The present is aimed at identifying the activation of TRAFs in n asopharyngeal carcinoma (NPC) in vitro. The differential expression of TRAF2\,TRAF3 was not detected in RN A and protein level, whereas the expression of TRAF1 in HNE2-LMP1 cell lines wa s much more abundant than that in HNE2 cell lines, suggesting that TRAF1 may be an inducible molecule; More importantly, TRAF1, TRAF2 or TRAF3 were activated in the HNE2-LMP1 cells, whereas TRAF1, TRAF2 or TRAF3 were not activated in HNE2 cells as detected by the immunoprecipitation-Western blotting assay. These data provide an experimental basis for our study beginning from the signal transduca tion pathway for the eluccidation of the mechanism of LMP1 carcinogenesis in NP C.

Objective To determine the cardiac structure and function by transthoracic highfrequency ultrasonography in Wistar rats, and to explore the patterns of age-related changes.Methods Male Wistar rats aged 1, 2, 5, 12, and 20 months (n= 12 each group) underwent transthoracic echocardiographic analysis to examine the parameters of cardiac structure and function.Finally, the rats were sacrificed and the left ventricles were weighed. Results The left atrial dimension (LAD), left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness at diastole (IVSD), left ventricular posterior wall thickness (LVPWd) and left ventricular mass (LVM) increased with age (all P ＜ 0.05 ) . There was a positive relationship between echocardiographic value and the autopsy weight LVM (r=0. 78, P＜0.01). There were no statistical significances in ejection fraction and fractional shortening among groups (all P＞0.05). Isovolumic relaxation time (IVRT) prolonged with age (P＜0. 01). After 2 month-old, tissue Doppler imaging Ea gradually decreased with age, Aa tended to increase with age. Ea/Aa ratio was more than 1 value in 1-, 2- and 5-months-old group, and it was less than 1 value in 12-, and 20-month-old group.Multivariate analysis showed that age was the influence factor of LAD, LVEDd and Ea. Conclusions Transthoracic high-frequency ultrasonography can be used to evaluate cardiac structure and function in rats; In aged rats, the wall-thickness, LAD and LVEDd are significantly increased. There is no significant change in systolic function, but diastolic function is decreased.

A phytochemical investigation on the roots and stems of Litsea cubeba led to the isolation of seven isoquinolone alkaloids. By spectroscopic analysis and comparison of their 1H and 13C-NMR data with those in literatures, these alkaloids were identified as (+)-norboldine (1), (+)-boldine (2), (+)-reticuline (3), (+)-laurotetanine (4), (+)-isoboldine (5), (+)-N-methyl-laurotetanine (6), and berberine (7), respectively. Among them, 7 was isolated from the genus for the first time. The evaluation of these compounds showed weak anti-inflammatory activity against NO production in RAW 267.4 and BV-2 cells.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Litsea ; chemistry ; Molecular Structure ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Spectrometry, Mass, Electrospray Ionization

The peeled stem of Syringa pinnatifolia is a Mongolia folk medicine, mainly distributed in Helan mountain, inner Mongolia and Ningxia provinces of China. It has been used for the treatment of cardiopalmus, angina pectoris, and cardiopulmonary diseases for a long history. Contemporary research revealed the presence of major lignans, sesquitepenes, and essential oils, and showed myocardial ischemia related diseases. This review summarizes the plant origins, taxonomic disputes, phytochemical and pharmacological research progress, hopefully to provide reference for full medicinal utilization, clarification of biological effective substance, and drug development.
Animals ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Mongolian Traditional ; Molecular Structure ; Syringa ; chemistry

OBJECTIVETo establish an animal model to replicate the blunt impact brain injury in forensic medicine.

METHODSTwenty-four New Zealand white rabbits were randomly divided into control group (n equal to 4), minor injury group (n equal to 10) and severe injury group (n equal to 10). Based on the BIM-II Horizontal Bio-impact Machine, self-designed iron bar was used to produce blunt brain injury. Two rabbits from each injury group were randomly selected to monitor the change of intracranial pressure (ICP) during the impacting process by pressure microsensors. Six hours after injury, all the rabbits were dissected to observe the injury morphology and underwent routine pathological examination.

RESULTSVarying degrees of nervous system positive signs were observed in all the injured rabbits. Within 6 hours, the mortality rate was 1/10 in the minor injury group and 6/10 in the severe injury group. Morphological changes consisted of different levels of scalp hematoma, skull fracture, epidural hematoma, subdural hematoma, subarachnoid hemo- rrhage and brain injury. At the moment of hitting, the ICP was greater in severe injury group than in mild injury group; and within the same group, the impact side showed positive pressure while the opposite side showed negative pressure.

CONCLUSIONSUnder the rigidly-controlled experimental condition, this animal model has a good reproducibility and stable results. Meanwhile, it is able to simulate the morphology of iron strike-induced injury, thus can be used to study the mechanism of blunt head injury in forensic medicine.

Animals ; Brain Injuries ; Head Injuries, Closed ; Intracranial Pressure ; Rabbits ; Reproducibility of Results ; Wounds, Nonpenetrating

Autophagosomes derived from tumor cells have been proved to induce potent T cell response both in mouse and human. In human in vitro study, dendritic cells(DC)loaded with cytomegalovirus(CMV)pp65 antigen-containing DRibble were capable to efficiently re-stimulate pp65-specific T-cell recall responses from freshly isolated or frozen humanperipheral blood mononuclear cell(PBMC). This study developed more robust assays using in vitro expanded antigen-specific T cells that contained a much higher percentage of antigen-specific T cells. DC cross-presentation efficiency of OX40 and CD80 modified pp65-DRibble was detected by intracellular IFN-γ staining. Compared with Ctrl/pp65 DRibble, the percentage of IFN-γ+ in total CD8+ T cells andCD4+ T cells was improvedwith OX40/pp65 DRibbleand CD80/pp65 DRibble stimulation. In addition, vaccine induced IL-12indendritic cells, whichpolarizes Th cells toward the IFN-γ high Th1 phenotype, evaluated by ELISA inco-culture supernatantwas dramatically higher in OX40/pp65 DRibble and CD80/pp65 DRibblegroups than in Ctrl/pp65 DRibble group. These results have implications for the immuneactivity of OX40 and CD80 modified DRibble and choice for prospective clinical use ofDRibble-based cancer immunotherapy.

This study was purposed to investigate the effects of thalidomide on proliferation of peripheral blood mononuclear cells (PBMNCs), levels of lymphocyte subsets, secretion of cytokines and its killing activity, and to elucidate the immunoregulation mechanisms in treatment of multiple myeloma with thalidomide. The method of MTT was used to detect the effects of thalidomide on the proliferations and the cytotoxic activity of PBMNC; the flow cytometer was used to analyze the lymphocyte subsets; the ELISA was used to measure the concentrations of cytokines in culture supernatants. The results showed that thalidomide enhanced the proliferations of the CD8+ T, NK cells in PHA-stimulated PBMNC from healthy volunteers, increased the secretion of IL-6 significantly, and decreased the secretion of IFN-gamma, and the secretions of IL-2 and IL-10 were not affected. Compared with control group, at the same ratio of effectors to targets the thalidomide (5 microg/ml) could enhance the cytotoxic activity of PBMNC (P < 0.01), the cytotoxic activity was maximal when the ratio of effectors to targets was 40:1. It is concluded that thalidomide preferentially enhances the proliferations of CD8+ T, NK cells in PHA-stimulated PBMNC from healthy volunteers, and enhances the cytotoxic activity of PBMNC by increasing the secretion of IL-6 significantly, in short, thalidomide can exert anti-myeloma effects by increasing cellular immune function.
Adjuvants, Immunologic ; pharmacology ; Adult ; CD8-Positive T-Lymphocytes ; cytology ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cytokines ; biosynthesis ; Female ; Humans ; Immunity, Cellular ; drug effects ; Killer Cells, Natural ; cytology ; immunology ; Leukocytes, Mononuclear ; cytology ; drug effects ; immunology ; Lymphocyte Subsets ; drug effects ; immunology ; Male ; Middle Aged ; Multiple Myeloma ; pathology ; T-Lymphocytes, Cytotoxic ; drug effects ; Thalidomide ; pharmacology ; Tumor Cells, Cultured

In recent years,a large number of studies have shown that myeloid cells in tumor microenvironment play an important role in tumorigenesis and tumor progression.On one hand,myeloid cells can regulate human immune system;on the other hand,myeloid cells can influence tumor progression,metastasis and clinical treatments.In this review,we summarize the interaction between myeloid cells and tumors,discuss the effects of myeloid cells after recruited to tumor sites and its mechanisms,try to put forward clinical therapy targeting myeloid cells and provide references for the following research and clinical treatments.

BACKGROUNDAmyloid β(1-42) (Aβ(42)) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models. But the phase II trial of Aβ(42) peptide vaccine was halted because of T cell-mediated meningoencephalitis. In this study, a DNA vaccine, p(Aβ(3-10))(10)-CpG, was constructed to test whether it would induce predominant T(H)2 immune response upon immunization of BALB/c mice.

METHODSBALB/c mice were vaccinated intramuscularly with p(Aβ(3-10))(10)-CpG plasmids. Aβ(42) peptide, pcDNA3.1(+) empty vector and PBS were injected to the control groups. Expression of interesting gene in injected muscle was identified by immunohistochemistry. Anti-Aβ antibody titers, isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA).

RESULTSP(Aβ(3-10))(10)-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry. The p(Aβ(3-10))(10)-CpG vaccine induced high titers of anti-Aβ antibodies in BALB/c mice. And isotype of the antibodies was mainly IgG1, the IgG1/IgG2a ratio for the p(Aβ(3-10))(10)-CpG group was approximately 5 times greater than that for the Aβ(42) peptide group. Ex vivo cultured splenocytes isolated from mice immunized with p(Aβ(3-10))(10)-CpG exhibited high interleukin-4 response and low interleukin-γ (IFN-γ) response.

CONCLUSIONSImmunization with p(Aβ(3-10))(10)-CpG vaccine primarily induces a T(H)2 type of response, thus reduces the probability of inflammation. This p(Aβ(3-10))(10)-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine.

Alzheimer Disease ; immunology ; therapy ; Amyloid beta-Peptides ; immunology ; Animals ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Immunity, Humoral ; immunology ; Immunoglobulin G ; metabolism ; Immunohistochemistry ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Mice ; Mice, Inbred BALB C ; Muscles ; metabolism ; T-Lymphocytes ; immunology ; Vaccines, DNA ; therapeutic use

Nanobody is a kind of antibody from camel, which misses light chain. Nanobody has the same antigen binding specificity and affinity as mAb. Moreover, because of its small molecular weight, high stability and easy preparation, nanobody has great value of biomedical applications. In this study, we successfully prepared highly pure antiEGFR nanobody in E.coli using genetic engineering techniques. Cell proliferation assay (CCK-8 assay) and migration experiments (cell scratch test and Transwell assay) indicated that the recombinant antiEGFRnano can significantly inhibit the proliferation and migration of endometrial cancer cells. These results provide a new way of thinking and methods for EGFR-targeted therapy of endometrial cancer.
Adenocarcinoma ; metabolism ; pathology ; Amino Acid Sequence ; Base Sequence ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Endometrial Neoplasms ; metabolism ; pathology ; Escherichia coli ; metabolism ; Estrogens ; metabolism ; Female ; Genetic Vectors ; Humans ; Plasmids ; Receptor, Epidermal Growth Factor ; genetics ; immunology ; Recombinant Proteins ; metabolism ; Single-Domain Antibodies ; genetics ; pharmacology