Open Access
Article
31 July 2025Reversal of Remimazolam-Mediated Inhibition of Jurkat T Cell Activation by TGFBI Depletion
GABAA receptors are well-recognized targets for intravenous anesthetics and have been identified in T lymphocytes. Remimazolam, a GABAA receptor-binding agent, enhances the inhibitory effects of γ-aminobutyric acid (GABA) and provides a rapid onset and offset of sedation, making it suitable for procedural sedation and anesthesia. However, the impact of remimazolam on T cell function remains poorly understood. In this study, we used mass spectrometry analysis to confirm that Jurkat T cells produce and secrete GABA de novo. Consequently, treatment with remimazolam inhibited Jurkat T cell activation, even in the absence of exogenous GABA. Transcriptomic profiling of remimazolam-treated Jurkat T cells exhibited a significant upregulation of TGFBI expression. Furthermore, CRISPR/Cas9-mediated knockout of TGFBI reversed the inhibitory effects of remimazolam on Jurkat T cell activation. These findings highlight the profound influence of anesthetics on T cell activation and could be crucial for optimizing their clinical application.
Open Access
Communication
05 August 2025Autoimmune Adverse Events Following Immunization
Adverse events (AEs) following immunization can include autoimmune AEs for some vaccines and combinations. This study retrospectively examines autoimmune AEs to detect safety signals for vaccines and concomitantly administered vaccines in the Vaccine Adverse Event Reporting System (VAERS) database. This study focuses on which vaccines were administered or coadministered for retrospective analysis of analyzed autoimmune AEs. Observed results include multiple autoimmune AE safety signals: human papillomavirus (HPV) Cervarix, HPV Gardasil, hepatitis (Hep) A + Hep B (Twinrix), Lyme disease (LYMErix), coadministered COVID-19 Moderna + Pfizer-BioNTech, Hep B (Engerix-B), and others. Identified arthritis AE safety signals include Lyme disease (LYMErix), rubella (Meruvax II), HPV (Cervarix), Anthrax (Biothrax) + Smallpox (Dryvax), and more. Coadministered DTaP + HepB + IPV (Pediarix) + Hib (Pedvaxhib) + Pneumococcal (Prevnar13) + Rotavirus (Rotarix) may be exhibiting synergy AE rate for eczema AEs. Thirty five influenza vaccines were observed with Guillain–Barré syndrome (GBS) AE safety signals, plus additional safety signals for multiple other vaccines. influenza (H1N1 monovalent) (GSK) exhibits a very high rate for narcolepsy AEs.
Open Access
Review
20 August 2025On the Utility of Nailfold Capillaroscopy in Detecting the Effects of Fibrinaloid Microclots in Diseases Involving Blood Stasis
A variety of chronic, inflammatory vascular and autoimmune diseases are accompanied by fibrinaloid microclots. Such diseases reflect endothelial dysfunction and may be detected using a ‘structural’ assay in the form of the fluorescence microscopic or flow ‘clotometry’ analysis of suitably stained platelet-poor plasma. Their amyloid nature and the presence of anti-fibrinolytic molecules therein make the fibrinaloid microclots comparatively resistant to the normal processes of clot degradation. By inhibiting the free flow of blood, the many effects of fibrinaloid microclots include those causing hypoxia, oxidative stress, and ‘blood stasis’ in the microcirculation. Nailfold capillaroscopy is an established observational technique (with both ‘structural’ and ‘functional’ elements) for assessing the microcirculation, and it is thus of interest to establish whether it too demonstrates changes when these syndromes are diagnosed. All diseases in which both methods have been applied show both the presence of fibrinaloid microclots and changes in capillary properties, indicating the complementary value of the structural and functional assays. This also suggests the potential value of nailfold capillaroscopy in a variety of other diseases involving coagulopathies or a deficient microcirculation, which has been little studied to date.
