AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by compu...AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.展开更多
Carotenoids have attracted greater attention due to the beneficial role on human health. It is an essential nutrient and has some biological functions such as species-specific coloration, photoprotection, light absorb...Carotenoids have attracted greater attention due to the beneficial role on human health. It is an essential nutrient and has some biological functions such as species-specific coloration, photoprotection, light absorbing, which is an important component because of its role as precursor of vitamin A. In this study was performed the production of fl-Carotene by Rhodotorula glutinis UCP/WFCC 1555 in presence and absence of blue and white using LED (light-emitting diodes) and evaluation of the cytotoxic effect. The production was investigated in low cost medium constituted by different concentrations of CG (crude glycerin) and CSL (corn steep liquor) from the CCD (Central Composite Design) and the identification and yield of the β-Carotene was investigated by chromatographic profile (HPLC). Additionally, the fl-Carotene produced was tested to evaluate its cytotoxic effect in human tumor cells MCF-7 (breast cancer) and HL-60 (promyelocytic leukemia) and healthy cells of macrophages. The results showed that in the medium composed by 6% glycerin and 0.6% corn steep liquor, in the absence of light, occurred the maximum production of total carotenoids with values of 160μg·g-1 and these 100.60μg·g-1 correspond to the β-Carotene that showed ability in inhibit cell growth in several tumor cells such as MCF-7 cells (breast cancer) and HL-60 (promyelocytic leukemia).展开更多
AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids(PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells ...AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids(PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations(IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μg·mL-1, respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION: The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells.These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.展开更多
Magnesium (Mg) based metals possess unique features of biodegradation that can be used for different purposes. In this study, two tumor cells, MG63 and KB, were cultured directly on a pure Mg with and without MAO co...Magnesium (Mg) based metals possess unique features of biodegradation that can be used for different purposes. In this study, two tumor cells, MG63 and KB, were cultured directly on a pure Mg with and without MAO coating to evaluate their cytotoxic effects on the tumor cells. It was found that both MG63 cells and KB cells adhered better on the surface of the coated Mg samples than those on the pure Mg samples. However, the survivals of two kinds of tumor cells were obviously inhibited on both Mg samples with and without coating, compared with that on the pure titanium. In addition, the survival of MG63 cells was more susceptive to the Mg degradation compared with the KB cells. Thus, the application of such effect should take account of that the degradation of Mg based metal may result in different cytotoxic effect on different cells.展开更多
Docetaxel(DTX),a paclitaxel analogue,can efficiently inhibit proliferation of vascular smooth muscle cells and has broadly been used as an antiangiogenesis drug.However,as a candidate drug of drug-eluting stent,the ef...Docetaxel(DTX),a paclitaxel analogue,can efficiently inhibit proliferation of vascular smooth muscle cells and has broadly been used as an antiangiogenesis drug.However,as a candidate drug of drug-eluting stent,the effects of DTX on human umbilical vein endothelial cells(HUVECs)are still not well understood.Herein,we investigated the effects of DTX on proliferation,apoptosis,adhesion,migration and morphology of HUVECs in vitro.We found that DTX had the cytostatic and cytotoxic effects at low and high concentrations,respectively.DTX could inhibit the proliferation and migration of HUVECs,induce HUVECs apoptosis,delay HUVECs adhesion and decrease spreading area and aspect ratio of individual cells.The signaling pathway that DTX led to the migration inhibition,adhesion delay and shape change of HUVECs is the VE-cadherin mediated integrin b1/FAK/ROCK signaling pathway.The study will provide a theoretical basis for the clinical application of DTX.展开更多
In this study,acetone extracts of thirteen different species distributed in Turkey Coasts including tunicates,sea anemones,sponges and corals were investigated for their superoxide(SO)radical scavenging and cytotoxic ...In this study,acetone extracts of thirteen different species distributed in Turkey Coasts including tunicates,sea anemones,sponges and corals were investigated for their superoxide(SO)radical scavenging and cytotoxic activities.VWhile SO radical scavenging activity was tested using alkaline DMSO method,cytotoxic activity was tested by MTT assay against Hep-2 cancer cell line.As a result of bioactivity studies,Paramuricea clavata extract showed展开更多
The in vivo effects of Phytolacca acinosa poly-saccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied....The in vivo effects of Phytolacca acinosa poly-saccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80 or 160 mg kg was given ip twice every 4 day. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 hrs to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbence assay of enzymatic reaction and proliferation of thymocytes co-stimulated assay separately. The optimal time for TNF production was found on day 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between them, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production.展开更多
The cytotoxic effect of extract of camellia ptilophyllachang(ECPC) and extract of camellia sinensis(ECS) onHeLa cell line, poorly differentiated nasopharyngealcarcinoma cell line(CNE2) and gastric cancer cell line(MGC...The cytotoxic effect of extract of camellia ptilophyllachang(ECPC) and extract of camellia sinensis(ECS) onHeLa cell line, poorly differentiated nasopharyngealcarcinoma cell line(CNE2) and gastric cancer cell line(MGC-803 ) in vitro was studied using MIT assay method.The results showed that ECPC and ECS possessed significantcytotoxic effect on above three cell lines. The anticancer testin mice showed that ECPC had marked inhibitory effectagainst Ehrlich solid carcinoma(ESC) with inhibition ratesof 17. 8 48. 3% and with inhibition rates of 28. 3-54. 5% against reticular cell sarcoma(L2), and that ECShad inhibition rates of 31 . 5 -49. 4 % against ESC and 35. 8- 50% against L2. These two extracts had only marginalinhibitory effect against sarcoma- 180. The unknottingactivity of DNA topoisomerase II was inhibited completelyby ECPC and ECS at the concentration of 50 μg/ mlsuggesting that DNA topoisomerase II might be a targetenzyme of these two extracts.展开更多
AIM:To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS: Colorectal carcinoma (HT29) and human hepatocellular carcin...AIM:To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS: Colorectal carcinoma (HT29) and human hepatocellular carcinoma (HepG2) cells were treated with spray-dried extracts of Phyllanthus niruri (SDEPN) either alone or in combination with cisplatin at differ- ent concentrations (0.5 mg/mL and 1 mg/mL) for 4 h and 24 h. To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability, we stained the cells with prop- idium iodide and assessed them by flow cytometry. The percentage of cells in different cell cycle phases was quantified and data were expressed as histo- grams. Significant differences between groups were determined using analysis of variance and Bonferroni's test, as indicated. A value of P 〈 0.05 was considered to be statistically significant. RESULTS: SDEPN had significantly different cyto- toxic effects on HT29 (2.81 4- 0.11 vs 3.51 4- 1.13, P 〉 0.05) and HepG2 (5.07± 0.3 vs 15.9 ± 1.04, P 〈 0.001) cells when compared to control cells for 4 h. SDEPN also had significantly different cytotoxic effects on HT29 (1.91 ± 0.57 vs 4.53± 1.22, P 〉 0.05) and HepG2 (14.56 ± 1.6 vs 35.67 ± 3.94, P 〈 0.001) cells when compared to control cells for 24 h. Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells (HepG2 cells for 4 h: 10.78 ± 1.58 vs 53.89 ± 1.53, P 〈 0.001; 24 h: 8.9 ± 1.43 vs 62.78 ± 1.87, P 〈 0.001 and HT29 cells for 4 h: 9.52 ±0.913 vs 49.86 ± 2.89, P 〈 0.001; 24 h: 11.78 ± 1.05 vs 53.34 ± 2.65, P 〈 0.001). In HT29 cells, pretreat- ment with SDEPN and subsequent treatment with cis-platin resulted in a greater number of cells being killed (12.78 ± 1.01 vs 93.76 ± 1.6, P 〈 0.001). HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin (12.87 ± 2.78 vs 78.8 ± 3.02, P 〈 0.001). CONCLUSION: SDEPN is selectively toxic against two cancer cell lines. Moreover, SDEPN in combination with cisplatin induces a synergistic increase in the cell death of both HT29 and HepG2 cells.展开更多
Cell-based biosensors have become a research hotspot in the biosensors and bioelectronics fields. The main feature of cell-based biosensors is immobilization of living cells on the surface of transducers. Different ty...Cell-based biosensors have become a research hotspot in the biosensors and bioelectronics fields. The main feature of cell-based biosensors is immobilization of living cells on the surface of transducers. Different types of polymers which are used as scaffolds for cell growth should be biocompatible and should have reac- tive functional groups for further attachment of biomolecules. In this work, cell attachment and proliferation on chitosan hydrogel, chitosan-gelatin and gold nanoparticle-chitosan nanocomposite membranes was stud- ied. Characterization of the membranes was performed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Cytotoxicity assessment on HEK293 cells was carried out for all mem- branes using the MTT assay. Cell morphology and viability were assessed to evaluate cell attachment and pro- liferation. Regarding cell studies, the findings revealed that none of the membranes induced cytotoxic effects. However, the data showed that gold nanoparticle nanocomposite membranes improved HEK293 attachment and adhesion more than other membranes, indicating that it provides an effective surface for immobilizing cells for sensing applications.展开更多
BACKGROUND: Rotenone-induced neurotoxicity in PC 12 cells has been widely used to study the pathogenesis of Parkinson's disease. However, the precise mechanisms underlying rotenone-induced dopaminergic neuronal dege...BACKGROUND: Rotenone-induced neurotoxicity in PC 12 cells has been widely used to study the pathogenesis of Parkinson's disease. However, the precise mechanisms underlying rotenone-induced dopaminergic neuronal degeneration in Parkinson's disease remains unclear. OBJECTIVE: To establish rotenone-induced neurotoxicity in PC 12 cells, and to investigate the possible action pathways to rotenone-induced neural cell injury at the protein level. DESIGN, TIME AND SETTING: A controlled proteomics study was performed at the Department of Neurology, First Hospital, Jilin University between March 2006 and March 2007. MATERIALS: PC 12 cells were obtained from Shanghai Cell Bank of Chinese Academy of Sciences, China. Rotenone was provided by Sigma, USA. METHODS: PC 12 cells in logarithmic growth phase were treated under experimental and control conditions, respectively. A total of 0.5 μmol/L rotenone, or the same amount of Dulbecco's modified eagle's medium (DMEM), was added in the experimental and control conditions, respectively. MAIN OUTCOME MEASURES: Following 72 hours of rotenone treatment, cellular survival rate was determined by methyl thiazolyl tetrazolium assay, and apoptotic changes were detected by Hoechst 33342 staining. Total cellular protein was extracted to acquire differential protein expression data utilizing two-dimensional differential in-gel electrophoresis. To identify differential protein spots, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) was used. RESULTS: In the MTT assay, the experimental condition induced significantly less cell survival compared to the control condition (P 〈 0.01). Hoechst 33342 staining revealed a larger number of apoptotic cells under the experimental condition compared to the control condition (P 〈 0.01), as determined by the presence of nuclear condensation, pyknosis, and nuclear fragmentation. Two-dimensional electrophoresis results showed that the differential expression of protein spots 1069 and 1538 was increased by 144% and 124%, respectively, while that of protein spot 1094 was decreased by 123% in the experimental condition compared to the control condition (P 〈 0.01). By MALDI-TOF-MS analysis and database retrieval, γ-enolase, triosephosphate isomerase 1, and eukaryotic translation initiation factor 4A were confirmed to be involved in rotenone-induced neural cell injury. CONCLUSION: γ-enolase, triosephosphate isomerase 1, and eukaryotic translation initiation factor 4A might participate in rotenone-induced neurotoxicity in PC 12 cells.展开更多
The two most important criteria for dental materials are their biofunctional and biocompatible endurance within the anticipated life-span of the dental restoration in the mouth. Biocompatibility relates mainly to the ...The two most important criteria for dental materials are their biofunctional and biocompatible endurance within the anticipated life-span of the dental restoration in the mouth. Biocompatibility relates mainly to the allergenicity and the toxicity of the material. To test the non-specific toxicity of dental materials, in vitro cell culture assays have been developed. For in vitro screening, such tests are recommended to check the cytotoxicity of dental materials (ISO 10993 5). Various studies have already been performed to quantitatively determine the cytotoxicity level of dental alloys. However, as long as only dental alloys and the cell culture technique are applied, it is not possible to determine which of the alloying elements cause the cytotoxicity. Therefore, an analytical method is needed. Wataha et al determined in 1991 the TC50 values of 9 metal cations of various dental casting alloys, using cell culture methods. Kapert et al reported in 1994 a complex in vitro test concept, where the ICP analysis (inductively coupled plasma emission spectroscopy) was introduced to measure the trace elements extracted from various alloys. Experimentelle Zahnheilkunde, Universitts ZMK Klinik Freiburg, Germany (Lü XY and Kappert HF) The aim of the present study was to find a relation between the ICP results, the TC50 value of metal cations, and the cytotoxicity of dental alloys. The cytotoxicity levels of various dental alloys and the TC50 values of 10 metal cations were established using the MTT assay, an effective cell culture of method. Then, the concentrations of the corrosively soluted metal cations in the extracts of the alloys were measured using the ICP method. From all these experimental results it was found that the relation between the effective cytotoxicity Z eff of an alloy, the concentrations C i of i th trace element and the TC50 values T Ci of the i th metal cation can approximately be expressed by Z eff =∑iC i2·T Ci . Two significant applications of this expression are a) The cytotoxicity of an alloy can be estimated by ICP analysis of the extract if the TC50 values of the trace elements are know. b) The cytotoxicity of a new-developed-alloy can be estimated in advance, according to the alloying components.展开更多
AIM: To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction (TSF), 25% ethanol fraction (25EF), 50% ethanol fraction (50EF), and 85% ethanol fraction (85EF) prepared by macro...AIM: To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction (TSF), 25% ethanol fraction (25EF), 50% ethanol fraction (50EF), and 85% ethanol fraction (85EF) prepared by macroporous resin from the leaves of Panax notoginseng. METHOD: The simultaneous determination of thirteen main saponins, as well as the chemical profiles of saponin fractions of different polarity, was made by HPLC-DAD and LC-ESI-MSn analysis. The cytotoxic effects were determined against KP4 cells (human pancreatic cancer), NCI-H727 ceils (human lung cancer), HepG2 cells (human hepatocellular cancer), and SGC-7901 cells (human gastric adenocarcinoma). RESULTS: Chemical analysis indicated that 85EF possessed the most abundant cytotoxic protopanaxadiol saponins, including the marker saponins F2, 20(R)-Rg3, 20(S)-Rg3, and Rh2. The MTT assay showed that 85EF also had the strongest cytotoxic effects among the four fractions. 25EF showed no anti-proliferative effects, while 50EF and TSF exhibited weak anti-proliferative activity. CONCLUSION: From the aspect of comprehensive utilization of resources, 85EF, enriched with low polarity PPD group saponins, is a new alternative source of anticancer saponins, and a promising botanical preparation for further anticancer studies.展开更多
A novel Diels-Alder adduct possesses a 6/6/6/5/6/6/6/6 octacyclic skeleton featured with bicyclo[2.2.2]octane moiety,biseupyiheoid A(1),along with another decacyclic 6/6/6/3/5/6/5/6/6/6 fused diterpenoid dimer,bisfisc...A novel Diels-Alder adduct possesses a 6/6/6/5/6/6/6/6 octacyclic skeleton featured with bicyclo[2.2.2]octane moiety,biseupyiheoid A(1),along with another decacyclic 6/6/6/3/5/6/5/6/6/6 fused diterpenoid dimer,bisfischoid C(2),were isolated from Euphorbia fischeriana.Their structures were determined by spectroscopic,X-ray crystallographic approaches,and quantum mechanical calculations.The structural features of 1 and 2 were hypothesized to involve intramolecular Diels-Alder reactions with different coupling patterns.Dimer 1 showed antiproliferative activity through apoptosis activation in LoVo cells.展开更多
Objective: To evaluate the cytotoxic effects of ampelopsin sodium(Amp-Na) and carboplatin(CBP) used alone or in combination on human non-small cell lung cancer(NSCLC) cells SPC-A1 in vitro and its related mecha...Objective: To evaluate the cytotoxic effects of ampelopsin sodium(Amp-Na) and carboplatin(CBP) used alone or in combination on human non-small cell lung cancer(NSCLC) cells SPC-A1 in vitro and its related mechanism. Methods: Cytotoxic effects were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assays. The synergistic effects of the drugs were calculated with coefficient of drug interaction(CDI). Cell cycle was determined by flow cytometry(FCM). The levels of p53, p21, cyclin E, cyclin D1, and phosphorylated cyclin-dependent kinase-2(p-CDK2) were evaluated by Western blot. Results: Amp-Na(6.25–200 μg/m L) and CBP(3.13–100 μg/m L) alone exhibited prominent cytotoxic activity in a concentration-dependent manner on SPC-A1 cells with 50% inhibitive concentration values of 57.07±14.46 and 34.97±6.30 μg/m L, respectively. Drug combinations were associated with significantly higher cytotoxic effects than each drug alone(P〈0.05 or 0.01). The CDI analysis confirmed the synergy of Amp-Na and CBP on inhibiting cancer cell viability across a wide concentration range(CDI 〈1). FCM and Western blot showed that synergistic cytotoxic effects of Amp-Na and CBP were related to G1 arrested which mainly mediated by p21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway. Conclusions: AmpNa exhibits anticancer activities and enhances the antitumor activities of CBP through up-regulation of p21 and inhibition of CDK2 activity in human NSCLC cells SPC-A1. These results suggest that Amp-Na may be applied to enhance the anticancer action of CBP.展开更多
Parasporins(PSs) represent a novel functional category of crystal proteins(Cry) produced by non-insecticidal Bacillus thuringiensis. A distinct feature for PSs is their specific cytotoxicity against human cancer cells...Parasporins(PSs) represent a novel functional category of crystal proteins(Cry) produced by non-insecticidal Bacillus thuringiensis. A distinct feature for PSs is their specific cytotoxicity against human cancer cells from diverse origins, other than hemolytic or insecticidal activity. As structurally/functionally Cry proteins, parasporins are expressed as protoxins that require protease cleavage for activation. Currently,identified PSs is classified into 6 groups: PS1, PS2, PS3, PS4, PS5 and PS6, which are heterogeneous in cytotoxic spectrum and activity level. Some PSs have been explored for their mode of anticancer activities, reports mainly include pore formation induced by binding to putative receptors on cell membrane and apoptosis by intracellular Ca2+concentration. Further work should focus on the identification of new PS or PS homologs and better understanding of their anticancer mechanism before possible application in cancer therapy.展开更多
We synthesised a series of ω-aminoalkyl sodium hydrogen phosphates (AAP-n-Na, n =3, 4, 5, 6, purity 〉 99%), which have potential applications as bioactive cosmetic ingredients and surface modifiers of bone minera...We synthesised a series of ω-aminoalkyl sodium hydrogen phosphates (AAP-n-Na, n =3, 4, 5, 6, purity 〉 99%), which have potential applications as bioactive cosmetic ingredients and surface modifiers of bone minerals (i.e. hydroxyapatites). Results from Fourier transformed infrared (FTIR), nuclear magnetic resonance (NMR) and high resolution mass spectroscopy, and elemental analysis all matched their chemical structures. The acid dissociation constants (pKa's) of each AAP-n (acid form of AAP-n-Na, n ; 2-6) were measured by potentiometric titration, showing a general increasing trend with an increase in the chain length of AAP-n. However, the pKa3 constant, which corresponds to the deprotonation of the ammonium group in AAP-n-Na, displayed an unusual decrease when n = even. This odd-even effect can be explained by the pairwise self-association of AAP-n-Na molecules in water where intermolecular hydrogen bonding in case of n=even is weaker than that in case of n=odd. All AAP-n-Na at concentrations up to 0.1% (w/v) were non-toxic to L929 fibroblasts and MG 63 osteoblast-like cells in terms of cell growth and morphology, These basic data were important for applications of AAP-n and their salts in biomedical engineering.展开更多
Background Immune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to...Background Immune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage (Me) in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Me in hematopoietic cell injury. Methods ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-y levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase (POX), nonspecific esterase (NSE), hemosiderin granules, and HLA-DR activity of Me in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Me membrane Fcyllreceptor (FcyllR), mannitose receptor (MR), IFN-y, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) hematopoietic cell islands (HI) in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Me bloodthirsty phenomenon; if necessary, association of Cyclosporine A (CsA) should be used and chalybeate should be supplemented. Results In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-y were increased. After treatment, the cytokine levels gradually became normal. The activated Me in the marrow highly expressed NSE and POX, and Me swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Me expressed HLA-DR, MR, ICAM-1, IFN-y, and IL-12. For patients with humoral immunity activation and bacterial infection, Me weakly expressed IL-17A but highly expressed FcyIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count (WBC) significantly reduced, Me weakly expressed FcyIIR, secretory highly expressed IL-17A, and the phenomena that Me adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Me occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve. Conclusions Me is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Me, upregulate the impression of immune molecule and receptors, form ADCC HI. aeGravate hematoBoietic iniurv, and accelerate the destruction on hematoDoietic cell.展开更多
基金Supported by the China Key Program on Basic Research,G1998051102 and G1998051021 National Science Foundation of China, 39870862
文摘AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.
文摘Carotenoids have attracted greater attention due to the beneficial role on human health. It is an essential nutrient and has some biological functions such as species-specific coloration, photoprotection, light absorbing, which is an important component because of its role as precursor of vitamin A. In this study was performed the production of fl-Carotene by Rhodotorula glutinis UCP/WFCC 1555 in presence and absence of blue and white using LED (light-emitting diodes) and evaluation of the cytotoxic effect. The production was investigated in low cost medium constituted by different concentrations of CG (crude glycerin) and CSL (corn steep liquor) from the CCD (Central Composite Design) and the identification and yield of the β-Carotene was investigated by chromatographic profile (HPLC). Additionally, the fl-Carotene produced was tested to evaluate its cytotoxic effect in human tumor cells MCF-7 (breast cancer) and HL-60 (promyelocytic leukemia) and healthy cells of macrophages. The results showed that in the medium composed by 6% glycerin and 0.6% corn steep liquor, in the absence of light, occurred the maximum production of total carotenoids with values of 160μg·g-1 and these 100.60μg·g-1 correspond to the β-Carotene that showed ability in inhibit cell growth in several tumor cells such as MCF-7 cells (breast cancer) and HL-60 (promyelocytic leukemia).
基金supported by the National Natural Science Foundation of China(No.81274078,81322052,81303222)China Postdoctoral Science Foundation(No.2013M532130)
文摘AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids(PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations(IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μg·mL-1, respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION: The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells.These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.
基金support of the National Natural Science Foundation of China(No.30970715 and No.2012CB619101)Chinese Academy of Sciences,Applied Research of Bioactive Bone Implanted Materials(No.KGCX2YW-207)
文摘Magnesium (Mg) based metals possess unique features of biodegradation that can be used for different purposes. In this study, two tumor cells, MG63 and KB, were cultured directly on a pure Mg with and without MAO coating to evaluate their cytotoxic effects on the tumor cells. It was found that both MG63 cells and KB cells adhered better on the surface of the coated Mg samples than those on the pure Mg samples. However, the survivals of two kinds of tumor cells were obviously inhibited on both Mg samples with and without coating, compared with that on the pure titanium. In addition, the survival of MG63 cells was more susceptive to the Mg degradation compared with the KB cells. Thus, the application of such effect should take account of that the degradation of Mg based metal may result in different cytotoxic effect on different cells.
基金The study was supported by grants from the National Natural Science Foundation of China(11332003,31370949 and 81400329)the National Key Technology R&D Program of China(2016YFC1102305 and 2012BAI18B02)+2 种基金the Chongqing Graduate Student Research Innovation Project(CYS14023)the Fundamental Research Funds for the Central Universities(106112016CDJXZ238802)as well as the support from the Chongqing Engineering Laboratory in Vascular Implants and the Public Experiment Center of State Bioindustrial Base(Chongqing),China.
文摘Docetaxel(DTX),a paclitaxel analogue,can efficiently inhibit proliferation of vascular smooth muscle cells and has broadly been used as an antiangiogenesis drug.However,as a candidate drug of drug-eluting stent,the effects of DTX on human umbilical vein endothelial cells(HUVECs)are still not well understood.Herein,we investigated the effects of DTX on proliferation,apoptosis,adhesion,migration and morphology of HUVECs in vitro.We found that DTX had the cytostatic and cytotoxic effects at low and high concentrations,respectively.DTX could inhibit the proliferation and migration of HUVECs,induce HUVECs apoptosis,delay HUVECs adhesion and decrease spreading area and aspect ratio of individual cells.The signaling pathway that DTX led to the migration inhibition,adhesion delay and shape change of HUVECs is the VE-cadherin mediated integrin b1/FAK/ROCK signaling pathway.The study will provide a theoretical basis for the clinical application of DTX.
基金supported by the Turkish Academy of Science,Young Scientist Award(TUBA-GEBIP/2013)
文摘In this study,acetone extracts of thirteen different species distributed in Turkey Coasts including tunicates,sea anemones,sponges and corals were investigated for their superoxide(SO)radical scavenging and cytotoxic activities.VWhile SO radical scavenging activity was tested using alkaline DMSO method,cytotoxic activity was tested by MTT assay against Hep-2 cancer cell line.As a result of bioactivity studies,Paramuricea clavata extract showed
文摘The in vivo effects of Phytolacca acinosa poly-saccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80 or 160 mg kg was given ip twice every 4 day. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 hrs to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbence assay of enzymatic reaction and proliferation of thymocytes co-stimulated assay separately. The optimal time for TNF production was found on day 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between them, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production.
文摘The cytotoxic effect of extract of camellia ptilophyllachang(ECPC) and extract of camellia sinensis(ECS) onHeLa cell line, poorly differentiated nasopharyngealcarcinoma cell line(CNE2) and gastric cancer cell line(MGC-803 ) in vitro was studied using MIT assay method.The results showed that ECPC and ECS possessed significantcytotoxic effect on above three cell lines. The anticancer testin mice showed that ECPC had marked inhibitory effectagainst Ehrlich solid carcinoma(ESC) with inhibition ratesof 17. 8 48. 3% and with inhibition rates of 28. 3-54. 5% against reticular cell sarcoma(L2), and that ECShad inhibition rates of 31 . 5 -49. 4 % against ESC and 35. 8- 50% against L2. These two extracts had only marginalinhibitory effect against sarcoma- 180. The unknottingactivity of DNA topoisomerase II was inhibited completelyby ECPC and ECS at the concentration of 50 μg/ mlsuggesting that DNA topoisomerase II might be a targetenzyme of these two extracts.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq (470179/2009-0) for financial support and Postgraduate Program in Pharmaceutical Sciences,Federal University of Rio Grande do Norte
文摘AIM:To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS: Colorectal carcinoma (HT29) and human hepatocellular carcinoma (HepG2) cells were treated with spray-dried extracts of Phyllanthus niruri (SDEPN) either alone or in combination with cisplatin at differ- ent concentrations (0.5 mg/mL and 1 mg/mL) for 4 h and 24 h. To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability, we stained the cells with prop- idium iodide and assessed them by flow cytometry. The percentage of cells in different cell cycle phases was quantified and data were expressed as histo- grams. Significant differences between groups were determined using analysis of variance and Bonferroni's test, as indicated. A value of P 〈 0.05 was considered to be statistically significant. RESULTS: SDEPN had significantly different cyto- toxic effects on HT29 (2.81 4- 0.11 vs 3.51 4- 1.13, P 〉 0.05) and HepG2 (5.07± 0.3 vs 15.9 ± 1.04, P 〈 0.001) cells when compared to control cells for 4 h. SDEPN also had significantly different cytotoxic effects on HT29 (1.91 ± 0.57 vs 4.53± 1.22, P 〉 0.05) and HepG2 (14.56 ± 1.6 vs 35.67 ± 3.94, P 〈 0.001) cells when compared to control cells for 24 h. Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells (HepG2 cells for 4 h: 10.78 ± 1.58 vs 53.89 ± 1.53, P 〈 0.001; 24 h: 8.9 ± 1.43 vs 62.78 ± 1.87, P 〈 0.001 and HT29 cells for 4 h: 9.52 ±0.913 vs 49.86 ± 2.89, P 〈 0.001; 24 h: 11.78 ± 1.05 vs 53.34 ± 2.65, P 〈 0.001). In HT29 cells, pretreat- ment with SDEPN and subsequent treatment with cis-platin resulted in a greater number of cells being killed (12.78 ± 1.01 vs 93.76 ± 1.6, P 〈 0.001). HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin (12.87 ± 2.78 vs 78.8 ± 3.02, P 〈 0.001). CONCLUSION: SDEPN is selectively toxic against two cancer cell lines. Moreover, SDEPN in combination with cisplatin induces a synergistic increase in the cell death of both HT29 and HepG2 cells.
文摘Cell-based biosensors have become a research hotspot in the biosensors and bioelectronics fields. The main feature of cell-based biosensors is immobilization of living cells on the surface of transducers. Different types of polymers which are used as scaffolds for cell growth should be biocompatible and should have reac- tive functional groups for further attachment of biomolecules. In this work, cell attachment and proliferation on chitosan hydrogel, chitosan-gelatin and gold nanoparticle-chitosan nanocomposite membranes was stud- ied. Characterization of the membranes was performed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Cytotoxicity assessment on HEK293 cells was carried out for all mem- branes using the MTT assay. Cell morphology and viability were assessed to evaluate cell attachment and pro- liferation. Regarding cell studies, the findings revealed that none of the membranes induced cytotoxic effects. However, the data showed that gold nanoparticle nanocomposite membranes improved HEK293 attachment and adhesion more than other membranes, indicating that it provides an effective surface for immobilizing cells for sensing applications.
文摘BACKGROUND: Rotenone-induced neurotoxicity in PC 12 cells has been widely used to study the pathogenesis of Parkinson's disease. However, the precise mechanisms underlying rotenone-induced dopaminergic neuronal degeneration in Parkinson's disease remains unclear. OBJECTIVE: To establish rotenone-induced neurotoxicity in PC 12 cells, and to investigate the possible action pathways to rotenone-induced neural cell injury at the protein level. DESIGN, TIME AND SETTING: A controlled proteomics study was performed at the Department of Neurology, First Hospital, Jilin University between March 2006 and March 2007. MATERIALS: PC 12 cells were obtained from Shanghai Cell Bank of Chinese Academy of Sciences, China. Rotenone was provided by Sigma, USA. METHODS: PC 12 cells in logarithmic growth phase were treated under experimental and control conditions, respectively. A total of 0.5 μmol/L rotenone, or the same amount of Dulbecco's modified eagle's medium (DMEM), was added in the experimental and control conditions, respectively. MAIN OUTCOME MEASURES: Following 72 hours of rotenone treatment, cellular survival rate was determined by methyl thiazolyl tetrazolium assay, and apoptotic changes were detected by Hoechst 33342 staining. Total cellular protein was extracted to acquire differential protein expression data utilizing two-dimensional differential in-gel electrophoresis. To identify differential protein spots, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) was used. RESULTS: In the MTT assay, the experimental condition induced significantly less cell survival compared to the control condition (P 〈 0.01). Hoechst 33342 staining revealed a larger number of apoptotic cells under the experimental condition compared to the control condition (P 〈 0.01), as determined by the presence of nuclear condensation, pyknosis, and nuclear fragmentation. Two-dimensional electrophoresis results showed that the differential expression of protein spots 1069 and 1538 was increased by 144% and 124%, respectively, while that of protein spot 1094 was decreased by 123% in the experimental condition compared to the control condition (P 〈 0.01). By MALDI-TOF-MS analysis and database retrieval, γ-enolase, triosephosphate isomerase 1, and eukaryotic translation initiation factor 4A were confirmed to be involved in rotenone-induced neural cell injury. CONCLUSION: γ-enolase, triosephosphate isomerase 1, and eukaryotic translation initiation factor 4A might participate in rotenone-induced neurotoxicity in PC 12 cells.
文摘The two most important criteria for dental materials are their biofunctional and biocompatible endurance within the anticipated life-span of the dental restoration in the mouth. Biocompatibility relates mainly to the allergenicity and the toxicity of the material. To test the non-specific toxicity of dental materials, in vitro cell culture assays have been developed. For in vitro screening, such tests are recommended to check the cytotoxicity of dental materials (ISO 10993 5). Various studies have already been performed to quantitatively determine the cytotoxicity level of dental alloys. However, as long as only dental alloys and the cell culture technique are applied, it is not possible to determine which of the alloying elements cause the cytotoxicity. Therefore, an analytical method is needed. Wataha et al determined in 1991 the TC50 values of 9 metal cations of various dental casting alloys, using cell culture methods. Kapert et al reported in 1994 a complex in vitro test concept, where the ICP analysis (inductively coupled plasma emission spectroscopy) was introduced to measure the trace elements extracted from various alloys. Experimentelle Zahnheilkunde, Universitts ZMK Klinik Freiburg, Germany (Lü XY and Kappert HF) The aim of the present study was to find a relation between the ICP results, the TC50 value of metal cations, and the cytotoxicity of dental alloys. The cytotoxicity levels of various dental alloys and the TC50 values of 10 metal cations were established using the MTT assay, an effective cell culture of method. Then, the concentrations of the corrosively soluted metal cations in the extracts of the alloys were measured using the ICP method. From all these experimental results it was found that the relation between the effective cytotoxicity Z eff of an alloy, the concentrations C i of i th trace element and the TC50 values T Ci of the i th metal cation can approximately be expressed by Z eff =∑iC i2·T Ci . Two significant applications of this expression are a) The cytotoxicity of an alloy can be estimated by ICP analysis of the extract if the TC50 values of the trace elements are know. b) The cytotoxicity of a new-developed-alloy can be estimated in advance, according to the alloying components.
基金supported by the National Natural Science Foundation of China(Nos.81274018,81274068)the Project funded by Jiangsu Branch of China Academy of Chinese Medical Science(JSBY1306)
文摘AIM: To evaluate the chemical profiles and cytotoxic effects among the total saponin fraction (TSF), 25% ethanol fraction (25EF), 50% ethanol fraction (50EF), and 85% ethanol fraction (85EF) prepared by macroporous resin from the leaves of Panax notoginseng. METHOD: The simultaneous determination of thirteen main saponins, as well as the chemical profiles of saponin fractions of different polarity, was made by HPLC-DAD and LC-ESI-MSn analysis. The cytotoxic effects were determined against KP4 cells (human pancreatic cancer), NCI-H727 ceils (human lung cancer), HepG2 cells (human hepatocellular cancer), and SGC-7901 cells (human gastric adenocarcinoma). RESULTS: Chemical analysis indicated that 85EF possessed the most abundant cytotoxic protopanaxadiol saponins, including the marker saponins F2, 20(R)-Rg3, 20(S)-Rg3, and Rh2. The MTT assay showed that 85EF also had the strongest cytotoxic effects among the four fractions. 25EF showed no anti-proliferative effects, while 50EF and TSF exhibited weak anti-proliferative activity. CONCLUSION: From the aspect of comprehensive utilization of resources, 85EF, enriched with low polarity PPD group saponins, is a new alternative source of anticancer saponins, and a promising botanical preparation for further anticancer studies.
基金the National Natural Science Foundation of China(No.81930112)Distinguished Professor Program of Liaoning Province(No.XLYC2002008)+1 种基金Natural Science Foundation of Liaoning Province(Nos.2020-BS-203 and 2020-MS-256)Natural Science Foundation of Fujian Province(No.2021J01509).
文摘A novel Diels-Alder adduct possesses a 6/6/6/5/6/6/6/6 octacyclic skeleton featured with bicyclo[2.2.2]octane moiety,biseupyiheoid A(1),along with another decacyclic 6/6/6/3/5/6/5/6/6/6 fused diterpenoid dimer,bisfischoid C(2),were isolated from Euphorbia fischeriana.Their structures were determined by spectroscopic,X-ray crystallographic approaches,and quantum mechanical calculations.The structural features of 1 and 2 were hypothesized to involve intramolecular Diels-Alder reactions with different coupling patterns.Dimer 1 showed antiproliferative activity through apoptosis activation in LoVo cells.
基金Supported by the Natural Science Foundation of Gansu Province,China(No.0710RJZA044)
文摘Objective: To evaluate the cytotoxic effects of ampelopsin sodium(Amp-Na) and carboplatin(CBP) used alone or in combination on human non-small cell lung cancer(NSCLC) cells SPC-A1 in vitro and its related mechanism. Methods: Cytotoxic effects were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assays. The synergistic effects of the drugs were calculated with coefficient of drug interaction(CDI). Cell cycle was determined by flow cytometry(FCM). The levels of p53, p21, cyclin E, cyclin D1, and phosphorylated cyclin-dependent kinase-2(p-CDK2) were evaluated by Western blot. Results: Amp-Na(6.25–200 μg/m L) and CBP(3.13–100 μg/m L) alone exhibited prominent cytotoxic activity in a concentration-dependent manner on SPC-A1 cells with 50% inhibitive concentration values of 57.07±14.46 and 34.97±6.30 μg/m L, respectively. Drug combinations were associated with significantly higher cytotoxic effects than each drug alone(P〈0.05 or 0.01). The CDI analysis confirmed the synergy of Amp-Na and CBP on inhibiting cancer cell viability across a wide concentration range(CDI 〈1). FCM and Western blot showed that synergistic cytotoxic effects of Amp-Na and CBP were related to G1 arrested which mainly mediated by p21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway. Conclusions: AmpNa exhibits anticancer activities and enhances the antitumor activities of CBP through up-regulation of p21 and inhibition of CDK2 activity in human NSCLC cells SPC-A1. These results suggest that Amp-Na may be applied to enhance the anticancer action of CBP.
基金The National Natural Science Foundation of Chinagrant number:31170092+3 种基金Hunan Provincial Natural Science Foundation of Chinagrant number:13JJ2021 and 14JJ4028State Key Laboratory of Agricultural Microbiologygrant number:AMLKF201209
文摘Parasporins(PSs) represent a novel functional category of crystal proteins(Cry) produced by non-insecticidal Bacillus thuringiensis. A distinct feature for PSs is their specific cytotoxicity against human cancer cells from diverse origins, other than hemolytic or insecticidal activity. As structurally/functionally Cry proteins, parasporins are expressed as protoxins that require protease cleavage for activation. Currently,identified PSs is classified into 6 groups: PS1, PS2, PS3, PS4, PS5 and PS6, which are heterogeneous in cytotoxic spectrum and activity level. Some PSs have been explored for their mode of anticancer activities, reports mainly include pore formation induced by binding to putative receptors on cell membrane and apoptosis by intracellular Ca2+concentration. Further work should focus on the identification of new PS or PS homologs and better understanding of their anticancer mechanism before possible application in cancer therapy.
基金financial support from the National Natural Science Foundation of China (No. 50973069)
文摘We synthesised a series of ω-aminoalkyl sodium hydrogen phosphates (AAP-n-Na, n =3, 4, 5, 6, purity 〉 99%), which have potential applications as bioactive cosmetic ingredients and surface modifiers of bone minerals (i.e. hydroxyapatites). Results from Fourier transformed infrared (FTIR), nuclear magnetic resonance (NMR) and high resolution mass spectroscopy, and elemental analysis all matched their chemical structures. The acid dissociation constants (pKa's) of each AAP-n (acid form of AAP-n-Na, n ; 2-6) were measured by potentiometric titration, showing a general increasing trend with an increase in the chain length of AAP-n. However, the pKa3 constant, which corresponds to the deprotonation of the ammonium group in AAP-n-Na, displayed an unusual decrease when n = even. This odd-even effect can be explained by the pairwise self-association of AAP-n-Na molecules in water where intermolecular hydrogen bonding in case of n=even is weaker than that in case of n=odd. All AAP-n-Na at concentrations up to 0.1% (w/v) were non-toxic to L929 fibroblasts and MG 63 osteoblast-like cells in terms of cell growth and morphology, These basic data were important for applications of AAP-n and their salts in biomedical engineering.
文摘Background Immune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage (Me) in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Me in hematopoietic cell injury. Methods ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-y levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase (POX), nonspecific esterase (NSE), hemosiderin granules, and HLA-DR activity of Me in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Me membrane Fcyllreceptor (FcyllR), mannitose receptor (MR), IFN-y, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) hematopoietic cell islands (HI) in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Me bloodthirsty phenomenon; if necessary, association of Cyclosporine A (CsA) should be used and chalybeate should be supplemented. Results In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-y were increased. After treatment, the cytokine levels gradually became normal. The activated Me in the marrow highly expressed NSE and POX, and Me swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Me expressed HLA-DR, MR, ICAM-1, IFN-y, and IL-12. For patients with humoral immunity activation and bacterial infection, Me weakly expressed IL-17A but highly expressed FcyIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count (WBC) significantly reduced, Me weakly expressed FcyIIR, secretory highly expressed IL-17A, and the phenomena that Me adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Me occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve. Conclusions Me is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Me, upregulate the impression of immune molecule and receptors, form ADCC HI. aeGravate hematoBoietic iniurv, and accelerate the destruction on hematoDoietic cell.