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1.
Epigenetics ; 19(1): 2298058, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145548

RESUMO

N6 methyladenosine (m6A), methylation at the sixth N atom of adenosine, is the most common and abundant modification in mammalian mRNAs and non-coding RNAs. Increasing evidence shows that the alteration of m6A modification level could regulate tumour proliferation, metastasis, self-renewal, and immune infiltration by regulating the related expression of tumour genes. However, the role of m6A modification in colorectal cancer (CRC) drug resistance is unclear. Here, MeRIP-seq and RNA-seq techniques were utilized to obtain mRNA, lncRNA expression, and their methylation profiles in 5-Fluorouracil (5-FU)-resistant colon cancer HCT-15 cells and control cells. In addition, we performed detailed bioinformatics analysis as well as in vitro experiments of lncRNA to explore the function of lncRNA with differential m6A in CRC progression and drug resistance. In this study, we obtained the m6A methylomic landscape of CRC cells and resistance group cells by MeRIP-seq and RNA-seq. We identified 3698 differential m6A peaks, of which 2224 were hypermethylated, and 1474 were hypomethylated. Among the lncRNAs, 60 were hypermethylated, and 38 were hypomethylated. GO and KEGG analysis annotations showed significant enrichment of endocytosis and MAPK signalling pathways. Moreover, knockdown of lncRNA ADIRF-AS1 and AL139035.1 promoted CRC proliferation and invasive metastasis in vitro. lncRNA- mRNA network showed that ADIRF-AS1 and AL139035.1 May play a key role in regulating drug resistance formation. We provide the first m6A methylation profile in 5-FU resistance CRC cells and analyse the functions of differential m6A-modified mRNAs and lncRNAs. Our results indicated that differential m6A RNAs were significantly associated with MAPK signalling and endocytosis after induction of 5-FU resistance. Knockdown of LncRNA ADIRF-AS1 and AL139035.1 promotes CRC progression and might be critical in regulating drug resistance formation.


We outline the first m6A methylation profile of mRNA and lncRNA in CRC cells involved in 5-FU resistance.This study sought to identify the critical genes that produced 5-FU resistance by analysing the functions of differentially m6A-modified mRNAs and lncRNAs.


Assuntos
Neoplasias do Colo , RNA Longo não Codificante , Animais , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Metilação de DNA , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Fluoruracila/farmacologia , Adenosina/farmacologia , Mamíferos
2.
Physiol Meas ; 42(9)2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34433135

RESUMO

Objective. Impedance cardiography (ICG) is a noninvasive and continuous method for evaluating stroke volume and cardiac output. However, the ICG measurement is easily interfered due to respiration and body movements. Taking into consideration about the spectral correlations between the simultaneously collected ICG, electrocardiogram (ECG), and acceleration signals, this paper introduces a two-step spectrum denoising method to remove motion artifacts of ICG measurements in both resting and exercising scenarios.Approach. First, the major motion artifacts of ECG and ICG are separately suppressed by the spectral subtraction with respect to acceleration signals. The obtained ECG and ICG are further decomposed into two sets of intrinsic mode functions (IMFs) through the ensemble empirical mode decomposition. We then extract the shared spectral information between the two sets of IMFs using the canonical correlation analysis in a spectral domain. Finally, the ICG signal is reconstructed using those canonical variates with largest spectral correlations with ECG IMFs.Main results. The denoising method was evaluated for 30 subjects under both resting and cycling scenarios. Experimental results show that the beat contribution factor of ICG signals increases from its original 80.1%-97.4% after removing the motion artifacts.Significance. The proposed denoising scheme effectively improves the reliability of diagnosis and analysis on cardiovascular diseases relying on ICG signals.


Assuntos
Cardiografia de Impedância , Processamento de Sinais Assistido por Computador , Algoritmos , Eletrocardiografia , Humanos , Reprodutibilidade dos Testes
3.
Exp Ther Med ; 21(6): 595, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33884033

RESUMO

The current study aimed to compare the outcomes of decompression and interlaminar stabilisation with those of decompression and fusion for the treatment of lumbar degenerative disease (LDD) at a minimum 8-year follow-up. The current study also aimed to analyse the risk factors of radiographic adjacent segment degeneration (ASD). A total of 82 consecutive patients with LDD who underwent surgery between June 2007 and February 2011 were retrospectively reviewed. Of these patients, 39 underwent decompression and Coflex interspinous stabilisation (Coflex group) and 43 underwent decompression and posterior lumbar interbody fusion (PLIF) (PLIF group). All patients had a minimum of 8-years of follow-up data. Radiographic and clinical outcomes were compared between the groups, and the risk factors of developing radiographic ASD were also evaluated. The Oswestry disability index and visual analogue scale leg and back pain scores of both groups significantly improved compared with the baseline (all P<0.05), and no difference were indicated between the two groups at each follow-up time point (P>0.05). The Coflex group exhibited preserved mobility (P<0.001), which was associated with a decreased amount of blood loss (P<0.001), shorter duration of surgery (P=0.001), shorter duration of hospital stay and a lower incidence of ASD (12.8 vs. 32.56%; P=0.040) compared with the fusion group. The current study indicated that coflex and fusion technologies are safe and effective for the treatment of LDD, based on long-term follow-up data. However, Coflex interspinous stabilisation was revealed to reduce ASD incidence. Under strict indications, Coflex interspinous stabilisation is an effective and safe treatment method.

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