Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.

Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.

Activation of the kynurenine pathway identified in individuals with covert hepatic encephalopathy.

Background: HE is a neuropsychiatric complication of liver disease characterized by systemic elevation in ammonia and proinflammatory cytokines. These neurotoxins cross the blood-brain barrier and cause neuroinflammation, which can activate the kynurenine pathway (KP). This results in dysregulated production of neuroactive KP metabolites, such as quinolinic acid, which is known to cause astrocyte and neuronal death.

A Proteomic Examination of Plasma Extracellular Vesicles Across Colorectal Cancer Stages Uncovers Biological Insights That Potentially Improve Prognosis.

Background: Recent advancements in understanding plasma extracellular vesicles (EVs) and their role in disease biology have provided additional unique insights into the study of Colorectal Cancer (CRC).

Methods: This study aimed to gain biological insights into disease progression from plasma-derived extracellular vesicle proteomic profiles of 80 patients (20 from each CRC stage I-IV) against 20 healthy age- and sex-matched controls using a high-resolution SWATH-MS proteomics with a reproducible centrifugation method to isolate plasma EVs.

Results: We applied the High-Stringency Human Proteome Project (HPP) guidelines for SWATH-MS analysis, which refined our initial EV protein identification from 1362 proteins (10,993 peptides) to a more reliable and confident subset of 853 proteins (6231 peptides).

Manipulation of Surface Potential Distribution Enhances Osteogenesis by Promoting Pro-Angiogenic Macrophage Polarization via Activation of the PI3K-Akt Signaling Pathway.

Regulation of the immune response is key to promoting bone regeneration by electroactive biomaterials. However, how electrical signals at the micro- and nanoscale regulate the immune response and subsequent angiogenesis during bone regeneration remains to be elucidated. Here, the distinctly different surface potential distributions on charged poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix surfaces are established by altering the dimensions of ferroelectric nanofillers from 0D BaTiO nanoparticles (homogeneous surface potential distribution, HOPD) to 1D BaTiO nanofibers (heterogeneous surface potential distribution, HEPD).