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Background: This study aimed to examine the expression level and prognostic value of microRNA-29a (miR-29a) in human cholangiocarcinoma (CCA). Patients and Methods: The expression of miR-29a was measured in tissues collected from 125 CCA patients using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Survival analysis was carried out using the Kaplan-Meier method and log-rank test. The prognostic value of miR-29a was examined with Cox regression analysis. Results: The results of qRT-PCR demonstrated that miR-29a expression was significantly upregulated in CCA tissue samples compared with matched noncancerous samples. Overexpression of miR-29a was found to be correlated with lymph node metastasis, clinical stage, and differentiation of CCA. The Kaplan-Meier survival curves suggested that patients with high miR-29a levels had poor overall survival compared to those with low miR-29a expression. From the results of the Cox regression analysis, we considered increased miR-29a expression to be an independent prognostic factor for patients with CCA. Conclusion: Our study data demonstrated that upregulated miR-29a expression is associated with progression of CCA and might act as a prognostic biomarker in CCA patients.

Context: Cepharanthine (CPA) has been reported to possess a wide range of pharmacological activities.Objective: This study investigates the pharmacokinetic characteristics after oral or intravenous administration of CPA by using a sensitive and rapid LC–MS/MS method.Materials and methods: A sensitive and rapid LC–MS/MS method was developed for the determination of CPA in Sprague–Dawley rat plasma. Twelve rats were equally randomized into two groups, including the intravenous group (1 mg/kg) and the oral group (10 mg/kg). Blood samples (250 μL) were collected at designated time points and determined using this method. The pharmacokinetic parameters were calculated.Results: The calibration curve was linear within the range of 0.1–200 ng/mL (r = 0.999) with the lower limit of quantification at 0.1 ng/mL. After 1 mg/kg intravenous injection, the concentration of CPA reached a maximum of 153.17 ± 16.18 ng/mL and the t1/2 was 6.76 ± 1.21 h. After oral administration of 10 mg/kg of CPA, CPA was not readily absorbed and reached Cmax 46.89 ± 5.25 ng/mL at approximately 2.67 h. The t1/2 was 11.02 ± 1.32 h. The absolute bioavailability of CPA by oral route was 5.65 ± 0.35%, and the bioavailability was poor.Discussion and conclusions: The results indicate that the bioavailability of CPA was poor in rats, and further research should be conducted to investigate the reason for its poor bioavailability and address this problem.

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Recent evidence has shown that demyelination occurs along with axonal degeneration in spinal cord injury (SCI) during the secondary injury phase. Oligodendrocyte precursor cells (OPC) are present in the lesions but fail to differentiate into mature oligodendrocytes and form new myelin. Given the limited recovery of neuronal functions after SCI in adults without effective treatment available so far, it remains unknown whether enhancing OPC differentiation and myelination could benefit the recovery of SCI. To show the significance of myelin regeneration after SCI, the injury was treated with clemastine in the rat model. Clemastine is an FDA-approved drug that is potent in promoting oligodendrocyte differentiation and myelination in vivo, for four weeks following SCI. Motor function was assessed using sloping boards and grid walking tests and scored according to the Basso, Beattie, and Bresnahan protocol. The myelin integrity and protein expression were evaluated using transmission electron microscopy and immunofluorescence, respectively. The results indicated that clemastine treatment preserves myelin integrity, decreases loss of axons and improves functional recovery in the rat SCI model. The presented data suggest that myelination-enhancing strategies may serve as a potential therapeutic approach for the functional recovery in SCI.

The study was supported by the Foundation of the Program of Technology of Education Committee of Chongqing (No. KJQN201800122) and the Program of Technology of Science and Technology Committee of Yuzhong District in Chongqing (No. 20180131) Background: Disruption of the blood-brain barrier (BBB) is a mechanism in the pathogenesis of traumatic brain injury. Basic fibroblast growth factor (bFGF) is expressed in angiogenesis, neurogenesis, and neuronal survival. This study aimed to investigate the role of bFGF in vitro in human brain microvascular endothelial cells (HBMECs) challenged by oxygen-glucose deprivation/reperfusion (OGD/R). Material/Methods: HBMECs were cultured in glucose-free medium and an environment with <0.5% oxygen in an anaerobic chamber. Immunocytochemistry, Western blot, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to measure the protein and mRNA expression levels of bFGF, tight junction, adherens junction, apoptotic proteins, and matrix metalloproteinases (MMPs). The effects of bFGF on the viability of HBMECs was evaluated using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated using the TUNEL assay, and endothelial permeability was quantified using a transwell migration assay with fluorescein isothiocyanate (FITC) conjugated with dextran. The effects of bFGF were evaluated following inhibition of fibroblast growth factor receptor 1 (FGFR1) with PD173074 and inhibition of ERK with PD98059. Results: Following OGD/R of HBMECs, bFGF significantly reduced cell permeability and apoptosis and significantly inhibited the down-regulation of the expressions of proteins associated with tight junctions, adherens junctions, apoptosis and matrix metalloproteinases (MMPs). The effects of bFGF were mediated by the activation of FGFR1 and ERK, as they were blocked by FGFR1 and ERK inhibitors. Conclusions: Permeability and apoptosis of HBMECs challenged by OGD/R were reduced by bFGF by activation of the FGFR1 and the ERK pathway.

Early brain injury (EBI) is a major contributor to the high mortality and morbidity after subarachnoid hemorrhage (SAH). Inflammatory responses and neuronal apoptosis are important causes of EBI. Because 5- lipoxygenase (5-LOX) is known to be involved various central nervous system diseases, we investigated the effects of 5-LOX inhibition during EBI after SAH. Zileuton and LY294002 were used to inhibit expression of 5-LOX and Akt, respectively. We found that 5-LOX expression was significantly increased in the cytoplasm of cortical neurons after SAH and was accompanied by upregulated expression of the inflammatory factors LTB4, TNF-α, IL-1β and IL-6; upregulation of the pro-apoptotic factor Bax; downregulation of the anti-apoptotic factor Bcl-2; and an increased apoptosis rate. Gastric Zileuton administration significantly suppressed all of those effects and improved neurological function. Zileuton also upregulated activated (phosphorylated) AKT levels, and these beneficial effects of Zileuton were abolished by intracerebroventricular infusion of the PI3K inhibitor LY294002. Taken together, these findings indicate that 5-LOX mediates pro-inflammatory and pro-apoptotic effects that contribute to EBI after SAH and that those effects are suppressed by activation of PI3K/Akt signaling. This suggests targeting 5-LOX may be an effective approach to treating EBI after SAH.