Acacetin inhibits activation of microglia to improve neuroinflammation after subarachnoid hemorrhage through the PERK signaling pathway mediated autophagy.

PURPOSE: To explore the effect of acacetin on subarachnoid hemorrhage (SAH) and its possible mechanism. METHODS: SAH model of rat was established, and intraperitoneally injected with three doses of acacetin. To verify the role of PERK pathway, we used the CCT020312 (PERK inhibitor) and Tunicamycin (activators of endoplasmic reticulum stress). The SAH score, neurological function score, brain edema content, and Evans blue (EB) exudate were evaluated. Western blot was used to determine the expression of inflammation-associated proteins and PERK pathway. The activation of microglia was also determined through Iba-1 detection. TEM and immunofluorescence staining of LC3B were performed to observe the autophagy degree of SAH rats after acacetin. Tunel/NeuN staining, HE and Nissl' staining were performed for neuronal damage. RESULTS: Acacetin increased the neurological function score, reduce brain water content, Evans blue exudation and SAH scores. The microglia in cerebral cortex were activated after SAH, while acacetin could inhibit its activation, and decreased the expression of TNF-α and IL-6 proteins. The pathological staining showed the severe neuronal damage and increased neuronal apoptosis after SAH, while acacetin could improve these pathological changes. We also visualized the alleviated autophagy after acacetin. The expression of Beclin1 and ATF4 proteins were increased, but acacetin could inhibit them. Acacetin also inactivated PERK pathway, which could improve the neuronal injury and neuroinflammation after SAH, inhibit the microglia activation and the overactivated autophagy through PERK pathway. CONCLUSION: Acacetin may alleviate neuroinflammation and neuronal damage through PERK pathway, thus having the protective effect on EBI after SAH.

Temozolomide with or without Radiotherapy in Patients with Newly Diagnosed Glioblastoma Multiforme: A Meta-Analysis.

BACKGROUND/AIM: The current meta-analysis evaluated the survival outcomes of newly diagnosed glioblastoma patients treated with radiotherapy (RT) alone and with RT + temozolomide (TMZ). METHODS: Relevant studies were identified by an extensive literature search in Medline, Current Contents and Cochrane databases by 2 independent reviewers using the terms "glioblastoma multiforme/glioblastoma, TMZ, radiation therapy/RT and survival." RESULTS: Results revealed a median survival of 13.41-19 months in the combined treatment group, as opposed to 7.7-17.1 months in the RT-alone group. Progression-free survival (PFS) was also significantly different between the 2 groups (RT + TMZ, 6.3-13 months; RT-alone, 5-7.6 months). While there was no significant difference in the 6-month survival and 6-month PFS rates between the RT + TMZ and RT groups (pooled OR 0.690; p = 0.057 and OR 0.429, p = 0.052, respectively), the 1-year survival and 1-year PFS rates showed significant difference (OR 0.469; p = 0.030 and OR 0.245, p < 0.001, respectively). CONCLUSIONS: Concomitant RT + TMZ is more effective and improves the overall survival and PFS in patients with newly diagnosed glioblastoma.