Long-Term Resveratrol Intake for Cognitive and Cerebral Blood Flow Impairment in Carotid Artery Stenosis/Occlusion.

BACKGROUND AND PURPOSE: Carotid artery stenosis or occlusion (CASO) is a causative disease of vascular cognitive impairment (VCI) attributed to cerebral hypoperfusion, even without the development of symptomatic ischemic stroke. Preclinically, resveratrol has been demonstrated to play an important role in improving cognitive function in rodent CASO models. This study investigated the association between long-term resveratrol intake and improvements in cognitive and cerebral hemodynamic impairments in patients with CASO. METHODS: A retrospective cohort study was conducted on patients with asymptomatic carotid artery stenosis of ≥50% or occlusion who underwent 15O-gas positron emission tomography (15O-gas PET) and neuropsychological tests such as Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog) twice between July 2020 and March 2022 allowing >125-day interval. Patients were administered 30 mg/day resveratrol after the first 15O-gas PET and neuropsychological tests were compared with those who were not. RESULTS: A total of 79 patients were enrolled in this study; 36 received resveratrol and 43 did not. Over a mean follow-up of 221.2 and 244.8 days, long-term resveratrol treatment significantly improved visuospatial/executive function (P=0.020) in MoCA, and memory domain (P=0.007) and total score (P=0.019) in ADAS-Cog. Cerebral blood flow demonstrated improvement in the right frontal lobe (P=0.027), left lenticular nucleus (P=0.009), right thalamus (P=0.035), and left thalamus (P=0.010) on 15O-gas PET. No adverse events were reported. CONCLUSION: Long-term daily intake of oral resveratrol may prevent or treat VCI by improving the cerebral blood flow in asymptomatic patients with CASO.

Codon-optimized antibiotic resistance gene improves efficiency of transient transformation in Frankia.

Frankia is a unique actinobacterium having abilities to fix atmospheric dinitrogen and to establish endosymbiosis with trees, but molecular bases underlying these interesting characteristics are poorly understood because of a lack of stable transformation system. Extremely high GC content of Frankia genome (more than 70 percent) can be a hindrance to successful transformation. We generated a synthetic gentamicin resistance gene whose codon usage is optimized to Frankia (fgmR) and evaluated its usefulness as a selection marker using a transient transformation system. Success rate of transient transformation and cell growth in selective culture were significantly increased by use of fgmR instead of a native gentamicin resistance gene, suggesting that codon optimization improved translation efficiency of the marker gene and increased antibiotic resistance. Our result shows that similarity in codon usage pattern is an important factor to be taken into account when exogenous transgenes are expressed in Frankia cells.