While dendritic cell (DC)‑based immunotherapy has achieved satisfactory results in animal models, its effects were not satisfactory as initially expected in clinical applications, despite the safety and varying degrees of effectiveness in various types of cancer. Improving the efficacy of the DC‑based vaccine is essential for cancer immunotherapy. The present study aimed to investigate methods with which to amplify and enhance the antitumor immune response of a DC‑based tumor vaccine by silencing the expression of indoleamine 2,3‑dioxygenase 2 (IDO2), a tryptophan rate‑limiting metabolic enzyme in DCs. In vitro experiments revealed that the silencing of IDO2 in DCs did not affect the differentiation of DCs, whereas it increased their expression of costimulatory molecules following stimulation with tumor necrosis factor (TNF)‑α and tumor lysate from Lewis lung cancer (LLC) cells. In a mixed co‑culture system, the IDO2‑silenced DCs promoted the proliferation of T‑cells and reduced the induction of regulatory T‑cells (Tregs). Further in vivo experiments revealed that the silencing of IDO2 in DCs markedly suppressed the growth of tumor cells. Moreover, treatment with the IDO2‑silenced DC‑based cancer vaccine enhanced cytotoxic T lymphocyte activity, whereas it decreased T‑cell apoptosis and the percentage of CD4+CD25+Foxp3+ Tregs. On the whole, the present study provides evidence that the silencing of the tryptophan rate‑limiting metabolic enzyme, IDO2, has the potential to enhance the efficacy of DC‑based cancer immunotherapy.
Aim To monitor the toxic effect of N,N-dimethylformamide on the Dugesia Japonica(Planarian).Methods The effect of DMF on behavior,regeneration,mortality rate,activities of superoxidedismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-PX) and the damage of DNA of planarian were detected.Results The mortality rate of planarian increased obviously with the rising of DMF concentration and exposure time;the planarian regeneration was inhibited by the low dose of DMF;obvious change of SOD activity was caused by DMF ranged from 0 to 0.5%;CAT activity was increased under the treatment of DMF from 0.2% to 0.4%;DNA damage of the planarian was observed after 1% DMF treatment.Conclusion Obvious toxic effects on planarian after treatment by DMF were observed.As planarian is sensitive to DMF,it has the potentiality of DMF contamination detection in water.
This study was designed to investigate the effect of salidroside (SAL) on bone marrow haematopoiesis in a mouse model of myelosuppressed anemia. After the mouse model was established by 60Co γ irradiation and cyclophosphamide, pancytopenia and a sharp reduction in bone marrow stromal cells and bone marrow haematopoietic stem cells (lineage-Sca1+c-kit+) were observed. This was greatly alleviated by SAL (25 mg/kg, 50 mg/kg, 100 mg/kg) in a dose-dependent manner (50% effective dose value of 35.7 mg/kg and 61.2 mg/kg, respectively), followed by a distinct increment in anti-apoptotic protein Bcl-2. For cell culture in vitro, treatment with SAL resulted in a significant recovery of burst-forming unit-erythroids, and colony-forming unit-granulocyte macrophages on Day 7, and colony-forming unit-erythroids on Day 3, dose-dependently, but not of colony-forming unit-megakaryocyte macrophages. Inoculation of bone marrow cells derived from SAL-administrated donor mice resulted in a 60% survival of recipient mice at the high dose of 100 mg/kg SAL at 2 months after surgery. SAL appeared to be able to stimulate the restoration of bone marrow haemopoietic regulation in myelosuppressed anemia. Based on the downregulation of Fas ligand associated with the expression of Caspase-3 at the protein level, it was suggested that SAL might have an anti-apoptotic effect on bone marrow cells in the Fas-apoptotic pathway of Fas/FasL-caspase-3.
Huanglian Jiedu Decoction (HLJJD) has a variety of pharmacological activities, such as anti-inflammatory and neuroprotection against ischaemic brain injury. This ex vivo study explores its antithrombosis activity and inhibition of platelet aggregation. To study the antithrombosis activity of HLJJD ex vivo, saline, or HLJDD (100, 200, and 500 mg/kg) was treated prophylactically by gavage for 3 days in Wistar rats (n = 4). Based on the rat model of transient middle cerebral artery infarction (MCAO) or normal rats (n = 4), the antithrombotic activity in the normal group and HLJDD subgroups on prothrombin time, thrombus weight, platelet aggregation, and others was evaluated, followed by the antiplatelet aggregation of its main components (n = 4). The weight of the thrombus increased significantly at 24 h after MCAO onset. HLJJD did not influence the change of PT, but significantly inhibited thrombosis by 12.5, 20.0, and 20.5% in reducing the dry weight of thrombus, and blocked collagen-induced platelet aggregation by 25.5, 39.0, and 42.7% and adhesion of blood platelet by 17.3, 26.2, and 27.3%. The IC50 value of HLJJD on collagen-induced platelet aggregation was 670 mg/kg. Geniposide only facilitated antiplatelet aggregation induced by collagen, but not AA or ADP. Both baicalin and berberine showed markedly antiplatelet aggregation induced by all activators. The antithrombotic activity of baicalin was relatively higher than that of berberine (35.0-47.8% vs. 20.6-33.5%). Our results indicated that HLJDD regulated blood circulation by inhibiting platelet aggregation and thrombosis, which might also extensively contribute to the clinical prevention and treatment of cerebrovascular diseases.
The piezoelectric bulk acoustic wave sensor technology has such unique advantages as high sensitivity, wide response spectrum, easy digitalization, simple structure and low cost and others, which are widely used in many fields of analytical chemistry, biochemistry, environmental monitoring, life science and molecular biology.This article has conducted research for theories and applications of several new systems on the basis of the tandem piezoelectric response to solution electrical conductivity and dielectric constant and the response of single-component piezoelectric bulk acoustic wave sonic sensors to the viscosity and density, which has broadened the application range of the piezoelectric bulk acoustic wave sensor applications in the life sciences and environmental monitoring.The article applies tandem piezoelectric sensor technology (SPQC) to study the adsorption properties of natural polymer chitosan to metal ions, and the influence from ion concentration, adsorbent dosage and degree of deacetylation of chitosan to chitosan sequestration performance has been investigated in the article.In addition, the determination of degree of deacetylation has been conducted with the application of tandem piezoelectric sensor technology in the article, this test method can effectively eliminate the influence of residual acid or residual alkali adsorbed by chitosan, making measurement results become more accurate and reliable.
In this study, the physiochemical properties and cellular-level biological effects of baicalin-lecithin complex (BLC)-loaded poly(lactic-co-glycolic acid) (PLGA) membranes were studied. Several parameters were measured to evaluate the preparation of these membranes, such as the coating thickness, scanning electron microscopy-detected surface morphology, X-ray diffraction, Fourier transform infrared spectroscopy, and thermodynamic behavior. The drug-release behavior was mainly controlled by the degradation of the PLGA. The release of BLC lasted for more than one month, which matched the development of the restenosis process. The BLC-coated PLGA (60:40) membrane had good drug release in terms of its long release cycle, and the efficacy of baicalin in the form of BLC in cardiovascular stents matched the development of restenosis. In vitro cell culture test showed that endothelial cells (ECs) and smooth muscle cells (SMCs) for 12 h, 1 d and 3 d, BLC-loaded PLGA membranes (1%, 5% and 10% (w/w)) had significant activity towards the proliferation of ECs and the inhibition of SMC proliferation ( P < 0.05). BLC-loaded PLGA film has good drug release trends.
The content of polysaccharides in Tuber sinense was investigated by isolation and purification, followed with the further antioxidant studies in total reducing capacity and radical scavenging activities. The crude extract of polysaccharides was purified by dialysis, column chromatography, and High Performance Liquid Chromatography. The main components of monosaccharide (s) and molecular structure of single polysaccharide were studied by using methylation, GC-MS, and NMR analysis. One new water-soluble non-starch polysaccharide (PTS-A with the yield of 0.41%) from T. sinense was purified and identified on structural characteristics for the first time. The characterizations of PTS-A were studied on physicochemical properties, main components of monosaccharide (s) and molecular structure. PTS-A was identified as glucan, only containing D-glucoses with the molecular structure of [→6) α-D-Glcp (1→6) α-D-Glcp (1→]n by methylation analysis and NMR. In the determination of total reducing capacity, their reducing abilities could be listed as vitamin C> PTS-A> crude polysaccharides-3> crude polysaccharides-2> crude polysaccharides-1. All of PTS-A, crude polysaccharides-2 and -3 were relatively good scavenger for 1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1- (2,4,6-trinitrophenyl) hydrazyl radicals with the IC50 of 2.81, 4.17 and 3.44 mg/mL, respectively. Thus, the separation and purification of polysaccharides were significant to increase the antioxidant activity in some degree. One new water-soluble 1,6-α-ᴅ-dextran was discovered with the polysaccharide structure identified for the first time. Both PTS-A and crude extracts of polysaccharide performed a potent potential on antioxidant activities. The bioactivities of PTS-A should be generalized to the broader pharmacological effects.
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