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OBJECTIVE: To explore molecular mechanisms by which umbilical cord-derived mesenchymal stem cells suppress the development of GVHD after bone marrow hematopoietic stem cell transplantation. METHODS: A mouse model of aGVHD was constructed after bone marrow hematopoietic stem cell transplantation, and the umbilical cord-derived mesenchymal stem cells were cultured, and then injected into the aGVHD mouse model, so as to investigate its prophylactic efficacy. Prophylactic effect of the exosomes isolated from umbilical cord-derived mesenchymal stem cells on aGVHD mice was assessed. Sequencing analysis of miRNA from exosomes was performed. RESULTS: aGVHD model was successfully constructed after hematopoietic stem cell transplantation. By injecting umbilical cord-derived mesenchymal stem cells into the GVHD mouse model, it was found that the treatment significantly prolonged survival time of mice compared to the untreated group. Injection exosomes derived from umbilical cord-derived mesenchymal stem cells into the GVHD mouse model significantly prolonged the survival time of mice compared to the untreated group. High-throughput sequencing data showed that microRNA such as miR-21 in exosomes isolated from umbilical cord-derived mesenchymal stem cells, which mainly affected the signaling pathways such as cell adhesion, RNA degradation. CONCLUSION: The umbilical cord-derived mesenchymal stem cells can prevent the occurrence of aGVHD after HSCT, which is mediate by MicroRNA in the exosomes derived from umbilical cord-derived mesenchymal stem cells.
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[This corrects the article DOI: 10.7150/ijbs.34785.].
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The application of a coordination container in biomedicine is hindered by single binding domains and unsatisfactory biostability and biocompatibility. Herein, we designed a sulfonylcalix[4]arene-based decahexanuclear zinc(II) coordination container employing a flexible tetracarboxylate ligand as a linker and utilized it as a novel drug delivery system. The coordination container consisting of one endo and four exo cavities provides multiple binding domains for efficient encapsulation of drug molecules as clearly revealed by systematic host-guest studies using NMR techniques of 1H NMR titration experiments and 2D NOESY and diffusion-ordered NMR spectroscopy studies. Incorporation of a flexible p-phenylene-bis(methanamino) spacer into the container via the carboxylate linker allowed a stepwise drug loading process through sequential binding at endo and exo cavities, as well as enabling pH-responsive stepwise drug release. The drug-loaded coordination container not only exhibits excellent biostability and biocompatibility but also provides encouraging therapeutic efficiency toward inflammatory macrophages as revealed by in vitro studies. The novel strategy for engineering the endo cavity of a coordination container provides a new approach to achieving controlled drug delivery and opens up new opportunities for designing novel functional supramolecular materials.
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Anti-Inflamatórios/farmacologia , Calixarenos/química , Complexos de Coordenação/química , Portadores de Fármacos/química , Naproxeno/farmacologia , Animais , Anti-Inflamatórios/química , Calixarenos/síntese química , Complexos de Coordenação/síntese química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Ligantes , Camundongos , Testes de Sensibilidade Microbiana , Naproxeno/química , Ácidos Ftálicos/síntese química , Ácidos Ftálicos/química , Células RAW 264.7 , Zinco/químicaRESUMO
Highly soluble d8-d10 heteronuclear phosphors afford an alternative approach to achieve high-efficiency organic light-emitting diodes (OLEDs) through a solution process. In this work, four highly phosphorescent d8-d10 heteronuclear complexes with significant Pt-Au interactions were prepared. By judicious selection of sterically hindered and π-conjugated substituents in triphosphine ligands, the phosphorescence is dramatically promoted through effectively prohibiting nonradiative thermal relaxation with an efficiency of 0.94-0.99 in doping films. Exploiting highly emissive Pt-Au complexes as phosphorescent dopants, ultrahigh-efficiency solution-processed OLEDs were attained. The peak current efficiency, power efficiency, and external quantum efficiency are 96.2 cd A-1, 65.0 lm W-1, and 26.4% for the green-emitting PtAu2 phosphor and 68.6 cd A-1, 42.5 lm W-1, and 25.1% for the orange-emitting Pt2Au phosphor, which represent the state-of-art for solution-processed OLEDs based on non-iridium phosphors.
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The reaction of 3,6-ditert-butyl-1,8-bis(diphenylphosphino)-9-methyl-9H-carbazole (L) with CuBr resulted in the isolation of tetranuclear copper(I) complex Cu4Br4L2 as two colorless crystal morphs, i.e., green-emitting 1G and yellow-emitting 1Y. As demonstrated by X-ray crystallography, the Cu4Br4 moiety in both 1G and 1Y adopts the same chair conformations. When L is bonded perpendicularly to the Cu4 plane, 1G with green emission is obtained, while it gives a yellow emission of 1Y once the L is parallelly bonded to Cu4 plane. Theoretical computational studies suggest that the variation in ligand orientation results in a different degree of structural distortion in triplet state and thus different luminescent energy. Particularly, 1Y undergoes dramatic structural distortion from the ground (S0) to triplet excied state (T1). Interestingly, 1G can be converted into 1Y upon exposed to saturated hexane vapor, which would return to 1G upon exposure to acetonitrile vapor. As demonstrated experimentally and theoretically, the reversible luminescence transformation between 1G and 1Y is ascribed to the variation of ligand L orientations.
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PURPOSE: To investigate the predictive capability of clinical parameters for long-term chemotherapy benefits among stage IIIB-IV non-squamous non-small cell lung cancer (NSCLC) patients without sensitive mutations. PATIENTS AND METHODS: We investigated the clinical features of 206 stage IIIB-IV non-squamous NSCLC patients without sensitive mutations and assessed their predictive value for disease control rate (DCR) at 6 and 12 months post-treatment. RESULTS: Seventy-two patients received docetaxel and platinum-based chemotherapy while 134 received pemetrexed and platinum-based chemotherapy. The 6-month and 12-month DCR were 33 (45.8%) and 6 (8.3%) in the docetaxel group and 69 (51.5%) and 19 (14.2%) in the pemetrexed group, respectively. Univariate Cox regression revealed that age, sex, smoking history, adrenal gland metastasis, stage IV disease, neutrophil-to-lymphocyte ratio (NLR), and serum albumin were associated with unfavorable progression-free survival (PFS). Age, stage IV disease, and NLR were identified as independent predictors of PFS using multivariate analysis. NLR was the only parameter that could predict 3-month and 6-month DCRs. NLR and age were able to predict 12-month DCR, with NLR presenting a larger area under the curve. Kaplan-Meier curves demonstrated that patients with NLR > 2.231 displayed significantly reduced long-term disease control. The group with higher NLR had more male patients, lower ALB levels, and serum sodium levels as well as higher platelet counts. CONCLUSION: NLR was an independent predictor of long-term chemotherapy benefits among non-squamous NSCLC patients without sensitive mutations. Patients with lower NLR were optimal candidates for chemotherapy. Patients with high NLR may receive alternative treatments or be included in clinical trials.
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Bis(diphenylphosphinomethyl)phenylphosphine (dpmp)-supported Pt2Au heterotrinuclear complexes [Pt2Au(dpmp)2(C≡CPh)4](ClO4) (1), [Pt2Au(dpmp)2(DEBf)(C≡CPh)2](ClO4) (2), and [Pt2Au(dpmp)2(DECz)(C≡CPh)2](ClO4) (3) were prepared and used in organic light-emitting diodes (OLEDs) as a new class of light emitters, where DEBf = dibenzofuran-4,6-diacetylide and DECz = 3,6-di-tert-butylcarbazole-1,8-diacetylide. Although the flexible structure of Pt2Au complex 1 (λem = 503 nm, Φem < 0.1%) results in weak photoluminescence in fluid CH2Cl2, complexes 2 (λem = 585 nm, Φem = 4.9%) and 3 (λem = 589 nm, Φem = 3.2%) with a rigid conformation give a much stronger phosphorescence. The displacement of two σ-bonded phenylacetylide ligands with a diacetylide ligand such as DEBf and DECz to fasten Pt2Au structures facilitates greatly luminescent emission so that the emissive quantum yield in doping film is as high as 89% for 2 and 93% for 3. As revealed by a theoretical study, the severe structural distortion of diacetylide-linked Pt2Au complexes 2 (λem = 585 nm) and 3 (λem = 589 nm) in a triplet excited state gives rise to significant red shifts of phosphorescent emission spectra relative to that of complex 1 (λem = 503 nm). By means of Pt2Au complexes as phosphorescent emitters, solution-processed OLEDs achieved a relatively low external quantum efficiency (EQE < 9.5%) when commercial poly(ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) was used as the hole-injection layer (HIL). In contrast, the peak EQE was increased to 18.3% with a dramatic increase of efficiency by the use of modified HILs composed of PEDOT:PSS and PSS-Na, which provide a higher work function and a better film morphology.
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Deletion of Chromosome 3p is one of the most frequently detected genetic alterations in nasopharyngeal carcinoma (NPC). We reported the role of a novel 3p26.3 tumor suppressor gene (TSG) CHL1 in NPC. Down-regulation of CHL1 was detected in 4/6 of NPC cell lines and 71/95 (74.7%) in clinical tissues. Ectopic expressions of CHL1 in NPC cells significantly inhibit colony formation and cell motility in functional study. By up-regulating epithelial markers and down-regulating mesenchymal markers CHL1 could induce mesenchymal-epithelial transition (MET), a key step in preventing tumor invasion and metastasis. CHL1 could also cause the inactivation of RhoA/Rac1/Cdc42 signaling pathway and inhibit the formation of stress fiber, lamellipodia, and filopodia. CHL1 could co-localize with adhesion molecule Integrin-ß1, the expression of CHL1 was positively correlated with Integrin-ß1 and another known tumor suppressor gene (TSG) Merlin. Down-regulation of Integrin-ß1 or Merlin was significantly correlated with the poor survival rate of NPC patients. Further mechanistic studies showed that CHL1 could directly interact with integrin-ß1 and link to Merlin, leading to the inactivation of integrin ß1-AKT pathway. In conclusion, CHL1 is a vital tumor suppressor in the carcinogenesis of NPC.
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Moléculas de Adesão Celular/metabolismo , Integrina beta1/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neurofibromina 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Western Blotting , Moléculas de Adesão Celular/genética , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/fisiologia , Linhagem Celular , Movimento Celular/genética , Movimento Celular/fisiologia , Metilação de DNA/genética , Metilação de DNA/fisiologia , Imunofluorescência , Humanos , Imunoprecipitação , Carcinoma Nasofaríngeo/genética , Regiões Promotoras Genéticas/genética , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
Three quinoline-based zinc(ii)-Schiff base complexes were synthesized and characterized by X-ray crystallography. They exhibit remarkable aggregation-induced emission enhancement (AIEE) in acetonitrile/diethyl ether mixtures due to the conversion of weak luminescence in homogeneous solution into strong emission in the nano-aggregated phase after increasing the fractions of diethyl ether. Interestingly, the AIEE performance can be significantly promoted by joining the two quinoline units through an alkoxy chain. Moreover, they show reversible mechanochromic luminescence behavior between dark and bright states during the grinding-fuming cycles, due to the modulation of morphologies between amorphous and crystalline states. Introducing an electron donating group in the para-position of aniline significantly improves the mechanochromic luminescence effect with a more accessible and distinct emission colour contrast. The molecular packing in the crystalline phase and time-dependent density functional theory (TD-DFT) calculations demonstrate that multiple intermolecular C-Hπ and π-π interactions significantly strengthen the molecular rigidity and enhance the intramolecular charge-transfer (ICT) characteristics, leading to the effective emission enhancement in crystalline/nano-aggregated states. The novel AIEE and reversible mechanochromic luminescence properties point to the promising potential applications of these complexes in smart fluorescent materials.
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[This corrects the article DOI: 10.1371/journal.pone.0056959.].
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We demonstrate a proof-of-concept design of a new platform for proton recognition and modulation. The new proton receptors are derived from a unique class of synthetic supercontainers that exhibit exceptional proton binding capacity (over 50 equiv.) and intriguing proton-dependent fluorescent switching behavior. Experimental and computational studies suggest that the proton-responsive event involves a two-step mechanism pertaining to proton binding by both amino and pyrenyl moieties of the supercontainer constructs. The high proton binding capacity of the supercontainers can be further modulated via small-molecule "regulators" that compete for the proton-binding sites, opening exiting new opportunities for proton manipulation in both chemistry and biology.
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A new sulfonylcalix[4]arene-based dinuclear terbium molecular container (1) was conveniently synthesized and utilized as a fluorescence probe for the detection of a well-known biomarker 1-hydroxypyrene (1-OHP), which is used for the evaluation of polycyclic aromatic hydrocarbons (PAHs). The sulfonylcalix[4]arene ligand could not only serve as an efficient antenna ligand to promote the ligand-to-metal energy transfer but also provide a suitable cavity to accommodate 1-OHP. Promising fluorescence quenching effects were well established during the titration of the compound 1 with 1-OHP, and these effects were due to the enhancement in the host-guest intermolecular charge transfer and the decrease in the ligand-to-metal energy transfer after the formation of the stable host-guest complex. The fluorescence sensing mechanism was clearly understood through the titration experiments, and the data could be fit with the Benesi-Hildebrand and Stern-Volmer models. The TbIII-TBSC-based luminescent sensor exhibited quick response, high sensitivity, and specific selectivity to 1-OHP, even in the presence of other constituents in urine, thus providing a new sensing platform for the clinical diagnosis of human exposure to PAHs.
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Background and Aims: Esophageal squamous cell carcinoma (ESCC), a major histologic subtype of esophageal cancer, is increasing in incidence, but the genetic underpinnings of this disease remain unexplored. The aim of this study is to identify the recurrent genetic changes, elucidate their roles and discover new biomarkers for improving clinical management of ESCC. Methods: Western blotting and immunohistochemistry were performed to detect the expression level of RHCG. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) were used to study the methylation status in the promoter region of RHCG. The tumor-suppressive effect of RHCG was determined by both in-vitro and in-vivo assays. Affymetrix cDNA microarray was used to identify the underlying molecular mechanism. Results:RHCG was frequently downregulated in ESCCs, which was significantly correlated with poor differentiation (P = 0.001), invasion (P = 0.003), lymph node metastasis (P = 0.038) and poorer prognosis (P < 0.001). Demethylation treatment and bisulfite genomic sequencing analyses revealed that the downregulation of RHCG in both ESCC cell lines and clinical samples was associated with its promoter hypermethylation. Functional assays demonstrated that RHCG could inhibit clonogenicity, cell motility, tumor formation and metastasis in mice. Further study revealed that RHCG could stabilize IκB by decreasing its phosphorylation, and subsequently inhibit NF-κB/p65 activation by blocking the nuclear translocation of p65, where it acted as a transcription regulator for the upregulation of MMP1 expression. Conclusions: Our results support the notion that RHCG is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC.
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Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Neoplasias Esofágicas/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Glicoproteínas de Membrana/metabolismo , Animais , Carcinoma de Células Escamosas/genética , Proteínas de Transporte de Cátions/genética , Linhagem Celular Tumoral , Metilação de DNA/genética , Metilação de DNA/fisiologia , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Metástase Linfática/genética , Masculino , Metaloproteinase 1 da Matriz/genética , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
Frizzled (FZD) proteins are receptors for secreted WNT proteins and play a critical role in the malignant progression of various cancers. However, the role of human FZD family members in esophageal squamous cell carcinoma (ESCC) was rarely investigated. In this study, we found that the FZD7 gene was the most commonly up-regulated FZD member in ESCC cell lines compared with other FZDs. TMA studies further validated that FZD7 protein was up-regulated in 165 of 252 (65.5%) informative ESCC patients and significantly correlated with poor overall survival (P=0.001). Additionally, multivariate Cox regression analysis showed that FZD7 overexpression was an independent prognostic factor for ESCC patients. Ectopic expression of FZD7 could promote ESCC cell metastasis both in vitro and in vivo. Under WNT3A stimulation, FZD7 was able to induce the nuclear translocation of ß-catenin and activate the downstream targets of WNT/ß-catenin signaling, as well as promote epithelial-mesenchymal transition (EMT) potential in ESCC cells. Our study demonstrated for the first time that FZD7 contributes to the malignant progression of ESCC and represents a novel prognostic marker and a potential therapeutic target for ESCC patients.
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A hexadentate macrocyclic N-heterocyclic carbene (NHC) ligand precursor (H4L)(PF6)4 containing four benzimidazolium and two secondary amine groups, has been synthesized and characterized. Coordination chemistry of this new macrocyclic diamine-tetracarbene ligand has been studied by the synthesis of its Ag(I), Au(I), Ni(II), and Pd(II) complexes. Reactions of (H4L)(PF6)4 with different equiv of Ag2O result in Ag(I) complexes [Ag(H2L)](PF6)3 (1) and [Ag2(H2L)](PF6)4 (2). A mononuclear Au(I) complex [Au(H2L)](PF6)3 (3) and a trinuclear Au(I) complex [Au3(H2L)(Cl)2](PF6) (4) are obtained by transmetalation of 1 and 2 with AuCl(SMe2), respectively. Reactions of (H4L)(PF6)4 with Ni(OAc)2 and Pd(OAc)2 in the presence of NaOAc yield [Ni(L)](PF6)2 (5) and [Pd(L)](PF6)2 (6), respectively, containing one Ni(II) and Pd(II) ion with distorted square-planar geometry. Using more NaOAc results in the formation of unusual dinuclear complexes [Ni2(L-2H)](PF6)2 (7) and [Pd2(L-2H)](PF6)2 (8) (L-2H = deprotonated ligand after removing two H+ ions from two secondary amine groups in L), respectively, featuring a rare M2N2 core formed by two bridging amides. 7 is also formed by the reaction of 5 with 1.0 equiv of Ni(OAc)2·4H2O in the presence of NaOAc. Transmetalation of 2 with 2.0 equiv of Ni(PPh3)2Cl2 gives [Ni2(L)(µ-O)](PF6)2 (9), the first example of a dinuclear Ni(II) complex with a singly bridging oxo group. 9 is converted to 7 in good yield through the treatment with NaOAc.
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Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3 Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Edição de RNA , Actinina/metabolismo , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Adulto , Idoso , Animais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Regulação para Baixo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/secundário , Carcinoma de Células Escamosas do Esôfago , Esôfago/citologia , Esôfago/metabolismo , Técnicas de Silenciamento de Genes , Estudo de Associação Genômica Ampla , Humanos , Metástase Linfática/genética , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Proteínas de Transporte de Cátions Orgânicos/deficiência , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de RiscoRESUMO
Cancer-associated fibroblasts (CAFs) are believed to influence tumor behavior and clinical outcomes. We previously showed that conditioned medium (CM) from CAFs induces proliferation and motility of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the molecular mechanisms by which the CAF-secreted proteins induce ESCC development and progression. Using antibody arrays, we identified urokinase plasminogen activator (uPA) as one of the main proteins whose release was increased in CAFs compared to normal fibroblasts (NFs). Immunohistochemical analysis of pathological sections showed that uPA-positive cells were localized at the boundaries of tumor and stroma tissues, in stroma between tumor nests, and within the tumors. Increased stromal uPA levels (132/146 cases) correlated with tumor invasion (p < 0.05) and overall survival of ESCC patients (p < 0.05). In vitro assays showed that uPA promotes ESCC cell proliferation, migration, and invasion via PI3K/AKT and ERK signaling pathways. In vivo, anti-uPA antibody suppressed tumor growth in ESCC xenografts. These results suggest that uPA released from stroma, and especially from CAFs, might be a predictive marker for ESCC diagnosis and prognosis, as well as an effective therapeutic target.
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Fibroblastos Associados a Câncer/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Idoso , Animais , Anticorpos Monoclonais/farmacologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Fibroblastos/metabolismo , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Células Estromais/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
Reprogramming of intracellular metabolism is common in liver cancer cells. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. In our previous study, we reported that a novel oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) promotes tumorigenesis under hypoxic condition. Here, we aim to investigate the role of EIF5A2 in cell metabolic reprogramming during hepatocellular carcinoma (HCC) development. In this study, we reported that the messenger RNA (mRNA) level of EIF5A2 was upregulated in 59 of 105 (56.2%) HCC clinical samples (P = 0.015), and EIF5A2 overexpression was significantly associated with shorter survival time of patients with HCC (P = 0.021). Ectopic expression of EIF5A2 in HCC cell lines significantly promoted cell growth and accelerated glucose utilization and lipogenesis rates. The high rates of glucose uptake and lactate secretion conferred by EIF5A2 revealed an abnormal activity of aerobic glycolysis in HCC cells. Several key enzymes involved in glycolysis including glucose transporter type 1 and 2, hexokinase 2, phosphofructokinase liver type, glyceraldehyde 3-phosphate dehydrogenase, pyruvate kinase M2 isoform, phosphoglycerate mutase 1 and lactate dehydrogenase A were upregulated by overexpression of EIF5A2. Moreover, EIF5A2 showed positive correlations with FASN and ACSS2, two key enzymes involved in the fatty acid de novo biosynthetic pathway, at both protein and mRNA levels in HCC. These results indicated that EIF5A2 may regulate fatty acid de novo biosynthesis by increasing the uptake of acetate. In conclusion, our findings demonstrate that EIF5A2 has a critical role in HCC cell metabolic reprogramming and may serve as a prominent novel therapeutic target for liver cancer treatment.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Glucose/metabolismo , Lipogênese , Neoplasias Hepáticas/metabolismo , Redes e Vias Metabólicas , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Reprogramação Celular , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Fatores de Iniciação de Peptídeos/genética , Prognóstico , Proteínas de Ligação a RNA/genética , Taxa de Sobrevida , Fator de Iniciação de Tradução Eucariótico 5ARESUMO
Cationic PtAu2 heterotrinuclear complexes [PtAu2(dpmp)2(C[triple bond, length as m-dash]CR)2]2+ (dpmp = bis(diphenylphosphinomethyl)phenylphosphine, R = aryl) of aromatic acetylides were prepared. The PtAu2 structures are supported through doubly bridging dpmp and stabilized by a significant Pt-Au interaction. They are highly phosphorescent in fluid CH2Cl2 solution (Φem = 23.5%-78.9%), the solid state (Φem = 15.4%-70.2%), the PMMA film (Φem = 39.9%-71.7%) and the doping film of 61% TCTA : 31% OXD-7 : 8% PtAu2 complex (Φem = 16.9%-67.9%). The phosphorescence arises mainly from 3[π (C[triple bond, length as m-dash]CR) â π* (dpmp)] 3LLCT and 3[π (C[triple bond, length as m-dash]CR) â s/p (PtAu2)] 3LMCT triplet excited states for carbazole-acetylide complexes, whereas other complexes display a 3LLCT character mixed with noticeable PtAu2 centered 3[d â s/p] parentage. Utilizing a mixed host composed of hole-transporting TCTA and electron-transporting OXD-7 doped with 8% PtAu2 species as a light-emitting layer and CuSCN as a hole-transporting layer through an orthogonal solution process, the devices exhibit highly efficient electrophosphorescence with the highest current efficiency (CEmax) of 51.7 cd A-1 and external quantum efficiency (EQEmax) of 14.5%. The efficiency roll-off is small in the practical brightness range of 500-5000 cd m-2. The PtAu2 complexes with carbazole-acetylides display a higher electroluminescence efficiency ascribed to their better hole-transporting character as well as more facile energy transfer from mixed host materials.
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Non-CG methylation has been associated with stemness regulation in embryonic stem cells. By comparing differentially expressed genes affected by non-CG methylation between tumour and corresponding non-tumour tissues in oesophageal squamous cell carcinoma (OSCC), we find that Integrin α7 (ITGA7) is characterized as a potential cancer stem cell (CSC) marker. Clinical data show that a high frequency of ITGA7+ cells in OSCC tissues is significantly associated with poor differentiation, lymph node metastasis and worse prognosis. Functional studies demonstrate that both sorted ITGA7+ cells and ITGA7 overexpressing cells display enhanced stemness features, including elevated expression of stemness-associated genes and epithelial-mesenchymal transition features, as well as increased abilities to self-renew, differentiate and resist chemotherapy. Mechanistic studies find that ITGA7 regulates CSC properties through the activation of the FAK-mediated signalling pathways. As knockdown of ITGA7 can effectively reduce the stemness of OSCC cells, ITGA7 could be a potential therapeutic target in OSCC treatment.