Hyperglycemic environments directly compromise intestinal epithelial barrier function in an organoid model and hyaluronan (∼35kDa) protects via a layilin dependent mechanism

Matrix Biology, Год журнала: 2024, Номер 133, С. 116 - 133

Опубликована: Авг. 24, 2024

Metabolic syndrome and diabetes in obese individuals are strong risk factors for development of inflammatory bowel disease (IBD) colorectal cancer. The pathogenic mechanisms low-grade metabolic inflammation, including chronic hyperglycemic stress, disrupting gut homeostasis poorly understood. In this study, we sought to understand the impact a environment on intestinal barrier integrity protective effects small molecular weight (35 kDa) hyaluronan epithelial function.

Язык: Английский

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Cellular interplay to 3D in vitro microphysiological disease model: cell patterning microbiota–gut–brain axis

Bio-Design and Manufacturing, Год журнала: 2024, Номер 7(3), С. 320 - 357

Опубликована: Май 1, 2024

Язык: Английский

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The Unfolded Protein Response and Its Implications for Novel Therapeutic Strategies in Inflammatory Bowel Disease

Biomedicines, Год журнала: 2023, Номер 11(7), С. 2066 - 2066

Опубликована: Июль 23, 2023

The endoplasmic reticulum (ER) is a multifunctional organelle playing vital role in maintaining cell homeostasis, and disruptions to its functions can have detrimental effects on cells. Dysregulated ER stress the unfolded protein response (UPR) been linked various human diseases. For example, activation of UPR signaling pathways intestinal epithelial cells either exacerbate or alleviate severity inflammatory bowel disease (IBD), contingent degree conditions activation. Our recent studies shown that EPICERTIN, recombinant variant cholera toxin B subunit containing an retention motif, induce protective colon cells, subsequently promoting restitution mucosal healing IBD models. These findings support idea compounds modulating may be promising pharmaceutical candidates for treatment disease. In this review, we summarize our current understanding IBD, focusing their roles dysregulation, pathogenesis. Additionally, discuss therapeutic strategies promote cytoprotection reduce inflammation via pharmacological manipulation UPR.

Язык: Английский

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Cellular and molecular mechanisms in the pathogenesis of pouchitis: more than just the microbiota

Gut, Год журнала: 2025, Номер unknown, С. gutjnl - 334445

Опубликована: Апрель 16, 2025

Pouchitis, defined as inflammation of the ileal pouch, is most common complication following restorative proctocolectomy for refractory ulcerative colitis. Antibiotics remain first line therapy pouchitis, but majority patients develop subsequent episodes and some are to antibiotic therapy. This highlights need more effective treatment options points a complex pathophysiology beyond role th pouch microbiome, similar what seen in inflammatory bowel disease. In this review, we outline putative mechanisms including genetic predisposition, microbiome alterations, dysfunction intestinal barrier immune system review available animal models pouchitis. addition, introduce concept pouchitis possible transmural disease discuss potential non-immune cells, stromal perpetuating dysfunction. We future directions, implications novel therapies propose multicellular that can better capture complexity pathogenesis.

Язык: Английский

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Pharmacokinetic Study of Eight Bioactive Components of Buyang Huanwu Decoction in LPS Induced Chronic Inflammatory and Control Rats Using UPLC‐MS/MS

Biomedical Chromatography, Год журнала: 2025, Номер 39(7)

Опубликована: Май 21, 2025

ABSTRACT Inflammation plays a pivotal role in the pathogenesis of numerous chronic inflammatory diseases, including cardiovascular diseases. Buyang Huanwu decoction (BYHWD) is widely employed to treat inflammation and related disorders. However, pharmacokinetics BYHWD's active compounds under conditions remain unclear. This study aims investigate comparative eight bioactive components control LPS‐induced rats following oral administration BYHWD. A rat model was established by administering low‐dose lipopolysaccharide (LPS, 200 μg / kg) via tail vein injection. An ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) method developed for simultaneous quantification major BYHWD plasma. Subsequently, pharmacokinetic profiles these analytes were characterized both rats. Excellent linearity ( R 2 > 0.9958) observed all plasma samples. Absolute recoveries ranged from 50.84% 111.86%, matrix effects varied between 85.04% 110.14%. The met criteria intra‐ inter‐day precision, accuracy, stability. In conclusion, UPLC‐MS/MS reliably investigated characteristics indicate that may reduce absorption compounds, providing valuable insights into clinical applications.

Язык: Английский

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A Narrative Review of Intestinal Microbiota’s Impact on Migraine with Psychopathologies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6655 - 6655

Опубликована: Июнь 17, 2024

Migraine is a common and debilitating neurological disorder characterized by the recurrent attack of pulsating headaches typically localized on one side head associated with other disabling symptoms, such as nausea, increased sensitivity to light, sound smell mood changes. Various clinical factors, including excessive use migraine medication, inadequate acute treatment stressful events, can contribute worsening condition, which may evolve chronic migraine, that is, headache present >15 days/month for at least 3 months. Chronic frequently various comorbidities, anxiety disorders, particularly depression, complicate prognosis, response overall outcomes. Emerging research indicates connection between alterations in composition gut microbiota mental health conditions, are considered disorders gut-brain axis. This underscores potential modulating new avenue managing these conditions. In this context, it interesting investigate whether its form, exhibits dysbiosis profile similar observed individuals depression. could pave way interventions aimed treating difficult-to-manage migraines.

Язык: Английский

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The relation between inflammatory biomarkers and drug pharmacokinetics in the critically ill patients: a scoping review

Critical Care, Год журнала: 2024, Номер 28(1)

Опубликована: Ноя. 19, 2024

Abstract Background The level of inflammation alters drug pharmacokinetics (PK) in critically ill patients. This might compromise treatment efficacy. Understanding the specific effects inflammation, measured by biomarkers, on absorption, distribution, metabolism, and excretion is help optimizing dosing strategies. Objectives review investigates relationship between inflammatory biomarkers PK parameters metabolism (ADME) patients, providing insight complexity drugs Method Following PRISMA guidelines, we conducted a comprehensive search Medline, Embase, Web Science, Cochrane databases (January 1946–November 2023). Studies examining parameters, or exposure patients were included. Records screened title, abstract, full text, with any discrepancies resolved through discussion consultation third reviewer. Results Of 4479 records screened, 31 met our inclusion criteria: 2 7 17 6 excretion. In general, results are only available for limited number drugs, most studies done looking at one components ADME. Higher levels may increase decrease absorption depending whether undergoes hepatic first-pass elimination. For negatively correlated protein binding capacity, positively cerebrospinal fluid penetration, peritoneal penetration. Metabolizing capacity was inversely biomarkers. Regarding excretion, can lead to reduced clearance, except neonatal population. Conclusion Inflammatory offer valuable information regarding altered Our findings emphasize need consider inflammation-driven variability when individualizing therapy this setting, same time research certain needs further research, also including pharmacodynamics.

Язык: Английский

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An MRI-informed histo-molecular analysis implicates ependymal cells in the pathogenesis of periventricular pathology in multiple sclerosis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Abstract It is now widely recognized that the cerebrospinal fluid (CSF)-adjacent brain surfaces – namely subpial cortical region and ependyma-adjacent periventricular are uniquely susceptible to a distinct, diffuse form of pathology in multiple sclerosis. So-called surface-in gradients predict future disease relapses independent classical white matter lesions thought occur as result cytotoxic factors CSF. Given underlying mechanisms driving appear be they represent novel treatment target. However, exactly how factor entry into regulated at these CSF-facing borders not understood, particularly ventricular interface. Indeed, although studies have indicated ependymal cells may damaged MS, there has yet comprehensive assessment cell health disease. We employed ultra-high-field MRI-guided immunohistochemistry, electron microscopy, multiomic single nucleus RNA/ATAC sequencing deeply phenotype human MS. Our data revealed direct correlate immune-responsive, reactive state assumed by associated with widespread transporter junctional protein gene dysregulation. then further defined regulatory networks underpinning MS state, predicted ligands known enriched CSF could drive emergence this tested one candidate vivo . found IFNγ increased murine permeability conditional knockout interferon gamma receptor 1 (Ifngr1) was sufficient reverse effect. directly implicate dysregulation More widely, we denote modulatory capacity on function influence inflammatory status region.

Язык: Английский

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Inflamed intestinal epithelial cells from patients with ulcerative colitis restore a non-inflamed transcriptional profile upon in vitro expansion

Laboratory Investigation, Год журнала: 2025, Номер unknown, С. 104172 - 104172

Опубликована: Апрель 1, 2025

Язык: Английский

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The green tea component (−)-epigallocatechin-3-gallate protects against cytokine-induced epithelial barrier damage in intestinal epithelial cells

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Май 14, 2025

Green tea consumption is associated with health benefits, which are mainly attributed to its catechins, especially the main catechin (-)-epigallocatechin-3-gallate (EGCG). Among other beneficial effects, EGCG was shown be protective in inflammatory bowel disease (IBD), a condition barrier dysfunction. To elucidate mechanisms behind this, present study analyzed impact of on properties and cytokine-induced dysfunction three different intestinal cell models. T84 cells served as colon model, while Caco-2 2D-organoids derived from human duodenum biopsies were used small Epithelial monolayers grown filter supports challenged combination two IBD cytokines, tumor necrosis factor α (TNFα) interferon γ (IFNγ). Barrier monitored by measuring transepithelial resistance (TER), macromolecule permeability, apoptosis, tight junction protein expression localization. protected against defects induced TNFα IFNγ. The cytokines decreased TER (T84: 11% ± 1% initial value; Caco-2: 65% 2% 2D-organoids: 57 8 Ω*cm2 versus control 239 29 Ω*cm2) prevented 200 µM 89% 5%; 3%; 343 24 Ω*cm2; all models p < 0.001). In parallel, attenuated increase macromolecular permeability reducing reduced caspase-3 cleavage >50% compared cytokine-stimulated controls (p Furthermore, alterations localization contributed protection. models, stabilized function, demonstrated an (Caco-2: 105% 3% 90% 182% 12% 2%, both 0.001), upregulation claudin-4 140% 15%, 0.05; 115% 5%, 0.01) claudin-2 75% 10%, 0.5; 66% 6%, claudin-7 64% 7%, 0.001; 9%, 0.01). delocalization claudin-1 -5 that green component stabilizes protects pro-inflammatory cytokines. These findings highlight potential supportive treatment strategy for IBD.

Язык: Английский

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