Objective To investigate the expression profiles and their clinical significance of TRAIL receptors (TRAILR) in human hepatocellular carcinoma (HCC). Methods The expression profiles of TRAILR were determined in 60 s...Objective To investigate the expression profiles and their clinical significance of TRAIL receptors (TRAILR) in human hepatocellular carcinoma (HCC). Methods The expression profiles of TRAILR were determined in 60 samples from hepatocellular carcinoma, 20 from normal liver tissue and two HCC cell lines HepG2, SMMC-7721 by in situ hybridization. Results Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples (higher DR expression level and lower DcR expression level) were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. The expression level of DR was correlated with HCC differentiation and stage. The weaker expression was more commonly found in HCC with poor differentiation and late stage, while the stronger expression was more common in HCC with middle to high-differentiation and early stage. No relationship was found between DR and gender, age, negative or positive HBsAg, tumor size, grade or metastasis. Multidrug resistance cell lines expressed lower level DR. Conclusion TRAILR expression was prevalent and discrepancy of receptor types was exited in HCC. Loss of DcR1 may contribute for TRAIL therapy for HCC. Key words TRAILR - apoptosis - hepatocellular carcinoma Supported by the Major Fundation of Ministry of Health, NO. 2001–2003展开更多
Identification of tumour necrosis factor apoptosis inducing ligand (TRAIL), a TNF family ligand, sparked a torrent of research, following an initial observation that it could kill tumour cells, but spare normal cells....Identification of tumour necrosis factor apoptosis inducing ligand (TRAIL), a TNF family ligand, sparked a torrent of research, following an initial observation that it could kill tumour cells, but spare normal cells. Almost a decade after its discovery, and with five known receptors, the true physiological role of TRAIL is still debated and its anti-tumorigenic properties limited by potential toxicity. This review takes a comprehensive look at the story of this enigmatic ligand, addressing its remaining potential as a therapeutic and providing an overview of the TRAIL receptors themselves.展开更多
In the present article, we report that DR4 or DR5 overexpression dramatically activates the release of the inflammatory cytokines IL-8, TNF-α, CCL20, MIP-2 and MIP-1β in an NF-κB-dependent manner in 293T, MDA-MB-23...In the present article, we report that DR4 or DR5 overexpression dramatically activates the release of the inflammatory cytokines IL-8, TNF-α, CCL20, MIP-2 and MIP-1β in an NF-κB-dependent manner in 293T, MDA-MB-231 and HCT-116 cells. We showed that death receptor-mediated signals were extracellular domain-independent, whereas the effect of overexpression of the DR4 intracellular domain was much less potent. The TRADD-TRAF2-NIK- IKKα/β signaling cascade, which plays an essential role in TNF-induced NF-κB activation, was found to be involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-mediated signal transduction. The FADD-caspase signaling pathway, which has been reported to be mostly related to apoptosis, was identified as being essential for DR4 or DR5 overexpression-mediated NF-κB activation and cytokine secretion and crosstalks with the TRADD-TRAF2-NIK-IKKα/β signaling cascade. Furthermore, a DR5 agonistic antibody (AD5-10) triggered the inflammatory cytokine release. These data, together with previous reports, provide strong evidence that TRAIL and TRAIL receptors play an important role in inflammation.展开更多
AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resis...AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.展开更多
Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiat...Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand (all P〈0.01). Insulin-induced glucose uptake was decreased upon the activation of NOD1 (P〈0.05). NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake (all P〈0.05). Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.展开更多
Objective: To investigate the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene transfection mediated by adenovirus into human pancreatic carcinoma cell line Panc-1, and the mech...Objective: To investigate the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene transfection mediated by adenovirus into human pancreatic carcinoma cell line Panc-1, and the mechanisms involved in this effect. Methods: TRAIL gene was transfected into pancreatic cancer cell line Panc-1 by an adenovirus vector (Ad-TRAIL). Level of TRAIL mRNA expression was determined using RT-PCR, and TRAIL protein synthesis was evaluated with Western blot. Cell-growth activities were determined by MTT assay. The bystander effect was observed by co-culturing the Panc-1 cells with the transfected TRAIL gene at different ratios. Apoptosis in pancreatic cancer cells was detected by flow cytometry. Procaspase-8 and procaspase-3 were determined by Western blot. Results: The stable overexpression of TRAIL was de-tected in Panc-1 cells transfected by Ad-TRAIL. Ad-TRAIL significantly inhibited of cell viability of Panc-1 cells. Furthermore, co-culture of cancer cells transfected with TRAIL with that nontransfected resulted in the cell death of both cells by bystander effect. Moreover, the percentage of apoptotic cells was significantly higher in the Ad-TRAIL-treatment group compared to the control groups (P < 0.01). And there was a diminished amount of procaspase-8 and procaspase-3 after infection with Ad-TRAIL. Conclusion: The overexpression of TRAIL gene in Panc-1 cells by Ad-TRAIL exerts its antitumor effects, and the mechanisms involved in this effect may be proapoptosis and bystander effect.展开更多
DNA mismatch repair (MMR) processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine (6-TG) and 5-fluorouracil (5-FU). MMR processing of thes...DNA mismatch repair (MMR) processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine (6-TG) and 5-fluorouracil (5-FU). MMR processing of these drugs has been implicated in activation of a prolonged G2/M cell cycle arrest for repair and later induction of apoptosis and/or autophagy for irreparable DNA damage. In this study, we investigated the role of Bcl2 and adenovirus EIB Nineteen-kilodalton Interacting Protein (BNIP3) in the activation of autophagy, and the temporal relationship between a G2/M cell cycle arrest and the activation of BNIP3-mediated autophagy following MMR processing of 6-TG and 5-FU. We found that BNIP3 protein levels are upregulated in a MLHI (MMR+)-dependent manner following 6-TG and 5-FU treatment. Subsequent small-interfering RNA (siRNA)-mediated BNIP3 knockdown abrogates 6-TG- induced autophagy. We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG- and 5-FU-induced upregulation of BNIP3 protein levels and autophagy. Furthermore, suppression of Checkpoint kinase 1 (Chkl) expression with a subsequent reduction in 6-TG-induced G2/M cell cycle arrest by Chkl siRNA promotes the extent of 6-TG-induced autophagy. These findings suggest that BNIP3 mediates 6-TG- and 5-FU-induced autophagy in a p53- and mTOR-dependent manner. Additionally, the duration of Chkl-activated G2/ M cell cycle arrest determines the level of autophagy following MMR processing of these nucleoside analogs.展开更多
This study is conducted to clone the cDNA encoding human TNF-related apoptosis-inducing ligand (hTRAIL) extracellular region (amino acids 41-281, hTRAIL41-281) and to express it in E.coli. The hTRAIL41-281 cDNA is amp...This study is conducted to clone the cDNA encoding human TNF-related apoptosis-inducing ligand (hTRAIL) extracellular region (amino acids 41-281, hTRAIL41-281) and to express it in E.coli. The hTRAIL41-281 cDNA is amplified by reverse transcription (RT) PCR from total RNA derived from human acute promyelocytic leukemia cell line HL-60. After sequenced, the cDNA is cloned into the vector pQE-80L and transformed into E.coli DH5 to express the recombinant hTRAIL41-281 (rhTRAIL41-281) induced by IPTG. The recombinant protein is analyzed by SDS-PAGE. The cloned cDNA is consistent with the cDNA sequence encoding hTRAIL41-281 reported in GenBankTM. After inducing, the hTRAIL41-281 protein is expressed, and the mass of the recombinant protein is about 30 % of total bacteria protein, which demonstrates that the cDNA encoding hTRAIL41-281 is successfully cloned and expressed in E.coli.展开更多
Decoy state method quantum key distribution (QKD) is one of the promising practical solutions for BB84QKD with coherent light pulses.The number of data-set size in practical QKD protocol is always finite,which will ca...Decoy state method quantum key distribution (QKD) is one of the promising practical solutions for BB84QKD with coherent light pulses.The number of data-set size in practical QKD protocol is always finite,which will causestatistical fluctuations.In this paper,we apply absolutely statistical fluctuation to amend the yield and error rate of thequantum state.The relationship between exchanged number of quantum signals and key generation rate is analyzed inour simulation,which offers a useful reference for experiment.展开更多
The authors have prepared suprameolecular systems of chiral Schiffbase ZnAZSB (Zn(II) complexes with azo-groups) or without ZnSB (azo-groups) and colloidal AuNP (gold nanoparticles) of 10, 40 and 80 nm diamete...The authors have prepared suprameolecular systems of chiral Schiffbase ZnAZSB (Zn(II) complexes with azo-groups) or without ZnSB (azo-groups) and colloidal AuNP (gold nanoparticles) of 10, 40 and 80 nm diameters. They exhibited gradual shifts of surface plasmon bands as well as fluorescence bands. The authors observed and discussed induced CD bands on gold nanoparticles from chiral ZnAZSB or ZnSB. Absence of cis-trans photoisomerization of ZnAZSB with AuNP also supported direct contact near the surface of AuNP. Quenching and splitting of fluorescence bands of ZnSB (λex = 550 nm and λem = 400 nm) depending on concentration of ZnSB and size of AuNP also suggested intermolecular (electric) interaction on the surface of AuNE Decrease of the intensity of the CD band around 380 nm resulted from reciprocal induced CD effect due to parallel arrangement of electric transition moments of ZnAZSB or ZnSB and surface of AuNP.展开更多
Three-dimensional tracking of submicron particles in flows in a micro-channel was carried out using in-line holographic microscopy.A fixed single 0.5 μm fluorescent particle was identified and isolated from dust part...Three-dimensional tracking of submicron particles in flows in a micro-channel was carried out using in-line holographic microscopy.A fixed single 0.5 μm fluorescent particle was identified and isolated from dust particles or overlapped particle pair using the laser induced fluorescent(LIF) method.Then in-line microscopic holograms of the fixed single particle were obtained at different positions on the optical axis,i.e.the defocus distances.The holograms of the single particle were used as the model templates with the known defocus distances.The particles in the in-line microscopic holograms of flow in the microchannel were then identified and located to obtain their two-dimensional positions.The defocus distances of those particles were determined by matching each hologram pattern to one of the model templates obtained in the single particle test.Finally the three-dimensional position and velocity of each particle were obtained.展开更多
In order to balance the temporal-spatial distribution of urban traffic flow, a model is established for combined urban traffic signal control and traffic flow guidance. With consideration of the wide use of fixed sign...In order to balance the temporal-spatial distribution of urban traffic flow, a model is established for combined urban traffic signal control and traffic flow guidance. With consideration of the wide use of fixed signal control at intersections, traffic assignment under traffic flow guidance, and dynamic characteristics of urban traffic management, a tri-level programming model is presented. To reflect the impact of intersection delay on traffic assignment, the lower level model is set as a modified user equilibrium model. The middle level model, which contains several definitional constraints for different phase modes, is built for the traffic signal control optimization. To solve the problem of tide lane management, the upper level model is built up based on nonlinear 0-1 integer programming. A heuristic iterative optimization algorithm(HIOA) is set up to solve the tri-level programming model. The lower level model is solved by method of successive averages(MSA), the middle level model is solved by non-dominated sorting genetic algorithm II(NSGA II), and the upper level model is solved by genetic algorithm(GA). A case study is raised to show the efficiency and applicability of the proposed modelling and computing method.展开更多
Measurement-device-independent quantum key distribution(MDI-QKD) is aimed at removing all detector side channel attacks,while its security relies on the assumption that the encoding systems including sources are fully...Measurement-device-independent quantum key distribution(MDI-QKD) is aimed at removing all detector side channel attacks,while its security relies on the assumption that the encoding systems including sources are fully characterized by the two legitimate parties. By exploiting the mismatched-basis statistics in the security analysis, MDI-QKD even with uncharacterized qubits can generate secret keys. In this paper, considering the finite size effect, we study the decoy-state MDI-QKD protocol with mismatchedbasis events statistics by performing full parameter optimization, and the simulation result shows that this scheme is very practical.展开更多
Considering fluctuant dark count rate in practical quantum key distribution(QKD) system,a new decoy-state method with one vacuum state and one weak decoy state is presented based on a heralded single photon source(HSP...Considering fluctuant dark count rate in practical quantum key distribution(QKD) system,a new decoy-state method with one vacuum state and one weak decoy state is presented based on a heralded single photon source(HSPS).The method assumes that the dark count rate of each pulse is random and independent.The lower bound of the count rate and the upper bound of the error rate of a single photon state are estimated.The method is applied to the decoy-state QKD system with and without the fluctuation of dark count rate.Because the estimation of the upper bound of a single photon state's error rate is stricter,the method can obtain better performance than the existing methods under the same condition of implementation.展开更多
A three-state protocol for the SARG04 decoy-state quantum key distribution(QKD)based on an unstable source is presented. The lower bound to the secure key generation rate is derived without using the basic hypothesis ...A three-state protocol for the SARG04 decoy-state quantum key distribution(QKD)based on an unstable source is presented. The lower bound to the secure key generation rate is derived without using the basic hypothesis of the original decoy-state idea.The three-state SARG04 decoy-state protocol with an unstable parametric down-conversion source is considered in the simulation.The simulation results show that the protocol in this paper with an unstable source gives a key generation rate that is close to that with a stable source,and only slight advantage appears by using a stable source when the transmission distance is long.So the SARG04 decoy-state protocol with an unstable source still can obtain the unconditional security with a slightly shortened final key.展开更多
Herein,a novel photonic coordination polymer material was constructed by aggregation-induced emission luminogen(AIEgen)containing a tripyridyl moiety used as the linking ligand.It displayed a spontaneous direct centro...Herein,a novel photonic coordination polymer material was constructed by aggregation-induced emission luminogen(AIEgen)containing a tripyridyl moiety used as the linking ligand.It displayed a spontaneous direct centrosymmetric to noncentrosymmetric phase transition in a single crystal.The two crystals,before and after the phase transition,were both controllably synthesized and characterized by single-crystal X-ray diffraction.After being exposed to air,the centrosymmetric metastable phase(1-α)transitioned to a new stable phase with a noncentrosymmetric structure(1-β).Interestingly,the 1-βstructure exhibited a strong phasematching second-harmonic generation(SHG)response,about4.5 times higher than that of KH2PO4(KDP).In order to better understand the relationship between the structure and the nonlinear optical properties,the dipole moments were calculated and discussed.Remarkably,the noncentrosymmetric phase with high thermal stability for 1-βretained and improved the initial photoluminescent properties of the AIEgen ligand after the structural phase transition from 1-α,and simultaneously produced the excellent SHG property,which are beneficial for the design and construction of excellent optical materials.展开更多
文摘Objective To investigate the expression profiles and their clinical significance of TRAIL receptors (TRAILR) in human hepatocellular carcinoma (HCC). Methods The expression profiles of TRAILR were determined in 60 samples from hepatocellular carcinoma, 20 from normal liver tissue and two HCC cell lines HepG2, SMMC-7721 by in situ hybridization. Results Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples (higher DR expression level and lower DcR expression level) were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. The expression level of DR was correlated with HCC differentiation and stage. The weaker expression was more commonly found in HCC with poor differentiation and late stage, while the stronger expression was more common in HCC with middle to high-differentiation and early stage. No relationship was found between DR and gender, age, negative or positive HBsAg, tumor size, grade or metastasis. Multidrug resistance cell lines expressed lower level DR. Conclusion TRAILR expression was prevalent and discrepancy of receptor types was exited in HCC. Loss of DcR1 may contribute for TRAIL therapy for HCC. Key words TRAILR - apoptosis - hepatocellular carcinoma Supported by the Major Fundation of Ministry of Health, NO. 2001–2003
文摘Identification of tumour necrosis factor apoptosis inducing ligand (TRAIL), a TNF family ligand, sparked a torrent of research, following an initial observation that it could kill tumour cells, but spare normal cells. Almost a decade after its discovery, and with five known receptors, the true physiological role of TRAIL is still debated and its anti-tumorigenic properties limited by potential toxicity. This review takes a comprehensive look at the story of this enigmatic ligand, addressing its remaining potential as a therapeutic and providing an overview of the TRAIL receptors themselves.
基金We thank Drs Hongbing Shu (Wuhan University, China), Jiandong Li (University of Rochester Medical Center, USA), Andrew Thorbum (University of Colorado Comprehensive Cancer Center, USA) and Andreas Strasser (The Walter and Eliza Hall Institute of Medical Research, Australia) for the generous gifts of the constructs. This work was partially supported by the National Natural Science Foundation of China (Grants 30571687 and 30721063) and the State Key Basic Research Program of China (Grant 2007CB507404).
文摘In the present article, we report that DR4 or DR5 overexpression dramatically activates the release of the inflammatory cytokines IL-8, TNF-α, CCL20, MIP-2 and MIP-1β in an NF-κB-dependent manner in 293T, MDA-MB-231 and HCT-116 cells. We showed that death receptor-mediated signals were extracellular domain-independent, whereas the effect of overexpression of the DR4 intracellular domain was much less potent. The TRADD-TRAF2-NIK- IKKα/β signaling cascade, which plays an essential role in TNF-induced NF-κB activation, was found to be involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-mediated signal transduction. The FADD-caspase signaling pathway, which has been reported to be mostly related to apoptosis, was identified as being essential for DR4 or DR5 overexpression-mediated NF-κB activation and cytokine secretion and crosstalks with the TRADD-TRAF2-NIK-IKKα/β signaling cascade. Furthermore, a DR5 agonistic antibody (AD5-10) triggered the inflammatory cytokine release. These data, together with previous reports, provide strong evidence that TRAIL and TRAIL receptors play an important role in inflammation.
基金Supported by Research grants from Merck KGaA,Darmstadt,Germany,to Schulze-Bergkamen H
文摘AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.
基金Supported by Grant from Department of Education of Liaoning Province(2008810)
文摘Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand (all P〈0.01). Insulin-induced glucose uptake was decreased upon the activation of NOD1 (P〈0.05). NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake (all P〈0.05). Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.
基金Supported by a grant from the National Natural Science Foundation of China (No. 30471693).
文摘Objective: To investigate the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene transfection mediated by adenovirus into human pancreatic carcinoma cell line Panc-1, and the mechanisms involved in this effect. Methods: TRAIL gene was transfected into pancreatic cancer cell line Panc-1 by an adenovirus vector (Ad-TRAIL). Level of TRAIL mRNA expression was determined using RT-PCR, and TRAIL protein synthesis was evaluated with Western blot. Cell-growth activities were determined by MTT assay. The bystander effect was observed by co-culturing the Panc-1 cells with the transfected TRAIL gene at different ratios. Apoptosis in pancreatic cancer cells was detected by flow cytometry. Procaspase-8 and procaspase-3 were determined by Western blot. Results: The stable overexpression of TRAIL was de-tected in Panc-1 cells transfected by Ad-TRAIL. Ad-TRAIL significantly inhibited of cell viability of Panc-1 cells. Furthermore, co-culture of cancer cells transfected with TRAIL with that nontransfected resulted in the cell death of both cells by bystander effect. Moreover, the percentage of apoptotic cells was significantly higher in the Ad-TRAIL-treatment group compared to the control groups (P < 0.01). And there was a diminished amount of procaspase-8 and procaspase-3 after infection with Ad-TRAIL. Conclusion: The overexpression of TRAIL gene in Panc-1 cells by Ad-TRAIL exerts its antitumor effects, and the mechanisms involved in this effect may be proapoptosis and bystander effect.
文摘DNA mismatch repair (MMR) processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine (6-TG) and 5-fluorouracil (5-FU). MMR processing of these drugs has been implicated in activation of a prolonged G2/M cell cycle arrest for repair and later induction of apoptosis and/or autophagy for irreparable DNA damage. In this study, we investigated the role of Bcl2 and adenovirus EIB Nineteen-kilodalton Interacting Protein (BNIP3) in the activation of autophagy, and the temporal relationship between a G2/M cell cycle arrest and the activation of BNIP3-mediated autophagy following MMR processing of 6-TG and 5-FU. We found that BNIP3 protein levels are upregulated in a MLHI (MMR+)-dependent manner following 6-TG and 5-FU treatment. Subsequent small-interfering RNA (siRNA)-mediated BNIP3 knockdown abrogates 6-TG- induced autophagy. We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG- and 5-FU-induced upregulation of BNIP3 protein levels and autophagy. Furthermore, suppression of Checkpoint kinase 1 (Chkl) expression with a subsequent reduction in 6-TG-induced G2/M cell cycle arrest by Chkl siRNA promotes the extent of 6-TG-induced autophagy. These findings suggest that BNIP3 mediates 6-TG- and 5-FU-induced autophagy in a p53- and mTOR-dependent manner. Additionally, the duration of Chkl-activated G2/ M cell cycle arrest determines the level of autophagy following MMR processing of these nucleoside analogs.
基金Funded by the Scientific Research Foundation of the Third Military Medical University.
文摘This study is conducted to clone the cDNA encoding human TNF-related apoptosis-inducing ligand (hTRAIL) extracellular region (amino acids 41-281, hTRAIL41-281) and to express it in E.coli. The hTRAIL41-281 cDNA is amplified by reverse transcription (RT) PCR from total RNA derived from human acute promyelocytic leukemia cell line HL-60. After sequenced, the cDNA is cloned into the vector pQE-80L and transformed into E.coli DH5 to express the recombinant hTRAIL41-281 (rhTRAIL41-281) induced by IPTG. The recombinant protein is analyzed by SDS-PAGE. The cloned cDNA is consistent with the cDNA sequence encoding hTRAIL41-281 reported in GenBankTM. After inducing, the hTRAIL41-281 protein is expressed, and the mass of the recombinant protein is about 30 % of total bacteria protein, which demonstrates that the cDNA encoding hTRAIL41-281 is successfully cloned and expressed in E.coli.
基金Supported by the National Basic Research Program (973) of China under Grant No.2010CB923200Chinese Universities Scientific Fund BUPT2009RC0709
文摘Decoy state method quantum key distribution (QKD) is one of the promising practical solutions for BB84QKD with coherent light pulses.The number of data-set size in practical QKD protocol is always finite,which will causestatistical fluctuations.In this paper,we apply absolutely statistical fluctuation to amend the yield and error rate of thequantum state.The relationship between exchanged number of quantum signals and key generation rate is analyzed inour simulation,which offers a useful reference for experiment.
文摘The authors have prepared suprameolecular systems of chiral Schiffbase ZnAZSB (Zn(II) complexes with azo-groups) or without ZnSB (azo-groups) and colloidal AuNP (gold nanoparticles) of 10, 40 and 80 nm diameters. They exhibited gradual shifts of surface plasmon bands as well as fluorescence bands. The authors observed and discussed induced CD bands on gold nanoparticles from chiral ZnAZSB or ZnSB. Absence of cis-trans photoisomerization of ZnAZSB with AuNP also supported direct contact near the surface of AuNP. Quenching and splitting of fluorescence bands of ZnSB (λex = 550 nm and λem = 400 nm) depending on concentration of ZnSB and size of AuNP also suggested intermolecular (electric) interaction on the surface of AuNE Decrease of the intensity of the CD band around 380 nm resulted from reciprocal induced CD effect due to parallel arrangement of electric transition moments of ZnAZSB or ZnSB and surface of AuNP.
基金Supported by the National Natural Science Foundation of China (50736002,61072005)Changjiang Scholars and Innovative Team Development Plan (IRT0957)
文摘Three-dimensional tracking of submicron particles in flows in a micro-channel was carried out using in-line holographic microscopy.A fixed single 0.5 μm fluorescent particle was identified and isolated from dust particles or overlapped particle pair using the laser induced fluorescent(LIF) method.Then in-line microscopic holograms of the fixed single particle were obtained at different positions on the optical axis,i.e.the defocus distances.The holograms of the single particle were used as the model templates with the known defocus distances.The particles in the in-line microscopic holograms of flow in the microchannel were then identified and located to obtain their two-dimensional positions.The defocus distances of those particles were determined by matching each hologram pattern to one of the model templates obtained in the single particle test.Finally the three-dimensional position and velocity of each particle were obtained.
基金Project(2014BAG01B0403)supported by the High-Tech Research and Development Program of China
文摘In order to balance the temporal-spatial distribution of urban traffic flow, a model is established for combined urban traffic signal control and traffic flow guidance. With consideration of the wide use of fixed signal control at intersections, traffic assignment under traffic flow guidance, and dynamic characteristics of urban traffic management, a tri-level programming model is presented. To reflect the impact of intersection delay on traffic assignment, the lower level model is set as a modified user equilibrium model. The middle level model, which contains several definitional constraints for different phase modes, is built for the traffic signal control optimization. To solve the problem of tide lane management, the upper level model is built up based on nonlinear 0-1 integer programming. A heuristic iterative optimization algorithm(HIOA) is set up to solve the tri-level programming model. The lower level model is solved by method of successive averages(MSA), the middle level model is solved by non-dominated sorting genetic algorithm II(NSGA II), and the upper level model is solved by genetic algorithm(GA). A case study is raised to show the efficiency and applicability of the proposed modelling and computing method.
基金supported by the National Basic Research Program of China(Grant Nos.2011CBA00200 and 2011CB921200)the National Natural Science Foundation of China(Grant Nos.61201239,61205118,11304397 and 61475148)+1 种基金China Postdoctoral Science Foundation(Grant No.2013M540514)Anhui Provincial Natural Science Foundation(Grant No.1408085QF102)
文摘Measurement-device-independent quantum key distribution(MDI-QKD) is aimed at removing all detector side channel attacks,while its security relies on the assumption that the encoding systems including sources are fully characterized by the two legitimate parties. By exploiting the mismatched-basis statistics in the security analysis, MDI-QKD even with uncharacterized qubits can generate secret keys. In this paper, considering the finite size effect, we study the decoy-state MDI-QKD protocol with mismatchedbasis events statistics by performing full parameter optimization, and the simulation result shows that this scheme is very practical.
基金supported by the National High Technology Research and Development Program of China (No.2009AAJ128)the Science Foundation of Naval University of Engineering (No.HGDQNJJ11022)
文摘Considering fluctuant dark count rate in practical quantum key distribution(QKD) system,a new decoy-state method with one vacuum state and one weak decoy state is presented based on a heralded single photon source(HSPS).The method assumes that the dark count rate of each pulse is random and independent.The lower bound of the count rate and the upper bound of the error rate of a single photon state are estimated.The method is applied to the decoy-state QKD system with and without the fluctuation of dark count rate.Because the estimation of the upper bound of a single photon state's error rate is stricter,the method can obtain better performance than the existing methods under the same condition of implementation.
基金supported by the National High Technology Research and Development Program of China(No.2009AAJ128)
文摘A three-state protocol for the SARG04 decoy-state quantum key distribution(QKD)based on an unstable source is presented. The lower bound to the secure key generation rate is derived without using the basic hypothesis of the original decoy-state idea.The three-state SARG04 decoy-state protocol with an unstable parametric down-conversion source is considered in the simulation.The simulation results show that the protocol in this paper with an unstable source gives a key generation rate that is close to that with a stable source,and only slight advantage appears by using a stable source when the transmission distance is long.So the SARG04 decoy-state protocol with an unstable source still can obtain the unconditional security with a slightly shortened final key.
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China(2019D01C059)the National Natural Science Foundation of China(21671003 and 21201005)+4 种基金the High Performance Computing Center of Henan Normal University and the 111 Project(D17007)Xinjiang Program of Cultivation of Young Innovative Technical Talents(2018Q061)the“2018 Tianchi Doctoral Plan”of Xinjiang Uygur Autonomous Region of Chinathe Doctoral Scientific Research Foundation of Anhui Jianzhu University(2017QD15)Xinjiang University.We thank LetPub(www.letpub.com)for its linguistic assistance during the preparation of this manuscript。
文摘Herein,a novel photonic coordination polymer material was constructed by aggregation-induced emission luminogen(AIEgen)containing a tripyridyl moiety used as the linking ligand.It displayed a spontaneous direct centrosymmetric to noncentrosymmetric phase transition in a single crystal.The two crystals,before and after the phase transition,were both controllably synthesized and characterized by single-crystal X-ray diffraction.After being exposed to air,the centrosymmetric metastable phase(1-α)transitioned to a new stable phase with a noncentrosymmetric structure(1-β).Interestingly,the 1-βstructure exhibited a strong phasematching second-harmonic generation(SHG)response,about4.5 times higher than that of KH2PO4(KDP).In order to better understand the relationship between the structure and the nonlinear optical properties,the dipole moments were calculated and discussed.Remarkably,the noncentrosymmetric phase with high thermal stability for 1-βretained and improved the initial photoluminescent properties of the AIEgen ligand after the structural phase transition from 1-α,and simultaneously produced the excellent SHG property,which are beneficial for the design and construction of excellent optical materials.