver dysfunction, dermatological disorders. Conclusions: Modulation represents promising strategy management addressing both local components. These findings advocate further mechanistic studies develop targeted interventions leverage novel avenue

Language: Английский

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Effectiveness of Lignocellulose Nanofibers (LNCFS) for removing nitrite, nitrate, and phosphate from Gamishan wastewater

Aquaculture Reports, Journal Year: 2025, Volume and Issue: 42, P. 102777 - 102777

Published: March 29, 2025

Language: Английский

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The bile acid profile

Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 565, P. 120004 - 120004

Published: Oct. 16, 2024

Language: Английский

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