Cerebralcare Granule® combined with nimodipine improves cognitive impairment in bilateral carotid artery occlusion rats by reducing lipocalin-2.

AIMS: Clinically, Cerebralcare Granule® (CG) has been widely utilized to treat various types of headache, chronic cerebral insufficiency and other diseases, and the effect is significant. Clinical studies have shown that CG can significantly relieve vascular dementia (VaD), however, the molecular mechanisms haven't been established. To clear the therapeutic mechanisms of CG against VaD, a hypothesis was proposed that CG could treat neurovascular injury by inhibiting the production of lipocalin-2 (LCN 2). MAIN METHODS: 90 dementia rats were selected by water maze test and randomly divided into 6 groups, including nimodipine (NM), CG L (low dose) (0.314 g kg-1), CG H (high dose) (0.628 g kg-1), and combined group (CG + NM). And in vitro neuronal cell OGD modeling to evaluate the effect of CG on JAK2/STAT3. KEY FINDINGS: CG could significantly shorten the escape latency of two-vessel occlusion (2-VO) rats, increase their exploratory behavior, alleviate the symptoms of VaD and improve the ultrastructural pathological damage of neurovascular unit and accelerate the recovery of cerebral blood perfusion. CG combined with NM is better than NM alone. It was further showed that CG could inhibit the pathogenicity of LCN 2 through JAK2/STAT3 pathway and suppress the production of inflammatory cytokines. It plays a role in the protection of cerebral microvasculature and BBB in 2-VO rats. SIGNIFICANCE: Taken together, there data has supported notion that CG can protect the integrity of cerebral blood vessels and BBB and improve cognitive impairment through mainly inhibiting LCN 2, which provides scientific evidence for clinical application.

Comparison of Multi-Gene Testing Data Between Fresh and Formalin-Fixed Specimens From Core Needle Biopsy in Patients With NSCLC.

Purpose: Currently, formalin-fixed paraffin-embedded (FFPE) tissue specimens are the conventional material for gene testing for non-small cell lung cancer (NSCLC) patients. In our study, we aimed to develop a quick gene testing procedure using fresh core needle biopsy samples from NSCLC patients. Methods: In total, 77 fresh NSCLC samples obtained from core needle biopsy were evaluated by frozen section examination. If the NSCLC diagnosis and adequate tumor cell counts were confirmed by histopathology, the fresh tissues were used to extract DNA and subsequent gene testing by ARMS-PCR. Meanwhile, the paired FFPE core needle biopsy samples from 30 NSCLC patients also underwent gene testing. Results: In total, 77 fresh samples showed an EGFR mutation rate of 61.0%, higher than the levels in the Asian. Following a comparison of gene testing results with fresh tissues and paired FFPE tissues from the 30 patients, no significant difference in the DNA concentration extracted from fresh tissues and FFPE tissues was found. However, DNA purity was significantly higher in fresh tissues than that in FFPE tissues. Gene testing detected the same gene mutations in 93.3% of cases in fresh tissues and paired FFPE tissues. The gene testing procedure using fresh biopsy samples greatly shortens the waiting time of patients. Conclusion: The multi-gene mutation testing using fresh core needle biopsy samples from NSCLC patients is a reasonable, achievable, and quick approach. Fresh tissues may serve as a potential alternative to FFPE tissues for gene testing in NSCLC patients.

The modulatory effects of garlic oil on hepatic cytochrome P450s in mice.

In order to probe into the effects of garlic oil (GO) on the hepatic CYP2E1, CYP1A2 and CYP3A, male Kun-Ming mice were treated with GO (100 mg/kg body weight) or corn oil for 1 day or consecutive 60 days, respectively, and then the protein expressions and the activities of the enzymes were examined. GO did not alter the physical activities of mice and did not induce lesion to the liver. However, it dramatically inhibited the activities and protein levels of hepatic CYP2E1 and 1A2, but not CYP3A. In addition, we noticed that the inhibition of CYP2E1 and 1A2 by GO was more potent in group of 1 day treatment than those in group of 60 days treatment. Compared with the respective control value, the protein levels of CYP2E1 were decreased by 87.40% (p < .01) and 62.26% (p < .01) by 1 day and 60 days of GO treatment, respectively, while the CYP1A2 protein levels were decreased by 70.76% (p < .01) and 41.49% (p < .01), respectively. These data indicated that the mice could adapt to the prolonged treatment, which might be one reasonable explanation for the conflicting data in the literature. The CYP2E1 and 1A2 suppression might contribute to its hepatoprotection, and data about CYP3A indicated that GO was unlikely to alter the metabolism of the concomitantly used drugs.