Quality Investigation of Quercetin-loaded PLGA-TPGS Nanoparticles / 医药导报

Objective To prepare quercetin ( QT )-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate ( PLGA-TPGS) nanoparticles ( QPTN) and QT-loaded polylactic-co-glycolic acid ( PLGA) nanoparticles ( QPN) by using QT as model drug and PLGA-TPGS or PLGA as carrier materials, and to investigate the quality of the two nanoparticles. Methods QPTN and QPN were prepared by using the ultrasonic emulsification-solvent evaporation method, and their surface morphology,size and surface charge were detected by using a transmission electron microscope ( TEM) and a Nano ZS90 light scattering and laser Doppler anemometry, respectively. Drug loading ( DL) , entrapment efficiency ( EE) and in vitro drug release of QT in the two nanoparticles were determined by using a reverse phase-high performance liquid chromatography (RP-HPLC) on Hypersil C18 column (4.6 mm×250 mm, 5 μm) with methanol and 0.03% phosphoric acid (3︰2) as mobile phase, and the detective wavelength was 370 nm. Results TEM images exhibited that two nanoparticles were all spherical and regular. The average sizes of QPTN and QPN were (155.4±2.7) nm and (363.8±3.2) nm, while DL and EE of QPTN were approximately (21.6±2.8)%, (93.7±2.9)% (n=6), and DL and EE of QPN were approximately (15.0±1.5)%, (64.6± 1.6)% (n=6), respectively. Both of nanoparticles exhibited sustained release, and the cumulative QT release of QPTN and QPN reached (85.8±2.8)% and (68.6±1.4)% (n=6) at day 30, respectively, with a significant difference between them (P<0.05) . Conclusion QPTN gets smaller size, higher DL and EE, and exhibits sustained release, and the in vitro cumulative QT release is faster and more complete than QPN relatively.

Quality Investigation of Quercetin-loaded PLGA-TPGS Nanoparticles / 医药导报

Objective To prepare quercetin ( QT )-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate ( PLGA-TPGS) nanoparticles ( QPTN) and QT-loaded polylactic-co-glycolic acid ( PLGA) nanoparticles ( QPN) by using QT as model drug and PLGA-TPGS or PLGA as carrier materials, and to investigate the quality of the two nanoparticles. Methods QPTN and QPN were prepared by using the ultrasonic emulsification-solvent evaporation method, and their surface morphology,size and surface charge were detected by using a transmission electron microscope ( TEM) and a Nano ZS90 light scattering and laser Doppler anemometry, respectively. Drug loading ( DL) , entrapment efficiency ( EE) and in vitro drug release of QT in the two nanoparticles were determined by using a reverse phase-high performance liquid chromatography (RP-HPLC) on Hypersil C18 column (4.6 mm×250 mm, 5 μm) with methanol and 0.03% phosphoric acid (3︰2) as mobile phase, and the detective wavelength was 370 nm. Results TEM images exhibited that two nanoparticles were all spherical and regular. The average sizes of QPTN and QPN were (155.4±2.7) nm and (363.8±3.2) nm, while DL and EE of QPTN were approximately (21.6±2.8)%, (93.7±2.9)% (n=6), and DL and EE of QPN were approximately (15.0±1.5)%, (64.6± 1.6)% (n=6), respectively. Both of nanoparticles exhibited sustained release, and the cumulative QT release of QPTN and QPN reached (85.8±2.8)% and (68.6±1.4)% (n=6) at day 30, respectively, with a significant difference between them (P<0.05) . Conclusion QPTN gets smaller size, higher DL and EE, and exhibits sustained release, and the in vitro cumulative QT release is faster and more complete than QPN relatively.

Food allergy:definitions, prevalence, diagnosis and therapy / 中华预防医学杂志

Food allergy is phenotypically an extremely heterogeneous group of diseases affecting multiple organs, sometimes in an isolated way, sometimes simultaneously, with the severity of reactions ranging from mild and local to full-blown anaphylaxis. Mechanistically, it is defined as a Th2-driven immune disorder in which food-specific IgE antibodies are at the basis of immediate-type adverse reactions. The sites of sensitization and symptoms do not necessarily overlap. Food allergy, which is the theme of this paper, is often confused with other adverse reactions to food of both animmune (e.g., celiac disease) and non-immune (e.g., lactose intolerance) nature. To reliably diagnose food allergy, a careful history (immediate-type reactions) needs to be complemented with demonstration of specific IgE (immune mechanism) and confirmed by an oral challenge. Co-factors such as exercise, medication, and alcohol may help trigger food allergy and further complicate accurate diagnosis. Where food extract-based diagnostic tests are poorly correlated to symptom severity, new generation molecular diagnostics that measure IgE against individual food allergens provide clinicians and patients with more reliable symptom severity risk profiles. Molecular diagnostics also support establishing whether food sensitization originates directly from exposure to food or indirectly (cross-reactivity) from pollen sensitization. Epidemiological surveys have indicated that allergy to peach primarily originates from peach consumption in Europe, whereas in China it is the result of primary sensitization to mugwort pollen, in both cases mediated by an allergen molecule from the same family. Epidemiological surveys give insight into the etiology of food allergy, the size of the problem (prevalence), and the risk factors involved, which together support evidence-based strategies for prevention. Over the past decade, food allergy has increased in the affluent world. Economic growth and urbanization in upcoming economies are likewise expected to lead to increased prevalence of food allergies, sometimes to different foods due to dietary habits. Molecular allergology and biotechnology now offer the possibility to combat the increasing burden of food allergy by developing safe immunotherapies for food allergy, using hypoallergenic mutant recombinant molecules. The first clinical trials to evaluate such approaches are underway. Last but not least, the identification and clinical risk characterization of a more and more complete list of food allergens additionally provides the allergenicity risk assessment of genetically modified foods a firmer basis.

Progress in the application of threshold of toxicological concern / 中华预防医学杂志

Threshold of toxicological concern (TTC) is a scientific and practical method for the food safety risk assessment of chemicals, and also an useful tool for the identification and screening of chemicals with risk assessment priority. However, there were still controversial opinions concerning the application of this method, which was established to provide risk characterization on the bases of chemical structures whereas in the lack of conventional toxicological data. Here, we reviewed the principles, critical factors, and recent progress in the application of TTC method, to explore and summarize the critical aspects that need particular considerations in the risk assessment of chemicals.

Regulation of α-tocopherol on NFκB and Nrf2 signaling pathway at early stage of N-nitrosomethylbenzylamine⁃induced human esophageal cell carcinogenesis / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the regulation of α-Tocopherol on NFκB and Nrf2 signaling pathway at early stage of N-nitrosomethylbenzylamine (NMBzA)-induced human esophageal carcinogenesis.</p><p><b>METHODS</b>Human normal esophageal HET-1A cells were treated with NMBzA at 50 µmol/L, 100 µmol/L for 24 h to intimate the initiation of esophageal carcinogenesis. For intervention groups, HET-1A cells were pre-treated with α-T at 25, 50, 100 µmol/L for 3 h and then co-treated with NMBzA (100 µmol/L) for 24 h. In comparison with HET-1A cells, human esophageal cancer EC109 cells were treated with α-T at corresponding concentrations. Cells treated with 0.1% DMSO were used as negative control. Immunofluorence staining was used for the determination of distribution and activation of NFκB p65 and Nrf2 in the cell. Real time PCR and Western blot were used to determine the expression levels of target genes including cyclinD1, KI67, proliferating cell nuclear antigen (PCNA), cyclo-oxygen-ase 2 (COX2), 5LOX, HO-1, NQO1 and GCLC. Flow cytometry was utilized to analyze the reactive oxygen species contents in the cells.</p><p><b>RESULTS</b>As compared to the control group (1.00 ± 0.08), the expression of CyclinD1 (2.99 ± 0.15), KI67 (2.35 ± 0.38) and PCNA (2.46 ± 0.25) in HET-1A were all markedly increased by NMBzA treatment (F values were 97.23, 65.28, 34.62, P < 0.001). Also, the proportion of cells with nucleus translocation of NFκB p65 (71.0%, 98/138) or Nrf2 (36.3%, 49/135) were significantly increased (χ² values were 194.71, 133.72, P < 0.001), and the expression of COX2 (3.22 ± 0.17), 5LOX (2.87 ± 0.12) as well as HO-1 (1.87 ± 0.22), NQO1 (2.14 ± 0.08), GCLC (2.63 ± 0.41) at protein levels were elevated (F values were 72.35, 43.87, 69.23, 71.34, 85.79, P values were 0.013, 0.015, 0.010, 0.011, 0.002). Under the treatment with 50 µmol/L α-T, comparing with the control group(59.1%,65/110),the nuclear translocation of NFκB p65 (77.7%, 8/104) was clearly inhibited (χ² = 148.1, P < 0.001), and protein expression levels of COX2 (0.74 ± 0.19) and 5LOX (0.42 ± 0.13) were decreased (F values were 56.31, 73.25, P values were 0.003, 0.001). However, no changes on Nrf2 signaling pathway were observed; α-T showed little impact on NFκB or Nrf2 pathway in EC109 cells.</p><p><b>CONCLUSIONS</b>At the early stage of NMBz-induced esophageal cancer, α-T could block the initiation of carcinogenesis through suppressing the activation of NFκB signaling pathway. It might be the major mechanism by which α-T is potentially chemopreventive to esophageal cancer. During the progression of esophageal cancer, the cells may acquire the adaptive functions to accommodate oxidative stress via activating Nrf2 pathway.</p>

Evaluation of the in vitro and in vivo genotoxicity of almond skins / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>It aims to study potential genotoxicity of almond skins.</p><p><b>METHODS</b>A bacterial reverse mutation assay was performed on S. typhimurium strains TA97, TA98, TA100, TA102, and TA1535 in the absence or presence of S-9 mixture at a dose range of 312.5 to 5 000 μg/plate. A micronucleus test and a mammalian bone marrow chromosome aberration tests were performed in Swiss Albino (CD-1) mice at doses of 625, 1 250, and 2 500 mg/kg bw used.</p><p><b>RESULTS</b>Almond skins exerted no mutagenic activity in various bacterial strains of Salmonella typhimurium in either the absence or the presence of metabolic activation at all doses tested. Various doses of almond skins did not affect the proportions of immature to total erythrocytes, the number of micronuclei in the immature erythrocytes, or the number of structural and numerical chromosomal aberrations of Swiss albino mice.</p><p><b>CONCLUSION</b>Almond skins are not genotoxic under the conditions of the in vitro bacterial reverse mutation assay and two in vivo tests - micronucleus test and mammalian bone marrow chromosome aberration test, which supports the safety of almond skins for dietary consumption.</p>

An assessment of androgenic/anti-androgenic effects of GH transgenic carp by Hershberger assay / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the androgenic and anti-androgenic effects of GH (growth hormone) transgenic carp in male rats.</p><p><b>METHODS</b>Hershberger assay was carried out in castrated male SD rats aged 4-5 weeks. Testosterone propionate (TP) (0.4 mg/kg BW) was administrated for a positive control, GH transgenic carp (3.0 g/kg BW)+TP (0.4 mg/kg BW), parental carp (3.0 g/kg BW) + TP (0.4 mg/kg BW), and flutamide (Flu) (3.0 g/kg BW) were used for negative controls, and vehicle was administered orally for a blank control. All groups were administrated for 10 consecutive days. At the end of the test, animals were anesthetized, then weights of accessory sex organ were measured. Serum testosterone (T), luteinizing hormone (LH), and Follicle-Stimulating Hormone (FSH) levels were detected.</p><p><b>RESULTS</b>The weights ratios of the accessory sex organs and body weights showed no significant differences between the solvent control and the GH transgenic carp-treated groups. Serum concentrations of FSH, LH, and T of the rats treated with GH transgenic carp + TP showed no significant changes, compared with those treated with TP only.</p><p><b>CONCLUSION</b>GH transgenic carp does not have any androgenic agonist or antagonist properties in vivo screening tests.</p>

Effects of tea polyphenols and tea pigments on cell cycle regulators in rat liver precancerous lesions / 中华预防医学杂志

<p><b>OBJECTIVES</b>This study is to investigate the effects of tea polyphenols and tea pigments on cell cycle regulators in rat liver precancerous lesions.</p><p><b>METHODS</b>The modified Solt-Farber precancerous liver rat model was used. Rats were given water, tea polypheol solution (0.1%) or tea pigment solution (0.1%) throughout the whole experiment (56 days). Cyclin D1, P21(WAF1/CIP1), GADD45 and PCNA protein expression were detected by Western blotting and the RT-PCR method was applied to study the expression of Cdk4.</p><p><b>RESULTS</b>Cyclin D1, Cdk4 and PCNA expressions were significantly inhibited, and the expression of P21(WAF1/CIP1) and GADD45 were significantly induced by tea polyphenols and tea pigments treatments.</p><p><b>CONCLUSION</b>Tea polyphenols and tea pigments induced cell cycle arrest and inhibited cell proliferation by regulating cell cycle regulators.</p>

EFFECT OF SELENIUM ON LIPID PEROXIDATION INDUCED BY HYPERLIPEMIC SERUM AND RADIATION / 营养学报

Cultured smooth muscle cells from bovine aortic media were incubated with hyperlipemic serum for 14 days. Lipid peroxides in the cells were higher than controls (P