Association of CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients.

Aim: To evaluate the association between CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation. Materials & methods: High performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentrations. First-generation sequencing was performed to detect gene polymorphisms. Results: Voriconazole concentrations of normal metabolizers were significantly higher than those of intermediate (p < 0.05) and ultrafast (p < 0.001) metabolizers. Patients with ABCC2 GG and GA genotypes exhibited significantly lower voriconazole concentrations compared with patients with the AA genotype (p < 0.05). Conclusion: These results demonstrate a significant association between voriconazole concentrations and the CYP2C19 phenotype in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation.

Deficiency of astrocyte CysLT1R ameliorates depression-like behaviors in mice by modulating glutamate synaptic transmission.

Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLT1R) could be involved in depression. Herein we hypothesize that CysLT1R may regulate depression by affecting synaptic glutamate cycling based on existence of CysLT1R in the astrocytes that participate in occurrence of depression. We found that CysLT1R expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLT1R astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLT1R in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLT1R in the astrocyte of depression-like mice, produced similar effects. Correspondingly, overexpression of CysLT1R in the astrocyte of DG induced depression-like behaviors in mice. The further study showed that CysLT1R AcKO ameliorated synaptic plasticity impairment, as reflected by increased synapse, LTP and PSD95, and promoted glutamate transporter 1 (GLT-1) expression by inhibiting NF-κB p65 nuclear translocation mediated by ß-arestin2 and clatrhin, subsequently decreased glutamate in synaptic cleft and GluN2B on postsynaptic membrane in depression-like mice. The present study also showed that GLT-1 agonist or NF-κB inhibitor ameliorated depressive-like behaviors induced by overexpression of the astrocyte CysLT1R of DG. Our study demonstrated that astrocyte CysLT1R regulated depression by modulating glutamate synaptic transmission, suggesting that CysLT1R could be a potential target for developing novel drugs of anti-depression.

[Effect of intranasal acupuncture on neurogenic inflammation in allergic rhinitis rabbits].

OBJECTIVE: To observe the effect of intranasal acupuncture on allergic rhinitis (AR), and expression of substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) proteins in the nasal mucosa and contents of serum immunoglobulin E (IgE), interleukin 4 (IL-4) and interferon-γ (IFN-γ) in AR rabbits, so as to explore its mechanisms underlying improvement of AR. METHODS: New Zealand rabbits were randomly divided into normal control, AR model, non-acupuoint acupuncture (NAA) and intranasal acupuncture (INA) groups, with 8 rabbits in each group. The AR model was established by intra-peritoneal injection of egg protein and nasal mucosal stimulation. In the INA group, bilateral "Neiyingxiang" (EX-HN9) within the nasal cavity (the anterior attachment area of the inferior turbinate, about 1 cm away from the nasal limen) were acupunctured by mani-pulating the filiform needles for a while with uniform reinforcing and reducing methods, followed by keeping the needles for 20 min. In the NAA group, shallow acupuncture was applied to the skin of the outer margin of the cheeks, followed by keeping the needle for 20 min. The acupuncture treatment was conducted once every other day for 7 days. The symptoms of sneezing frequency, nasal secretion amount and nasal itching were scored. The expression levels of SP, VIP and NPY in the nasal mucosa tissue were detected by immunohistochemistry, and the serum IgE, IL-4, and IFN-γ contents were detected by ELISA. RESULTS: After modelling, the symptom score, expression of SP and VIP, and serum IgE and IL-4 contents were significantly higher (P<0.01,P<0.05), NPY expression and serum IFN-γ content significantly lower (P<0.05, P<0.01) in the model group than in the normal control group. Following the intervention, the symptom scores, expressions of SP and VIP, and serum IgE and IL-4 contents were remarkably decreased (P<0.05, P<0.01), while the NPY expression and serum IFN-γ content were significantly up-regulated (P<0.05, P<0.01) in the INA group than in the model group. The effects of INA group were significantly superior to those of NAA group in reducing symptom score, SP and VIP expression, and serum IgE and IL-4 contents and up-regulating NPY expression and IFN-γcontent (P<0.05, P<0.01). There were a positive correlation between the expressions of SP and VIP and contents of serum IgE and IL-4 (P<0.05), and a negative correlation between the expressions of SP and VIP and IFN-γ content (P<0.05). CONCLUSION: INA treatment can relieve symptoms of AR in AR rabbits, which may be associated with its effects in regulating the expression of SP, VIP and NPY of the nasal mucosa, and contents of serum IgE, IL-4 and IFN-γ to improve neurogenic inflammation.

[Screening active ingredients of Shenkangwan that regulate endothelial-mesenchymal transition of endothelial cells in vitro].

OBJECTIVE: To screen the effective components of Shenkangwan that regulate endothelial-mesenchymal transition in endothelial cells for optimizing prescription of Shenkangwan. METHODS: ALK5 was identified as one of the target receptors that regulate endothelial-mesenchymal transition of endothelial cells using molecular docking technique. Nine molecules were screened as the candidate effective components in Shenkangwan, among which calycosin, ononin and stigmasterol were selected for testing. Glomerular epithelial cells were exposed to high glucose and treated with calycosin, ononin, or stigmasterol, and the cellular expressions of α-smooth muscle actin (α-SMA) and vimentin mRNA were detected with real-time fluorescence quantitative PCR. The phosphorylation of SMAD2/3 in the cells was detected using Western blotting. RESULTS: Calycosin, ononin and stigmasterol did not produce significant cytotoxicity in glomerular epithelial cells (P>0.05). The cells exposed to high glucose and calycosin treatment showed significantly decreased mRNA levels of α-SMA and vimentin (P<0.05) and inhibited phosphorylation of SMAD2/3. Ononin and stigmasterol did not produce such effects in the cells. CONCLUSION: In endothelial cells with high glucose-induced injury, calycosin can inhibit the up-regulation of α-SMA and vimentin and inhibit phosphorylation of SMAD2/3 to regulate endothelial-mesenchymal transition and improve diabetic nephropathy.

[V89L polymorphism of the testosterone 5-alpha-reductase II gene and prognostic factors of prostate cancer].

OBJECTIVE: To investigate the association of V89L polymorphism of the SRD5A2 gene with the prognostic factors of prostate cancer (PCa). METHODS: We identified the V89L polymorphic sites of the SRD5A2 gene after Rsa-1 restriction enzyme digestion, observed the distribution of V89L (VV, VL and LL) polymorphism in 112 PCa and 89 benign prostate hyperplasia (BPH) patients, and determined the association of V89L polymorphism with the age, free PSA (fPSA), total PSA (tPSA), fPSA/tPSA ratio, tumor stage and Gleason score of the PCa patients. RESULTS: No statistically significant differences were found in the V89L polymorphism-induced genetic risk frequencies between the PCa and BPH groups (chi2 = 3. 606, df = 2, P = 0. 165), nor any significant correlation between the genotypes of VV and VL + LL and the differences in the fPSA, tPSA, fPSA/tPSA ratio, tumor stage, Gleason score and age of the PCa patients. VV and VL + LL showed no obvious association with the prognostic factors of PCa. CONCLUSION: V89L polymorphism is not related with the prognosis of PCa, but may be indirectly associated with its risk.

[HPLC fingerprint for the Corydalis saxicola Bunting injection].

AIM: To establish the fingerprint of Corydalis saxicola Bunting injection. METHODS: It was performed by HPLC Kromasil column was used with acetonitrile and H2O as mobile phase. The flow rate was 0.5 mL x min(-1). The detection wavelength was 254 nm. The mass spectrometry detection was performed on a trap equipped with an ESI interface and operated in positive-ionization mode. RESULTS: Eleven components of Corydalis saxicola Bunting were identified by LC-MS and 7 of them were quantified. CONCLUSION: The fingerprint chromatogram could represent the characteristics of Corydalis saxicola Bunting injection. Evaluation of resemblances and results of precision were satisfactory. This method could be used as quality and quantity control.