Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg.kg-1 per day) and the high dose of BR combined with glycyrrhetinic acid (GA, 25 mg.kg-1 per day) or liquiritin (LQ, 20 mg.kg-1 per day) for 7 consecutive days. Compared with the control, brucine caused 24.5% and 34.6% decrease of CYP3A-associated testosterone 6beta-hydroxylation (6betaTesto-OH) and CYP2C-associated tolbutamide hydroxylation (Tol-OH), respectively, and 146.1% increase of CYP2El-associated para-nitrophenol hydroxylation (PNP-OH) at the high dose level. On the other hand, (BR+GA) caused 51.4% and 33.5% decrease, respectively, of CYP2El-associated PNP-OH and CYP1A2-associated ethoxyresorufin-O-de-ethylation (EROD) as compared with the high dose of BR group. Meanwhile, (BR+LQ) caused 41.1% decrease of CYP2El-associated PNP-OH and 37.7% increase of CYP2C-associated Tol-OH. The results indicated that the co-administration of BR with GA or LQ had effect on mRNA expression and activities of the CYP450 enzymes mentioned above to some extent, and the in vivo antagonism of LQ on BR-induced CYPs adverse effects and the in vivo inhibitory action of GA on CYP2E1 and 1A2 might play an important role in the detoxification of Radix Glycyrrhizae against Strychnos nux-vomica L.

OBJECTIVE:To establish a method for determining recombinant human calmodulin B subunit(rhCNB)in rat plas-ma,and study its pharmacokinetics characteristics. METHODS:ELISA double-antibody sandwich method was adopted. 1 μg/ml rhCNB monoclonal antibody mAb was wrapped,added to the to-be-test sample,rhCNB polyclonal antibody pAb(dilution ratio of 1∶5 000)and HRP-labeled conjugate of anti-IgG(dilution ratio of 1∶10 000)were added. Using tetramethylbenzidine for develop-ing,microplate reader was conducted in wavelength of 450 nm to determine the absorbance value(OD value)and plasma concen-tration of 6 rats after 2,15,30,60,120,240,480,720 min of iv 2.5 mg/kg rhCNB,and the pharmacokinetic parameters were calculated by BAPP 3.0 software. RESULTS:The linear range of rhCNB were 0.195-12.5 ng/ml(r2=0.995 0),lower limit of quan-titation was 0.195 ng/ml,accuracy were 97.300%-103.622%(RSD<7.5%,n=6);RSDs of within-batch,inter-batch,freezing and thawing 3 times were no higher than 8.5%(n=6,18,15). rhCNB pharmacokinetics characteristics in rat fitted to two-com-partment model,AUC0-720 min was 173.038 mg·min/L and t1/2 was 94.62 min. CONCLUSIONS:The established method has high specificity and sensitivity,good accuracy and precision,which can be used for rhCNB quantitative detection and pharmacokinetics study in biological samples.

Flammulin, an anti-tumor protein, was purified from the aqueous extract of basidiomes of Flammulina Velutipes. Purified flammulin emulsified with Freund's adjuvant was injected subcutaneously into New Zealand white rabbits. After several immune enhancements, these animals were bled and sera were separated. Antiserum against flammulin in Western blots were applied to determine if flammulin be present in the liquid state culture or fruiting body. The result showed that anti-flammulin serum could recognize the aqueous extract of fruiting body in SDS-PAGE gels under the reducing conditions, no flammulin was detected in mycelia of Flammulina Velutipes.

OBJECTIVETo explore an ideal method for repairing the skin-soft tissue defects according to the different anatomical units of cheek, and find reasonable design principles to transfer the expanded flaps.

METHODSAccording to the location of the defect, we placed 1-3 appropriate expanders nearby, when the flap expanded enough we adopted advanced skin flaps, rotation-advanced skin flaps or transposition skin flaps to repair the defect. In this group of 269 cases, the defects were secondary to hemangioma, various scars, nevus or nevus excision.

RESULTSIn all 269 cheek defects, 305 expanded flaps were developed which included 145 rotation-advanced flaps, 121 advanced skin flaps and 39 transposition skin flaps. 52 of them generated complications, including blood circulation disorder of the distal part of flaps, hematoma, infection, injection, lower eyelid ectropion, expander extrusion and capsule contracture. Mostly, these complications didn't affect the final results.

CONCLUSIONSThe principles presented in this article are the guidelines to treat the skin-soft tissue defect of check with tissue expansion. The satisfied results come from the reasonable flap designs.

Adolescent ; Adult ; Cheek ; surgery ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Surgical Flaps ; Tissue Expansion ; methods ; Young Adult

Alzheimer’s disease (AD) remains to be a grand challenge for the international commu-nity despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripo-tent cells (iPSCs). Comprehensive information collection, better understanding of the disease mech-anisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.

OBJECTIVETo study the effects of drug plasma of musk and olibanum (DP-M&O) on the release of inflammatory cytokines from monocytes and the expressions of the proteins associated with inflammation of prostatic or endothelial cells induced by prostate antigen (PAg) stimulation.

METHODSWe prepared DP-M&O using SD rats and monocytes and PAgs using BALB/c mice. We pre-treated the monocytes with DP-M&O at the gradient concentrations of 0, 2.5, 5, 10, and 20% for 1 hour, activated them with PAgs, and then cultured them for 96 hours, followed by detection of the release of inflammatory cytokines. We co-cultured the prostate RWPE-1 cells with the endothelial EA. hy926 cells, pre-treated them with the same gradient concentrations of DP-M&O as above for 1 hour, activated with PAgs, and cultured for 96 hours. Then we determined the expression levels of the proteins associated with inflammation of RWPE-1 and EA. hy926 cells by Western blot.

RESULTSDP-M&O decreased the levels of TNF-alpha, IL-1beta, IL-6, and IL-8 and increased that of IL-10 in a concentration-dependent manner. Significant differences were found between the 20% P-M&O and PAg groups in the release of the inflammatory cytokines TNF-alpha (70.8 +/- 22.3 vs. 277.1 +/- 65.5, P < 0.01) , IL-113 (277.5 +/- 22.6 vs. 630.4 +/- 89.7, P <0.01), IL-6 (232.7 +/- 62.7 vs. 994.2 vs. 182.3, P < 0.01), IL-8 (227.3 +/- 79.2 vs. 769.3 +/- 284.1, P < 0.01), and IL-10 (640.2 +/- 201.2 vs. 271.1 +/- 55.8, P < 0.01). Compared with the PAg group, the 10 and 20% P-M&O groups showed remarkable decreases in the protein expression of MCP-1/CCL2 in the RWPE-1 cells (1.12 +/- 0.34 vs. 0.56 +/- 0.11 and 0.34 +/- 0.08) and that of VCAM-1 in the EA. hy926 cells (0.94 +/- 0.22 vs. 0.52 +/- 0.17 and 0.38 +/- 0.12) (P < 0.05 or 0.01).

CONCLUSIONThe compatibility of musk and olibanum can decrease the expression of MCP-1/CCL2 in prostate cells and VCAM-1 in vascular endothelial cells, blocking the adhesion of leucocytes and suppressing inflammatory response.

Animals ; Blotting, Western ; Cytokines ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; Fatty Acids, Monounsaturated ; pharmacology ; Frankincense ; pharmacology ; Inflammation ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; Male ; Mice ; Mice, Inbred BALB C ; Monocytes ; drug effects ; metabolism ; Prostate ; cytology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

Circular RNA (circRNA) is a new type of non-coding RNA with closed circular structures that are widely distributed in various tissues Compared with traditional linear RNA, circRNA does not have 5′ and 3′ ends and will not be easily degraded by exonuclease It can stably exist in a variety of body fluids and is evolutionarily conserved It has become a key research object of clinical non-coding RNA Malignant tumors have the characteristics of late detection, rapid progression, and easy recurrence Currently, effective treatment methods are lacking, and their morbidity and mortality have been high Therefore, how to carry out early diagnosis, treatment intervention and prognosis evaluation is one of the research frontier of contemporary medical research CDR1as is the most widely studied circRNA It can regulate the expression of downstream genes through sponge microRNA (miRNA) or directly bind to RNA-binding proteins (RBPs) to activate related signaling pathways, thereby promoting or inhibiting tumor progression, and even affecting tumor chemotherapy sensitivity CDR1as mainly exists in the cytoplasm and can be released into the blood at the early stage of the disease Therefore, CDR1as may become a bi-omarker for early diagnosis of malignant tumors or an ideal target for therapeutic intervention Focusing on the characteristics and biological functions of circRNA, this article reviews the expression level, mechanism of action and related signaling pathways of CDR1as in the occurrence and development of malignant tumors At the same time, this article analyzes the current research status of CDR1as, preliminarily summarizes the problems it may face in clinical applications in the future, and puts forward ideas and suggestions on the future research direction of CDR1as

AIMTo rapidly separate and determine the nucleosides from natural and cultured Cordyceps kyushuensis Kob., and to compare the content of cordycepin and adenosine in different parts of Cordyceps kyushuensis Kob., which are the main nucleoside active components in medicinal fungus belonging to Cordyceps (Fr.) Link.

METHODSThe nucleosides were separated and determined by the high performance capillary zone electrophoresis (CZE). Beckman P/ACE system MDQ apparatus equipped with a PDA detector and a uncoated fused-silica capillary (41 cm x 45 microns ID, 30 cm effective length) were used. The experimental conditions were as follows: the running buffer was borax solution (adjust to pH 9.4 with sodium hydroxide), applied voltage was 20 kV, operated temperature was 20 degrees C and the detector wavelength was 258 nm. The content of cordycepin and adenosine in the fruiting body, stroma and host worm of natural and cultured C. kyushuensis were respectively investigated and quantitatively analyzed.

RESULTSThere are at least 8 kinds of nucleoside or nitrogen base in Cordyceps kyushuensis Kob. The content of cordycepin which is a bio-active substance with anti-tumor activity in C. kyushuensis is significantly higher than that in C. sinensis and C. militaris, and furthermore the cordycepin in the cultured C. kyushuensis is notably higher than the natural one. Adenosine was mainly found from the stroma of C. kyushuensis, While the cordycepin content is high in the stroma of both natural and cultured C. kyushuensis as well as in the host worm of the cultured one.

CONCLUSIONThere are some differences about the nucleoside components between the natural and cultured C. kyushuensis and between the different parts of them. With a high cordycepin content, C. kyushuensis should have a considerable medicinal potential.

Adenosine ; analysis ; isolation & purification ; Animals ; Cordyceps ; chemistry ; classification ; Deoxyadenosines ; analysis ; isolation & purification ; Lepidoptera ; chemistry ; microbiology ; Nucleosides ; analysis ; isolation & purification

OBJECTIVETo observe the effect of acupoint catgut embedding on height of adolescents with spleen qi deficiency.

METHODSThree hundred voluntary adolescents with spleen qi deficiency syndrome who want to increase height were stratified according to sex first, and then randomly divided into an observation group, a control group and a placebo group, 100 cases in each group. The observation group was treated with acupoint catgut embedding at Zusanli (ST 36), Pishu (BL 20), Weishu (BL 21) etc. The control group was treated with oral administration of Lysine Dicalcium Phosphate particles, and the placebo group was treated with oral administration of flour capsule. The height was measured and the therapeutic effects were detected after treatment of 3 months and 6 months respectively.

RESULTSThe total effective rate of 95.0% (95/100) in the observation group was superior to that of 49.0% (49/100) in the control group and 0 (0/100) in the placebo group (both P < 0.05). The height increased more obviously in the observation group than that of the control group and the placebo group, there were significant differences among three groups (all P < 0.01).

CONCLUSIONAcupoint catgut embedding can increase the height and improve the symptoms of the adolescents with slow growth caused by spleen qi deficiency.

Acupuncture Points ; Adolescent ; Adolescent Development ; Body Height ; Catgut ; Female ; Humans ; Male ; Qi ; Spleen ; physiopathology

OBJECTIVETo explore the effect and mechanism of Poly I:C in inducing growth inhibition and apoptosis of human hepatocellular carcinoma SMMC-7721 cells.

METHODSSMMC-7721 cells were treated with different doses of Poly I:C for 24, 48, and 72 h, and the cell growth inhibition rate was analyzed with CCK-8 assay. The cell cycle and the apoptosis were analyzed using flow cytometry with Annexin-V and PI staining, and quantitative RT-PCR analysis were used to detect the expression of TLR3, TRIF, and IFN-beta mRNA in cells.

RESULTSIn the cells exposed to Poly I:C at low, moderate, and high doses, the inhibitory rates was the highest in high-dose Poly I:C group, and at a given Poly I:C dose, prolonged exposure resulted in significantly increased cell growth inhibition rate (P<0.05). Flow cytometry showed that Poly I:C induced cell apoptosis in a time- and dose-dependent manner and significantly increased the percentage of G1-phase cells as compared with that in the control group. The mRNA level of TLR3, TRIF, and IFN-beta were also increased following Poly I:C treatment in comparison with the control group.

CONCLUSIONPoly I:C can induce significant growth inhibition and apoptosis of SMMC-7721 cells in a dose- and time-dependent manner possibly by causing cell cycle arrest and TLR3 signaling pathway activation that leads to IFN-beta production and cell apoptosis.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Interferon-beta ; genetics ; metabolism ; Liver Neoplasms ; pathology ; Poly I-C ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Receptors, Cholecystokinin ; metabolism ; Signal Transduction ; Toll-Like Receptor 3 ; genetics ; metabolism