1.Advances in lymphatic targeted drug delivery system for treatment of tumor metastasis
Journal of China Pharmaceutical University 2020;51(4):425-432
Lymphatic metastasis is one of the main routes of tumor metastasis. The limitation of traditional medicine in the treatment of lymphatic tumor metastasis lies in the low concentration of the drug in lymphatic metastases resulting in poor efficacy. Nanocarrier-based drug delivery system plays an important role in enhancing drug targeting, improving drug bioavailability, and reducing side effects. This review introduces the composition and function of the lymphatic system as well as its role in tumor metastasis, enumerates the present therapeutic means and limitations of anti-tumor lymphatic metastasis, and focuses on the recent advances in the passive, active and antigen-presenting cell-mediated lymphatic targeted drug delivery systems in tumor metastasis are highlighted.
2.Clinical observation of recent Hormone sequential therapy for active rheumatoid arthritis
Ran ZHANG ; Fan YANG ; Bo WANG ; Li HE ; Nanping XIAO
Chinese Journal of Primary Medicine and Pharmacy 2014;21(1):51-53
Objective To observe the recent clinical efficacy of the sequential therapy hormone in the treatment of active rheumatoid arthritis.Methods In accordance with the principle of digital sheet,160 patients with active rheumatoid arthritis were randomly divided into the observation group and the control group,80 cases in each group.On the basis of methotrexate and leflunomide in both groups,the hormone sequential therapy was given in the observation group,but prednisone was given in the control group.The clinical efficacy of treatment after 1 week and 3 months were compared in two groups.Results In the observation group,the indicators in 7 d after treatment were significantly reduced,compared with untreated(t =19.90,7.63,14.73,7.58,6.84,14.09,all P <0.01),In the control group,three indicators of the duration of morning stiffness,joint tenderness index and joint swelling index in 7d after treatment were significantly reduced,compared with untreated (t =13.42,3.34,7.24,all P < 0.01),Compared the indicators in the two groups in 7 d after treatment,there were statistically significant differences (t =13.07,4.92,10.51,5.23,5.74,15.03,all P < 0.01).The indicators in the 3 months after treatment in both groups were signifi cantly decreased,buttherewasnosignificantdifferencebetweenthetwogroups (t =1.80,1.73,1.59,1.22,1.21,1.35,all P > 0.05).The total effective rate was 80% in the observation group; but the rate was 75 % in the control group;there was no statistically significant difference in the two groups(x2 =0.57,P > 0.05).Conclusion The sequential hormone therapy is an effective means for the treatment of active rheumatoid arthritis,by controlled the symptoms of rheumatoid arthritis effectively and alleviated the patient's condition.
3.Preparation of monoclonal antibody against human tissue kallikrein and development of an ELISA kit
Xiao RAN ; Qin ZHANG ; Zhixiong XIANG ; Hui YANG
Chinese Journal of Microbiology and Immunology 2011;31(2):178-182
Objective To prepare monoclonal antibody(McAb) against human tissue kallikrein (HK) and develop an ELISA kit allows for the in vitro quantitative determination of human tissue kallikrein in urine. Methods To generate a monoclonal antibody specific for TK, the synthetic TK peptide consisting of 12 amine acids(12P), was fused to keyhole limpet hemocyanin(KLH) and used for immunization. Using hybridoma screening, monoclonal secreting cell lines were identified and used to generate ascites in BALB/c mouse. Antibody was purified by affinity column chromatography. 12% SDS-PAGE and Western blot were used to visualize the purified antibody. This kit employs indirect competitive ELISA technique and BiotinAvidin System. 12P was fused to bovine serum albumin(BSA) and has been pre-coated onto a microplate at first. Standards and samples were added to the appropriate microplate wells with a biotin-conjugated McAb croplate well. A TMB substrate solution is added to each well. The enzyme-substrate reaction is terminating by the addition of a sulphuric acid solution and the color change is measured spectrotometrically at a wavelength of 450 nm. The concentration of tissue kallikrein in the samples is then determined by comparing the O.D. of the samples to the standard curve. Results 8 hybridoma cell lines secreting mAbs special to HK,SDS-PAGE and Western blot demonstrated successful preparing and purification of McAb( 100% ). The linearity of this ELISA kit is demonstrated(r =0. 990). The range of detection of the assay is 0.008 μg/ml to 0. 5 μg/ml. The assay remained stable, with no change in the values measured, over five cycles of freezing and thawing. Conclusion 8 McAbs against HK have been prepared successfully and possess high titer and specificity. The development of an ELISA kit for detecting HK can meet the needs of detection of HK in urine samples.
4.Study on pharmacokinetics of geniposide in mice administrated by xingnaojing microemulsion and mPEG2000-PLA modified xingnaojing microemulsion.
Ran WEN ; Xiao-Lan CHEN ; Hui-Yun LI ; Qing-Li GUO ; Yang LU ; Shou-Ying DU
China Journal of Chinese Materia Medica 2014;39(6):1111-1114
An HPLC method for the determination of geniposide concentration in mouse plasma was developed and the pharmacokinetics after intranasal administration of Xingnaojing microemulsion (XNJ-M) and mPEG2000-PLA modified Xingnaojing microemulsion (XNJ-MM) were investigated. Eighty mice were treated by XNJ-M and XNJ-MM nasally. The plasma samples were collected at different times and the drug in samples was detected by HPLC. The pharmacokinetic parameters were calculated by the software of Kinetica. The pharmacokinetic parameters of geniposide of XNJ-M were C(max) (4.36 +/- 2.69) mg x L(-1), t(max) 1 min, MRT (29.73 +/- 4.54) min, AUC (53.63 +/- 14.03) mg x L(-1) x min. The pharmacokinetic parameters of geniposide of XNJ-MM were C(max) (9.75 +/- 4.14) mg x L(-1), t(max) 1 min, MRT(22.34 +/- 2.90) min, AUC (131.87 +/- 40.13) mg x L(-1) x min. Geniposide can be absorbed into blood in a higher degree after intranasal administration with XNJ-MM compared to XNJ-M, which maybe caused by its less irritating and more absorption.
Animals
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Drugs, Chinese Herbal
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administration & dosage
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chemistry
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Emulsions
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Iridoids
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blood
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pharmacokinetics
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Lactic Acid
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chemistry
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Male
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Mice
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Polyesters
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Polyethylene Glycols
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chemistry
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Polymers
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chemistry
5.Effect of calcium alginate gel-bone morphogenetic protein-red bone marrow compound on the osteoinductivity
Zhongshi XU ; Shuhua YANG ; Deming XIAO ; Bowen LIN ; Xiaoming ZHANG ; Ran LI
Chinese Journal of Tissue Engineering Research 2007;11(18):3640-3643
BACKGROUND: The bone marrow stromal cells in red bone marrow (RBM) are the non-specific bone growth factors,and the target cells of bone morphogenetic protein (BMP), and they have the activities of osteoinduction and osteogenesis.Injectable calcium alginate gel (CaAG) is a degradable biomaterial with good histocompatibility,it provides scaffold for the proliferation and adhesion of osteoblasts and chondroblasts,and it is good for the proliferation of new capillaries.OBJECTIVE:To prepare CaAG-BMP-RBM gel compound,and observe its osteoinductivity.DESIGN:A randomized controlled animal trial.SETTINGS:Department of Orthopaedics,Shenzhen People's Hospital;Department of Orthopaedics,Union Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology.MATERIALS:The experiments were carried out in Shenzhen People's Hospital from February 2002 to February 2003.Twenty-seven pure SD rats, either male or female,weighing (200±20) g,were purchased from the Animal Experimental Center of Southern Medical University (No.SCXK2002-99).BMP was bought from Xijing Hospital affiliated to the Fourth Military Medical University of Chinese PLA.METHODS:The rats were randomly divided into three groups:CaAG-BMP-RBM group(n=9),CaAG.BMP group (n=9) and CaAG group (n=9).In the CaAG-BMP-RBM group,the rats were anesthetized,then 0.1 mL RBM collected from trochanteric section of fetour was added into the prepared CaAG-BMP compound (0.4 mL),sufficiently mixed,and then injected into posterior femoral muscle.The rats in the CaAG-BMP group and CaAG group were implanted with CaAG-BMP and CaAG into bilateraI posterior femoral muscles respectively.①The conditions of becoming conscious after anesthesia, incision healing, diet and activities were observed, the size and consistency of the implants and distribution of vessels were also observed.②The indexes were detected at 1,2 and 4 weeks after model establishment respectively,and 3 rats were used for each time point.The sections were observed under light microscope.and the activity of alkaline phosphatase (ALP) was determined.MAIN OUTCOME MEASURES: ①General conditions of animals and gross observation of the implants;②Histopathological observation;③ALP activities.RESULTS: All the 27 SD rats were involved in the analvsis of results.The rats became conscious at 4.6 hours after anesthesia,and they could eat normally;Hematom at incision disappeared.and the rats could move normally at 24 hours;No sign of infection at incision was observed at 72 hours;The incisions healed completely and suture shed after 2 weeks.The incisions were stage Ⅰ healing in all the 27 rats.①Results of gross observation of the implants:At 1 week after implantation.the size of implant did not decrease and vessels in-grew in both the CaAG-BMP-RBM group and CaAG-BMP group;At 2 weeks,lhe quality was hard, and the section appeared as gray and white with deposition of bone-like tissues;At 4 weeks,a great amount of vessels in-grew,and there were many depositions of hard bone-like tissues.②Results of the histopathological observation under light microscope:In the CaAG-BMP.RBM group.many mesenchymal cells aggregated, osteoblasts and chondroblasts proliferated actively al 1 week;The chondrocytes tended to mature with cartilage-like and bone-like matrixes at 2 weeks; Many osteocytes were observed and fibrous bone formed at 4 weeks.which were more then those in the other two groups.③Results of ALP activity:At 1.2 and 4 weeks after implantation.the ALP activities in the CaAG group [(0.179±0.018),(0.058±0.017).(0.027±0.018)IU/g] were lower than those in the CaAG-BMP-RBM group[(0.922±0.226),(1.169±0.249),(0.431±0.081)IU/g,P<0.01);At 1 and 4 weeks,the ALP activities in the CaAG-BMP group[(0.447±0.015),(0.276±0.081)IU/g]were lower than those in the CaAG-BMP-RBM group (P<0.05).CONCLUSION:The compound of CaAG-BMP-RBM possesses stable and lasting osleoinductivity.
6.Meta-Analysis on the relationship between children,s high iodine goiter and excessive iodine
Sisi REN ; Lu XIAO ; Shunli RAO ; Jing YANG ; Dong ZHENG ; Xin LUO ; Lijun LIU ; Kaifen RAN
Chongqing Medicine 2015;(2):229-231,234
Objective To comprehensively evaluate the relationship between children's high iodine goiter and excessive iodine . Methods A computerized literature search was carried out to collect articles published before 2014 in electronic databases CBM , WabFang ,VIP ,CNKI ,PubMed ,EMbase ,Ovid and Cochrane Library .The study type was randomized controlled trial or quasi‐ran‐domized control trial .Literature was analyzed by RevMan5 .0 software ,then calculated and combine RR and 95% CI .Publication bi‐as of Meta analysis was evaluated by Begg's test ,Egger's test and Macaskill's test .The result stability of Meta analysis was tested by sensibility analysis .Results A total of 10 controlled before and after studies were included in our meta‐analysis .The result showed that the iodine content of 150 -300 μg/L (RR:1 .54 ;95% CI:1 .14 -2 .07);301 -600 μg/L (RR:2 .33;95% CI:1 .43 -3 .82);601-900 μg/L (RR:2 .72 :95% CI:1 .01-7 .33) and greater than 900μg/L (RR:2 .41 ;95% CI:1 .38-4 .23) would result in chil‐dren goiter .Conclusion Iodine content greater than 150 μg/L would result in children goiter .
8.Isoflavonoids from Caragana changduensis and their nitric oxideinhibitory activities.
Xiao-dong SUN ; Shi-ming FANG ; Mao-dan ZANG ; Cheng-xiong YANG ; He-ran LI ; Susumu KITANAKA ; Xue-dong YANG
China Journal of Chinese Materia Medica 2015;40(16):3220-3223
Ten isoflavonoids were isolated from the heartwoods of Caragana changduensis Lion f. by means of various column chromatographic techniques. Based on the detailed spectral data analysis (MS and NMR), as well as comparison with the literatures, their chemical structures were determined as 7,2'-dihydroxy-8,4'-dimethoxyisoflavone (1), 4'-hydroxy-7,3'-dimethoxyisoflavone (2), 5, 7, 4'-trihydroxy-2',5'-dimethoxyisoflavone (3), prunetin (4), afrormosin (5), odoratin (6), genistein (7), texasin (8), pratensein (9), and 6,7,3'-trihydroxy-4'-methoxyisoflavone (10). Among them, compounds 1-3 and 9-10 were isolated from the Caragana genus for the first time. All the compounds were obtained from this species for the first time. In the preliminary assays, compounds 1, 2, 6, and 7 possessed significant inhibitory effects on NO production, with IC50 values of 48.12, 25.32, 62.71, 43.59 μmol x L(-1), respectively.
Animals
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Caragana
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chemistry
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Drugs, Chinese Herbal
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chemistry
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isolation & purification
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pharmacology
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Isoflavones
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chemistry
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isolation & purification
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pharmacology
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Macrophages
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drug effects
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metabolism
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Mice
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Molecular Structure
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Nitric Oxide
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antagonists & inhibitors
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metabolism
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RAW 264.7 Cells
9.Protective effect of DIZE on heart function of rats with diabetic cardio-myopathy
Min YANG ; Xin-Ran CAO ; Yuan-Yuan WANG ; Xiao-Qiong WANG ; Shi-Ran YU ; Bo DONG ; Jing GAO
Chinese Journal of Pathophysiology 2018;34(1):147-151,177
AIM:To observed the protective effect of diminazene aceturate(DIZE),an angiotensin-converting enzyme 2(ACE2)activator,on rats with diabetic cardiomyopathy(DCM).METHODS:Male Wistar rats(n=30)were randomly divided into normal control group ,DCM group and DIZE treatment group(DIZE group).The rats in DCM group and DIZE group were intraperitoneally injected with streptozotocin(65 mg/kg )to establish diabetic model.After 12 weeks,the diabetic rats were infused with DIZE at 15 mg· kg-1 · d-1 or the same volume of saline for 4 weeks using os-motic minipump.The cardiac function was measured at the end of the 16th week.The methods of Mason staining and HE staining were used to observe the morphological changes of the myocardial tissue.Western blot ,ELISA and immunohisto-chemistry were used to observe the changes of ACE2,angiotensin(Ang)Ⅱ,Ang-(1-7),interleukin(IL)-1,IL-6 and connective tissue growth factor(CTGF).RESULTS:DIZE significantly improved the expression of ACE 2 in diabetic rats(P<0.05).Compared with DCM group,the levels of IL-1 and IL-6 in DIZE group were significantly decreased ,and the cardiac function in DIZE group was significantly improved(P<0.05).CONCLUSION:ACE2 endogenous agonist DIZE significantly increases the ACE 2 level and reduces the level of inflammation ,thus protecting the heart function of DCM rats.
10.Effects of stereoscopic cultivation on soil microorganism, enzyme activity and the agronomic characters of Panax notoginseng.
Pei-ran LIAO ; Xiu-ming CUI ; Lei LAN ; Wei-dong CHEN ; Cheng-xiao WANG ; Xiao-yan YANG ; Da-hui LIU ; Ye YANG
China Journal of Chinese Materia Medica 2015;40(15):2915-2920
Compartments of soil microorganism and enzymes between stereoscopic cultivation (three storeys) and field cultivation (CK) of Panax notoginseng were carried out, and the effects on P. notoginseng agronomic characters were also studied. Results show that concentration of soil microorganism of stereoscopic cultivation was lower than field cultivation; the activity of soil urea enzyme, saccharase and neutral phosphatase increased from lower storey to upper storey; the activity of soil urea enzyme and saccharase of lower and upper storeys were significantly lower than CK; agronomic characters of stereoscopic cultivated P. notoginsengin were inferior to field cultivation, the middle storey with the best agronomic characters among the three storeys. The correlation analysis showed that fungi, actinomycetes and neutral phosphatase were significantly correlated with P. notoginseng agronomic characters; concentration of soil fungi and bacteria were significantly correlated with the soil relative water content; actinomycete and neutral phosphatase were significantly correlated with soil pH and relative water content, respectively; the activities of soil urea enzyme and saccharase were significantly correlated with the soil daily maximum temperature difference. Inconclusion, The current research shows that the imbalance of soil microorganism and the acutely changing of soil enzyme activity were the main reasons that caused the agronomic characters of stereoscopic cultivated P. notoginseng were worse than field cultivation. Thus improves the concentration of soil microorganism and enzyme activity near to field soil by improving the structure of stereoscopic cultivation is very important. And it was the direction which we are endeavoring that built better soil ecological environment for P. notoginseng of stereoscopic cultivation.
Hydrogen-Ion Concentration
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Panax notoginseng
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growth & development
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Phosphoric Monoester Hydrolases
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metabolism
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Soil
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chemistry
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Soil Microbiology
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beta-Fructofuranosidase
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metabolism