2.Long-circulating liposomal daptomycin enhances protection against systemic methicillin-resistant Staphylococcus aureus infection with improved therapeutic potential.
Xing-Liang HUANG ; Jin WU ; Ting-Ting SU ; Yan-Hong LI ; Zhang-Bao CHEN ; Chong LI
Acta Pharmaceutica Sinica 2014;49(5):701-710
In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.
Animals
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Anti-Bacterial Agents
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pharmacology
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Daptomycin
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pharmacology
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Liposomes
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Methicillin-Resistant Staphylococcus aureus
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drug effects
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Mice
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Staphylococcal Infections
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drug therapy
3.Characterization of intertype specific epitopes on adenoviruses hexon.
Ting ZHANG ; Ruolei XIN ; Qin ZHANG ; Yihua BAO ; Jianxin WU
Chinese Journal of Experimental and Clinical Virology 2002;16(1):44-47
BACKGROUNDTo characterize the intertype epitopes on human adenovirus (HAdV) hexon.
METHODSBased on computerized analysis on adenoviruses sequence of genomic alignment, antigenicity prediction and 3-D structure characteristics of hexon subunit, several peptides of hexon of adenoviruses were chosen to be synthesized or recombinant proteins of the hexon were expressed in E. coli by use of PGEX-5X. To identify the existence of intertype epitopes, the antisera raised with synthetic peptides or purified recombinant proteins were analyzed with Western blot and immunofluorescent assay.
RESULTSThe results of Western blot indicated that both peptide and recombinant antibodies showed specific reactivities with hexons of HADv-3, 4, 7 individually. Meanwhile, typical stain of immunofluorescence was found on HeLa cells infected with these HAdV by incubation with peptide as well as recombinant antibodies. Also, antibodies raised against peptide recognized the recombinant hexon protein in which a corresponding region of peptides was covered.
CONCLUSIONSMost of the predicted intertype epitopes of HAdV hexon wer e exclusively found in synthetic peptides and recombinant proteins. These intertype epitopes showed to be continuous and sequential which could be employed for development of antibodies of diagnostic use.
Adenoviruses, Human ; immunology ; Amino Acid Sequence ; Animals ; Capsid ; chemistry ; immunology ; Capsid Proteins ; immunology ; Epitopes ; immunology ; HeLa Cells ; Humans ; Mice ; Peptide Fragments ; immunology
4.Effects of Jianpi Jiedu Recipe on TCRVβCDR3 Spectratyping of Liver Cancer Rats with Pi Deficiency Syndrome.
Bao-guo SUN ; Lei ZHANG ; Ting XIANG ; Ze-xiong CHEN ; Shi-jun ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(6):735-743
OBJECTIVETo observe anti-cancer effects of Jianpi Jiedu Recipe (JJR) on liver cancer (LC) rats with Pi deficiency syndrome (PDS) and its relation with the third complementary-determining region gene spectratyping of TCRVβ-chain (TCRVβCDR3).
METHODSRats were divided into 8 groups according to random digit table, i.e., the blank control group (normal), the PDS group, the LC model group, the LC-PDS group, high, middle, and low dose JJR groups (75.00, 37.50, 18.75 g/kg, respectively by gastrogavage, once per day), the thymus pentapeptide group (5 mg/kg, intramuscular injection, twice per week), 8 in each group. Rats in the normal group were administered with physiological saline by gastrogavage once per day. PDS rat model was prepared by bitter-cold purgation. LC model was prepared by orthotopic transplantation method. Twenty gene subfamilies of TCRβCDR3 in the thymus, liver, and LC tissues were detected by Gene Scan.
RESULTSHigh and middle dose JJR could postpone the growth of LC volume (P < 0.05), with equivalent liver index and thymus index to those of the normal group (P > 0.05). In thymus and liver tissue of the normal group, the number of clones (20 and 19), gene fragment number (220 and 113), Quasi-Gaussian distribution ratio of TCRVβCDR3 gene repertoire (100.0% and 42.1%), and fragment fluorescence peak area (6,539 ± 2,325 and 1,238 ± 439) were at the highest level among the 8 groups. TCRVβCDR3 expressions in thymus and liver tissue of high and middle dose JJR groups were approximate to those of the normal group. They were in the middle of the thymus pentapeptide group, the PDS group, the LC model group, and poorest in the LC-PDS group. TCRVβCDR3 in liver tissue expressed the best in the thymus pentapeptide group.
CONCLUSIONJJR might inhibit the growth of LC cells, and its mechanism might be related to enhancing TCRVβCDR3 spectratype expression.
Animals ; Complementarity Determining Regions ; genetics ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; Genes, T-Cell Receptor beta ; Liver Neoplasms ; drug therapy ; genetics ; Random Allocation ; Rats
5.Role of 64-slices spiral CT in acute chest pains
Xi-Ming WANG ; Bao-Ting CHAO ; Le-Bin WU ; Yun-Ting ZHANG ; Hai-Song CHEN ; Zhen-Jia LI ; Cheng LIU ;
Chinese Journal of Radiology 2001;0(08):-
Objective To explore role of 64-slices spiral CT in differetiation of acute chest pains.Methods Thirty six patients with acute chest pains were performed 64-slices spiral CT chest angiography.Two-dimensional and three-dimensional reconstruction was performed in all patients by means of multiplanar reconstruction(MPR)(coronal,sgittal oblique),curved planar reformation(CPR), maximum intensity projection(MIP),and volume rendering(VR).All images were blindly reading by two experienced radiologist.DSA were performed at the same time in 16 cases.Results The coronary artery branches,pulmonary artery and aortic artery in all patients were showed clearly,The acute myocardial infarction were showed in 10 cases,The pulmonary artery embolism in 14 cases,The aortic dissection in 6 cases respectively,The Coronary embolism in One case ,pneumothorax In One case The constrictive pericarditis in 1 case respectively.Normal findings in 4 cases.Conclusion 64-slices spiral CT is a useful and noninvasive examination in acute chest pain.
6.Microsurgical treatment of lateral ventricular tumors
Zhengming YANG ; Jian CHEN ; Jincao CHEN ; You ZHOU ; Yuping WANG ; Ping ZHANG ; Wengong BAO ; Ting LEI
Chinese Journal of Microsurgery 2008;31(5):332-334
Objective To investigate the clinical characteristics,minimal invasive operation technique and perioperative management of lateral ventrieular tumors.Methods The clinical characteristics,image diagnosis,surgical approaches and postoperative management and surgical outcomes of 65 consecutive cases of lateral ventricular tumors were retrospectively analyzed.Results In our series,total resection was achieved in 54 cases,and subtotal resection was achieved in 11 cases.Lateral ventricular tumors were mostly found in male and in the left side.Headache caused by increased intracranial pressure was the most common clinical symptom.Ependymocytoma and astrocytic glioma are the most common pathologic diagnosis.Postoperative complications included fever (26 cases),hydrocephalus (9 cases),intraventricular hematoma (7 cases) of which 2 cases were evacuated by craniotomy,epilepsy (7 cases),wound infection (3 cases).Postoperative death was happened in 3 cases.Two of them died of respiratory failure due to postoperative epilepsy.Conclusion Early discovery of lateral ventricle tumors,meticulous operation,subtle micromanipulation and right postoperative treatment are the criticality to improve the rate of total resection of lateral ventricle tumors through microsurgical treatment and reduce postoperative complications and mortality.
7.Analysis on correlation between biofilm formation and bacterial resistance in Staphylococcus epidermidis
Yangqin YE ; Yujie BAO ; Ke MA ; Wenyan ZHANG ; Ting XI ; Fangying CHEN ; Ming ZONG ; Lieying FAN
International Journal of Laboratory Medicine 2016;37(5):618-620
Objective To investigate the formation of biofilm in clinical isolates of Staphylococcus epidermidis ,and to analyse the correlation between biofilm formation and antibacterial resistance of Staphylococcus epidermidis .Methods A total of 62 strains of Staphylococcus epidermidis isolated from blood specimens of inpatients with bloodstream infection ,from January 2014 to February 2015 ,were collected .The biofilm formation of Staphylococcus epidermidis was detected by using the semi‐quantitative adherence as‐say and polymerase chain reaction(PCR) amplification experiment .The antibacterial susceptibility test was carried out according to K‐B method .Results The positive rate of biofilm formation detected by using the semi‐quantitative adherence assay and PCR for icaA gene were 37 .1% (23 strains) and 43 .5% (27 strains) respectively ,and there was no statistically significant difference(P>0 .05) .There were 14 positive strains detected by both methods .The resistance rates of strains producing biofilm to antibacterial a‐gents were generally higher than those of non‐producing biofilm strains ,and there were statistically significant differences in resist‐ance rates of strains to gentamicin ,penicillin ,oxacillin ,levofloxacin and cefoxitin(P<0 .05) .All bacteria were sensitive to vancomy‐cin ,linezolid and quinupristin/dalfopristin .Conclusion There is no significant difference between the two methods in detecing bio‐film formation .The resistance rates of strains producing biofilm to antibacterial agents were generally higher than those of non‐pro‐ducing biofilm strains .
8.Effects of ultraviolet-B laser irradiation on lens α-crystallin and protection of indole-3-carbinol to chaperone activity of α-crystallin
Qin, ZHANG ; Xiao-guang, CAO ; Xue-ting, PEI ; Yong-zhen, BAO
Chinese Journal of Experimental Ophthalmology 2012;30(6):538-542
Background Ultraviolet radiation is one of factors of the formation of age-related cataract.Indole-3-carbinol(I3C) is a plant chemical material with inhibitory effect on oxidative-induced cell damage and formation of amyloid fibrils,and the oxidative damage and amyloid fibrils are associated with cataract.However,the relationship between I3C and α-crystallin is in study. Objective This study was to evaluate the effects of ultraviolet-B laser irradiation on the secondary structure of α-crystallin and to explore the protection of I3C to chaperone activity of α-crystallin. Methods The fresh eyeballs were obtained from 1-year-old cattle to prepare the purified lens α-crystallin by gel chromatography.α-Crystallin was isolated from cattle lenses using gel chromatography.The purified α-crystallin was collected using fast protein liquid chromatography ( FPLC ) and exposed to 1:308 nmultraviolet-B at different irradiation intensities ( 23.75,118.75,475.00,1187.50,2375.00,4750.00,11 875.00,23 750.00 mJ/cm2 ) and then to ultraviolet-B 2:308 nm with irradiation intensities of 28 535.00,6730.00,3435.00,1910.00,1040.00 mJ/cm2.Ultraviolet-absorbance spectra,tryptophan fluorescence and N-formylkynurenine (N-FK)fluorescence spectra of both irradiated and non-irradiated α-crystallin were measured.I3C at the concentrations of 50 μmol/L and 100 μmoL/L were added to the α-crystallin solution to perform a catalase (CAT) thermal aggregation to confirm the chaperone activity of the α-crystallin,and the α-crystallin solution without any I3C was used as control.The ratios of A360 between various intervene groups with control group were calculated using spectrophotometry.Results The A280 values of the α-crystallin declined to 10% at the ultraviolet-B irradiation intensity of 1187.5 mJ/cm2 and that at the intensity of 23.75 J/cm2 lowed to 2%.A negative correlation was seen between the ultraviolet-B irradiation intensity and the A280 value of the α-crystallin (R2=0.925 ) and a positive correlation was found between ultraviolet-B with N-FK ( R2 =0.949 ).Ultraviolet-B irradiation intensity showed a negative correlation with Trp fluorescence intensity (R2 =0.996 ).CAT hot condensed experiment revealed that after addition of different concentrations of indole-3-carbinol,the relative A360 values at various ultraviolet-B irradiation group were significantly higher than those of the control group (P =0.000),and the decreasing degree of chaperone activity of α-crystallin was lower than that of the control group ( P =0.000 ). Conclusions The study suggests that I3C can protect the chaperone activity of α-crystallin from photooxidation,and the ultraviolet-B laser may be a good exposure source compared with ultraviolet lamp.The ultraviolet-B laser irradiation causes the alteration of structure and chaperone activity of α-crystallin.
9.Clinical Observation on Efficacy of Ulinastatin in Treatment of Sepsis Induced Acute Renal Injury
Bo CHEN ; Min QIU ; Dongjing RONG ; Ting WANG ; Yuqiong YANG ; Hongyun BAO ; Yang ZHANG
Progress in Modern Biomedicine 2017;17(23):4529-4532
Objective:To research the clinical effects of ulinastatin in the treatment of sepsis induced acute renal injury and its possible mechanisms.Methods:114 cases of patients with sepsis induced acute kidney injury from 2014.02 ~ 2016.08 were selected and randomly divided into the control group (n=57) and experimental group (n=57) according to the draw method,the control group was given conventional treatment,while the experimental group was treated by ulinastatin based on the control group,the urine urinary injury molecule-1 (KIM-1),atrialnatriuretic peptide (ANP),cyscatin-c (CYS-C),interleukin l,6 (IL-1,IL-6),c-reactive protein (CRP),tumor necrosis factor-α(TNF-α),nitric oxide (NO),endothelin 1 (ET-1),immunoglobulin A,G,M (IgA,IgG,IgM) levels,APACHE-Ⅱ score were compared between two groups before and after the treatment.Results:After treatmented,the urine of KIM-1,ANP,serum of CYS-C,IL-l,IL-6,CRP,TNF-α,ET-1 levels and APACHE-Ⅱ score of experimental group were significantly lower than those of the control group (P<0.05).The serum NO,IgA,IgG,IgM levels of experimental group were significantly higher than those of the control group (P<0.05).Conclusion:Ulinastatin could significantly relieve sepsis induced acute renal injury,which might be related to the inhibition of inflammatory response,improvement of the renal blood flow and immune function.
10.Silica-coated ethosome as a novel oral delivery system for enhanced oral bioavailability of curcumin.
Chong LI ; Li DENG ; Yan ZHANG ; Ting-Ting SU ; Yin JIANG ; Zhang-Bao CHEN
Acta Pharmaceutica Sinica 2012;47(11):1541-1547
The aim of this study is to investigate the feasibility of silica-coated ethosome as a novel oral delivery system for the poorly water-soluble curcumin (as a model drug). The silica-coated ethosomes loading curcumin (CU-SE) were prepared by alcohol injection method with homogenization, followed by the precipitation of silica by sol-gel process. The physical and chemical features of CU-SEs, and curcumin release were determined in vitro. The pharmacodynamics and bioavailability measurements were sequentially performed. The mean diameter of CU-SE was (478.5 +/- 80.3) nm and the polydispersity index was 0.285 +/- 0.042, while the mean value of apparent drug entrapment efficiency was 80.77%. In vitro assays demonstrated that CU-SEs were significantly stable with improved release properties when compared with curcumin-loaded ethosomes (CU-ETs) without silica-coatings. The bioavailability of CU-SEs and CU-ETs was 11.86- and 5.25-fold higher, respectively, than that of curcumin suspensions (CU-SUs) in in vivo assays. The silica coatings significantly promoted the stability of ethosomes and CU-SEs exhibited 2.26-fold increase in bioavailablity relative to CU-ETs, indicating that the silica-coated ethosomes might be a potential approach for oral delivery of poorly water-soluble drugs especially the active ingredients of traditional Chinese medicine with improved bioavailability.
Administration, Oral
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Animals
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Biological Availability
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Coated Materials, Biocompatible
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chemistry
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Curcumin
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administration & dosage
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chemistry
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pharmacokinetics
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Drug Carriers
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Ethanol
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chemistry
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Liposomes
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chemistry
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Male
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Particle Size
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Rats
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Rats, Sprague-Dawley
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Silicon Dioxide
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chemistry
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Solubility