Preparation,physicochemical characterization and cyctotoxicity of solid dispersion of paclitaxel and polyvinylpyrrolidone

The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid dispersion systems were prepared by solvent method. The release rate ofpaclitaxel was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The cytotoxicities ofpaclitaxel in solid dispersion to the SKOV-3 cells were assayed by a SRB staining method. The results showed that the solubility and dissolution rate of paclitaxel were significantly improved in solid dispersion system compared with that of the pure drug and physical mixture. The results of DSC and PXRD showed that the paclitaxel in solid dispersion was amorphous form. No paclitaxel crystals in the solid dispersions was found during SEM analysis. Cytotoxicity study suggested that the inhibitory rates of PTX-PVP solid dispersion to SKOV-3 cells were higher than that of pure paclitaxel. The solubility and dissolution of paclitaxel were improved by solid dispersion technique. In vitro cytotoxicity of paclitaxel in solid dispersion was higher than that of pure drug.

Genetic Diversity,Antibiotic Resistance,and Pathogenicity of Aeromonas Species from Food Products in Shanghai,China

Objective Aeromonas has recently been recognized as an emerging human pathogen.Aeromonasassociated diarrhea is a phenomenon occurring worldwide.This study was designed to determine the prevalence,genetic diversity,antibiotic resistance,and pathogenicity of Aeromonas strains isolated from food products in Shanghai.Methods Aeromonas isolates(n=79)collected from food samples were analyzed using concatenated gyrB-cpn60 sequencing.The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing.Pathogenicity was assessed usingβ-hemolytic,extracellular protease,virulence gene detection,C.elegans liquid toxicity(LT),and cytotoxicity assays.Results Eight different species were identified among the 79 isolates.The most prevalent Aeromonas species were A.veronii[62(78.5%)],A.caviae[6(7.6%)],A.dhakensis[3(3.8%)],and A.salmonicida[3(3.8%)].The Aeromonas isolates were divided into 73 sequence types(STs),of which 65 were novel.The isolates were hemolytic(45.6%)and protease-positive(81.0%).The most prevalent virulence genes were act(73.4%),fla(69.6%),aexT(36.7%),and ascV(30.4%).The results of C.elegans LT and cytotoxicity assays revealed that A.dhakensis and A.hydrophila were more virulent than A.veronii,A.caviae,and A.bivalvium.Antibiotic resistance genes[tetE,blaTEM,tetA,qnrS,aac(6)-Ib,mcr-1,and mcr-3]were detected in the isolates.The multidrug-resistance rate of the Aeromonas isolates was 11.4%,and 93.7%of the Aeromonas isolates were resistant to cefazolin.Conclusion The taxonomy,antibiotic resistance,and pathogenicity of different Aeromonas species varied.The Aeromonas isolates A.dhakensis and A.hydrophila were highly pathogenic,indicating that food-derived Aeromonas isolates are potential risks for public health and food safety.The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.

Antioxidant,cytotoxic,and anti-venom activity of Alstonia parvifolia Merr.Bark

Objective:To evaluate antioxidant,cytotoxic,and anti-venom capacity of crude bark extracts of Alstonia parvifolia Merr.Methods:Gas chromatography-mass spectrometry(GC-MS)and energy dispersive X-ray analyses were accomplished to characterize the chemical constituents of Alstonia parvifolia.Biochemical characterization was evaluated using an inhibitory phospholipase A_(2)(PLA_(2))assay,DPPH,and cytotoxicity assays.Using the constituents listed in the GC-MS analyses,molecular docking was conducted to inspect the binding energies between the chosen compounds and selected PLA_(2) isoforms.Results:GC-MS analyses showed that the Alstonia parvifolia crude extract consisted predominantly of acetylmarinobufogenin(14.89%),γ-sitosterol(10.44%),3-O-methyl-D-glucose(5.88%),3,5-dimethoxy-4-hydroxyphenylacetic acid(5.30%),(2α,5α)-17-methoxyaspidofracti­nin-3-one(AFM)(4.08%),and 2,3,5,6,7,8,9-heptahydro-1-phenyl-5-(p-chlorophenylimino)-1H-benzo[e][1,4]thiazepine(HPT)(1.37%).The principal elemental components of Alstonia parvifolia were Ca(4.012%)and K(1.496%),as exhibited by energy dispersive X-ray examination.Alstonia parvifolia showed significant free radical scavenging ability(IC_(50):0.287 mg/mL)and was non-cytotoxic to normal HDFn cells(IC_(50)>100μg/mL).Moreover,Alstonia parvifolia was favorably cytotoxic to MCF-7(IC_(50):4.42µg/mL),followed by H69PR,HT-29,and THP-1,with IC_(50) values of 4.94,5.07,and 6.27µg/mL,respectively.Alstonia parvifolia also displayed notable inhibition against PLA_(2) activity of Naja philippinensis Taylor venom with IC_(50) of(15.2±1.8)μg/mL.Docking and cluster analyses projected negative binding energies from AFM(−6.36 to−9.68 kcal/mol),HPT(−7.38 to−9.77 kcal/mol),and acetylmarinobufogenin(−7.22 to−9.59 kcal/mol).These calculations were for the particular interactions of Alstonia parvifolia constituents to PLA_(2) homologues where the utmost affinity was detected in HPT owing to the dipole interactions with amino acid residues.Conclusions:The bark extract of Alstonia parvifolia shows great potential as an anti-venom agent due to its low cytotoxic profile,remarkable PLA_(2) inhibition,and docking binding energies between its bioactive constituents and PLA_(2) homologues.

Chemical constituents of marine medicinal mangrove plant Sonneratia caseolaris

Twenty-four compounds including eight steroids （1-8）, nine triterpenoids （9-16, 24）, three flavonoids （20-22）, and four benzenecarboxylic derivatives （17-19, 23） were isolated and identified from stems and twigs of medicinal mangrove plant Sonneratia caseolaris. The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data. Among these rnetabolites, compounds 1, 4-20 and 22-24 were isolated and identified for the first time from S. caseolaris. In the in vitro cytotoxic assay against SMMC-7721 human hepatoma cells, compound 21 （3＇,4＇,5,7-tetrahydroxyflavone） exhibited significant activity with IC50 2.8 μg/mL, while oleanolic acid （14）, 3,3＇-di-O-methyl ether ellagic acid （18）, and 3,3＇,4-O-tri-O-methyl ether ellagic acid （19） showed weak activity. None of these compounds displayed significant antibacterial activites.

Design and Synthesis of New Compounds Derived from Phenyl Hydrazine and Different Aldehydes as Anticancer Agents

In this work we synthesized new derivatives from Phenyl Hydrazine and series of different Aldehydes (derivatives of benzylidenes). The synthesized compounds contain different aromatic Aldehydes which attached by Benzene ring via Hydrazine moiety in glacial acetic acid. These derivatives were characterized by TLC, melting points, Infrared Red, Proton Nuclear Magnetic Resonance, Carbon Thirteen Nuclear Magnetic Resonance and Mass Spectroscopy. Finally, these synthesized derivatives were tested for antiproliferative activity against multiple normal and cancerous cell lines, HepG2 (Liver cancer) and MCF-7 (Breast cancer) cell lines were used for cytotoxic assay.

EXPERIMENTAL STUDY ON ANTITUMOR EFFECT OF MONOCLONAL ANTI－IDIOTYPIC ANTIBODY－DNR CONJUGATE TO LEUKEMIA

In this experiment,the Dcxtran-T40(Dex-T40) served as intermidiate carrier,conjugated SM6 monoclonal antiidiotypic antibody(anti-Id-McAb) against B lymphocytic leukemia cells and chemotherapeutical drug daunorubicin(DNR) to form SM6:Dex: DNR immunoconjugate.The activity of anti-Id-McAb and DNR of the immunoconjugate and their extent of the substitution were measured,and the autitumor activity of SM6:hex:DNR was assayed in vitro.The results demonstrateil that using Dex-T40 to prepare immunoconjugate could get a higher extent of substitution of McAb and DNR and maintain the activity of McAb and drug well.The results of cytotoxic assay in vitro suggested that the immunoconjugate SM6:Dex:DNR possess a specific cytotoxic effett to target tumor cells.

Preliminary Findings on Anticancer and Lymphocyte Stimulated Activities of Bioactive Compounds Extracted from Vietnam Carica papaya Leaves

In this study, the target bioactive compounds （e.g., alkaloids, flavonoids, saponins and other polar compounds） in Vietnamese Caricapapaya leaves were extracted. The cytotoxic activities of the papaya leaves extracts on the selected tumor cell lines, such as lung cancer cell line LU-1, carcinoma cell line KB, breast cancer cells MCF7 and leukemia cell line HL-60, were examined. Preliminary findings showed a high inhibitive activity of papaya leave extracts against the four tested tumor cell lines at the concentration of 100 μg/mL. Out of the bioactive compounds in papaya leaves extract, alkaloids showed the highest inhibitive activity （105.95% on MCF7 and 91.86% on LU-1）, followed by polar compounds （62.88% on LU-1 and 21.80% on KB）, and saponins （59.74% on MCF7 and 25.25% on LU-1）. Flavonoids has the lowest inhibitive activity on cell lines （e.g., 45.51% on MCF7 and 20.32% on LU-1）. Taken together, the results suggest that alkaloids have a relatively high inhibitive activity on the selected tumor cell lines and their stimulated concentration at 50% （IC50） values for on MCF7 and KB were 24.67 μg/mL and 33.56 μg/mL, respectively. However, the result pointed out the immunostimulatory ability of only polar compounds and saponins which could stimulate the growth of in vitro lymphocytes but not flavonoids and alkaloids. The SC50 （stimulated concentration at 50%） values of polar compounds and saponins were 287.87μg/mL and 192.99 μg/mL, respectively.

Design and Synthesis of Some New Oxadiazole Derivatives as Anticancer Agents

In this work, some new oxadiazole derivatives have been prepared, by reacting phenyl hydrazine and acetic anhydride together, which furnished 2,4-dimethyl-4-phenyloxadiazole. This product was reacted with a series of aromatic aldehydes, to obtain a series of oxadiazole derivatives. These derivatives were characterized by TLC, melting points, infrared red, proton nuclear magnetic resonance, carbon thirteen nuclear magnetic resonance and mass spectroscopy. Finally, these synthetized derivatives were tested for antiproliferative activity by two different cell lines. MCF-7 (Breast cancer cell line) and HepG2 (Liver cancer cell line) were used to assess the antiproliferative activity of the prepared compounds.

An analytical method for quantitative estimation of the cytotoxicity of dental alloys using MTT assay,ICP analysis and effective cytotoxicity calculation

The two most important criteria for dental materials are their biofunctional and biocompatible endurance within the anticipated life-span of the dental restoration in the mouth. Biocompatibility relates mainly to the allergenicity and the toxicity of the material. To test the non-specific toxicity of dental materials, in vitro cell culture assays have been developed. For in vitro screening, such tests are recommended to check the cytotoxicity of dental materials (ISO 10993 5). Various studies have already been performed to quantitatively determine the cytotoxicity level of dental alloys. However, as long as only dental alloys and the cell culture technique are applied, it is not possible to determine which of the alloying elements cause the cytotoxicity. Therefore, an analytical method is needed. Wataha et al determined in 1991 the TC50 values of 9 metal cations of various dental casting alloys, using cell culture methods. Kapert et al reported in 1994 a complex in vitro test concept, where the ICP analysis (inductively coupled plasma emission spectroscopy) was introduced to measure the trace elements extracted from various alloys. Experimentelle Zahnheilkunde, Universitts ZMK Klinik Freiburg, Germany (Lü XY and Kappert HF) The aim of the present study was to find a relation between the ICP results, the TC50 value of metal cations, and the cytotoxicity of dental alloys. The cytotoxicity levels of various dental alloys and the TC50 values of 10 metal cations were established using the MTT assay, an effective cell culture of method. Then, the concentrations of the corrosively soluted metal cations in the extracts of the alloys were measured using the ICP method. From all these experimental results it was found that the relation between the effective cytotoxicity Z eff of an alloy, the concentrations C i of i th trace element and the TC50 values T Ci of the i th metal cation can approximately be expressed by Z eff =∑iC i2·T Ci . Two significant applications of this expression are a) The cytotoxicity of an alloy can be estimated by ICP analysis of the extract if the TC50 values of the trace elements are know. b) The cytotoxicity of a new-developed-alloy can be estimated in advance, according to the alloying components.

Therapeutic antitumor response to cervical cancer in mice immunized with U14 vaccines transfected with costimulatory B7 gene

Objective To investigate the effect of U14 vaccine transfected with the B7 gene in inducing antitumor immune response to murine cervical carcinoma in Chinese 615-strain mice.Methods A recombinant retroviral plasmid vector expressing mouse B7-1 gene (pLNSX-mB7) was transfected into 615-strain mouse cervical carcinoma cell line No. 14 (U14) by electroporation to set up a highly-expressed mB7-1 U14 cell clonal strain (B7+U14). In vivo experiments: (1) B7+U14 vaccine was primed to protect the 615-strain mice against U14 re-challenge. (2) B7+U14 vaccine was injected into tumor-bearing mice with different tumor sizes. Lifetimes and tumor sizes were recorded. In vitro cytotoxicity assay: Mice were immunized with B7+U14 or U14 vaccine and 2 weeks later, spleen cells of those mice were cultured for 2 days. The cytotoxicity of these cells against U14 was detected by 5-diphenyl tetrazolium bromide assay.Results We obtained several B7-1 high expression clonal U14 lines. In vivo experiment, we did not find tumor growing in 3 of the 6 mice primed by B7+U14 vaccine during their entire life after re-challenge with U14. The other 3 mice developed tumors and their average survival time was longer than that of the control group (P<0.01). All 6 mice grew tumors in the control group. When the transplanted tumors became palpable, the mice were randomly divided into 3 groups to be injected with B7+U14 vaccine. It was effective for tumor-bearing mice only when the tumor diameters were <3?mm. When the diameters were ≥3?mm, it was not efficacious to inject B7+U14 vaccine (P<0.05). In vitro cytotoxicity assay, cytotoxic T lymphocytes induced by B7+U14 vaccine had a higher cytotoxicity against U14 than that induced by U14 vaccine (F=310.8, P<0.001).Conclusions Vaccines of cervical cancer cells transfected with the costimulatory molecule B7 gene can induce antitumor immune protection in host mice against U14 re-challenge. This treatment may cure part of the tumor-bearing mice but be restricted by tumor size. The results suggest that transfecting the B7 gene into cervical cancer as a cell vaccine may be an efficient supplementary method to treat cervical cancer after operation.