Evaluation of Prognostic Implication of Serum Mixed Lineage Kinase Domain‐Like Protein in Acute Primary Supratentorial Intracerebral Hemorrhage: A Multicenter Prospective Cohort Study

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Abstract Objective Mixed lineage kinase domain‐like protein (MLKL) is a key component of necroptosis. Here, serum MLKL levels were measured with the intent to assess its prognostic significance in acute intracerebral hemorrhage (ICH). Methods A collective 161 patients primary supratentorial ICH and 73 controls enlisted this multicenter prospective cohort study. Serum at admission all patients, study entry controls, on post‐ICH days 1, 3, 5, 7, 10, 15 patients. Multivariate analyses adopted relationships between levels, severity, early neurological deterioration (END), poststroke 6‐month modified Rankin Scale (mRS) scores, poor prognosis (mRS scores 3–6). Results Patients, relative had significantly promoted from until Day 15, peaking value 3 ( p < 0.001). Admission independently correlated National Institutes Health Stroke (NIHSS) (beta, 0.133; 95% confidence interval (CI), 0.088–0.178; = 0.011), hematoma volume 0.051; 95%CI, 0.037–0.064; 0.001), mRS 0.707; 0.487–0.927; 0.023), as well predicted END (odds ratio, 1.902; 1.229–2.945; 0.014) 2.286; 1.324–3.946; 0.038). linearly connected risks > 0.05) 0.05), no interactions age, gender, hypertension, so forth (all possessed similar areas under receiver operating characteristic curve NIHSS 0.05). The models integrating graphically represented by nomogram good consistency calibration curve. Conclusions are markedly increased shortly following ICH, may accurately mirror disease efficaciously anticipate six‐month bad strengthening biomarker prospect ICH.

Language: Английский

Discovery and optimization of 3‐(indolin‐5‐yloxy)pyridin‐2‐amine derivatives as potent necroptosis inhibitors

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(10)

Published: July 2, 2024

Necroptosis is a form of regulated necrotic cell death and has been confirmed to play pivotal roles in the pathogenesis multiple autoimmune diseases such as rheumatoid arthritis (RA) psoriasis. The development necroptosis inhibitors may offer promising therapeutic strategy for treatment these diseases. Herein, starting from in-house hit compound 1, we systematically performed structural optimization discover potent with good pharmacokinetic profiles. resulting 33 was inhibitor both human I2.1 cells (IC

Language: Английский

Newcastle Disease Virus Induces Profound Lymphoid Depletion with Different Patterns of Necroptosis, Necrosis, and Oxidative DNA Damage in Bursa, Spleen, and Other Lymphoid Tissues

Pathogens, Journal Year: 2024, Volume and Issue: 13(8), P. 619 - 619

Published: July 26, 2024

This study delves into the pathogenesis of virulent genotype VII strains Newcastle disease virus (NDV), focusing on experimentally infected birds. Predominant and consistent lesions observed include bursal atrophy extensive depletion all lymphoid tissues. Immunohistochemistry (IHC) analysis, targeting apoptosis (Caspase-3), necroptosis (MLKL), NDV markers, indicates that is linked to a non-apoptotic programmed cell death pathway known as "necroptosis". Repair assisted damage detection (RADD) bursa reveal oxidative DNA patterns with death, aligning MLKL expression. Contrastingly, in spleen, our findings suggest necrosis (non-programmed death) predominantly contributes depletion. conclusion supported by evidence karyorrhexis, fibrinous inflammation, RADD analyses, IHC. Moreover, addition being pathogenic its own right, caused rapid should be expected contribute profound immunosuppression. The elucidation NDV-infected chickens provides good rationale investigate this mechanism other paramyxoviral diseases such human measles.

Language: Английский