ABSTRACT:Objective To prepare polymeric nanomicelles capable of simultaneously loading doxorubicin (DOX) and Bcl‐2 small interfering RNA (Bcl‐2 siRNA ) , and to explore their in vitro cytotoxicity and cellular uptake in MCF‐7 human breast cancer cells .Methods Copolymer poly (ethylene glycol )‐g‐polyethylenimine‐g‐poly(γ‐benzyl‐L‐glutamate) was synthesized by the combination of reductive amination and carbodiimide methods , and its chemical structure was verified by 1 H NMR .Empty and drug‐loaded copolymeric nanomicelles were prepared by dialysis method and characterized by transmission electron microscope and dynamic light scattering .The ability of the nanomicelles to compress Bcl‐2 siRNA was measured by by agarose gel electrophoresis method . The release profiles of DOX and Bcl‐2 siRNA from the nanomicelles were explored by means of fluorescence spectrometry and dialysis method .The in vitro cytotoxicity and cellular uptake of DOX and Bcl‐2 siRNA co‐loaded nanomicelles in MCF‐7 human breast cancer cells were characterized by MTT assay and confocal laser scanning microscopy , respectively .Results The critical micelle concentration of the copolymer was about 4 mg/L ,and the sizes of self‐assembled empty and drug‐loaded nanomicelles were smaller than 200 nm .The drug‐loading efficiency and drug‐loading content of DOX in the nanomicelles were 88 .7% and 15 .1% ,respectively .The DOX‐loaded nanomicelles could efficiently compress Bcl‐2 siRNA when an N/P ratio was ≥64 .The zeta potential of DOX and Bcl‐2 siRNA co‐loaded nanomicelles was +30 mV .The release behavior of the cargoes from the nanomicells was pH‐sensitive , and the release of Bcl‐2 siRNA was more sensitive to acidic pH than that of DOX . The nanomicelles could simultaneously deliver DOX and Bcl‐2 siRNA into MCF‐7 cells , and the co‐delivered DOX and Bcl‐2 siRNA significantly increased the cytotoxicity of DOX (P<0 .05) .Conclusion The polymeric nanomicelles can co‐load DOX and Bcl‐2 siRNA and deliver them into MCF‐7 cells , and DOX in combination with Bcl‐2 siRNA can synergistically inhibit the growth of MCF‐7 cells and promote cell apoptosis ,suggesting that the nanomicells may be a promising carrier for the co‐delivery for chemotherapeutics and genes .

Objective: Analyze the ecological adaptable regions for the resource reservation and the expanding cultiva-tion of Quisqualis indica L. Methods: The Traditional Chinese Medicine Geographic Information System (TCMGIS) was used to analyze the ecological adaptable region. Results: The 17 provinces (city, municipalities) were the ecolog-ical adaptable region for Q. indica L. The 100% ecology similarity regions are mainly in 16 provinces (city, munici-palities), including Guangxi, Guangdong, Hunan, Fujian etc., which area accounts for 1 012 895.98 km2. Among these, the area in Guangxi province is the largest (195 313.64 km2), the second is Guangdong (150 276.36 km2), the following order is Hunan(128 925.29 km2), Fujian (101 471.16 km2) and Y unnan (100 660.83 km2). The 95%~100%ecology similarity regions is located in 16 provinces (city, municipalities), including Y unnan, Sichuan, Guizhou, Hubei province etc., which area accounts for 362 366.25 km2. The largest area is in Y unnan province (92 399.04 km2), followed by Sichuan(76 122.32 km2), Guizhou (43 902.38 km2), Hubei (31 760.32 km2) and Jiangxi (29 770.09 km2). Conclusion: The results are consistent with the survey results and the previous reports. To promote the develop-ment of Q. indica L. cultivation, the planting scientifically and quality evalution should be further conducted on the basis of the results by system analysis.

Objective To observe and compare the atomic force microscopy (AFM) images of Yersinia pestis EV76 and the changes in the morphology of the bacteria treated with normal serum and F1 antibody from rabbit,and to explore the immunoassay method to detect Yersinia pestis by AFM. Methods The Yersinia pestis were treated with normal serum and F1 antibody from rabbit and control buffer. All the prepared samples were observed and analyzed by AFM. The changes in the cell surface structures were probed and characterized through sectional analysis,especially the changes of Ra and Rq value. Results The normal morphology of Yersinia pestis was oval in shape with a relatively smooth surface, the size dimension of which was about 1.1-1.3 μm in length with a section profile of 0.8-1.0 μm in width and 0.04-0.06 μm in step height. The step height of the bacteria treated with the normal serum and F1 antibody was obviously enlarged. The shape of the bacteria treated with F1 antibody changed irregularly. Furthermore, the surface of the bacteria was more roughened. Conclusion The morphological characters of Yersinia pestis has been acquired through its AFM images. The morphology of Yersinia pestis treated with F1 antibody has changed greatly, and the index of roughness can be regarded as the distinguished index to detect Yersinia pestis by AFM.

Objective To systematic evaluate whether combining drugs influence renal function could increases the risk of nephrotoxicity caused by vancomycin. Methods Electronic databases such as PubMed , EMBase, the Cochrane library and Chinese database (CNKI, WanFang, CBM) were searched from establishment dates of databases to January 2014.The clinical observational studies which include vancomycin com-bines other drugs which could influence renal function was identified . The studies were screened according to the inclusion and exclusion crite-ria, the data were extracted, the quality of the included studies was as-sessed , and Meta-analysis was performed using RevMan 5.3 software. Results A total of six cohort studies were included , containing 1312 pa-tients, 791 patients of them using vancomycin alone , the other 521 patients combining other renal influence drugs .Compare with singly using vancomy-cin, combining renal influence drugs could increase nephrotoxicity signifi-cantly(P<0.01), but the heterogeneity is huge(P<0.05).After the sensi-tivity analysis , nephrotoxicity increasing still significantly ( P <0.01 ) . Conclusion Combining drugs which influence renal function could increase nephrotoxicity caused by vancomycin , so we should avoid combining drugs in clinical practice , or focus on monitoring when combining .

Objective To systematic evaluate the necessity of vancomy-cin therapeutic drug monitoring in cancer patients .Methods Electronic databases such as PubMed , EMBase, Cochrane library and Chinese data-base (CNKI, WanFang, CBM) were searched from establishment dates of databases to January 2014.The clinical observational studies which in-clude cancer patients using vancomycin intravenously was identified .The studies were screened according to the inclusion and exclusion criteria , the data were extracted , the quality of the included studies was assessed , and Meta -analysis was performed using Rev Man 5.3 software. Results Six cohort studies were identified .Compared with no -cancer patients, infectious treatment failure increases significantly (P<0.05), the target concentration rate of vancomycin decrease significantly (P<0.05).Conclusion As the decrease of target concentration rate and increase of treatment failure , cancer patients need therapeutic drug monitoring ( TDM) to adjust the dose of vancomycin .

Objective To systematic evaluate the necessity of vancomy-cin therapeutic drug monitoring in intensive care unit ( ICU ) patients compare with general ward patients . Methods Electronic databases such as PubMed , Embase , the Cochrane library and Chinese database (CNKI, WanFang, CBM) were searched from establishment dates of databases to January 2014.The clinical observational studies which in-clude ICU patients using vancomycin intravenously was identified .The studies were screened according to the inclusion and exclusion criteria , the data were extracted , the quality of the included studies was assessed , and Meta-analysis was performed using Rev Man 5.3 software. Results Three cohort studies were identified . One study shows no difference in the rate of treatment failure of ICU compare with general ward patients ( P>0.05 ) .Two studies shows nephrotoxicity increased significantly of ICU patients compare with general ward patients (P<0.05).Conclusion As the increase of nephrotoxicity and large individual difference , ICU patients need vancomycin TDM more .Due to the low methodological quality of the included studies , more high -quality clinical studies need to be conducted to verify this conclusion .

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-kappaB, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.
Animals ; Apoptosis ; Asia ; Asian Continental Ancestry Group ; Blotting, Western ; Caspase 3 ; Caspase 9 ; Chromatin ; Colon ; Colonic Neoplasms ; Down-Regulation ; Flow Cytometry ; HCT116 Cells ; Humans ; Inflammation ; Methanol ; Mice* ; Neoplasm Metastasis ; NF-kappa B ; Up-Regulation

Numerous studies have shown that the health of spiral ganglion neurons is highly important for hearing. As a trophic factor of spiral ganglion neurons, neurotrophin 3 (NT3) is a potential candidate for prevention of spiral ganglion neuron degeneration in human. In our experiments, efficient transduction and long term expression of foreign gene of cochlea cells has been found with adenovirus carried lacZ gene (Ad-lacZ). A model of guinea pig deafness was made by intense noise exposure, which destroyed the entire organ of Corti in the middle part of the cochlea. Seven days after noise exposure, the animals were anesthetized and 1 10(8) recombinant adenoviral particles were injected into the scala tympani through the round window membrane. Animals inoculated with neurotrophin 3 adenovirus(Ad-NT3) were designated as the experimental group, animals inoculated with Ad-lacZ vector served as the control group. Four weeks after the inoculation of the virus, NT3 immunoreactivity was observed in the Ad-NT3 inoculated group. HE histochemical staining results showed that in the Ad-lacZ injected group, the neuronal degeneration was severer and the density of spiral ganglion neurons was significantly lower than those in the Ad-NT3 injected group. Our results demonstrate that with adenovirus-mediated overexpression NT3 may be developed into a new treatment to prevent secondary spiral ganglion degeneration following the damage to Corti organ.
Adenoviridae ; genetics ; Animals ; Cochlea ; pathology ; Gene Transfer Techniques ; Genetic Therapy ; Guinea Pigs ; Hearing Loss, Noise-Induced ; pathology ; In Vitro Techniques ; Neurotrophin 3 ; genetics ; Recombination, Genetic

OBJECTIVETo investigate the dynamic expression of Heat shock protein 70 (Hsp70) in the lungs and plasma of rats with pulmonary fibrosis induced by silicon dioxide (SiO2).

METHODSForty-eight Wistar rats were randomly divided into the control group exposed to normal solution and group exposed to SiO2 (50 mg/ml) with intratracheal injection. Each group was divided into four subgroups. The animals of SiO2 group and control group were sacrificed and lungs were collected on the 7th, 14th and 28th days after exposure, respectively. The left lung tissues were examined with the histopathologic HE staining. The expression and localization of Hsp70 protein in the lung tissues were examined with western blot assay and immunohistochemistry, respectively. The expression levels of Hsp70 protein in the plasma were measured by ELISA.

RESULTSThe expression of Hsp70 in lung tissues of SiO2 group increased on the 7th day and reached the peak value on the 14th day then decreased, but still was significantly higher than that of the control group, the expression of Hsp70 in plasma of SiO2 group still was significantly higher than that of the control group (P < 0.05). The maximum expression level of Hsp70 in plasma of SiO2 group on the 21st day after exposure was 0.216 ± 0.027 µg/ml.

CONCLUSIONThe expression levels of Hsp70 protein in the lung tissues and plasma of the group exposed to SiO2 significantly increased, which were associated with the process of pulmonary fibrosis. It was suggested that Hsp70 protein may play an important biological role in the pulmonary fibrosis induced by SiO2.

Animals ; HSP70 Heat-Shock Proteins ; blood ; metabolism ; Lung ; metabolism ; pathology ; Male ; Pulmonary Fibrosis ; chemically induced ; metabolism ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity

OBJECTIVETo study and establish the GC fingerprint of essential oils of 10 batches the flower of Lonicera japonica.

METHODThe essential oils were extracted by steam distillation from ten batches of the flowers, then separated by capillary gas chromatography.

RESULTThe similarity of 10 batches of the flower of L. japonica was high.

CONCLUSIONThe method was reliable, and can be used to evaluate the quality of the flower of L. japonica.

Chromatography, Gas ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Flowers ; chemistry ; Gas Chromatography-Mass Spectrometry ; Lonicera ; chemistry ; classification ; Oils, Volatile ; chemistry ; isolation & purification ; Phylogeny ; Reproducibility of Results