Angiogenesis Inhibitors ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Phytotherapy ; Precancerous Conditions ; drug therapy ; Stomach Neoplasms ; blood supply ; drug therapy

To explore the effective ingredients and mechanism of Ligusticum wallichii in treating brain ischemia. Four brain ischemia-related target proteins were selected in the joint screening for the 45 component in L. wallichii reported in literatures based on molecular docking by reference to the corresponding drugs in the market. According to the docking results, multiple components in L. wallichii, such as phthalides, were superior to the corresponding drugs in the market, suggesting that they may be the major effective components in L. wallichii for treating brain ischemia. The method can be used to study the material base and molecular mechanism of traditional Chinese medicines.
Brain Ischemia ; drug therapy ; Ligusticum ; chemistry ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Nitric Oxide Synthase Type II ; antagonists & inhibitors ; Peroxidase ; antagonists & inhibitors ; Phytotherapy ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors

To collect small molecule drugs and their drug target data such as enzymes, ion channels, G-protein-coupled receptors and nuclear receptors from KEGG database as the training sets, in order to establish drug-target interaction models based on the random forest algorithm. The accuracies of the models were evaluated by the 10-fold cross-validation test, showing that the predicted success rates of the four drug target models were 71.34%, 67.08%, 73.17% and 67.83%, respectively. The models were adopted to predict the targets of 26 chemical components and establish the compound-target-disease network. The results were well verified by literatures. The models established in this paper are highly accurate, and can be used to discover potential targets in other traditional Chinese medicine ingredients.
Algorithms ; Drugs, Chinese Herbal ; pharmacology ; Gene Regulatory Networks ; drug effects ; Humans ; Ligusticum ; chemistry ; Molecular Targeted Therapy ; Rhizome ; chemistry

Action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis were discussed based on gene expression profile and molecular fingerprint in this paper. First, gene expression profiles of atherosclerotic carotid artery tissues and histologically normal tissues in human body were collected, and were screened using significance analysis of microarray (SAM) to screen out differential gene expressions; then differential genes were analyzed by Gene Ontology (GO) analysis and KEGG pathway analysis; to avoid some genes with non-outstanding differential expression but biologically importance, Gene Set Enrichment Analysis (GSEA) were performed, and 7 chemical ingredients with higher negative enrichment score were obtained by Cmap method, implying that they could reversely regulate the gene expression profiles of pathological tissues; and last, based on the hypotheses that similar structures have similar activities, 336 ingredients of compound Danshen dripping pills were compared with 7 drug molecules in 2D molecular fingerprints method. The results showed that 147 differential genes including 60 up-regulated genes and 87 down regulated genes were screened out by SAM. And in GO analysis, Biological Process ( BP) is mainly concerned with biological adhesion, response to wounding and inflammatory response; Cellular Component (CC) is mainly concerned with extracellular region, extracellular space and plasma membrane; while Molecular Function (MF) is mainly concerned with antigen binding, metalloendopeptidase activity and peptide binding. KEGG pathway analysis is mainly concerned with JAK-STAT, RIG-I like receptor and PPAR signaling pathway. There were 10 compounds, such as hexadecane, with Tanimoto coefficients greater than 0.85, which implied that they may be the active ingredients (AIs) of compound Danshen dripping pills in treatment of carotid atherosclerosis (CAs). The present method can be applied to the research on material base and molecular action mechanism of TCM.
Carotid Artery Diseases ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Humans ; Salvia miltiorrhiza ; chemistry ; Signal Transduction ; drug effects

Objective:To investigate the levels of periphreal blood free carnitine and amino acids in healthy pregnant women in the third trimester and their association with maternal, fetal, and neonatal cardiac function and structure.Methods:This prospective descriptive study included healthy singleton pregnancies who underwent routine obstetric examination and delivered in two district maternal and child health hospitals (one in the urban and one in the suburb an area) in Beijing from June 2017 to February 2018. All recruiters had serology Down's syndrome screening test at (18±1) gestational weeks. Besides measurement of amino acids and free carnitine levels in whole blood and urine samples by liquid chromatography-tandem mass spectrometry, all cases underwent maternal and fetal echocardiography at (35±1) weeks of gestation. And neonatal echocardiography was performed after delivery to assess the heart function and structure. Antenatal factors were also collected, including maternal education background, age at first marriage and conception, gravidity, and folic acid supplement in early pregnancy. Statistical analysis was performed using t-test, ANOVA, Chi-square test, Pearson correlation coefficient, and Kappa test. Results:A total of 493 mother-neonate dyads were enrolled in this study. Blood free carnitine levels in the healthy pregnant women in the third trimester ranged from 5.09 to 59.17 μmol/L (reference value: 10.00-50.00 μmol/L) with an average value of (13.03±3.87) μmol/L. None was found with structural abnormalities by cardiac ultrasound, showing an average left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) of (45.70±3.08) mm and (29.17±3.12) mm, respectively, and left ventricular ejection fraction (LVEF) of all cases were over 55%. No cardiac malformation was detected by the third-trimester fetal echocardiography. The average birth weight of the 493 newborns was (3 340±313) g. Those whose birth weight <2 500 g and >4 000 g were accounted for 1.0% (5 cases) and 3.0% (15 cases) with the average maternal blood free carnitine level of (13.25±2.17) μmol/L (10.46-19.21 μmol/L) and (12.64±2.50) μmol/L (8.78-17.73 μmol/L) ( t=0.42, P>0.05). The average LVEDD and LVESD of the 493 newborns were (17.21±1.27) mm and (11.03±1.30) mm, respectively. For the 64 newborns (13.0%) whose LVEF<60%, the maternal blood free carnitine level was (12.93±2.78) μmol/L (7.34-22.13 μmol/L), showing no statistical difference ( t=-0.29, P>0.05) with those 59 neonates (12.0%) whose LVEF over 75% and maternal carnitine level of (13.09±3.24) μmol/L (8.66-27.49 μmol/L). All cases were divided into four groups based on the quartiles of maternal blood free carnitine level and no significant difference in maternal or neonatal LVEDD or LVEF was observed among these groups (all P>0.05). Conclusions:Blood free carnitine concentration in healthy pregnant women in the third trimester is at the lower limit of normal range, and no significant effect on maternal cardiac function and fetal cardiac structure is seen. However, the effect of low maternal carnitine level in the third trimester on children's myocardial function and whether carnitine should be supplemented in the third trimester are worthy of further investigation with larger sample size.

Objective To study the immunologic and pathologic features of an accelerated rejection model of renal allotransplantation in presensitized monkeys.Methods The accelerated rejection model of renal allotransplantation was established in presensitized monkeys,which received donor skin transplantation in advance(n=3).The changes of donor specific antibody(DSA)levels in the recipient monkeys before/after skin and kidney transplantation were measured.The kidney grafts were examined for routine pathology,antibody and complement depositions,various lymphocyte subsets infiltration by HE staining,immunofluorescence,or immunohistochemistry.Results All renal allografts in 3 presensitized monkeys developed accelerated rejection within 4 days.In 2 presentized monkeys,the levels of DSA and their mediated complement-dependent cytotoxicity(CDC)were significantly increased after skin transplantation,and further markedly elevated at the time of kidney graft rejection.In the rejected renal grafts,massive C3,C4,C5b-9 and IgG deposits with few lymphocytes infiltration were found.Typical pathologic changes included severe arterionecrosis,thrombosis,interstitial hemorrhage,and infiltration of neutrophils.In the rest one presentized monkey,the levels of DSA and CDC were only marginally increased,and the pathological changes of the rejected renal graft were characterized mainly by the injury of renal tubules.Conclusion Presensitization by donor skin transplantation could elevate the levels of DSA and CDC in recipient monkeys,which resulted in severe antibody-mediated acute humoral rejection in most of the following renal transplants.

Objective To establish the method for isolation and culture of porcine Sertoli cell sand detect the expression of the immune privilege-related molecules in the cultured cells. MethodsTestes were aseptically removed from the 10-to 15-days old Large White piglets. Testes were decap-sulated, minced and then digested with 0.2% (W/V) collagenase type V, 0.25% (W/V) trypsin and 0.05% (W/V) DNaseI. In the primary isolation, Sertoli cells were cultured at 37℃with 5% CO2.Inverted phase contrast microscopy and HE staining were used to observe the morphology of Sertoliceils, and the Sertoli cells were identified under an electron microscope. Viability and apoptosis ofcultured cells were measured with the AnnexinV-PI staining by flow cytometry. The expression of sox9, FasL, TGF-β and clusterin in Sertoli cells was detected by RT-PCR. The viability of long-termcultured Sertoli cells was assayed by MTT. Results In the cultured total cells, Sertoli cells accountedfor more than 90%. The apoptosis rate and mortality of Sertoli cells was (2.61±0.96)% and (2.12±0.74)% respectively. RT-PCR revealed that the expression of sox9, TGF-β and clusterin in theSertoli cells was strongly positive, but FasL was weakly positive. Viability of cultured cells measuredby MTT conformed that the sertloli cells could survive more than 21 days. Conclusion The isolationand culture methods of the neonatal porcine Sertoli cells was established. Under the culturedconditions, the Sertoli cells can express the immune privilege molecules and successfully survive at least 21 days.

OBJECTIVETo observe the effects of electroacupuncture (EA) on circadian rhythm of temperature and melatonin (MT) in depression rats model induced by chronic stress, so as to explore the biological mechanism of EA for depression.

METHODSTwenty-four SD rats were randomly divided into a control group, a model group and an EA group, 8 cases in each one. Rats in the control group were treated with normal diet for 21 days without any treatment. In the model and EA group, rat model was established by chronic unpredictable stress combined with solitarily feeding method, and rats in the EA group was treated with EA at "Baihui" (GV 20), "Yintang" (GV 29) 1 h before stress stimulation everyday, 2 Hz in frequency and intensity was favorable with the head of rat slightly shivering. The needles were retained for 20 min, once a day for totally 21 days. After EA treatment, open-field experiment was adopted to observe the behavioral improvement; the rats temperatures were monitored at six time points (2:00, 6:00, 10:00, 14:00, 18:00, 22:00) and orbital blood sampling was collected. The level of serum MT was tested by enzyme linked immunosorbent assay. The circadian rhythm changes of temperature and serum MT in each group were compared.

RESULTSThe numbers of horizontal movement and vertical movement in the model group were obviously lower than those in the control group (both P < 0.05), while those in the EA group were significantly improved compared with those in the model group (both P < 0.01). The circadian rhythm of temperature and MT disappeared in the model group, which was improved into normal level after EA treatment.

CONCLUSIONThe electroacupuncture has regulation effects on circadian rhythm of temperature and melatonin in depression rat model induced by chronic stress.

Animals ; Circadian Rhythm ; Depression ; metabolism ; physiopathology ; therapy ; Electroacupuncture ; Humans ; Male ; Melatonin ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of decompresion through double-incision of foot dorsum on the treatment of osteofascial compartment syndrome of the foot under the monitoring of saturation of blood oxygen.

METHODSFrom January 2000 to June 2007, 26 cases of osteofascial compartment syndrome of the foot were decompressed through double-incision of foot dorsum under the monitoring of saturation of blood oxygen, and relaxation suture or skin grafting were operated within 3 to 10 days after decompressing. Among them, 22 patients were males and 4 were females, with an average age of 36.3 years old ranging from 22 to 68 years. According to AOFAS system, the pain, function, autonomic activities and support were evaluated.

RESULTSAll patients were followed-up for from 6 to 43 months with the average of 19 months. All patients were healed. According to AOFAS system, the total scores increased from preoperative (30.4 +/- 8.02) to postoperative (92.5 +/- 5.0) (t = 3.13, P < 0.01); the results were excellent in 21 cases, good in 4 and poor in 1.

CONCLUSIONThe patients of fracture-dislocated, swelling and injured in the soft tissue because of severe violence should observed closely on osteofascial compartment syndrome of the foot early. Feet are operated and thoroughly decompressed as soon as it is diagnosed as the compartment syndrome. Osteofascial compartment syndrome of the foot decompressed by foot dorsum double-incision is convenient and satisfied, and the operation is performed by internal fixation if it is displacedly fractured at the same time.

Adult ; Aged ; Compartment Syndromes ; blood ; diagnosis ; physiopathology ; surgery ; Early Diagnosis ; Female ; Foot ; blood supply ; physiopathology ; surgery ; Humans ; Male ; Middle Aged ; Oxygen ; blood ; Young Adult

OBJECTIVETo evaluate the effect of neuronal differentiation induced by nerve growth factor (NGF) on the tolerance-dosage of ultraviolet radiation of PC12 Cells.

METHODSNeuron-differentiated PC12 cells and untreated PC12 cells were exposed to different ultraviolet radiation dosage of 10, 30, 60, 80, 100, and 200 mJ/cm2. Cell survival rates were determined by MTT assay.

RESULTSNeuron-differentiated PC12 cells had increased tolerance dose to ultraviolet radiation with noticeable apoptosis at the radiation dose of 100 mJ/cm2 in contrast to 30 mJ/cm2 for normal PC12 cells.

CONCLUSIONNeuronal differentiation exerts the effect of increasing the tolerance dose of PC12 cells to ultraviolet radiation.

Animals ; Cell Differentiation ; Cell Transformation, Neoplastic ; drug effects ; radiation effects ; Dose-Response Relationship, Radiation ; Nerve Growth Factor ; pharmacology ; Neurons ; cytology ; PC12 Cells ; Rats ; Ultraviolet Rays