Rabbit Anti-Human Phospho-Per2 (S662) Polyclonal antibody

Objective: This study was to investigate the underlying mechanisms of valsartan chronotherapy in regulating blood pressure variability. Methods: RT-PCR was used to assay clock genes expression rhythm in the hypothalamus, aortic vessels, and target organs after valsartan chronotherapy. WB was used to measure Period 1 (Per1), Period 2 (Per2) protein expression in aortic vessels, as well as to measure phosphorylation of 20-kDa regulatory myosin light chain (MLC20) in VSMCs. Results: Specific clock genes in the hypothalamus, and Per1 and Per2 in aorta abdominalis, exhibited disordered circadian expression in vivo. Valsartan asleep time administration (VSA) restored circadian clock gene expression in a tissue- and gene-specific manner. In vitro, VSA was more efficient in blocking angiotensin II relative to VWA, which led to differential circadian rhythms of Per1 and Per2, ultimately corrected MLC20 phosphorylation. Conclusion: VSA may be efficacious in regulating circadian clock genes rhythm, then concomitantly correct circadian blood pressure rhythms.

Background: Fatigue is a consistently reported, severe symptom among patients with gliomas throughout the disease trajectory. Genomic pathways associated with fatigue in glioma patients have yet to be identified. Methods: Clinical factors (performance status, tumor details, age, gender) were collected by chart review on glioma patients with fatigue ("I have lack of energy" on Functional Assessment of Cancer Therapy-Brain), as well as available genotyping data. Candidate genes in clock and inflammatory pathways were identified from a literature review, of which 50 single nucleotide polymorphisms (SNPs) in 7 genes were available. Clinical factors and SNPs identified by univariate analyses were included in a multivariate model for moderate-severe fatigue. Results: The study included 176 patients (median age = 47 years, 67% males). Moderate-severe fatigue was reported by 43%. Results from multivariate analysis revealed poor performance status and 2 SNPs were associated with fatigue severity. Moderate-severe fatigue was more common in patients with poor performance status (OR = 3.52, P < .01). For each additional copy of the minor allele in rs934945 (PER2) the odds of fatigue decreased (OR = 0.51, P < .05). For each additional copy of the minor allele in rs922270 (ARTNL2) the odds of fatigue increased (OR = 2.38, P < .01). Both of these genes are important in the circadian clock pathway, which has been implicated in diurnal preference, and duration and quality of sleep. No genes in the inflammatory pathway were associated with fatigue in the current study. Conclusions: Identifying patients at highest risk for fatigue during treatment allows for improved clinical monitoring and enrichment of patient selection for clinical trials.