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1.
Cancer Cell Int ; 24(1): 130, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584256

RESUMO

BACKGROUND: Fatty acids synthesis and metabolism (FASM)-driven lipid mobilization is essential for energy production during nutrient shortages. However, the molecular characteristics, physiological function and clinical prognosis value of FASM-associated gene signatures in hepatocellular carcinoma (HCC) remain elusive. METHODS: The Gene Expression Omnibus database (GEO), the Cancer Genome Atlas (TCGA), and International Cancer Genome Consortium (ICGC) database were utilized to acquire transcriptome data and clinical information of HCC patients. The ConsensusClusterPlus was employed for unsupervised clustering. Subsequently, immune cell infiltration, stemness index and therapeutic response among distinct clusters were decoded. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to anticipate the response of patients towards immunotherapy, and the genomics of drug sensitivity in cancer (GDSC) tool was employed to predict their response to antineoplastic medications. Least absolute shrinkage and selection operator (LASSO) regression analysis and protein-protein interaction (PPI) network were employed to construct prognostic model and identity hub gene. Single cell RNA sequencing (scRNA-seq) and CellChat were used to analyze cellular interactions. The hub gene of FASM effect on promoting tumor progression was confirmed through a series of functional experiments. RESULTS: Twenty-six FASM-related genes showed differential expression in HCC. Based on these FASM-related differential genes, two molecular subtypes were established, including Cluster1 and Cluster2 subtype. Compared with cluster2, Cluster1 subtype exhibited a worse prognosis, higher risk, higher immunosuppressive cells infiltrations, higher immune escape, higher cancer stemness and enhanced treatment-resistant. PPI network identified Acetyl-CoA carboxylase1 (ACACA) as central gene of FASM and predicted a poor prognosis. A strong interaction between cancer stem cells (CSCs) with high expression of ACACA and macrophages through CD74 molecule (CD74) and integrin subunit beta 1 (ITGB1) signaling was identified. Finally, increased ACACA expression was observed in HCC cells and patients, whereas depleted ACACA inhibited the stemness straits and drug resistance of HCC cells. CONCLUSIONS: This study provides a resource for understanding FASM heterogeneity in HCC. Evaluating the FASM patterns can help predict the prognosis and provide new insights into treatment response in HCC patients.

2.
Adv Nutr ; 14(5): 1050-1066, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37187454

RESUMO

Serine has been recently identified as an essential metabolite for oncogenesis, progression, and adaptive immunity. Influenced by many physiologic or tumor environmental factors, the metabolic pathways of serine synthesis, uptake, and usage are heterogeneously reprogrammed and frequently amplified in tumor or tumor-associated cells. The hyperactivation of serine metabolism promotes abnormal cellular nucleotide/protein/lipid synthesis, mitochondrial function, and epigenetic modifications, which drive malignant transformation, unlimited proliferation, metastasis, immunosuppression, and drug resistance of tumor cells. Dietary restriction of serine or phosphoglycerate dehydrogenase depletion mitigates tumor growth and extends the survival of tumor patients. Correspondingly, these findings triggered a boom in the development of novel therapeutic agents targeting serine metabolism. In this study, recent discoveries in the underlying mechanism and cellular function of serine metabolic reprogramming are summarized. The vital role of serine metabolism in oncogenesis, tumor stemness, tumor immunity, and therapeutic resistance is outlined. Finally, some potential tumor therapeutic concepts, strategies, and limitations of targeting the serine metabolic pathway are described in detail. Taken together, this review underscores the importance of serine metabolic reprogramming in tumorigenesis and progression and highlights new opportunities for dietary restriction or selective pharmacologic intervention.


Assuntos
Neoplasias , Serina , Humanos , Serina/metabolismo , Carcinogênese , Neoplasias/terapia , Proteínas
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-306570

RESUMO

Three-dimensional poly (epsilon-caprolactone)/silk sericin (PCL/SS) porous nanofibrous scaffolds were prepared by electrospinning. The structure and properties of the scaffolds were characterized by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectroscopy (FTIR) and water contact angle instrument. Studies on cell adhension and proliferation were carried out by culturing human primary skin fibroblast cells (FEK4) on these scaffolds using SEM and MTS. The experimental results showed that the PCL/SS nanofibrous scaffolds with SS nanoparticles had porous non-woven mesh structure with nanofibrous cross-linked with each other. Fiber diameter was very uniform and precise, and the secondary structure of SS protein had not been changed. Furthermore, the capability of hydrophile increased with the SS addition, which improved FEK4 cells adhesion and proliferation on the scaffolds.


Assuntos
Materiais Biocompatíveis , Química , Adesão Celular , Células Cultivadas , Fibroblastos , Biologia Celular , Microscopia Eletrônica , Nanofibras , Química , Poliésteres , Química , Sericinas , Química , Seda , Química , Espectroscopia de Infravermelho com Transformada de Fourier , Alicerces Teciduais , Química
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-341680

RESUMO

Although the mechanism by which migratory trophoblasts reach the spiral arteries is currently obscure, yet the process has been noted to involve the attachment, adhesion and migration of trophoblasts on the blood vessel walls. To test this, micropipette and flow chamber were used to measure quantitatively the adhesion forces and migration of early gestation human trophoblast cells (TCs) cultured on the glass slides coated with type I rat collagen or cultured with human umbilical vein endothelial cells (HUVECs). The results showed that the interdiction of integrin beta1 interaction remarkably reduced the adhesion forces of TCs to type I rat collagen or endothelial cells, and remarkably resisted the displacement of TCs induced by shear stress. By contact between TCs and endothelial cells, the TCs' adhesion force and TCs' resistance to shear stress were significantly enhanced. The results indicated that the contacts of TCs with endothelial cells enhanced the adhesion forces of human TCs, and regulated the migration of human TCs by shear stress.


Assuntos
Adulto , Feminino , Humanos , Adesão Celular , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais da Veia Umbilical Humana , Biologia Celular , Integrina beta1 , Fisiologia , Trofoblastos , Biologia Celular
5.
Colloids Surf B Biointerfaces ; 42(3-4): 259-62, 2005 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-15893227

RESUMO

Isolation of high-quality RNA from Dendrobium candidum is particularly difficult. D. candidum contains considerable amounts of polysaccharides that coprecipitate with RNA, which render RNA unsuitable for either cDNA synthesis and/or PCR amplification. In this paper, a rapid and efficient method was described for functional RNA isolation from the callus of D. candidum. The procedure included: (i) an extraction with phenol and isopropyl alcohol, to remove proteins and polyphenols; (ii) purifications by lithium chloride, pre-cooled (-20 degrees C) ethanol successively to remove polysaccharides. The method resulted in high-quality RNA suitable for DDRT-PCR and cDNA library analysis finally.


Assuntos
Dendrobium/química , Polissacarídeos/química , RNA de Plantas/isolamento & purificação , DNA Complementar/biossíntese , DNA Complementar/genética , Dendrobium/genética , Eletroforese em Gel de Ágar , Flavonoides/química , Cloreto de Lítio/química , Fenóis/química , Proteínas de Plantas/química , Polifenóis , RNA de Plantas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Soluções , Solventes , Espectrofotometria Ultravioleta
6.
Colloids Surf B Biointerfaces ; 37(3-4): 101-5, 2004 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15342019

RESUMO

Seeds of Echinacea angustifolia are known for their deep dormancy. In this paper, we studied the responses of E. angustifolia seeds to some chemical and physical factors, such as scarification, chilling (5 degrees C) period, light and applied BA (6-benzylaminopurine), GA3 (gibberellic acid) and sound stimulation. When the seed coat layers were removed, the germination rate grew up from 6 to 20% (incubated in light) and the mean time germination (MTG) was reduced from 18 to 6.6 days. On the basis of layers-removed, chilling and continuous light gave significantly higher germination rate (up to 70%). Compare the data of seeds chilled by 0, 6, 12, 18 and 24 days, the maximum germination rate (up to 70%) achieved at 18-days chilling treatment. Further increases in the chilling period could slightly improve germination. Exogenous application of 0.1, 0.2, 0.3 mg/L GA3 or BA in the previous pretreatment increased germination to 78, 90 and 84% or 76, 86 and 84%, respectively. Obviously, the best concentration of GA or BA is 0.3 mg/L. And the GA3 or BA treatment shortened the MTG to about 4 days. The influence of sound stimulation was also tested in the experiment. The result showed that one 100 dB and 1000 Hz sound wave (sine-wave) was beneficial to the germination of E. angustifolia seeds.


Assuntos
Echinacea/crescimento & desenvolvimento , Germinação/fisiologia , Sementes/fisiologia , Dessecação , Cinética , Fatores de Tempo
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