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1.
Pharmacol Res ; 206: 107280, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914382

RESUMO

Digestive tract cancers are among the most common malignancies worldwide and have high incidence and mortality rates. Thus, the discovery of more effective diagnostic and therapeutic targets is urgently required. The development of technologies to accurately detect RNA modification has led to the identification of numerous RNA chemical modifications in humans (epitranscriptomics) that are involved in the occurrence and development of digestive tract cancers. RNA modifications can cooperatively regulate gene expression to facilitate normal physiological functions of the digestive system. However, the dysfunction of relevant RNA-modifying enzymes ("writers," "erasers," and "readers") can lead to the development of digestive tract cancers. Consequently, targeting dysregulated enzyme activity could represent a potent therapeutic strategy for the treatment of digestive tract cancers. In this review, we summarize the most widely studied roles and mechanisms of RNA modifications (m6A, m1A, m5C, m7G, A-to-I editing, pseudouridine [Ψ]) in relation to digestive tract cancers, highlight the crosstalk between RNA modifications, and discuss their roles in the interactions between the digestive system and microbiota during carcinogenesis. The clinical significance of novel therapeutic methods based on RNA-modifying enzymes is also discussed. This review will help guide future research into digestive tract cancers that are resistant to current therapeutics.

2.
Front Pharmacol ; 15: 1351929, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895621

RESUMO

Background: Serous ovarian carcinoma (SOC) is considered the most lethal gynecological malignancy. The current lack of reliable prognostic biomarkers for SOC reduces the efficacy of predictive, preventive, and personalized medicine (PPPM/3PM) in patients with SOC, leading to unsatisfactory therapeutic outcomes. N6-methyladenosine (m6A) modification-associated long noncoding RNAs (lncRNAs) are effective predictors of SOC. In this study, an effective risk prediction model for SOC was constructed based on m6A modification-associated lncRNAs. Methods: Transcriptomic data and clinical information of patients with SOC were downloaded from The Cancer Genome Atlas. Candidate lncRNAs were identified using univariate and multivariate and least absolute shrinkage and selection operator-penalized Cox regression analyses. The molecular mechanisms of m6A effector-related lncRNAs were explored via Gene Ontology, pathway analysis, gene set enrichment analysis, and gene set variation analysis (GSVA). The extent of immune cell infiltration was assessed using various algorithms, including CIBERSORT, Microenvironment Cell Populations counter, xCell, European Prospective Investigation into Cancer and Nutrition, and GSVA. The calcPhenotype algorithm was used to predict responses to the drugs commonly used in ovarian carcinoma therapy. In vitro experiments, such as migration and invasion Transwell assays, wound healing assays, and dot blot assays, were conducted to elucidate the functional roles of candidate lncRNAs. Results: Six m6A effector-related lncRNAs that were markedly associated with prognosis were used to establish an m6A effector-related lncRNA risk model (m6A-LRM) for SOC. Immune microenvironment analysis suggested that the high-risk group exhibited a proinflammatory state and displayed increased sensitivity to immunotherapy. A nomogram was constructed with the m6A effector-related lncRNAs to assess the prognostic value of the model. Sixteen drugs potentially targeting m6A effector-related lncRNAs were identified. Furthermore, we developed an online web application for clinicians and researchers (https://leley.shinyapps.io/OC_m6A_lnc/). Overexpression of the lncRNA RP11-508M8.1 promoted SOC cell migration and invasion. METTL3 is an upstream regulator of RP11-508M8.1. The preliminary regulatory axis METTL3/m6A/RP11-508M8.1/hsa-miR-1270/ARSD underlying SOC was identified via a combination of in vitro and bioinformatic analyses. Conclusion: In this study, we propose an innovative prognostic risk model and provide novel insights into the mechanism underlying the role of m6A-related lncRNAs in SOC. Incorporating the m6A-LRM into PPPM may help identify high-risk patients and personalize treatment as early as possible.

3.
Epigenomics ; 16(5): 309-329, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38356435

RESUMO

Background: To explore the role of fatty acid metabolism (FAM)-related lncRNAs in the prognosis and antitumor immunity of serous ovarian cancer (SOC). Materials & methods: A SOC FAM-related lncRNA risk model was developed and evaluated by a series of analyses. Additional immune-related analyses were performed to further assess the associations between immune state, tumor microenvironment and the prognostic risk model. Results: Five lncRNAs associated with the FAM genes were found and used to create a predictive risk model. The patients with a low-risk profile exhibited favorable prognostic outcomes. Conclusion: The established prognostic risk model exhibits better predictive capabilities for the prognosis of patients with SOC and offers novel potential therapy targets for SOC.


Assuntos
Neoplasias Ovarianas , RNA Longo não Codificante , Feminino , Humanos , Prognóstico , RNA Longo não Codificante/genética , Carcinoma Epitelial do Ovário , Microambiente Tumoral/genética , Neoplasias Ovarianas/genética , Ácidos Graxos
4.
J Minim Invasive Gynecol ; 31(3): 193-199, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38016630

RESUMO

OBJECTIVE: The investigation of the role of preoperative conization in cervical cancer aiming to explore its potential clinical significance. DATA SOURCES: Cochrane Library, Embase, PubMed, and Web of Science, up to April 28, 2023. METHODS OF STUDY SELECTION: (1) Observational cohort studies, (2) studies comparing radical hysterectomy with preoperative conization (CO) vs radical hysterectomy without preoperative conization (NCO) in patients with early-stage cervical cancer, and (3) studies comparing disease-free survival outcomes. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted the data and assessed the quality of the studies. The meta-analysis used combined hazard ratios along with their corresponding 95% confidence intervals to compare CO and NCO. We conducted a Bayesian network meta-analysis using Markov chain Monte Carlo methods to compare minimally invasive CO, open CO, minimally invasive NCO, and open NCO. Our study included 15 retrospective trials, 10 of which were used to traditional pairwise meta-analysis and 8 for network meta-analysis. The NCO group exhibited a notably higher probability of cancer recurrence than the CO group (hazard ratio, 0.52; 95% confidence interval, 0.41-0.65). In the network meta-analysis, minimally invasive NCO showed the worst survival outcome. CONCLUSION: Preoperative conization seems to be a protective factor in decreasing recurrence risk, assisting clinicians in predicting survival outcomes for patients with early-stage cervical cancer. It may potentially aid in selecting suitable candidates for minimally invasive surgery in clinical practice.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Conização , Estudos Retrospectivos , Teorema de Bayes , Metanálise em Rede , Recidiva Local de Neoplasia/cirurgia , Intervalo Livre de Doença , Histerectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias
5.
iScience ; 26(4): 106521, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37123245

RESUMO

Small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs), play vital roles in intercellular communication. We optimized a method that extracts EVs from epithelial ovarian cancer (EOC) tissues for the purpose of investigating whether cryopreservation of EOC tissues affects the phenotypes, contents, and biological functions of extracted EVs. EV morphology, the number and size distribution of EVs, and EV-related markers were analyzed. Storage of lysates at -80°C decreased lEV yield and increased sEV yield, whereas storage of tissues at -80°C increased both sEV and lEV yields; neither changed the morphology or particle mass ratio of EVs. The two cryopreservation groups retained over 90% of proteins and 80% of miRNAs detected in the "fresh" group. EVs extracted following lysate/tissue storage at -80°C could also promote angiogenesis and invasive migration ability in human endothelial cells. Cryopreserved EOC tissue may benefit clinical applications for studies of tissue-derived EVs, especially EV proteins-related ones.

6.
Neural Netw ; 162: 11-20, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36878167

RESUMO

Detecting object skeletons in natural images presents challenges due to varied object scales and complex backgrounds. The skeleton is a highly compressing shape representation, which can bring some essential advantages but cause difficulties in detection. This skeleton line occupies a small part of the image and is overly sensitive to spatial position. Inspired by these issues, we propose the ProMask, which is a novel skeleton detection model. The ProMask includes the probability mask representation and vector router. This skeleton probability mask describes the gradual formation process of skeleton points, which can achieve high detection performance and robustness. Moreover, the vector router module possesses two sets of orthogonal basis vectors in a two-dimensional space, which can dynamically adjust the predicted skeleton position. Experiments show that our approach realizes better performance, efficiency, and robustness than state-of-the-art methods. We consider that our proposed skeleton probability representation will serve as a standard configuration for future skeleton detection, since it is reasonable, simple, and very effective.


Assuntos
Esqueleto
7.
Wiley Interdiscip Rev RNA ; 14(5): e1784, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36811232

RESUMO

Ovarian cancer (OC) is the most common female cancer worldwide. Patients with OC have high mortality because of its complex and poorly understood pathogenesis. RNA epigenetic modifications, such as m6 A, m1 A, and m5 C, are closely associated with the occurrence and development of OC. RNA modifications can affect the stability of mRNA transcripts, nuclear export of RNAs, translation efficiency, and decoding accuracy. However, there are few overviews that summarize the link between m6 A RNA modification and OC. Here, we discuss the molecular and cellular functions of different RNA modifications and how their regulation contributes to the pathogenesis of OC. By improving our understanding of the role of RNA modifications in the etiology of OC, we provide new perspectives for their use in OC diagnosis and treatment. This article is categorized under: RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease.


Assuntos
Neoplasias Ovarianas , RNA , Humanos , Feminino , Neoplasias Ovarianas/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro , Epigênese Genética
8.
Front Psychol ; 13: 938840, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118465

RESUMO

With the rapid expansion of Internet technology, this research aims to explore the teaching strategies of ceramic art for contemporary students. Based on deep learning (DL), an automatic question answering (QA) system is established, new teaching strategies are analyzed, and the Internet is combined with the automatic QA system to help students solve problems encountered in the process of learning. Firstly, the related theories of DL and personalized learning are analyzed. Among DL-related theories, Back Propagation Neural Network (BPNN), Convolutional Neural Network (CNN), Long Short-Term Memory (LSTM), and Gated Recurrent Unit (GRU) are compared to implement a single model and a mixed model. Secondly, the collected student questions are selected and processed, and experimental parameters in different models are set for comparative experiments. Experiments reveal that the average accuracy and Mean Reciprocal Rank (MRR) of traditional retrieval methods can only reach about 0.5. In the basic neural network, the average accuracy of LSTM and GRU structural models is about 0.81, which can achieve better results. Finally, the accuracy of the hybrid model can reach about 0.82, and the accuracy and MRR of the Bidirectional Gated Recurrent Unit Network-Attention (BiGRU-Attention) model are 0.87 and 0.89, respectively, achieving the best results. The established DL model meets the requirements of the online automatic QA system, improves the teaching system, and helps students better understand and solve problems in the ceramic art courses.

9.
Front Cell Dev Biol ; 10: 954214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120577

RESUMO

Background: N6-methyladenosine (m6A) modification is a dynamic and reversible post-transcriptional RNA modification prevalent in eukaryotic cells. YT521-B homology domain family 2 (YTHDF2) has been identified as a member of m6A reader protein involving in many vital biological processes, whereas its role and functional mechanisms in cancers remain unclear. Methods: Bioinformatics analyses were performed on multiple databases including GTEx, TCGA, GEO and Cbioportal to explore the connection between YTHDF2 expression and its genomic changes including tumor mutation burden, microsatellite instability and mismatch repair in 33 different cancer types. We also investigated the association of YTHDF2 expression with prognosis, immune infiltration, tumor microenvironment, immune checkpoints and chemokines. Besides, the correlation of YTHDF2 expression with copy number variation and promoter methylation was also studied in tumors compared with normal tissues. At last, we analyzed the protein-protein interacting network and related genes of YTHDF2 to enrich its potential functional mechanism in tumor development and progression. Real-time qPCR was used to verify the expression of YTHDF2-related genes in colorectal cancer cells, and immunohistochemical staining was adopted to verify immune infiltration in tissue sections from 51 hepatocellular carcinoma patients. Results: YTHDF2 was overexpressed in a majority of tumor types and associated with their poor overall survival, progression-free interval, and disease-specific survival. The correlation of YTHDF2 expression with tumor mutation burden, microsatellite instability and mismatch repair was also detected in most of the tumor types. Moreover, YTHDF2 might participate in the immune regulation through influencing the expression of immune checkpoint genes and the infiltration of immunocytes in tumor microenvironment. Notably, we demonstrated a positive correlation between YTHDF2 expression and the infiltration of CD8+ T cells and macrophages in many tumors, and it was verified in 51 clinic hepatocellular carcinoma tissues. In addition, the involvement of YTHDF2 in "Spliceosome" and "RNA degradation" were two potential functional mechanisms underlying its influence on tumor progression. The regulation of YTHDF2 on predicted genes has been verified in CRC cells. Conclusion: YTHDF2 might be a new therapeutic target and a potential biomarker of cancer immune evasion and poor prognosis.

10.
Front Psychol ; 13: 900176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814096

RESUMO

There are many films and televisions (FATs) on the Internet, but the quality is uneven. This study explores the ability of college students to screen good films and resist bad films in television works in such a large environment. In the deep learning model of FAT, the ability of college students to think about the ideas expressed and the degree of influence on college students' values are analyzed. Based on this conceptual basis, a questionnaire is designed for the intention and influencing factors of college students' FAT innovation and entrepreneurship. It reflects the influence of concentration on FAT learning, the cognitive level of deep learning, the ability to process deep learning ideas, the feeling of the teaching process, and the process of self-learning, which all positively impact college students' FAT entrepreneurial intentions. The importance of innovative deep learning is highlighted, which proves that a good deep learning course guidance method can improve students' interest and ability and provide a reference for relevant colleges and universities to cultivate pertinent talents of the field of FAT.

11.
Front Psychol ; 13: 870448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814095

RESUMO

The purpose of this study was to understand the influence mechanism of college students' entrepreneurial intention in view of the increasing number of college students at present to alleviate college students' employment competition. The psychological factors that influence the entrepreneurial tendency of art graduates were analyzed and studied. First, venture capital and factors affecting entrepreneurial performance were analyzed. Second, the coefficient calculation is carried out for college students majoring in art through the regression analysis of the logistic model. Finally, a team entrepreneurial performance questionnaire was designed, and team reward levels were discussed. The results show that the logistic model can well reflect the real situation of the respondents. The significance level of the entrepreneurial team was 0.02, which was correlated. Additionally, corresponding suggestions were put forward according to the questionnaire results. Clear team goals, assignment of tasks to members, good pressure resistance, and psychological quality of members are necessary qualities for successful entrepreneurship. This conclusion provides a certain theoretical basis for the current college students' entrepreneurial learning and a reliable inspiration for helping college students to successfully start a business.

12.
Front Psychol ; 13: 880649, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35859840

RESUMO

This exploration aims to promote the organic integration of innovation and entrepreneurship education and art education, further promote the reform of college Students' cultural and aesthetic education, improve college Students' aesthetic perception ability, and help contemporary colleges establish a correct political morality. This thesis aims to further promote the reform of college Students' cultural and aesthetic education, improve college Students' aesthetic perception ability, and help contemporary colleges establish correct political and moral values. First, the connotation of college Students' aesthetic education and the definition of cultural aesthetics are introduced, which is based on the characteristics of two-way interaction, multiple selectivity, timeliness and popularization of film and television media in the new media era; then, the way of questionnaire is adopted. With five universities as the research object, 250 questionnaires are distributed, and 235 valid questionnaires are collected, with a valid response rate of 94%. Finally, through the six questions, it is concluded that 68.9% of the students watch 3-5 h a day, and 4.3% of the students watch more than 7 h; 89.4% of the students hold that the same products as stars in film and television will exert an impact on consumption. Film and television culture and art have a positive and negative impact on college Students' cultural aesthetic perception. The positive impact is that the film and television media not only provides a good way to cultivate the aesthetic perception ability of contemporary college students, but also helps them to establish the correct aesthetic values. The negative impact is mainly reflected in two levels, namely, the vulgarization of film and television media works and the consumption of aesthetic concepts. The advantage of this exploration is to put forward the reform measures of college Students' cultural and artistic aesthetic education under the current educational background in China to help colleges better carry out college Students' cultural and artistic aesthetic education. Based on this, the reform measures of college Students' cultural aesthetic education under the current education in China were put forward, so as to help colleges and universities better carry out college Students' cultural aesthetic education.

13.
Front Psychol ; 13: 843484, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832923

RESUMO

The purpose of this study is to analyze the relationship between psychology and modern art design education in colleges, and to provide the basis for improving the quality of art education in colleges. Based on the relevant theory, the characteristics of educational psychology and art psychology and the correlation between them were analyzed from the angle of art education. According to the characteristics of college students' psychological development, the significance of art psychology-related courses was analyzed. Through the form of questionnaire, a total of 200 students (400 students in total) were randomly selected from Xi'an Academy of Fine Arts (professional art college) and Xi'an University of Science and Technology (comprehensive university), respectively. A total of 400 questionnaires were issued, and 382 valid questionnaires were recovered. The results show that almost all students in two colleges think pedagogy and educational psychology are the theoretical basis for art teachers, while less than one-third of students in Xi'an University of Science and Technology think that art psychology is the theoretical basis for art teachers. The difference between the students' aesthetic and life values in the two colleges is significant (p < 0.01). In the 15 directions of life values, there are significant differences in five directions: spirit-material (p < 0.05), enrichment-emptiness (p < 0.05), enthusiasm-apathy (p < 0.05), hope-despair (p < 0.01), and dedication-acceptance (p < 0.01). It shows that the psychological and values of college students are changeable, and the educators should pay attention to the education in the related fields of psychology. This exploration was conducted based on educational psychology, which is of great significance for improving the educational level of art psychology in colleges and enable students to form correct aesthetic standards and life values.

14.
Front Immunol ; 13: 863484, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35585970

RESUMO

Serous ovarian carcinoma (SOC) is a gynecological malignancy with high mortality rates. Currently, there is a lack of reliable biomarkers for accurate SOC patient prognosis. Here, we analyzed SOC RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify prognostic biomarkers. Through the pearson correlation analysis, univariate Cox regression analysis, and LASSO-penalized Cox regression analysis, we identified nine lncRNAs significantly associated with four types of RNA modification writers (m6A, m1A, APA, and A-I) and with the prognosis of SOC patients (P <0.05). Six writer-related lncRNAs were ultimately selected following multivariate Cox analysis. We established a risk prediction model based on these six lncRNAs and evaluated its prognostic value in multiple groups (training set, testing set, and entire set). Our risk prediction model could effectively predict the prognosis of SOC patients with different clinical characteristics and their responses to immunotherapy. Lastly, we validated the predictive reliability and sensitivity of the lncRNA-based model via a nomogram. This study explored the association between RNA modification writer-related lncRNAs and SOC prognosis, providing a potential complement for the clinical management of SOC patients.


Assuntos
Neoplasias Ovarianas , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário , Feminino , Humanos , Imunoterapia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Prognóstico , RNA Longo não Codificante/genética , Reprodutibilidade dos Testes
15.
J Inflamm Res ; 15: 775-791, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153501

RESUMO

OBJECTIVE: Enhancer RNAs (eRNAs), a class of non-coding RNAs, play indispensable roles in regulating target gene transcription and maintaining cell identity in cooperation with promoters. In this study, we investigated the transcriptional landscape and potential functions of eRNAs in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). METHODS: PBMCs from five patients with stable SLE, five patients with active SLE, and ten healthy individuals (HCs) were subjected to RNA-sequencing. Putative regulators, differential expression, and pathways were analyzed. eRNAs that were significantly upregulated were first validated by RT-qPCR in 12 samples. Then, candidate eRNAs were confirmed in a validation cohort of 45 samples. We conducted comprehensive pathway analyses to explore the correlations between the candidate eRNAs and SLE pathology. RESULTS: By analyzing eRNA transcript data from PBMCs from SLE patients and HCs, we identified various eRNAs and functional super-enhancers potentially related with SLE. The SLE-specificity of eRNAs seemed to be largely driven by SLE-specific transcription factors (TFs). A Venn diagram of eRNAs differentially expressed in stable, active, and total SLE vs HCs revealed that 13 and 23 eRNAs were commonly upregulated and downregulated, respectively, in patients with stable SLE and those with active SLE. The commonly upregulated eRNAs participate in regulating SLE-related pathways. Only eRNA TCONS_00034326 was significantly (P < 0.05) upregulated in PBMCs of patients with SLE when compared with those of HCs as indicated by RT-qPCR. The area under the receiver-operating curve of TCONS_00034326 for distinguishing SLE patients from HCs was 0.691. Through its putative SLE-related master TF, TCONS_00034326 is involved in multiple SLE-relevant signaling pathways, especially tumor necrosis factor signaling. CONCLUSION: This study unraveled the transcriptional landscape of eRNAs, eRNA-related TFs, and super-enhancers in PBMCs from SLE patients and HCs. We identified a panel of SLE-relevant eRNAs, providing potential targets in SLE pathogenesis.

16.
Mol Ther Nucleic Acids ; 26: 575-593, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34631286

RESUMO

5-methylcytosine (m5C) post-transcriptional modifications affect the maturation, stability, and translation of the mRNA molecule. These modifications play an important role in many physiological and pathological processes, including stress response, tumorigenesis, tumor cell migration, embryogenesis, and viral replication. Recently, there has been a better understanding of the biological implications of m5C modification owing to the rapid development and optimization of detection technologies, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA-BisSeq. Further, predictive models (such as PEA-m5C, m5C-PseDNC, and DeepMRMP) for the identification of potential m5C modification sites have also emerged. In this review, we summarize the current experimental detection methods and predictive models for mRNA m5C modifications, focusing on their advantages and limitations. We systematically surveyed the latest research on the effectors related to mRNA m5C modifications and their biological functions in multiple species. Finally, we discuss the physiological effects and pathological significance of m5C modifications in multiple diseases, as well as their therapeutic potential, thereby providing new perspectives for disease treatment and prognosis.

17.
Front Microbiol ; 11: 2104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013768

RESUMO

The human cytomegalovirus (HCMV), whose genome is 235 ± 1.9 kbp long, is a common herpesvirus. However, the functions of many of its genes are still unknown. HCMV is closely associated with various human diseases and infects 60-90% of the global population. It can infect various human cells, including fibroblasts, epithelial cells, endothelial cells, smooth muscle cells, and monocytes. Although HCMV infection is generally asymptomatic and causes subtle clinical symptoms, it can generate a robust immune response and establish a latent infection in immunocompromised individuals, including those with AIDS, transplant recipients, and developing fetuses. Currently available antivirals approved for the treatment of HCMV-associated diseases are limited by dose-limiting toxicity and the emergence of resistance; however, vaccines and immunoglobulins are unavailable. In this review, we have summarized the recent literature on 43 newly identified HCMV genes. We have described their novel functions on the viral replication cycle, latency, and host immune evasion. Further, we have discussed HCMV-associated diseases and current therapeutic targets. Our review may provide a foundational basis for studies aiming to prevent and develop targeted therapies for HCMV-associated diseases.

18.
Front Cell Dev Biol ; 8: 842, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984334

RESUMO

The emerging epitranscriptome plays an essential role in autoimmune disease. As a novel mRNA modification, N4-acetylcytidine (ac4C) could promote mRNA stability and translational efficiency. However, whether epigenetic mechanisms of RNA ac4C modification are involved in systemic lupus erythematosus (SLE) remains unclear. Herein, we detected eleven modifications in CD4+ T cells of SLE patients using mass spectrometry (LC-MS/MS). Furthermore, using samples from four CD4+ T cell pools, we identified lower modification of ac4C mRNA in SLE patients as compared to that in healthy controls (HCs). Meanwhile, significantly lower mRNA acetyltransferase NAT10 expression was detected in lupus CD4+ T cells by RT-qPCR. We then illustrated the transcriptome-wide ac4C profile in CD4+ T cells of SLE patients by ac4C-RIP-Seq and found ac4C distribution in mRNA transcripts to be highly conserved and enriched in mRNA coding sequence regions. Using bioinformatics analysis, the 3879 and 4073 ac4C hyper-acetylated and hypoacetylated peaks found in SLE samples, respectively, were found to be significantly involved in SLE-related function enrichments, including multiple metabolic and transcription-related processes, ROS-induced cellular signaling, apoptosis signaling, and NF-κB signaling. Moreover, we demonstrated the ac4C-modified regulatory network of gene biological functions in lupus CD4+ T cells. Notably, we determined that the 26 upregulated genes with hyperacetylation played essential roles in autoimmune diseases and disease-related processes. Additionally, the unique ac4C-related transcripts, including USP18, GPX1, and RGL1, regulate mRNA catabolic processes and translational initiation. Our study identified novel dysregulated ac4C mRNAs associated with critical immune and inflammatory responses, that have translational potential in lupus CD4+ T cells. Hence, our findings reveal transcriptional significance and potential therapeutic targets of mRNA ac4C modifications in SLE pathogenesis.

19.
Epigenomics ; 12(11): 973-988, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32677847

RESUMO

Aim: We aimed to identify differentially expressed Long noncoding RNAs (lncRNAs) and explore their functional roles in systemic lupus erythematosus (SLE). Materials & methods: We identified dysregulated lncRNAs and investigated their prognostic values and potential functions using MiRTarget2, catRAPID omics and Bedtools/blast/Pearson analyses. Results: Among the 143 differentially expressed lncRNAs, TCONS_00483150 could be used to distinguish patients with SLE from healthy controls and those with rheumatoid arthritis and patients with active/stable SLE from healthy controls. TCONS_00483150 was significantly correlated with anti-Rib-P antibody positivity and low C3 levels; TCONS_00483150 dysregulation might contribute to the metabolism of RNA and proteins in SLE patients. Conclusion: Overall, our findings offer a transcriptome-wide overview of aberrantly expressed lncRNAs in patients with SLE and highlight TCONS_00483150 as a potential novel diagnostic biomarker.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , RNA Longo não Codificante , Artrite Reumatoide , Biomarcadores , Estudos de Casos e Controles , Humanos , Lúpus Eritematoso Sistêmico/genética , RNA Longo não Codificante/genética , Transcriptoma
20.
Front Cell Dev Biol ; 8: 410, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574318

RESUMO

Since the first reports that the novel coronavirus was showing human-to-human transmission characteristics and asymptomatic cases, the number of patients with associated pneumonia has continued to rise and the epidemic has grown. It now threatens the health and lives of people across the world. The governments of many countries have attached great importance to the prevention of SARS-CoV-2, via research into the etiology and epidemiology of this newly emerged disease. Clinical signs, treatment, and prevention characteristics of the novel coronavirus pneumonia have been receiving attention worldwide, especially from medical personnel. However, owing to the different experimental methods, sample sizes, sample sources, and research perspectives of various studies, results have been inconsistent, or relate to an isolated aspect of the virus or the disease it causes. Currently, systematic summary data on the novel coronavirus are limited. This review combines experimental and clinical evidence into a systematic analysis and summary of the current progress of research into SARS-CoV-2, from multiple perspectives, with the aim of gaining a better overall understanding of the disease. Our report provides important information for current clinicians, for the prevention and treatment of COVID-19 pneumonia.

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