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1.
Inorg Chem ; 63(1): 842-851, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38100035

RESUMO

Rapid and sensitive electrochemical determination of trace carcinogenic Cr(VI) pollutants remains an urgent and important task, which requires the development of active sensing materials. Herein, four cases of reduced phosphomolybdates with formulas of the (H2bib)3[Zn(H2PO4)]2{Mn[P4Mo6O31H7]2}·6H2O (1), (H2bib)2[Na(H2O)]2[Mn(H2O)]2{Mn[P4Mo6O31H6]2}·5H2O (2), (H2bib)3[Mo2(µ2-O)2(H2O)4]2{Ni[P4Mo6O31H2]2}·4H2O (3), and (H2bib)2{Ni[P4Mo6O31H9]2}·9H2O (4) (bib = 4,4'-bis(1-imidazolyl)-biphenyl) were hydrothermally synthesized under the guidance of a bridging component strategy, which function as effective electrochemical sensors to detect trace Cr(VI). The difference of hybrids 1-4 is in the inorganic moiety, in which the reduced phosphomolybdates {M[P4MoV6O31]2} (M{P4Mo6}2) exhibited different arrangements bridged by different cationic components ({Zn(H2PO4)} subunit for 1, [Mn2(H2O)2]4+ dimer for 2, and [MoV2(µ2-O)2(H2O)4]6+ for 3). As a result, hybrids 1 and 3 display noticeable Cr(VI) detection activity with low detection limits of 14.3 nM (1.48 ppb) for 1 and 6.61 nM (0.69 ppb) for 3 and high sensitivities of 97.3 and 95.3 µA·mM-1, respectively, which are much beyond the World Health Organization's detection threshold (0.05 ppm) and superior to those of the contrast samples (inorganic Mn{P4Mo6}2 salt and hybrid 4), even the most reported noble-metal catalysts. This work supplies a prospective pathway to build effective electrochemical sensors based on phosphomolybdates for environmental pollutant treatment.

2.
J Gastroenterol Hepatol ; 39(3): 596-607, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059880

RESUMO

BACKGROUND AND AIM: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC. METHODS: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a. RESULTS: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. CONCLUSION: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment.


Assuntos
Carcinoma Hepatocelular , RNA Helicases DEAD-box , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamento farmacológico , RNA Mensageiro/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/uso terapêutico , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitina/uso terapêutico , Domínios RING Finger , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/uso terapêutico , Proteínas Estimuladoras de Ligação a CCAAT/química , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Fatores de Iniciação de Peptídeos/uso terapêutico , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Fator de Iniciação 4A em Eucariotos/genética , Fator de Iniciação 4A em Eucariotos/metabolismo
3.
Proc Natl Acad Sci U S A ; 118(26)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34172566

RESUMO

The spread of pathological α-synuclein (α-syn) is a crucial event in the progression of Parkinson's disease (PD). Cell surface receptors such as lymphocyte activation gene 3 (LAG3) and amyloid precursor-like protein 1 (APLP1) can preferentially bind α-syn in the amyloid over monomeric state to initiate cell-to-cell transmission. However, the molecular mechanism underlying this selective binding is unknown. Here, we perform an array of biophysical experiments and reveal that LAG3 D1 and APLP1 E1 domains commonly use an alkaline surface to bind the acidic C terminus, especially residues 118 to 140, of α-syn. The formation of amyloid fibrils not only can disrupt the intramolecular interactions between the C terminus and the amyloid-forming core of α-syn but can also condense the C terminus on fibril surface, which remarkably increase the binding affinity of α-syn to the receptors. Based on this mechanism, we find that phosphorylation at serine 129 (pS129), a hallmark modification of pathological α-syn, can further enhance the interaction between α-syn fibrils and the receptors. This finding is further confirmed by the higher efficiency of pS129 fibrils in cellular internalization, seeding, and inducing PD-like α-syn pathology in transgenic mice. Our work illuminates the mechanistic understanding on the spread of pathological α-syn and provides structural information for therapeutic targeting on the interaction of α-syn fibrils and receptors as a potential treatment for PD.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Amiloide/metabolismo , Antígenos CD/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo , Animais , Linhagem Celular Tumoral , Endocitose , Humanos , Camundongos , Degeneração Neural/patologia , Neurônios/metabolismo , Fosforilação , Fosfosserina/metabolismo , Ligação Proteica , Eletricidade Estática , alfa-Sinucleína/química , alfa-Sinucleína/toxicidade , Proteína do Gene 3 de Ativação de Linfócitos
4.
Sheng Li Xue Bao ; 76(3): 487-495, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38939942

RESUMO

Copper is a vital trace metal element necessary for the functioning of living organisms. It serves as a co-factor or structural component in numerous enzymes, participating in crucial biological metabolic processes. Disruptions in copper homeostasis, whether inherited or acquired, such as copper overload, deficiency, or uneven distribution, can contribute to or exacerbate various diseases, including Menkes disease, Wilson's disease, neurodegenerative disorders, anemia, cardiovascular diseases, kidney diseases and cancer. Recent research has highlighted the close correlation between chronic kidney disease and intracellular copper overload. Therefore, renal cells must establish a well-organized and efficient copper regulation network to maintain intracellular copper homeostasis. This review summarizes the processes of copper uptake, intracellular trafficking, storage, and excretion in renal cells, and elucidates the underlying mechanisms involved, aiming to provide a theoretical foundation and potential therapeutic targets for the fundamental investigation and clinical management of kidney-related diseases.


Assuntos
Cobre , Homeostase , Rim , Homeostase/fisiologia , Humanos , Cobre/metabolismo , Rim/metabolismo , Rim/fisiologia , Animais , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/fisiologia , Nefropatias/metabolismo , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/fisiologia , ATPases Transportadoras de Cobre/metabolismo , ATPases Transportadoras de Cobre/genética , Transportador de Cobre 1/metabolismo
5.
Cancer Sci ; 113(2): 796-801, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34812554

RESUMO

Identifying molecular features is an essential component of the management and targeted therapy of brain metastases (BMs). The molecular features are different between primary lung cancers and BMs of lung cancer. Here we report the DNA and RNA mutational profiles of 43 pathological samples of BMs. In addition to previously reported mutational events associated with targeted therapy, PTPRZ1-MET, which was previously exclusively identified in glioma, was present in two cases of BMs of lung cancer. Furthermore, MET exon 14 skipping may be more common (6/37 cases) in BMs of lung cancer than the frequency previously reported in lung cancer. These findings highlight the clinical significance of targeted DNA plus RNA sequencing for BMs and suggest PTPRZ1-MET and MET exon 14 skipping as critical molecular events that may serve as targets of targeted therapy in BMs.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Fusão Oncogênica , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genética , Adulto , Idoso , Neoplasias Encefálicas/metabolismo , Éxons , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo
6.
Small ; 18(38): e2202109, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35957527

RESUMO

The design and synthesis of advanced semiconductors is crucial for the full utilization of solar energy. Herein, colloidal selective-epitaxial hybrid of tripartite semiconducting sulfides CuInS2 Cd(In)SMoS2 heteronanostructures (HNs) via lateral- and vertical-epitaxial growths, followed by cation exchange reactions, are reported. The lateral-epitaxial CuInS2 and Cd(In)S enable effective visible to near-infrared (NIR) solar spectrum absorption, and the vertical-epitaxial ultrathin MoS2 offer sufficient edge sulfur sites for the hydrogen evolution reaction (HER). Furthermore, the integrated structures exhibit unique epitaxial-staggered type II band alignments for continuous charge separation. They achieve the H2 evolution rate up to 8 mmol h-1 g-1 , which is ≈35 times higher than bare CdS and show no deactivation after long-term cycling, representing one of the most efficient and robust noble-metal-free photocatalysts. This design principle and transformation protocol open a new way for creating all-in-one multifunctional catalysts in a predictable manner.

7.
BMC Vet Res ; 18(1): 289, 2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35871002

RESUMO

BACKGROUND: This study investigated the effects of chronic heat stress on liver inflammatory injury and its potential mechanisms in broilers. Chickens were randomly assigned to the 1-week control group (Control 1), 1-week heat stress group (HS1), 2-week control group (Control 2), and a 2-week heat stress group (HS2) with 15 replicates per group. Broilers in the heat stress groups were exposed to heat stress (35 ± 2 °C) for 8 h/d for 7 or 14 consecutive days, and the rest of 26 hours/day were kept at 23 ± 2 °C like control group broilers. Growth performance and liver inflammatory injury were examined for the analysis of liver injury. RESULTS: The results showed that heat stress for 2 weeks decreased the growth performance, reduced the liver weight (P < 0.05) and liver index (P < 0.05), induced obvious bleeding and necrosis points. Liver histological changes found that the heat stress induced the liver infiltration of neutrophils and lymphocytes in broilers. Serum levels of AST and SOD were enhanced in HS1 (P < 0.01, P < 0.05) and HS2 (P < 0.01, P < 0.05) group, compared with control 1 and 2 group broilers. The MDA content in HS1 group was higher than that of in control 1 group broilers (P < 0.05). Both the gene and protein expression levels of HSP70, TLR4 and NF-κB in the liver were significantly enhanced by heat stress. Furthermore, heat stress obviously enhanced the expression of IL-6, TNF-α, NF-κB P65, IκB and their phosphorylated proteins in the livers of broilers. In addition, heat stress promoted the activation of NLRP3 with increased NLRP3, caspase-1 and IL-1ß levels. CONCLUSIONS: These results suggested that heat stress can cause liver inflammation via activation of the TLR4-NF-κB and NLRP3 signaling pathways in broilers. With the extension of heat stress time, the effect of heat stress on the increase of NF-κB and NLRP3 signaling pathways tended to slow down.


Assuntos
NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Galinhas/metabolismo , Resposta ao Choque Térmico , Inflamação/veterinária , Fígado/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
8.
J Am Chem Soc ; 143(48): 20395-20402, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34817987

RESUMO

The manipulation of molecular motions to construct highly ordered supramolecular architectures from chaos in the solid state is considered to be far more complex and challenging in comparison to that in solution. In this work, a bottom-up molecular assembly approach based on a newly designed skeleton-trimmed pillar[5]arene analogue, namely the permethylated leggero pillar[5]arene MeP[5]L, is developed in the solid state. An amorphous powder of MeP[5]L can take up certain guest vapors to form various ordered linker-containing solid-state molecular assemblies, which can be further used to construct a thermodynamically favored linker-free superstructure upon heating. These approaches are driven by vapor-induced solid-state molecular motions followed by a thermally triggered phase-to-phase transformation. The intermolecular interactions play a crucial role in controlling the molecular arrangements in the resulting assemblies. This research will open new insights into exploring controllable molecular motions and assemblies in the solid state, providing new perspectives in supramolecular chemistry and materials.

9.
J Pathol ; 251(3): 272-283, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418210

RESUMO

Isocitrate dehydrogenase (IDH) wild-type diffuse lower-grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We present here a robust gene expression-based molecular classification of IDH wild-type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild-type diffuse LGGs from the Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. Seventy-three tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings. Consensus clustering of transcriptional data uncovered concordant classification of two robust and prognostically significant subtypes of IDH wild-type LGG. Subtype 1, associated with poorer outcomes, was characterized by significantly higher immune and cytolytic scores, M2 macrophages, and up-regulation of immune exhaustion markers, while Subtype 2, which had elevated lymphocytes and plasma cells, showed relatively favorable survival. Somatic alteration analysis revealed that Subtype 1 showed more frequently deleted regions, such as the locus of CDKN2A/CDKN2B, DMRTA1, C9orf53, and MTAP. Furthermore, we developed and validated a five-gene signature for better application of this acquired stratification. Our data demonstrate the biological and prognostic heterogeneity within IDH wild-type diffuse LGGs and deepen our molecular understandi-g of this tumor entity. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Transcriptoma , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/imunologia , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Glioma/classificação , Glioma/enzimologia , Glioma/imunologia , Humanos , Masculino , Gradação de Tumores , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
10.
Foodborne Pathog Dis ; 18(4): 290-296, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33512258

RESUMO

Streptococcus suis remains a serious threat to the worldwide swine industry and human health. In this study, rapid assays for the detection of three common virulence-related factors (mrp, epf, and sly) were developed, evaluated, and applied. Loop-mediated isothermal amplification (LAMP) primers were designed using Primer Explorer V5 software. The sensitivity and specificity of the LAMP assays were determined based on sample turbidity. For all three genes, LAMP assays were performed at 62°C with a reaction time of 60 min. The detection limit of conventional polymerase chain reaction (PCR) was 1 ng/µL, 10 pg/µL, and 100 fg/µL for the epf, sly, and mrp genes, respectively. For the LAMP assays, the detection limits were 10 pg/µL, 10 fg/µL, and 100 fg/µL for epf, sly, and mrp, respectively, representing sensitivities 100-1000 times higher than those of the PCR assay. Furthermore, when the LAMP assays were applied to clinical strains, the results were consistent with those of the PCR assay, confirming the LAMP assays as rapid and reliable detection techniques. In conclusion, the LAMP assays described in this study have the potential to become standard methods to detect the virulence factors mrp, epf, and sly. To the best of our knowledge, this is the first study to report the application of LAMP to detect the mrp, epf, and sly genes.


Assuntos
Proteínas de Bactérias/análise , Técnicas de Diagnóstico Molecular/estatística & dados numéricos , Técnicas de Amplificação de Ácido Nucleico/estatística & dados numéricos , Streptococcus suis/genética , Doenças dos Suínos/microbiologia , Fatores de Virulência/genética , Animais , Antígenos de Bactérias/análise , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos
11.
J Cell Mol Med ; 24(22): 13171-13180, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33006444

RESUMO

Alternative splicing (AS) is assumed to play important roles in the progression and prognosis of cancer. Currently, the comprehensive analysis and clinical relevance of AS in lower-grade diffuse gliomas have not been systematically addressed. Here, we gathered alternative splicing data of lower-grade diffuse gliomas from SpliceSeq. Based on the Percent Spliced In (PSI) values of 515 lower-grade diffuse glioma patients from the Cancer Genome Atlas (TCGA), we performed subtype-differential AS analysis and consensus clustering to determine robust clusters of patients. A total of 48 050 AS events in 10 787 genes in lower-grade diffuse gliomas were profiled. Subtype-differential splicing analysis and functional annotation revealed that spliced genes were significantly enriched in numerous cancer-related biological phenotypes and signalling pathways. Consensus clustering using AS events identified three robust clusters of patients with distinguished pathological and prognostic features. Moreover, each cluster was also associated with distinct genomic alterations. Finally, we developed and validated an AS-related signature with Cox proportional hazards model. The signature, significantly associated with clinical and molecular features, could serve as an independent prognostic factor for lower-grade diffuse gliomas. Thus, our results indicated that AS events could discriminate molecular subtypes and have prognostic impact in lower-grade diffuse gliomas.


Assuntos
Processamento Alternativo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Biomarcadores Tumorais/genética , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sequência de RNA , Transdução de Sinais
12.
BMC Microbiol ; 20(1): 70, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228454

RESUMO

BACKGROUND: It has been performed worldwidely to explore the potential of animals that might be a reservoir for community associated human infections of Clostridioides difficile. Several genetically undistinguished PCR ribotypes of C. difficile from animals and human have been reported, illustrating potential transmission of C. difficile between them. Pig and calf were considered as the main origins of C. difficile with predominant RT078 and RT033, respectively. As more investigations involved, great diversity of molecular types from pig and calf were reported in Europe, North American and Australia. However, there were quite limited research on C. difficile isolates from meat animals in China, leading to non-comprehensive understanding of molecular epidemiology of C. difficile in China. RESULTS: A total of 55 C. difficile were isolated from 953 animal stool samples, within which 51 strains were from newborn dairy calf less than 7 days in Shandong Province. These isolates were divided into 3 STs and 6 RTs, of which ST11/RT126 was predominant type, and responsible for majority antibiotic resistance isolates. All the isolates were resistant to at least one tested antibiotics, however, only two multidrug resistant (MDR) isolates were identified. Furthermore, erythromycin (ERY) and clindamycin (CLI) were the two main resistant antibiotics. None of the isolates were resistant to vancomycin (VAN), metronidazole (MTZ), tetracycline (TET), and rifampin (RIF). CONCLUSIONS: In this study, we analyzed the prevalence, molecular characters and antibiotic resistance of C. difficile from calf, sheep, chicken, and pig in China. Some unique features were found here: first, RT126 not RT078 were the dominant type from baby calf, and none isolates were got from pig; second, on the whole, isolates from animals display relative lower resistant rate to these 11 tested antibiotics, compared with isolates from human in China in our previous report. Our study helps to deep understanding the situation of C. difficile from economic animals in China, and to further study the potential transmission of C. difficile between meat animals and human.


Assuntos
Antibacterianos/farmacologia , Clostridioides difficile/classificação , Infecções por Clostridium/epidemiologia , Farmacorresistência Bacteriana , Animais , Animais Recém-Nascidos , Bovinos , Galinhas , China/epidemiologia , Clindamicina/farmacologia , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Infecções por Clostridium/veterinária , Eritromicina/farmacologia , Fezes/microbiologia , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem Molecular , Prevalência , Ovinos , Suínos
13.
Carcinogenesis ; 40(7): 853-860, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-30877769

RESUMO

Isocitrate dehydrogenase (IDH) mutant glioblastoma (GBM), accounts for ~10% GBMs, arises from lower grade diffuse glioma and preferentially appears in younger patients. Here, we aim to establish a robust gene expression-based molecular classification of IDH-mutant GBM. A total of 33 samples from the Chinese Glioma Genome Atlas RNA-sequencing data were selected as training set, and 21 cases from Chinese Glioma Genome Atlas microarray data were used as validation set. Consensus clustering identified three groups with distinguished prognostic and molecular features. G1 group, with a poorer clinical outcome, mainly contained TERT promoter wild-type and male cases. G2 and G3 groups had better prognosis differed in gender. Gene ontology analysis showed that genes enriched in G1 group were involved in DNA replication, cell division and cycle. On the basis of the differential genes between G1 and G2/G3 groups, a six-gene signature was developed with a Cox proportional hazards model. Kaplan-Meier analysis found that the acquired signature could differentiate the outcome of low- and high-risk cases. Moreover, the signature could also serve as an independent prognostic factor for IDH-mutant GBM in the multivariate Cox regression analysis. Gene ontology and gene set enrichment analyses revealed that gene sets correlated with high-risk group were involved in cell cycle, cell proliferation, DNA replication and repair. These finding highlights heterogeneity within IDH-mutant GBMs and will advance our molecular understanding of this lethal cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Isocitrato Desidrogenase/genética , Adulto , Neoplasias Encefálicas/patologia , Conjuntos de Dados como Assunto , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA-Seq , Fatores Sexuais , Transcriptoma/genética
14.
Carcinogenesis ; 40(10): 1229-1239, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31157866

RESUMO

1p/19q codeletion, which leads to the abnormal expression of 1p19q genes in oligodendroglioma, is associated with chemosensitivity and favorable prognosis. Here, we aimed to explore the clinical implications of 1p19q gene expression in 1p/19q non-codel gliomas. We analyzed expression of 1p19q genes in 668 1p/19q non-codel gliomas obtained from The Cancer Genome Atlas (n = 447) and the Chinese Glioma Genome Atlas (n = 221) for training and validation, respectively. The expression of 1p19q genes was significantly correlated with the clinicopathological features and overall survival of 1p/19q non-codel gliomas. Then, we derived a risk signature of 25 selected 1p19q genes that not only had prognosis value in total 1p/19q non-codel gliomas but also had prognosis value in stratified gliomas. The prognosis value of the risk signature was superior than known clinicopathological features in 1p/19q non-codel gliomas and was also highly associated with the following features: loss of CDKN2A/B copy number in mutant-IDH-astrocytoma; telomerase reverse transcriptase (TERT) promoter mutation, combined chromosome 7 gain/chromosome 10 loss and epidermal growth factor receptor amplification in wild-type-IDH-astrocytoma; classical and mesenchymal subtypes in glioblastoma. Furthermore, genes enriched in the biological processes of cell division, extracellular matrix, angiogenesis significantly correlated to the signature risk score, and this is also supported by the immunohistochemistry and cell biology experiments. In conclusion, the expression profile of 1p19q genes is highly associated with the malignancy and prognosis of 1p/19q non-codel gliomas. A 25-1p19q-gene signature has powerfully predictive value for both malignant molecular pathological features and prognosis across distinct subgroups of 1p/19q non-codel gliomas.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Deleção Cromossômica , Cromossomos Humanos Par 19/genética , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Movimento Celular , Proliferação de Células , Seguimentos , Glioma/genética , Glioma/cirurgia , Humanos , Pessoa de Meia-Idade , Prognóstico , RNA-Seq , Taxa de Sobrevida , Transcriptoma , Células Tumorais Cultivadas , Adulto Jovem
15.
J Cell Mol Med ; 23(11): 7741-7748, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31475440

RESUMO

Lipid metabolism reprogramming plays important role in cell growth, proliferation, angiogenesis and invasion in cancers. However, the diverse lipid metabolism programmes and prognostic value during glioma progression remain unclear. Here, the lipid metabolism-related genes were profiled using RNA sequencing data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. Gene ontology (GO) and gene set enrichment analysis (GSEA) found that glioblastoma (GBM) mainly exhibited enrichment of glycosphingolipid metabolic progress, whereas lower grade gliomas (LGGs) showed enrichment of phosphatidylinositol metabolic progress. According to the differential genes of lipid metabolism between LGG and GBM, we developed a nine-gene set using Cox proportional hazards model with elastic net penalty, and the CGGA cohort was used for validation data set. Survival analysis revealed that the obtained gene set could differentiate the outcome of low- and high-risk patients in both cohorts. Meanwhile, multivariate Cox regression analysis indicated that this signature was a significantly independent prognostic factor in diffuse gliomas. Gene ontology and GSEA showed that high-risk cases were associated with phenotypes of cell division and immune response. Collectively, our findings provided a new sight on lipid metabolism in diffuse gliomas.


Assuntos
Neoplasias Encefálicas/genética , Genes Neoplásicos , Glioma/genética , Metabolismo dos Lipídeos/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Divisão Celular , Estudos de Coortes , Feminino , Glioma/imunologia , Glioma/patologia , Humanos , Masculino , Análise Multivariada , Gradação de Tumores , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
16.
Cancer Sci ; 110(1): 321-333, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30431206

RESUMO

Metabolic reprogramming has been proposed to be a hallmark of cancer. Aside from the glycolytic pathway, the metabolic changes of cancer cells primarily involve amino acid metabolism. However, in glioma, the characteristics of the amino acid metabolism-related gene set have not been systematically profiled. In the present study, RNA sequencing expression data from 309 patients in the Chinese Glioma Genome Atlas database were included as a training set, while another 550 patients within The Cancer Genome Atlas database were used to validate. Consensus clustering of the 309 samples yielded two robust groups. Compared with Cluster1, Cluster2 correlated with a better clinical outcome. We then developed an amino acid metabolism-related risk signature for glioma. Our results showed that patients in the high-risk group had dramatically shorter overall survival than low-risk counterparts in any subgroup, stratified by isocitrate dehydrogenase and 1p/19q status based on the 2016 World Health Organization classification guidelines. The 30-gene signature showed better prognostic value than the traditional factors "age" and "grade" by analyzing the receiver operating characteristic curve with areas under curve of 0.966, 0.692, 0.898 and 0.975, 0.677, 0.885 for 3- and 5-year survival, respectively. Moreover, univariate and multivariate analysis showed that the 30-gene signature was an independent prognostic factor for glioma. Furthermore, Gene Ontology analysis and Gene Set Enrichment Analysis showed that tumors with a high risk score correlated with various aspects of the malignancy of glioma. In summary, we demonstrated a novel amino acid metabolism-related risk signature for predicting prognosis for glioma.


Assuntos
Aminoácidos/metabolismo , Neoplasias Encefálicas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/metabolismo , Criança , Análise por Conglomerados , Feminino , Glioma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
17.
Mod Pathol ; 32(1): 4-15, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30291347

RESUMO

The methylation status of the promoter of MGMT gene is a crucial factor influencing clinical decision-making in patients with gliomas. MGMT pyrosequencing results are often dichotomized by a cut-off value based on an average of several tested CpGs. However, this method frequently results in a "gray zone", representing a dilemma for physicians. We therefore propose a novel analytical model for MGMT methylation pyrosequencing. MGMT CpG heterogeneity was investigated in 213 glioma patients in two tested cohorts: cohort A in which CpGs 75-82 were tested and cohort B in which CpGs 72-78 were tested. The predictive performances of the novel and traditional averaging models were compared in 135 patients who received temozolomide using receiver operating characteristic curves and Kaplan-Meier curves, and in patients stratified according to isocitrate dehydrogenase gene mutation status. The results were validated in an independent cohort of 65 consecutive patients with high-grade gliomas from the Chinese Glioma Genome Atlas database. Heterogeneity of MGMT promoter CpG methylation level was observed in most gliomas. The optimal cut-off value for each individual CpG varied from 4-16%. The current analysis defined MGMT promoter methylation as occurring when at least three CpGs exceeded their respective cut-off values. This novel analysis could accurately predict the prognosis of patients in the methylation "gray zone" according to the standard averaging method, and improved the area under the curves from 0.67, 0.76, and 0.67 to 0.70, 0.84, and 0.72 in cohorts A, B, and the validation cohort, respectively, demonstrating superiority of this analytical method in all three cohorts. Furthermore, the advantages of the novel analysis were retained regardless of WHO grade and isocitrate dehydrogenase gene mutation status. In conclusion, this novel analytical model offers an improved clinical predictive performance for MGMT pyrosequencing results and is suitable for clinical use in patients with gliomas.


Assuntos
Neoplasias Encefálicas/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas Supressoras de Tumor/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Opt Lett ; 44(7): 1714-1717, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30933129

RESUMO

Herein, we report a simple laser holography technology for hierarchically structuring and synchronous photoreduction of graphene oxides (GO), toward the development of efficient graphene-based electrodes for supercapacitor applications in cost effectively manners. Hierarchical micro-nanostructures, formed due to laser treatment induced photoreduction and ablation effect. Interestingly, both the morphology and reduction degree of the laser holography reduced GO (LHRGO) show strong dependence on the laser intensity, providing the feasibility for controlling the micro-nanostructures, chemical composition, and the conductivity of the graphene electrodes. Furthermore, the supercapacitors based on LHRGO show higher capacitance values and better electrochemical performance compared to that based on thermal reduced GO (TRGO) of same reduction level. Photoredution and micro-nanostructuring of GO using laser holography may hold great promise for production of effective carbon-based electrodes towards practical applications in energy storage devices.

19.
Cancer Cell Int ; 19: 155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171919

RESUMO

BACKGROUND: Abnormal expression of the eukaryotic initiation factor 3 (eIF3) subunits plays critical roles in tumorigenesis and progression, and also has potential prognostic value in cancers. However, the expression and clinical implications of eIF3 subunits in glioma remain unknown. METHODS: Expression data of eIF3 for patients with gliomas were obtained from the Chinese Glioma Genome Atlas (CGGA) (n = 272) and The Cancer Genome Atlas (TCGA) (n = 595). Cox regression, the receiver operating characteristic (ROC) curves and Kaplan-Meier analysis were used to study the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were utilized for functional prediction. RESULTS: In both the CGGA and TCGA datasets, the expression levels of eIF3d, eIF3e, eIF3f, eIF3h and eIF3l highly were associated with the IDH mutant status of gliomas. The expression of eIF3b, eIF3i, eIF3k and eIF3m was increased with the tumor grade, and was associated with poorer overall survival [All Hazard ratio (HR) > 1 and P < 0.05]. By contrast, the expression of eIF3a and eIF3l was decreased in higher grade gliomas and was associated with better overall survival (Both HR < 1 and P < 0.05). Importantly, the expression of eIF3i (located on chromosome 1p) and eIF3k (Located on chromosome 19q) were the two highest risk factors in both the CGGA [eIF3i HR = 2.068 (1.425-3.000); eIF3k HR = 1.737 (1.166-2.588)] and TCGA [eIF3i HR = 1.841 (1.642-2.064); eIF3k HR = 1.521 (1.340-1.726)] databases. Among eIF3i, eIF3k alone or in combination, the expression of eIF3i was the more robust in stratifying the survival of glioma in various pathological subgroups. The expression of eIF3i was an independent prognostic factor in IDH-mutant lower grade glioma (LGG) and could also predict the 1p/19q codeletion status of IDH-mutant LGG. Finally, GO and GSEA analysis showed that the elevated expression of eIF3i was significantly correlated with the biological processes of cell proliferation, mRNA processing, translation, T cell receptor signaling, NF-κB signaling and others. CONCLUSIONS: Our study reveals the expression alterations during glioma progression, and highlights the prognostic value of eIF3i in IDH-mutant LGG.

20.
Langmuir ; 35(3): 815-823, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30563345

RESUMO

Inspired from fish scales that exhibit unique underwater superoleophobicity, artificial porous membranes featuring similar wettability have been successfully developed for oil-water separation. However, most of the superoleophobic meshes are workable only for underwater oil/water separation and become disabled in air. In this article, we reported the facile fabrication of underwater superoleophobic kraft mesh and demonstrated efficient oil-water separation using kraft mesh origamis. Kraft paper that features porosity, natural hydrophilicity, and relatively high elasticity and tear resistance has been found to be an ideal candidate for developing underwater superoleophobic origami. Direct laser drilling has been employed to make microhole arrays on the kraft paper, forming a flexible mesh. The hydrophilic nature and the hierarchical microstructures that consist of microhole arrays and porous microfiber networks make the resultant kraft mesh superoleophobic underwater, enabling oil-water separation. More importantly, the kraft mesh can retain a large amount of water (2.5 times its weight under dry conditions) owing to its porous and hydrophilic structure. Thus, the wet kraft mesh became a slippery surface for oil droplets when it was taken out of the water. This unique feature makes it possible to directly fish out oil droplets from water using a simple kraft mesh origami. Direct laser drilling of paper mesh for flexible origami may open up a new route to the rational design and fabrication of oil-water separation devices.

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