A cationic liposome was prepared with a ligand directed at folate receptor in cancer cells to improve selectivity and facilitate its access to the cancer cells. Folate-polyethyleneglycol-distearoylphosphatidylethanolamine (F-PEG-DSPE) was synthesized by reacting folic acid (F), polyoxyethylene-bis-amine (NH2-PEG-NH2), succinic anhydride (SUC) with distearoylphosphatidylethanolamine (DSPE). Folate receptor-targeted liposomes composed of DPPC/DC-Chol/F-PEG-DSPE (10:10:0.75, molar ratio) were prepared by film dispersion method. A negative charged dextran fluorescein anionic (DFA) was used as a model to explore the in vitro properties and cell uptake efficiencies of liposomal DFA on KB and HpeG2 cells. The formulations were investigated by orthogonal experiment using encapsulation efficiency as the optimized indexes. The size, 4 potential, entrapment efficiency and DFA release in vitro were investigated. The results showed that DFA loaded folate receptor-targeted liposomes had high encapsulation efficiency and the mean size approximately 144 nm. The cationic liposomes had some toxicity to HepG2 cells, and at low concentration (0.0125-0.1 micromol x L(-1)) , the toxicity was linear with the concentration of DC-chol. The folate receptor-targeted liposomes showed great effects on increasing liposome cellular uptake of DFA. In summary, the method of film dispersion method is suitable for producing DFA loaded lipsomes with high entrapment efficiency, small size and slow release. The folate receptor-targeted liposomes can efficiently deliver DFA into cells in vitro. This may represent a promising option for researches on cancer gene therapy.
Carrier Proteins ; metabolism ; Dextrans ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Fluoresceins ; chemistry ; Folate Receptors, GPI-Anchored ; Folic Acid ; chemistry ; Genetic Therapy ; Hep G2 Cells ; Humans ; KB Cells ; Liposomes ; administration & dosage ; chemical synthesis ; metabolism ; Particle Size ; Phosphatidylethanolamines ; chemistry ; Polyethylene Glycols ; chemistry ; Receptors, Cell Surface ; metabolism ; Transfection

Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
Cell-Penetrating Peptides ; chemistry ; Drug Delivery Systems ; Enzymes ; chemistry ; Humans ; Neoplasms ; drug therapy

OBJECTIVETo explore the potential effect of Guizhi plus Gegen Decoction (GGD) in improving learning and memory of lipopolysaccharides (LPS) induced neuroinflammatory mice and its possible mechanisms.

METHODSTotally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n = 14), and the positive control group (n = 13). Mice were intraperitoneally injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze.

RESULTSOpen field test showed there was no statistical difference in the movement time and the movement distance among all groups (P > 0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS (P < 0.05), while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze showed that AD mice exhibited increased escape latency (P < 0.05) and spent much less time in swimming across the original platform (both P < 0.05). However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming (P < 0.05, P < 0.01).

CONCLUSIONGGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.

Alzheimer Disease ; chemically induced ; drug therapy ; psychology ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Lipopolysaccharides ; adverse effects ; Male ; Memory Disorders ; prevention & control ; Mice ; Mice, Inbred ICR ; Neuritis ; chemically induced ; drug therapy ; psychology ; Phytotherapy

OBJECTIVETo observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.

METHODSEAPDS rat model was prepared in 50 Wistar rats by feeding with high fat forage. Meanwhile, a normal control group consisting of 10 Wistar rats was set up by feeding with normal forage. After 25-week continuous feeding, 22 rats with body weight (BW) and blood pressure (BP) exceeding 25% those of the control group were selected as a model group. BW, BP, blood lipids, and related serological indicators were detected in all rats. Morphological changes of target organs were observed. mRNA expression levels of leptin receptor (LepR), Janus kinase2 (Jak2), signal transducer and activator of transcription 3 (Stat3), suppressor of cytokine signaling-3 (Socs3), angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), phosphatidylinositol 3 kinase (P13K), serine threonine kinase (Akt), nuclear factor of kappa B (NF-κBp65), inhibitor of nuclear factor kappa-B kinase α (IKKα), NF-kappa-B inhibitor β (lKKβ), NF-kappa-B inhibitor α (IKBα), and AMP-activated protein kinase (AMPK) were detected by quantitative real-time PCR (qPCR). Expression levels of AT1 and LepR in aorta were detected by immunohistochemical assay and Western blot respectively.

RESULTSCompared with the control group, BW, BP, and blood lipids increased; serum levels of leptin (Lep) , Ang II, Hcy, ET-1, TNF-α, IL-6, and p2-MG increased, but NO decreased in the model group (P < 0.05, P < 0.01). Aortal endothelial injury and smooth muscle cell proliferation occurred in the model group, accompanied with heart and renal injury. Compared with the control group, mRNA expression levels of LepR, Jak2, Stat3, Socs3, AT1 , PI3K, Akt, NF-κB p65, IKKβ, IKBα, and AMPK in aorta were up-regulated significantly (P < 0.05), while the expression of IKKa decreased (P < 0.05). Immunohistochem- ical staining showed, brownish yellow deposit of AT1 and LepR was obviously increased, with more extensively positive distribution. Western blot results showed, as compared with the control group, protein expression levels of AT1 and LepR obviously increased in the model group (P < 0.05).

CONCLUSIONSModel rats exhibited typical syndromes of EAPDS. They put up weight with fat abdomen, gloomy hair, poor appetite, hypersomnia, lowered activities , reduced food intake, loose stool, dark red tongue, white tongue with white, thick, greasy fur. Lep could be taken as one of objective indicators for evaluating hypertension rat model with EAPDS.

Animals ; Aorta ; Cell Proliferation ; Disease Models, Animal ; Hypertension ; physiopathology ; I-kappa B Proteins ; Interleukin-6 ; Leptin ; blood ; NF-KappaB Inhibitor alpha ; NF-kappa B ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Wistar ; Suppressor of Cytokine Signaling Proteins ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha

Objective To set a rapid,simple gene diagnosis method for Down syndrome.Methods Three short tandem repeats(D21S11,D21S1270,D21S1437)loci in or near Down syndrome critical region(DSCR) were analyzed and detected by polymerase chain reaction and DNA quantitative analysis in 11 core ancestry.Results There were four types by DNA quantitative analysis to different individuals at a short tandem repeats(STR) locus.In type one,a homozygote of one allelic gene was detected.In type two,a normal heterozygote of two allelic genes was found,the content or two DNA electrophoresis bands was approximately 1∶1.In type three,a Down syndrome patient of two allelic genes was discovered.The quantity of two electrophoresis bands was nearly 2∶1.In type four,the patient showed three DNA electrophoresis bands which the content was approximately 1∶1∶1.Conclusion A rapid gene diagnosis and prenatal diagnosis method for Down syndrome can be used for quantitative analysis of STR polymorphism loci.

OBJECTIVETo study the expression of the cyclooxygenase-2 (COX-2) gene in breast cancer in contrast to that of normal breast tissues or benign breast tumors and its significance in the carcinogenesis and development of breast cancer.

METHODSWith reference to the expression of the beta-actin gene, the expression of COX-2 mRNA was examined in cancerous tissues and adjacent normal breast tissue from 30 patients and benign breast tumors from 15 patients by reverse transcription-polymerase chain reaction (RT-PCR). Quantitation of relative band densities was performed using densitometry-scanning software. Estrogen receptors of 30 breast cancers were investigated by immunohistochemistry.

RESULTSEnhanced expression of COX-2 was observed in ninety percent of cancers tissue with a range of 0.05 - 0.91 (median 0.53). Rare cases showed significant COX-2 expression in normal breast tissues with a range of 0 - 0.09 (median 0). In part of benign breast tumors, COX-2 expressions were obviously elevated with a range of 0 - 0.68 (median 0.07). The difference of expression of COX-2 mRNA among breast cancers, normal breast tissues, mastopathy or fibroadenomas was significant (rank-sum test, P < 0.05) and the difference of that between estrogen receptor negative and positive was also observed (rank-sum test, P < 0.01).

CONCLUSIONThe level of expression of COX-2 mRNA is obviously higher in breast cancer tissue than in normal breast tissue, mastopathy or fibroadenomas. The expression of COX-2 in hormone-dependent breast cancer is higher than that in hormone-independent breast cancer. The overexpression of COX-2 may play a crucial role in the carcinogenesis and development of cancer in patients with breast carcinoma.

Breast ; enzymology ; Breast Neoplasms ; enzymology ; Cyclooxygenase 2 ; Female ; Humans ; Isoenzymes ; genetics ; Membrane Proteins ; Middle Aged ; Prostaglandin-Endoperoxide Synthases ; genetics ; RNA, Messenger ; analysis ; Receptors, Estrogen ; analysis

0.05).Three coronary artery aneurysm in the distal RCA was missed by 2DE.MSCT could not detect slight or moderate mitral regurgitation in 2 patients and artery wall thickening in 5 patients.Conclusion MSCT would be an effective complementary or alternative method for CDEC to evaluate coronary artery lesions non-invasively in pediatric patients with Kawasaki disease.

OBJECTIVEThe Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL.

METHODSA total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.

RESULTSToxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality.

CONCLUSIONSThe drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Asparaginase ; adverse effects ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Remission Induction

OBJECTIVETo study the clinicopathologic features of primitive neuroectodermal tumor (PNET) in female genital tract.

METHODSSix cases of PNET arising in female genital tract were retrospectively reviewed. The clinicopathologic features, immunohistochemical findings and EWS gene translocation study results were analyzed.

RESULTSThe age of patients ranged from 10 to 27 years (mean = 20 years). The sites of involvement included ovary (1 case), uterus (1 case), vulva (2 cases) and vagina (2 cases). The greatest diameter of the tumor ranged from 2 to 10 cm (mean = 5.4 cm). The tumor had nodular appearance and showed grayish-pink fleshy cut surface, accompanied by foci of hemorrhage and necrosis. Histologically, the tumor was composed of malignant small round cells with indistinct cell borders, hyperchromatic nuclei, dense chromatin, tiny nucleoli and scanty cytoplasm. The tumor cells were arranged in sheets or lobules. Homer-Wright rosettes were identified in 1 case. Immunohistochemical study showed that the tumor cells were positive for CD99, FLI-1 and CD56 (6/6). Focal expression of vimentin (5/6), NSE (5/6), nestin (4/6), synaptophysin (4/6), S-100 protein (2/6) and chromogranin A (1/6) was also demonstrated. EWS gene translocation was detected in 5 cases studied. Follow-up information was available in 2 patients (7 and 17 months of follow up, respectively). One of them died of tumor metastasis 17 months after diagnosis. The other patient was still alive.

CONCLUSIONSPNET arising in female genital tract is rare. It mainly involves ovary, uterus, vulva and vagina. Immunohistochemical study using a panel of antibodies and fluorescence in-situ hybridization play an important role in definitive diagnosis of this rare malignancy.

12E7 Antigen ; Adolescent ; Adult ; Antigens, CD ; metabolism ; CD56 Antigen ; metabolism ; Cell Adhesion Molecules ; metabolism ; Child ; Female ; Follow-Up Studies ; Genital Neoplasms, Female ; genetics ; metabolism ; pathology ; surgery ; Humans ; Neuroectodermal Tumors, Primitive, Peripheral ; genetics ; metabolism ; pathology ; surgery ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Proto-Oncogene Protein c-fli-1 ; metabolism ; RNA-Binding Protein EWS ; genetics ; Retrospective Studies ; Translocation, Genetic ; Uterine Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Vaginal Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Vimentin ; metabolism ; Vulvar Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Young Adult

Grounding technique is very important to ensure the human safety, imaging devices' safety and the devices' reliable running. This paper expatriates the principles of the grounding safety, interference rejection earth, and the grounding modes and the mode selection for each imaging devices and equipments, and related grounding requirements.
Equipment Safety ; methods ; Magnetic Resonance Imaging ; instrumentation