Urolithin B Attenuates Cerebral Ischemia-reperfusion Injury by Modulating Nrf2-regulated Anti-oxidation in Rats.

Ischemia-reperfusion (IR) induces a wide range of irreversible injuries. Cerebral IR injury (IRI) refers to additional brain tissue damage that occurs after blood flow is restored following cerebral ischemia. Currently, no established methods exist for treating IRI. Oxidative stress is recognized as a primary mechanism initiating IRI and a crucial focal target for its treatment. Urolithin B, a metabolite derived from ellagitannins, antioxidant polyphenols, has demonstrated protective effects against oxidative stress in various disease conditions. However, the precise mechanism underlying UB's effect on IRI remains unclear. In our current investigation, we assessed UB's ability to mitigate neurological functional impairment induced by IR using a neurological deficit score. Additionally, we examined cerebral infarction following UB administration through TTC staining and neuron Nissl staining. UB's inhibition of neuronal apoptosis was demonstrated through the TUNEL assay and Caspase-3 measurement. Additionally, we examined UB's effect on oxidative stress levels by analyzing malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, and immunohistochemistry analysis of inducible nitric oxide synthase (iNOS) and 8-hydroxyl-2'-deoxyguanosine (8-OHdG). Notably, UB demonstrated a reduction in oxidative stress levels. Mechanistically, UB was found to stimulate the Nrf2/HO-1 signaling pathway, as evidenced by the significant reduction in UB's neuroprotective effects upon administration of ATRA, an Nrf2 inhibitor. In summary, UB effectively inhibits oxidative stress induced by IR through the activation of the Nrf2/HO-1 signaling pathway. These findings suggest that UB holds promise as a therapeutic agent for the treatment of IRI.

Diagnostic and prognostic value of serum vitronectin levels in human glioma.

OBJECTIVE: Vitronectin is an extracellular matrix protein, the synthesis of which by glioma cells correlates with tumor grade. The current study was designed to investigate the relationship between serum vitronectin levels and clinicopathological characteristics, diagnosis and prognosis in glioma patients. METHODS: In a prospective observatory study, a total of 98 glioma patients, 98 healthy controls, 98 other non-glioma brain tumors, and 98 other non-tumor neurological diseases were recruited. Following univariate analyses, multivariate analyses were performed to explore the associations of serum vitronectin levels with survival and clinicopathological parameters. Receiver operating characteristic curve analysis was done to assess its diagnostic and prognostic predictive value. RESULTS: Serum vitronectin levels were significantly elevated in glioma patients as compared with other groups. High Wealth Health Organization grade was independently associated with high vitronectin levels. Serum vitronectin levels could significantly distinguish glioma patients from other groups and discriminate high-grade glioma from low-grade glioma. Vitronectin levels markedly predicted 5-year progression and 5-year mortality. Moreover, serum vitronectin was identified as an independent predictor for 5-year overall survival and 5-year progression-free survival as well as 5-year mortality and 5-year progression. CONCLUSION: Serum vitronectin may be a promising diagnostic and prognostic biomarker that can be detected in the peripheral blood of patients with glioma.

The prognostic value of plasma soluble CD40 ligand levels following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Increased circulating soluble CD40 ligand (sCD40L) levels have been reported to be associated with severity and mortality of severe traumatic brain injury. The current study tested the hypothesis that elevated plasma sCD40L levels are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Plasma sCD40L concentrations of 120 aSAH patients and 120 healthy volunteers were measured using enzyme-linked immunosorbent assay. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. RESULTS: Plasma sCD40L levels were significantly elevated in aSAH patients compared with healthy controls; plasma sCD40L levels were highly associated with clinical severity reflected by World Federation of Neurological Surgeons (WFNS) score and Fisher score; sCD40L emerged as an independent predictor of 6-month mortality and unfavorable outcome and 6-month overall survival; although a combined logistic-regression model did not demonstrate the additive benefit of sCD40L to WFNS score and Fisher score, sCD40L possessed similar predictive value to WFNS score and Fisher score based on receiver operating characteristic curves. CONCLUSIONS: Higher plasma sCD40L levels on presentation are associated with clinical severity and have potential to be a good prognostic biomarker of aSAH.