Objective: : We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods: : We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results: : Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56–0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80–1.47; p=0.5929). Three other variants, rs16944 (IL-1β), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01Conclusion : Our updated meta-analysis with increased statistical power highlights that rs1800796 which maps on the IL-6 gene is associated with IA, and in particular confers a protective effect against occurrence of IA in the East-Asian population.

OBJECTIVETo research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.

METHODSThe effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.

RESULTSKH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.

CONCLUSIONSKH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.

Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Amyloid beta-Peptides ; Angelica ; chemistry ; Animals ; Brain ; pathology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cognitive Dysfunction ; complications ; drug therapy ; physiopathology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Disease Models, Animal ; Male ; Maze Learning ; drug effects ; Memory, Short-Term ; drug effects ; Mice, Inbred C57BL ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plaque, Amyloid ; drug therapy ; pathology ; physiopathology ; Signal Transduction ; drug effects