ABSTRACT Aims Pyrroloquinoline quinone (PQQ) was reported to be neuroprotective after experimental traumatic brain injury (TBI), but its mechanisms remain undefined. We tested whether PQQ protects against TBI in mice and identified the associated pathways. Methods Male C57BL/6 mice received intraperitoneal PQQ (6.25, 12.5 or 25 mg/kg) immediately after controlled cortical impact. Mortality, modified neurological severity score (mNSS) and beam balance were followed to day 14; histopathology, immunofluorescence, western blot, ELISA and ATP assays were performed on day 3. Transcriptomics, metabolomics, network pharmacology and docking were integrated to identify candidate mechanisms. Results PQQ reduced mortality (lowest at 12.5 mg/kg) and dose‐dependently improved neurological deficits, neuronal apoptosis, brain edema, pro‐inflammatory cytokines, and oxidative stress; the mNSS and beam balance benefits persisted to day 14. At 12.5 mg/kg, multi‐omics and network pharmacology identified arginine biosynthesis, mediated by argininosuccinate synthetase 1 (ASS1) and carbamoyl phosphate synthetase 1 (CPS1), as the top‐ranked pathway suppressed by PQQ; docking predicted binding of PQQ to both enzymes, suggesting putative targets pending validation. PQQ concurrently restored PTEN‐induced kinase 1 (PINK1)/Parkin‐mediated mitophagy and ATP production. Conclusion PQQ attenuates secondary injury after TBI in male mice, in association with increased markers of PINK1/Parkin‐mediated mitophagy initiation and suppressed ASS1/CPS1‐driven arginine biosynthesis, identifying a candidate dual‐axis mechanism and nominating the mitophagy‐arginine axis as a target for neuroprotection in TBI.
Ya-Nan He, Lu-Fei Yu, Yi-Xun Lu et al.· CNS Neuroscience & Therapeut...· 0 citations
BACKGROUND
Multiple scales are available to evaluate the health status of older surgical patients; however, their relative ability to predict postoperative major adverse cardiac and cerebrovascular events (MACCE) remains unclear.
OBJECTIVE
To examine the association between preoperative health status, as measured by four commonly used scales, and 30-day postoperative MACCE in older surgical patients, and to compare their predictive performance and incremental value against the Revised Cardiac Risk Index (RCRI).
DESIGN
A retrospective study of a large multicentre cohort.
SETTING
Nineteen tertiary hospitals across China participating in a perioperative database.
PATIENTS
Patients aged ≥65 years who underwent noncardiac, non-neurosurgical surgery between April 2020 and April 2022 were included in the analysis. The Activities of Daily Living (ADL), EuroQol Five-Dimension Five-Level (EQ-5D-5L), Metabolic Equivalent of Task (MET), FRAIL, and RCRI were evaluated preoperatively.
MAIN OUTCOME MEASURE
The primary outcome was the occurrence of MACCE within 30 days after surgery, defined as any of the following: stroke, myocardial infarction, angina pectoris, congestive heart failure, cardiac arrest, or all-cause mortality.
RESULTS
Among the 7996 patients, 126 (1.6%) experienced MACCE. Similar to the RCRI, the four health assessments were significantly associated with MACCE risk. The RCRI alone yielded an area under the curve (AUC) of 0.610 [95% confidence interval (CI): 0.563 to 0.658]. Incorporating each scale improved the predictive performance of the RCRI. The RCRI-Plus model, comprising RCRI, age, severity of anaemia, and surgical duration, achieved an AUC of 0.692 (95% CI: 0.643 to 0.741). Further addition of the four scales to the RCRI-Plus increased discrimination, with the highest AUC observed for the RCRI-Plus model incorporating FRAIL (AUC 0.724; 95% CI: 0.679 to 0.770). However, DeLong's test showed no significant differences between this model and the RCRI-Plus models incorporating ADL, EQ-5D-5L, or MET.
CONCLUSIONS
Preoperative health status assessed by four geriatric scales was significantly correlated with postoperative MACCE and provided improved risk discrimination beyond the RCRI. Adding any of these assessments to the RCRI enhanced predictive performance, with FRAIL showing the greatest incremental benefit. These findings underscore the value of multidimensional health status evaluation for preoperative cardiac and cerebrovascular risk stratification, with frailty assessment warranting particular attention.
TRIAL REGISTRY
ClinicalTrials.gov, NCT04911530.
Shiyi Han, Fan Li, Duo Hou et al.· European Journal of Anaesthe...· 0 citations
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