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1.
Biomed Pharmacother ; 169: 115897, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37981459

RESUMO

The Polycomb Repressor Complex (PRC) plays a pivotal role in gene regulation during development and disease, with dysregulation contributing significantly to various human cancers. The intricate interplay between PRC and cellular signaling pathways sheds light on cancer complexity. PRC presents promising therapeutic opportunities, with inhibitors undergoing rigorous evaluation in preclinical and clinical studies. In this review, we emphasize the critical role of PRC complex in gene regulation, particularly PcG proteins mediated chromatin compaction through phase separation. We also highlight the pathological implications of PRC complex dysregulation in various tumors, elucidating underlying mechanisms driving cancer progression. The burgeoning field of therapeutic strategies targeting PRC complexes, notably EZH2 inhibitors, has advanced significantly. However, we explore the need for combination therapies to enhance PRC targeted treatments efficacy, providing a glimpse into the future of cancer therapeutics.


Assuntos
Neoplasias , Complexo Repressor Polycomb 2 , Humanos , Complexo Repressor Polycomb 2/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias/metabolismo , Proteínas do Grupo Polycomb/genética , Cromatina , Complexo Repressor Polycomb 1/genética
2.
Nat Commun ; 11(1): 379, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953408

RESUMO

Insig-2 is an ER membrane protein negatively controlling lipid biosynthesis. Here, we find that Insig-2 is increased in the tissues, including liver, but unaltered in the muscle of gp78-deficient mice. In hepatocytes and undifferentiated C2C12 myoblasts, Insig-2 is ubiquitylated on Cys215 by gp78 and degraded. However, the C215 residue is oxidized by elevated reactive oxygen species (ROS) during C2C12 myoblasts differentiating into myotubes, preventing Insig-2 from ubiquitylation and degradation. The stabilized Insig-2 downregulates lipogenesis through inhibiting the SREBP pathway, helping to channel the carbon flux to ATP generation and protecting myotubes from lipid over-accumulation. Evolutionary analysis shows that the YECK (in which C represents Cys215 in human Insig-2) tetrapeptide sequence in Insig-2 is highly conserved in amniotes but not in aquatic amphibians and fishes, suggesting it may have been shaped by differential selection. Together, this study suggests that competitive oxidation-ubiquitylation on Cys215 of Insig-2 senses ROS and prevents muscle cells from lipid accumulation.


Assuntos
Cisteína/metabolismo , Proteínas de Membrana/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Ubiquitinação , Anfíbios , Animais , Células CHO , Linhagem Celular , Cricetulus , Regulação para Baixo , Evolução Molecular , Peixes , Hepatócitos/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipogênese , Fígado/metabolismo , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Receptores do Fator Autócrino de Motilidade/genética , Análise de Sequência de Proteína , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Transcriptoma
3.
Bioresour Technol ; 264: 261-267, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29852415

RESUMO

In this work, p-hydroxybenzenesulfonic acid-formaldehyde resin acid catalyst (MSPFR), was synthesized by a hydrothermal method, and employed for the furfural production from raw corn stover. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption-desorption, elemental analysis (EA), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FT-IR) were used to characterize the MSPFR. The effects of reaction time, temperature, solvents and corn stover loading were investigated. The MSPFR presented high catalytic activity for the formation of furfural from corn stover. When the MSPFR/corn stover mass loading ratio was 0.5, a higher furfural yield of 43.4% could be achieved at 190 °C in 100 min with 30.7% 5-hydroxymethylfurfural (HMF) yield. Additionally, quite importantly, the recyclability of the MSPFR for xylose dehydration is good, and for the conversion of corn stover was reasonable.


Assuntos
Furaldeído/química , Zea mays , Ácidos , Formaldeído , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Carbohydr Polym ; 181: 885-892, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29254050

RESUMO

A montmorillonite@chitosan-poly (ethylene oxide) nanofibrous membrane (MMT@CPF) enhancing poly (vinyl alcohol-co-ethylene) (EVOH-MMT@CPF) composite film was developed by using a space-filling embedding method. The structure of EVOH-MMT@CPF was characterized, and the thermal stability, mechanical and barrier properties of the films were investigated. The CPF was fabricated via electrospinning technique and the self-assembly of MMT nano-platelets on CPF was achieved by the driving of electrostatic interactions between MMT nano-platelet and CPF. The experimental results indicated that the well-kept MMT@CPF after embedding in the EVOH matrix significantly improved the thermal stability and mechanical properties of the film, and also endowed the film with outstanding oxygen barrier (0.2×10-16cm3cmcm-2s-1Pa-1) and good moisture barrier (4.6×10-6gmm-2s-1atm-1 under a relative humidity of 90%) by prolonging the tortuous paths for molecule penetration. The composite film may have a great potential application in food packaging.

6.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(2): 210-215, 2016 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-28219865

RESUMO

OBJECTIVE: To develop a novel colorimetric method for detecting the tumor biomarker vascular endothelial growth factor (VEGF) based on aptamer and magnetic beads. METHODS: The capture aptamer was hybridized to urease functionalized single-stranded DNA (ssDNA) and immobilize on the surface of magnetic beads by specific biotin-avidin binding. In the presence of VEGF, aptamers bound to VEGF to form a specific stem-loop structure to release the urease functionalized ssDNA. After separation, the supernatant was transferred to a tube and urea and phenol red were added. Urease hydrolyzed urea to produce ammonia to cause an increase of the pH value and a color change of phenol red. The results were inspected with either the naked eyes or by a UV spectrophotometer. RESULTS: Under optimized conditions, the detection system showed a good linear relationship for VEGF detection in the range of 0.1 to 10 pmol/L with a detection limit as low as 0.06 pmol/L. The results of VEGF detection in the serum of patients with lung cancer were consistent with those using an ELISA Kit. The results of examination of 10 serum samples with this aptamer-based method and ELISA kit showed that the accuracy of this method was 90%. CONCLUSION: This aptamer-based system provides an simple and convenient method for VEGF detection with a high sensitivity and selectivity.


Assuntos
Aptâmeros de Nucleotídeos , Colorimetria , DNA de Cadeia Simples , Fator A de Crescimento do Endotélio Vascular/análise , Biomarcadores Tumorais , Humanos , Neoplasias Pulmonares , Hibridização de Ácido Nucleico
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