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Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity.
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Fibroblastos Associados a Câncer , Comunicação Celular , Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Animais , Humanos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Transição Epitelial-Mesenquimal/genética , Junções Comunicantes/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Análise Espaço-Temporal , Junções Íntimas/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Autoantígenos/genética , Autoantígenos/metabolismoRESUMO
Three d10 metal complexes, ZnL(OAc)2 (1), CdL(OAc)2 (2) and [CdL2(NO3)2]·CH3CN (3) were synthesized using the ligand (E)-N-(3-methoxy-4-methylphenyl)-1-(quinolin-2-yl)methanimine (L) and characterized by FT-IR spectra, NMR spectra, and CHN elemental analysis. Single-crystal X-ray diffraction analysis revealed that complexes 1 and 2 are isostructural, with the central metal adopting a hexacoordinate octahedral geometry, while complex 3 adopts a triangular dodecahedron geometry. Thermal gravimetric analysis showed that these complexes exhibit good thermal stability. Solid-state fluorescence spectroscopy measurements demonstrated that complexes 1-3 exhibit bright yellow-green fluorescence (λem = 564 nm for 1; 524 nm for 2; 542 nm for 3), suggesting their potential as photoluminescent materials. Furthermore, DFT calculations, including frontier molecular orbitals, energy levels, and surface electrostatic potential, provided insights into the structural and electronic spectral properties of complexes 1-3.
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Exosomal miRNAs activates hepatic stellate cell (HSC) and promote fibrosis. miR-222 was found to be increased in hepatitis B virus (HBV)-infected hepatocytes, and ferroptosis was reported to ameliorate liver fibrosis (LF). Although miR-222 and ferroptosis have been implicated in LF, the association between miR-222 and ferroptosis and how they coordinate to regulate LF are still not explicit. This study investigates the roles of miR-222 and transferrin receptor (TFRC) in LF. Lipid reactive oxygen species (ROS) level was analyzed by flow cytometry. FerroOrange staining was used to measure intracellular iron level. Luciferase reporter assay was adopted to confirm the binding of miR-222 and TFRC. Real-time quantitative PCR and immunoblots were applied to analyze gene and protein expression. The results showed that supplementation of exosomes derived from HBV-infected LO2 cells remarkably enhanced LX-2 cell activation, evidenced by elevated hydroxyprolin (Hyp) secretion and α-SMA and COL1A2 expression. miR-222 was significantly increased in HBV-Exo. Overexpressing miR-222 upregulated cell viability, secretion of Hpy, and expression of α-SMA and COL1A2, which were all blocked by overexpression of TFRC. Further study showed that TFRC was a target of miR-222, and miR-222 promoted LX-2 cell activation through suppressing TFRC-induced ferroptosis in LX-2 cells. Exosomal miR-222 derived from HBV-infected hepatocytes promoted LF through inhibiting TFRC and TFRC-induced ferroptosis. This study emphasizes the significance of miR-222/TFRC axis in LF and suggests new insights in clinical decision making while treating LF. Exosomes derived from HBV-infected LO2 cells promote LX-2 cell activation and liver fibrosis in mouse Exosomal miR-222 derived from HBV-infected LO2 cells promotes LX-2 cell activation TFRC is a target of miR-222 and inhibits LX-2 cell activation induced by miR-222 miR-222 promotes LX-2 cell activation through inhibiting TFRC-induced ferroptosis.
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Exossomos , MicroRNAs , Animais , Camundongos , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Exossomos/genética , Exossomos/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Receptores da Transferrina/metabolismoRESUMO
BACKGROUND: To explore the roles of Annexin A2 (ANXA2) on hepatocyte pyroptosis and hepatic fibrosis in nonalcoholic steatohepatitis (NASH) and underlying molecular mechanism. METHODS: Bioinformatics analyses were performed on transcriptome data of liver tissues from mice and patients with liver fibrosis for screening the hepatocyte pyroptosis-related differential genes. The in vivo NASH mouse model and in vitro NASH cellular model were established. The expression levels of Anxa2/ANXA2 were quantified. Then, the upstream transcription factor of Anxa2 was screened by ChIP-Seq and experimentally verified. The effects of the p-STAT3/ANXA2 axis on Caspase-1 mediated pyroptosis and fibrosis were explored by in vivo and in vitro experiments. RESULTS: Bioinformatics analyses suggested that the expression of Anxa2/ANXA2 was significantly up-regulated in liver tissues of both NASH mice and patients scoring with high pyroptotic activity. Experimental data showed that the ANXA2 expression was positively associated with the development of hepatocyte pyroptosis and fibrosis. As a transcription factor of ANXA2, p-STAT3 can bind to the promoter of Anxa2 and promote its transcription. The inhibition of p-STAT3 can significantly suppress hepatocyte pyroptosis and fibrosis, which was significantly reversed after the over-expression of Anxa2. Caspase-1 was verified as the player of the p-STAT3/ANXA2 axis to promote pyroptosis and fibrosis. By specifically inhibiting Caspase-1, the promotion effect of the p-STAT3/ANXA2 axis on pyroptosis and fibrosis can be significantly weakened. CONCLUSION: The p-STAT3 promoted Anxa2 expression at the transcription level, thus activating the Caspase-1 mediated hepatocyte pyroptosis and fibrosis in NASH.
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Anexina A2 , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Anexina A2/metabolismo , Anexina A2/farmacologia , Caspase 1/metabolismo , Caspase 1/farmacologia , Fibrose , Hepatócitos/patologia , Fígado/patologia , Cirrose Hepática/complicações , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/complicações , PiroptoseRESUMO
Jasmonates (JAs) are important for pathogen resistance in many plants, but the role of these phytohormones in fungal pathogen resistance in rose is unclear. Here, we determined that exogenous application of methyl jasmonate increased resistance to the important fungal pathogen Botrytis cinerea in Rosa chinensis 'Old blush', whereas silencing the JA biosynthetic pathway gene Allene Oxide Synthase (AOS) and JA co-receptor gene CORONATINE INSENSITIVE 1 (COI1) suppressed this response. Transcriptome profiling identified various MYB transcription factor genes that responded to both JA and B. cinerea treatment. Silencing Ri-RcMYB84/Ri-RcMYB123 increased the susceptibility of rose plants to B. cinerea and inhibited the protective effects of JA treatment, confirming the crucial roles of these genes in JA-induced responses to B. cinerea. JAZ1, a key repressor of JA signaling, directly interacts with RcMYB84 and RcMYB123 to deplete their free pools. The JAZ1-RcMYB84 complex binds to the RcMYB123 promoter via the CAACTG motifs to block its transcription. Upon JA treatment, the expression of RcMYB123 is de-repressed, and free forms of RcMYB84 and RcMYB123 are released due to JAZ1 degradation, thereby activating the defense responses of plants to B. cinerea. These findings shed light on the molecular mechanisms underlying JA-induced pathogen resistance in roses.
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Botrytis , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Reguladores de Crescimento de Plantas/fisiologia , Proteínas de Plantas/fisiologia , Rosa/imunologia , Fatores de Transcrição/fisiologia , Resistência à Doença , Perfilação da Expressão Gênica , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Rosa/metabolismo , Rosa/microbiologia , Transdução de Sinais , Fatores de Transcrição/metabolismoRESUMO
Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for liver CSCs expansion remains unclear. Herein, we report that miR-124 is downregulated in liver CSCs and associated with the poor prognosis of HCC. Functional studies revealed that a forced expression of miR-124 inhibits liver CSCs self-renew and tumorigenesis. Conversely, miR-124 knockdown promotes liver CSCs self-renew and tumorigenesis. Mechanistically, miR-124 directly target Caveolin-1 (CAV1) via its mRNA 3'UTR in liver CSCs. Furthermore, miR-124 expression determines the responses of hepatoma cells to sorafenib treatment. The analysis of patient cohort and patient-derived xenografts (PDXs) further demonstrated that miR-124 may predict sorafenib benefits in HCC patients. In conclusion, our findings revealed the crucial role of the miR-124 in liver CSCs expansion and sorafenib response, rendering miR-124 an optimal target for the prevention and intervention in HCC.
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Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Sorafenibe/farmacologia , Animais , Sequência de Bases , Caveolina 1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , MicroRNAs/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , PrognósticoRESUMO
KEY MESSAGE: We genome-wide identified 28 JmjC domain-containing genes, further spatio-temporal expression profiling and genetic analysis defined them as epigenetic regulators in flowering initiation of Rosa chinensis. The JmjC domain-containing histone demethylases play critical roles in maintaining homeostasis of histone methylations, thus are vital for plant growth and development. Genome-wide identification of the JmjC domain-containing genes have been reported in several species, however, no systematic study has been performed in rose plants. In this paper, we identified 28 JmjC domain-containing genes from the newly published genome database of Rosa chinensis. The JmjC domain-containing proteins in R. chinensis were divided into seven groups, KDM3 was the largest group with 13 members, and JmjC domain-only A and KDM5B were the smallest clades both with only one member. Although all the JmjC domain proteins having a conserved JmjC domain, the gene and protein structure experienced differentiation and specification during the evolution, especially in KDM3 clade, one gene (RcJMJ40) was found carrying site deletions for cofactors Fe (II) and α-KG binding which were crucial for demethylase activities, three genes (RcJMJ41, RcJMJ43 and RcJMJ44) had no intron while two of them had tandem JmjC domains. Spatial expression pattern analysis of these JmjC domain-containing genes in different tissues showed most of them were highly expressed in reproductive tissues such as floral meristem and closed flowers than vegetative tissues, demonstrating their important functions in developmental switch from vegetative to reproductive growth of roses. Temporal expression profiling indicated majority of JmjC domain-containing genes from R. chinensis fluctuated along with floral bud differentiation and development, further proving their essential roles in flower organogenesis. VIGS induced silencing of RcJMJ12 led to delayed flowering time, and decreased the expression levels of flowering integrator such as RcFT, RcSOC1, RcFUL, RcLFY and RcAP1, therefore providing the genetic evidence of RcJMJ12 in flowering initiation. Collectively, spatio-temporal expression profiling and genetic analysis defined the JmjC domain-containing genes as important epigenetic regulators in flower development of R. chinensis.
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Epigênese Genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Histona Desmetilases com o Domínio Jumonji/genética , Meristema/genética , Rosa/genética , Deleção de Genes , Perfilação da Expressão Gênica , Inativação Gênica , Genoma de Planta , Histona Desmetilases com o Domínio Jumonji/fisiologia , Metilação , Filogenia , Proteínas de Plantas/genética , Domínios Proteicos , TranscriptomaRESUMO
The widespread application of zinc oxide nanoparticles (nano-ZnO) has received increasing attention because of their potential risks to human health and the environment. This review summarizes the relationship between the toxic effects and physicochemical properties of nano-ZnO and the underlying toxicity mechanisms of nano-ZnO. This study presents the possible human health hazards posed by nano-ZnO exposure and the biotoxicity to bacteria, algae, higher plants, aquatic animals, terrestrial invertebrates and vertebrates in vitro and in vivo. The advances in research on the ecotoxicity of nano-ZnO and the potential risks to human health are discussed. Finally, the current research deficiencies in this area are identified, and recommendations for future research are proposed.
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Poluentes Ambientais/toxicidade , Nanopartículas Metálicas/toxicidade , Óxido de Zinco/toxicidade , Animais , Ecotoxicologia , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental/métodos , Humanos , Medição de Risco/métodosRESUMO
INTRODUCTION: Hereditary haemochromatosis (HH) caused by a homozygous p.C282Y mutation in haemochromatosis (HFE) gene has been well documented. However, less is known about the causative non-HFE mutation. We aimed to assess mutation patterns of haemochromatosis-related genes in Chinese patients with primary iron overload. METHODS: Patients were preanalysed for mutations in the classic HH-related genes: HFE, HJV, HAMP, TFR2 and SLC40A1. Whole exome sequencing was conducted for cases with variants in HJV signal peptide region. Representative variants were analysed for biological function. RESULTS: None of the cases analysed harboured the HFE p.C282Y; however, 21 of 22 primary iron-overload cases harboured at least one non-synonymous variant in the non-HFE genes. Specifically, p.E3D or p.Q6H variants in the HJV signal peptide region were identified in nine cases (40.9%). In two of three probands with the HJV p.E3D, exome sequencing identified accompanying variants in BMP/SMAD pathway genes, including TMPRSS6 p.T331M and BMP4 p.R269Q, and interestingly, SUGP2 p.R639Q was identified in all the three cases. Pedigree analysis showed a similar pattern of combination of heterozygous mutations in cases with HJV p.E3D or p.Q6H, with SUGP2 p.R639Q or HJV p.C321X being common mutation. In vitro siRNA interference of SUGP2 showed a novel role of downregulating the BMP/SMAD pathway. Site-directed mutagenesis of HJV p.Q6H/p.C321X in cell lines resulted in loss of membrane localisation of mutant HJV, and downregulation of p-SMAD1/5 and HAMP. CONCLUSION: Compound heterozygous mutations of HJV or combined heterozygous mutations of BMP/SMAD pathway genes, marked by HJV variants in the signal peptide region, may represent a novel aetiological factor for HH.
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Proteínas Ligadas por GPI/genética , Variação Genética , Proteína da Hemocromatose/genética , Hemocromatose/genética , Sobrecarga de Ferro/genética , Sinais Direcionadores de Proteínas/genética , Proteínas Smad/genética , Adolescente , Adulto , Idoso , China , Estudos de Coortes , Feminino , Proteínas Ligadas por GPI/metabolismo , Hemocromatose/diagnóstico , Proteína da Hemocromatose/metabolismo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Smad/metabolismo , Sequenciamento do Exoma , Adulto JovemRESUMO
OBJECTIVE: To investigate the effect of the interaction between methylenetetrahydrofolate reductase(MTHFR) genotype and allele and long-term exposure to organophosphorus pesticides on the development of type 2 diabetes mellitus(T2 DM). METHODS: A total of 209 cases of T2 DM(case group) and 216 cases without T2 DM(control group) were selected as subjects. The polymorphism of MTHFR(rs1801133) was detected by TaqMan probe technique. The relationship between genes, long-term exposure to organophosphorus pesticides and T2 DM was analyzed by Logistic regression. The interaction between gene and long-term exposure to organophosphorus pesticides was discussed by crossover analysis and generalized multifactor dimensionality reduction. RESULTS: BMIâ¿4, residence in countryside, long-term exposure to organophosphorus pesticides and family history of diabetes mellitus were risk factors for T2 DM. MTHFR genotype distribution conformed to Hardy-Weinberg equilibrium(P>0. 05). There was no significant difference in genotype distribution frequency between case group and control group. The risk of T2 DM in individuals with CT and TT genotypes was 1. 667 times higher than that of CC genotypes after adjusting the covariates at rs1801133 locus in the dominant model(95%CI 1. 057-2. 627, P=0. 028). It suggested that the samples of allele T had a increased risk of T2 DM compared with those without allele T. The above models still had statistical significance(P<0. 05) after adjusting the covariates. Forth, crossover analysis showed that the gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides had multiplication interaction. The interaction between gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides may play a role in the pathogenesis of T2 DM. Generalized multifactor dimensionality reduction(GMDR)analysis showed that the interaction model of MTHFR(rs1801133) gene and family history of diabetes mellitus was the best model. CONCLUSION: MTHFR(rs1801133) gene CT and TT genotype may be risk factors for T2 DM. The interaction between genetic polymorphism and environmental factors increases the risk of T2 DM.
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Diabetes Mellitus Tipo 2/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Compostos Organofosforados/toxicidade , Praguicidas/toxicidade , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: A model was constructed using clinical and serum variables to discriminate between chronic hepatitis B (CHB) patients with and without significant necroinflammatory activity (score 4-18 vs. score 0-3). METHODS: Consecutive CHB patients who underwent liver biopsy were divided into two sequential groups: a training group (n = 401) and a validation group (n = 401). Multivariate analysis identified alanine aminotransferase, γ-glutamyltransferase, prothrombin time and albumin as independent predictors of necroinflammatory activity. RESULTS: The area under the receiver operating characteristic curve was 0.826 for the training group and 0.847 for the validation group. Using a cut-off score of H ≤ 0.375, significant necroinflammatory activity (score 4-18) was excluded with high accuracy [78.2% negative predictive value (NPV), 72% positive predictive value (PPV), and 90.8% sensitivity] in 238 (59.4%) of 401 patients in the training group and with the same certainty (88.1% NPV, 61.2% PPV, and 95.1% sensitivity) among 204 (50.9%) of 401 patients in the validation group. Similarly, applying a cut-off score of H > 0.720, significant necroinflammatory activity was correctly identified with high accuracy (90.8% PPV, 57.7% NPV, and 92.0% specificity) in 150 (37.4%) of 401 patients in the training group and with the same certainty (91.8% PPV, 64.6% NPV, and 95.4% specificity) in 188 (46.9%) of 401 patients in the validation group. CONCLUSIONS: A predictive model based on easily accessible variables identified CHB patients with and without significant necroinflammatory activity with a high degree of accuracy. This model may decrease the need for liver biopsy for necroinflammatory activity grading in 72.1% of CHB patients.
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Hepatite B Crônica/patologia , Inflamação/patologia , Fígado/patologia , Modelos Biológicos , Adulto , Biópsia , Estudos de Coortes , Feminino , Hepatite B Crônica/diagnóstico , Humanos , Modelos Logísticos , Masculino , Curva ROC , Reprodutibilidade dos TestesRESUMO
Silver nanoparticles (Ag-NPs) are increasingly being applied in many consumer products due to their unique properties. Widespread use of Ag-NPs leads to an increasing human exposure to Ag-NPs in many different pathways. This review summarized the toxicity mechanisms of Ag-NPs based on various environmentally relevant test species, such as bacteria, cells, plants, aquatic animals and mammals, in both in vitro and in vivo experiments. Nanoparticles were usually exposed to combination chemicals but to single chemicals in the environment and thereby exert combined toxicities to the organisms. Therefore, the joint effects of nanomaterials and their co-existing characteristics were also discussed. The current knowledge gaps and safe product designs of Ag-NPs have been discussed in detail. The limited and existing data implied that understanding the toxicity mechanisms is crucial to the future research development of nanomaterials.
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Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Animais , Ecotoxicologia , Humanos , Nanopartículas Metálicas/química , Prata/químicaRESUMO
Perfluorooctane sulfonate (PFOS) and ZnO nanoparticles (Nano-ZnO) are two kinds of environmental contaminants that have been frequently detected in natural waters. The potential joint toxicity of PFOS and nano-ZnO remains to be fully elucidated. The objective of this study was to evaluate co-exposure effects of PFOS and nano-ZnO on growth in initial generation (F0) zebrafish after chronic exposure and to examine possible parental transfer of PFOS and nano-ZnO transgenerational effects on the growth of first generation (F1) larvae. When zebrafish (2â¯h after incubation) were exposed to single- and co-exposure groups for 120 days, bioconcentration resulted in significantly less growth as measured by body length and body weight, higher mortality, and less spawning in the F0 generation. These effects were possibly due to the down-regulation of the expression of Vtg1 genes along with a sex hormone (T/E2) involved in the hypothalamus-pituitary-gonad (HPG) axis. Furthermore, after long-term exposure, less fertilization, less hatching, greater mortality and more malformation were found in the F1 generation. The down-regulation of genes and hormones might be responsible for transgenerational toxicity. This study suggested that chronic exposure to PFOS and nano-ZnO adversely impacts development, reproduction in the F0 generation, and offspring embryonic growth.
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Ácidos Alcanossulfônicos/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Fluorocarbonos/toxicidade , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidade , Óxido de Zinco/toxicidade , Animais , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Reprodução/efeitos dos fármacos , Testosterona/metabolismo , Vitelogeninas/genética , Peixe-Zebra , Proteínas de Peixe-Zebra/genéticaRESUMO
Using Schiff-base ligands (E)-N-(6-methoxypyridin-2-yl)(CHâNAr) (where Ar = C6H5, L1; 2-MeC6H4, L2; 2,4,6-Me3C6H2, L3), six Zn(II)/Hg(II) complexes, namely, [ZnL1Cl2] (Zn1), [HgL1Cl2] (Hg1), [ZnL2Cl2] (Zn2), [HgL2Cl2] (Hg2), [ZnL3Cl2] (Zn3), and [HgL3Cl2] (Hg3) have been synthesized under solvothermal conditions. The structures of six complexes have been established by X-ray single-crystal analysis and further physically characterized by EA, FT-IR, (1)H NMR, and ESI-MS. The crystal structures of these complexes indicate that noncovalent interactions, such as hydrogen bonds, C-H···Cl, and π···π stacking, play essential roles in constructing the resulting supramolecular structures (1D for Hg3; 2D for Zn2, Hg2; 3D for Zn1, Hg1, and Zn3). Upon irradiation with UV light, the emission of complexes Zn1-Zn3 and Hg1-Hg3 could be finely tuned from green (480-540 nm) in the solid state to blue (402-425 nm) in acetonitrile solution. It showed that the ligand and metal cation can influence the structures and luminescence properties of complexes such as emission intensities and maximum wavelengths. Since these ligands and complexes could compensate for the absorption of N719 in the low-wavelength region of the visible spectrum and reduce charge recombination of the injected electron, the ligands L1-L3 and complexes Zn3/Hg3 were employed to prepare cosensitized dye-sensitized solar cells devices for investigating the influences of the electron-donating group and coordination on the DSSCs performance. Compared to DSSCs only being sensitized by N719, these prepared ligands and complexes chosen to cosensitize N719 in solar cell do enhanced its performance by 11-41%. In particular, a DSSC using L3 as cosensitizer displays better photovoltaic performance with a short circuit current density of 18.18 mA cm(-2), corresponding to a conversion efficiency of 7.25%. It is much higher than that for DSSCs only sensitized by N719 (5.14%).
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Longstranded noncoding RNAs (lncRNAs) are RNAs that consist of >200 nucleotides. The majority of lncRNAs do not encode proteins but have been revealed to mediate a variety of important physiological functions. AntisenselncRNAs (ASlncRNAs) are transcribed from the opposite strand of a protein or nonprotein coding gene as part of the antisense strand of the coding gene. ASlncRNAs can serve an important role in the tumorigenesis, prognosis, metastasis and drug resistance of a number of malignancies. This has been reported to be exerted through various mechanisms, such as endogenous competition, promoter interactions, direct interactions with mRNAs, acting as 'scaffolds' to regulate mRNA halflife, interactions with 5untranslated regions and regulation of sense mRNAs. ASlncRNAs have been found to either inhibit or promote tumor aggressiveness by regulating cell proliferation, energy metabolism, inflammation, inflammatorycarcinoma transformation, invasion, migration and angiogenesis. In addition, accumulating evidence has documented that ASlncRNAs can regulate tumor therapy resistance. Therefore, targeting aberrantly expressed ASlncRNAs for cancer treatment may prove to be a promising approach to reverse therapy resistance. In the present review, research advances on the role of ASlncRNAs in tumor occurrence and development were summarized, with the aim of providing novel ideas for further research in this field.
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Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias/genética , Regulação Neoplásica da Expressão GênicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. AIM OF THE STUDY: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. MATERIALS AND METHODS: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC. RESULTS: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1ß, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. CONCLUSION: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.
Assuntos
Neoplasias Associadas a Colite , Sulfato de Dextrana , Medicamentos de Ervas Chinesas , Células Supressoras Mieloides , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Neoplasias Associadas a Colite/tratamento farmacológico , Neoplasias Associadas a Colite/prevenção & controle , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Citocinas/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Colite/tratamento farmacológico , Colite/complicações , Colite/metabolismo , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Camundongos Endogâmicos C57BLRESUMO
AIM: As liver biopsy has considerable limitations in the assessment of liver fibrosis, non-invasive models have achieved great progress in the past. However, many tests consist of variables that are not readily available, and there are few data about patients with hepatitis B e-antigen (HBeAg) negative chronic hepatitis B (CHB). The aim of this study was to develop a model using routine data to predict liver fibrosis in HBeAg negative CHB patients. METHODS: We randomly divided 349 patients who underwent liver biopsy into training (n = 200) and validation (n = 149) sets. Multivariable logistic regression and receiver-operator curve (ROC) analyses were used to develop a model for predicting both significant fibrosis (stages 2-4) and cirrhosis (stage 4) in the training set. The model was validated in 149 patients in comparison to FIB-4, Forn's, S and aspartate aminotransferase-to-platelet ratio index indices using ROC. RESULTS: Multivariable logistic regression analysis showed that the parameters of the model for predicting both significant fibrosis and cirrhosis included sex, age, prothrombin time, platelet count, cholesterol and γ-glutamyltransferase. In the training set, the areas under the ROC (AUC) for predicting significant fibrosis and cirrhosis were 0.856 and 0.956, respectively. In the validation group, the AUC for predicting significant fibrosis and cirrhosis were 0.889 and 0.937, respectively. Using the best cut-off values, significant fibrosis and cirrhosis can be accurately predicted in 40.9% and 91.3% of patients, respectively. CONCLUSION: Our model can accurately predict both significant fibrosis and cirrhosis and may decrease the need of liver biopsy in a considerable proportion of patients with HBeAg negative CHB.
RESUMO
The 3D netlike coordination polymer of Zn II with benzimidazole-5,6-dicarboxylic acid (H3BIDC), [Zn(HBIDC) x H2O]n was synthesized by the hydrothermal method through self-assembling. The crystal structure of complex 1 was characterized by single-crystal X-ray diffraction, elemental analysis and IR spectra, and we also studied the fluorescence properties of complex 1 in DMSO and in the solid state with UV-Vis absorption spectra, fluorescence spectra and fluorescence lifetime. Complex 1 has blue luminescence in solutions of DMSO with emission band at 481 nm; and has blue luminescence in the solid state at room temperature with a strong emission band at 493 nm, and these all can be attributed to the pi* --> pi transition based on the benzimidazole-5,6-dicarboxy acid. The experimental results indicate that complex 1 displays higher fluorescence quantum efficiency and can be used as a potential blue luminescence material.
RESUMO
Background: Spurred by the seriousness of liver fibrosis, we evaluated the correlation between Y-box binding protein 1 (YB-1) and transforming growth factor-beta 3 (TGF-ß3) expression levels in the signaling pathways of the disease. Methods: Based on a mouse model of carbon tetrachloride-induced liver fibrosis, YB-1 overexpression lentivirus was used to explore the effect of YB-1 on liver fibrosis in vivo. In addition, a hepatic stellate cell (HSC) activation model in the HSC line LX-2 was developed using TGF-ß1. Western blot assays were used to investigate the effects of YB-1 overexpression and knockdown on liver fibrosis. Finally, chromatin immunoprecipitation and luciferase reporter assays were used to elucidate the relationship between YB-1 and its downstream signaling pathways. Results: YB-1 was overexpressed in fibrotic liver tissue, which enhanced both fibrosis and the relative protein expressions of the TGF-ß pathway. Moreover, YB-1 overexpression promoted HSC activation in response to TGF-ß1 stimulation, but its knockdown inhibited liver fibrosis in vitro. Both in vitro and in vivo experiments indicated the expression of TGF-ß3 in the YB-1 overexpression group to be suppressed, and liver fibrosis was more obvious in the YB-1-overexpression group than in the YB-1-inhibition group. YB-1 attenuated TGF-ß3 transcription by binding to its promoter, which is involved in the effect of YB-1 on liver fibrosis. Conclusions: YB-1 overexpression in HSCs promoted liver fibrosis by attenuating TGF-ß3 transcription.
RESUMO
OBJECTIVE: To investigate the effects of 18α-glycyrrhetinic acid (18α-GA) on the expression of type I and III collagen in human and rat hepatic stellate cells (HSC) and to explore the role of TGF-ß1/Smad signaling pathway involved. METHODS: Following 18α-GA treatment, the cell viability and cell growth were detected to determine the optimal concentration of 18α-GA. The expressions of TGF-ß1/Smad signaling-related genes including type I and III collagen in human and rat HSCs before and after 18α-GA treatment were measured by real time PCR. The expression of related proteins was verified by western blot assay. The phosphorylation level of Smad2 and Smad3 was detected by immunocytochemistry. The DNA binding activities of SP-1, AP-1 and NF-κB were measured by both EMSA and ArrayStar transcription factor activity assay. RESULTS: 18α-GA could decrease the mRNA and protein expression of Smad3, type I and III collagen, increase the Smad7 expression in human and rat HSCs (P<0.05), and reduce phosphorylation level of Smad3 at 24 h and 48 h after treatment. The DNA binding activities of transcription factors were suppressed by 18α-GA in human and rat HSCs at 24 h, and the activities reduced in a time dependent manner with the lowest activities at 48 h, especially for SP-1. CONCLUSION: 18α-GA could inhibit the mRNA and protein expression of type I and III collagen in human and rat HSCs, which may be attributed to down-regulation of Smad3, up-regulation of Smad7, and inhibition of DNA binding activities of SP-1, AP-1 and NF-κB.