keyword
https://read.qxmd.com/read/38537151/development-and-validation-of-a-machine-learning-prognostic-model-of-m5c-related-immune-genes-in-lung-adenocarcinoma
#1
JOURNAL ARTICLE
Xiong Cao, Yuxing Ji, Jiajia Li, Zhikang Liu, Chang Chen
BACKGROUND: The aim of this retrospective research was to develop an immune-related genes significantly associated with m5C methylation methylation (m5C-IRGs)-related signature associated with lung adenocarainoma (LUAD). METHODS: We introduced transcriptome data to screen out m5C-IRGs in The Cancer Genome Atlas (TCGA)-LUAD dataset. Subsequently, the m5C-IRGs associated with survival were certificated by Kaplan Meier (K-M) analysis. The univariate Cox, least absolute shrinkage and selection operator (LASSO) regression, and xgboost...
2024: Cancer Control: Journal of the Moffitt Cancer Center
https://read.qxmd.com/read/38536911/select-ezh2-inhibitors-enhance-viral-mimicry-effects-of-dnmt-inhibition-through-a-mechanism-involving-nfat-ap-1-signaling
#2
JOURNAL ARTICLE
Alison A Chomiak, Rochelle L Tiedemann, Yanqing Liu, Xiangqian Kong, Ying Cui, Ashley K Wiseman, Kate E Thurlow, Evan M Cornett, Michael J Topper, Stephen B Baylin, Scott B Rothbart
DNA methyltransferase inhibitor (DNMTi) efficacy in solid tumors is limited. Colon cancer cells exposed to DNMTi accumulate lysine-27 trimethylation on histone H3 (H3K27me3). We propose this Enhancer of Zeste Homolog 2 (EZH2)-dependent repressive modification limits DNMTi efficacy. Here, we show that low-dose DNMTi treatment sensitizes colon cancer cells to select EZH2 inhibitors (EZH2is). Integrative epigenomic analysis reveals that DNMTi-induced H3K27me3 accumulates at genomic regions poised with EZH2. Notably, combined EZH2i and DNMTi alters the epigenomic landscape to transcriptionally up-regulate the calcium-induced nuclear factor of activated T cells (NFAT):activating protein 1 (AP-1) signaling pathway...
March 29, 2024: Science Advances
https://read.qxmd.com/read/38536879/comprehensive-mutagenesis-maps-the-effect-of-all-single-codon-mutations-in-the-aav2-rep-gene-on-aav-production
#3
JOURNAL ARTICLE
Nina K Jain, Pierce J Ogden, George M Church
Recombinant adeno-associated viruses (rAAVs) are the predominant gene therapy vector. Several rAAV vectored therapies have achieved regulatory approval, but production of sufficient rAAV quantities remains difficult. The AAV Rep proteins, which are essential for genome replication and packaging, represent a promising engineering target for improvement of rAAV production but remain underexplored. To gain a comprehensive understanding of the Rep proteins and their mutational landscape, we assayed the effects of all 39,297 possible single-codon mutations to the AAV2 rep gene on AAV2 production...
March 27, 2024: ELife
https://read.qxmd.com/read/38536662/natural-killer-group%C3%A2-2d-major-histocompatibility-complex-class%C3%A2-i-polypeptide-related-sequence%C3%A2-a-activation-enhances-natural-killer-cell-mediated-immunity-against-hepatocellular-carcinoma-a-review
#4
REVIEW
Jun Arai, Akinori Okumura, Naoya Kato, Kiyoaki Ito
The recent clinical introduction of immune checkpoint inhibitors has improved therapeutic outcomes in patients with advanced hepatocellular carcinoma. However, these therapies targeting CD8+ T lymphocytes have a response rate of approximately 30%. In addition to CD8+ T lymphocytes, natural killer (NK) cells represent promising therapeutic targets for hepatocellular carcinoma, because they comprise 30%-50% of all lymphocytes in the liver and contribute to antitumor immunity. A recent meta-analysis revealed that the percentage of infiltrating NK cells in hepatocellular carcinoma correlates with a better patient outcome...
March 27, 2024: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://read.qxmd.com/read/38536617/whole-transcriptome-mapping-reveals-the-lncrna-regulatory-network-of-tfp5-treatment-in-diabetic-nephropathy
#5
JOURNAL ARTICLE
Hongyan Luo, Lirong Yang, Guoqing Zhang, Xi Bao, Danna Ma, Bo Li, Li Cao, Shilu Cao, Shunyao Liu, Li Bao, Jing E, Yali Zheng
BACKGROUND: TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear. OBJECTIVE: This study aims to characterize the transcriptome profiles of mRNA and lncRNA in TFP5-treated DN mice to mine key lncRNAs associated with TFP5 efficacy. METHODS: We evaluated the role of TFP5 in DN pathology and performed RNA sequencing in C57BL/6J control mice, C57BL/6J db/db model mice, and TFP5 treatment C57BL/6J db/db model mice...
March 27, 2024: Genes & Genomics
https://read.qxmd.com/read/38536168/persistent-cutaneous-lesions-of-darier-disease-and-second-hit-somatic-variants-in-atp2a2-gene
#6
JOURNAL ARTICLE
Lihi Atzmony, Fadia Zagairy, Banan Mawassi, Majd Shehade, Yasmin Tatour, Nada Danial-Farran, Morad Khayat, Nassim Warrour, Roni Dodiuk-Gad, Eran Cohen-Barak
IMPORTANCE: Darier disease (DD) is a rare genetic skin disorder caused by heterozygous variants in the ATP2A2 gene. Clinical manifestations include recurrent hyperkeratotic papules and plaques that occur mainly in seborrheic areas. Although some of the lesions wax and wane in response to environmental factors, others are severe and respond poorly to therapy. OBJECTIVE: To investigate the molecular mechanism underlying the persistency of skin lesions in DD. DESIGN, SETTING, AND PARTICIPANTS: In this case series, DNA was extracted from unaffected skin, transient and persistent lesional skin, and blood from 9 patients with DD...
March 27, 2024: JAMA Dermatology
https://read.qxmd.com/read/38536067/targeted-and-shallow-whole-genome-sequencing-identifies-therapeutic-opportunities-in-p53abn-endometrial-cancers
#7
JOURNAL ARTICLE
Amy Jamieson, Juliana Sobral de Barros, Dawn R Cochrane, J Maxwell Douglas, Sameer Shankar, Branden J Lynch, Samuel Leung, Spencer Martin, Janine Senz, Amy Lum, Yvette Drew, C Blake Gilks, David G Huntsman, Jessica N McAlpine
PURPOSE: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. EXPERIMENTAL DESIGN: sWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs...
March 27, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38535994/npepps-is-a-druggable-driver-of-platinum-resistance
#8
JOURNAL ARTICLE
Robert T Jones, Mathijs Scholtes, Andrew Goodspeed, Maryam Akbarzadeh, Saswat Mohapatra, Lily Elizabeth Feldman, Hedvig Vekony, Annie Jean, Charlene B Tilton, Michael V Orman, Shahla Romal, Cailin Deiter, Tsung Wai Kan, Nathaniel Xander, Stephanie P Araki, Molishree Joshi, Mahmood Javaid, Eric T Clambey, Ryan Layer, Teemu D Laajala, Sarah J Parker, Tokameh Mahmoudi, Tahlita C M Zuiverloon, Dan Theodorescu, James C Costello
UNLABELLED: There is an unmet need to improve the efficacy of platinum-based cancer chemotherapy, which is used in primary and metastatic settings in many cancer types. In bladder cancer, platinum-based chemotherapy leads to better outcomes in a subset of patients when used in the neoadjuvant setting or in combination with immunotherapy for advanced disease. Despite such promising results, extending the benefits of platinum drugs to a greater number of patients is highly desirable. Using the multiomic assessment of cisplatin-responsive and -resistant human bladder cancer cell lines and whole-genome CRISPR screens, we identified puromycin-sensitive aminopeptidase (NPEPPS) as a driver of cisplatin resistance...
March 27, 2024: Cancer Research
https://read.qxmd.com/read/38535531/the-intricate-interplay-between-apobec3-proteins-and-dna-tumour-viruses
#9
REVIEW
Nika Lovšin, Bhavani Gangupam, Martina Bergant Marušič
APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to hypermutation of the viral genome, resulting in loss of viral fitness and, in many cases, inactivation of the virus. APOBEC3 proteins inhibit the replication of a number of DNA tumour viruses, including herpesviruses, papillomaviruses and hepadnaviruses...
February 20, 2024: Pathogens
https://read.qxmd.com/read/38534951/ductal-adenocarcinoma-of-the-prostate-with-novel-genetic-alterations-characterized-by-next-generation-sequencing
#10
Alexandra Zara Rozalen, Jose Manuel Martin, Rithika Rajendran, Maneesh Jain, Victor E Nava
Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy...
March 19, 2024: Current Oncology
https://read.qxmd.com/read/38534922/unlocking-the-potential-of-therapy-induced-cytokine-responses-illuminating-new-pathways-in-cancer-precision-medicine
#11
REVIEW
Dilip R Gunturu, Mohammed Hassan, Deepa Bedi, Pran Datta, Upender Manne, Temesgen Samuel
Precision cancer medicine primarily aims to identify individual patient genomic variations and exploit vulnerabilities in cancer cells to select suitable patients for specific drugs. These genomic features are commonly determined by gene sequencing prior to therapy, to identify individuals who would be most responsive. This precision approach in cancer therapeutics remains a powerful tool that benefits a smaller pool of patients, sparing others from unnecessary treatments. A limitation of this approach is that proteins, not genes, are the ultimate effectors of biological functions, and therefore the targets of therapeutics...
February 23, 2024: Current Oncology
https://read.qxmd.com/read/38533165/bee-sting-venom-as-a-viable-therapy-for-breast-cancer-a-review-article
#12
REVIEW
Aabhas Bindlish, Anupama Sawal
Breast cancer is a kind of aggressive cancer that significantly affects women worldwide, thus making research on alternative and new therapies necessary. The potential impact of bee venom on breast cancer is the main subject of this analysis of this research article. Bee venom has drawn the attention of the world with the help of its constituent ingredients, namely the bioactive compounds, enzymes, and complex blend of proteins. They have a particularly varied chemical makeup and proven anti-cancer capabilities...
February 2024: Curēus
https://read.qxmd.com/read/38532596/potential-of-the-quorum-quenching-and-plant-growth-promoting-halotolerant-bacillus-toyonensis-aa1ec1-as-biocontrol-agent
#13
JOURNAL ARTICLE
Amalia Roca, Mónica Cabeo, Carlos Enguidanos, Fernando Martínez-Checa, Inmaculada Sampedro, Inmaculada Llamas
The use of fertilizers and pesticides to control plant diseases is widespread in intensive farming causing adverse effects together with the development of antimicrobial resistance pathogens. As the virulence of many Gram-negative phytopathogens is controlled by N-acyl-homoserine lactones (AHLs), the enzymatic disruption of this type of quorum-sensing (QS) signal molecules, mechanism known as quorum quenching (QQ), has been proposed as a promising alternative antivirulence therapy. In this study, a novel strain of Bacillus toyonensis isolated from the halophyte plant Arthrocaulon sp...
March 2024: Microbial Biotechnology
https://read.qxmd.com/read/38532578/biological-agent-exerts-therapeutic-effects-by-reversing-abnormalities-in-amino-acid-metabolic-pathways-in-psoriasis
#14
JOURNAL ARTICLE
Haijun Miao, Yaxing Bai, Shengxian Shen, Mengyang Chu, Chang Miao, Jundan Yang, Xia Li, Liang Li, Shuai Shao, Gang Wang, Erle Dang
Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis involving immune system dysregulation and inflammation. Previous studies have indicated that metabolic abnormalities are closely related to the development and occurrence of psoriasis. However, the specific involvement of amino acid metabolism in the pathogenesis of psoriasis remains unclear. In this study, we conducted a comprehensive analysis of amino acid metabolism pathway changes in psoriasis patients using transcriptome data, genome-wide association studies (GWASs) data, and single-cell data...
March 2024: Experimental Dermatology
https://read.qxmd.com/read/38532369/preliminary-findings-on-the-development-of-a-predictive-model-for-blca-based-on-disulfidptosis-associated-incrnas-signature
#15
JOURNAL ARTICLE
Chao Tang, Yanpeng Fan, Shusheng Zhu
BACKGROUND: Bladder urothelial carcinoma (BLCA) is the most common malignancy of the urinary tract, presenting with a wide range of clinical symptoms and prognosis. Disulfidptosis is a newly identified cell death method and closely associated with BLCA progression, prognosis, and treatment outcome. Currently, we need to construct a new prognostic model for disulfidptosis-related long noncoding RNAs (drlncRNAs) to improve the treatment strategy of BLCA. METHODS: The data for BLCA samples were obtained from The Cancer Genome Atlas (TCGA), and then 10 unique genes related to disulfidoptosis (DRGs) were identified from research papers...
March 26, 2024: BMC Urology
https://read.qxmd.com/read/38531793/characterizing-the-efficacy-and-safety-of-chemotherapy-plus-everolimus-in-her2-negative-metastatic-breast-cancer-harboring-altered-pi3k-akt-mtor
#16
JOURNAL ARTICLE
Rong Wang, Qiao-Yan Zhu, Wei-Wu Ye, Yuan Huang, Zhan-Hong Chen, Ya-Bing Zheng, Xiao Zou, Jian Wang, Dan-Lu Jiang, Xiao-Jia Wang, Zheng-Yang Xu, Wen-Ming Cao
BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance...
March 2024: Discovery Medicine
https://read.qxmd.com/read/38531334/drug-target-mendelian-randomization-study-of-pcsk9-and-hmg-coa-reductase-inhibition-and-atrial-fibrillation
#17
JOURNAL ARTICLE
Fuyuan Li, Yibin Mei, Qiongbi Wu, Xianjun Wu
INTRODUCTION: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia with significant clinical implications. The potential influence of lipid-lowering therapies, specifically PCSK9 inhibitors (PCSK9i) and HMG-CoA reductase inhibitors (statins), on AF risk remains a topic of interest. This Mendelian Randomization (MR) study aimed to elucidate the causal relationship between genetically predicted inhibition of PCSK9 and HMG-CoA reductase and the risk of AF. METHODS: Utilizing publicly available, summary-level genome-wide association study (GWAS) data, we employed single-nucleotide polymorphisms (SNPs) associated with lower LDL-C levels as instruments for gene-simulated inhibition of PCSK9 and HMG-CoA reductase...
March 26, 2024: Cardiology
https://read.qxmd.com/read/38530861/aminoglycoside-resistance-genes-in-early-members-of-the-acinetobacter-baumannii-st78a-smal-italian-clone-reside-in-an-is26-bounded-island-in-the-chromosome
#18
JOURNAL ARTICLE
Christopher J Harmer, Sarah M Cahill, Johanna J Kenyon, Ruth M Hall
BACKGROUND: The Acinetobacter baumannii isolate called SMAL, previously used to determine the structures of capsular polysaccharide and lipooligosaccharide, was recovered in Pavia, Italy in 2002 among the collection of aminoglycoside-resistant isolates designated as SMAL type. This type was later called the Italian clone, then ST78. ST78 isolates are now widely distributed. OBJECTIVES: To establish the resistance gene complement and the location and structure of acquired resistance regions in early members of the Italian/ST78 clone...
March 26, 2024: Journal of Antimicrobial Chemotherapy
https://read.qxmd.com/read/38530810/dysregulation-of-linc00324-promotes-poor-prognosis-in-patients-with-glioma
#19
JOURNAL ARTICLE
Xin Jin, Jiandong Zhu, Haoyun Yu, Shengjun Shi, Kecheng Shen, Jingyu Gu, Ziqian Yin, Zhengquan Yu, Jiang Wu
BACKGROUND: LINC00324 is a long-stranded non-coding RNA, which is aberrantly expressed in various cancers and is associated with poor prognosis and clinical features. It involves multiple oncogenic molecular pathways affecting cell proliferation, migration, invasion, and apoptosis. However, the expression, function, and mechanism of LINC00324 in glioma have not been reported. MATERIAL AND METHODS: We assessed the expression of LINC00324 of LINC00324 in glioma patients based on data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to identify pathways involved in LINC00324-related glioma pathogenesis...
2024: PloS One
https://read.qxmd.com/read/38530778/graphpath-a-graph-attention-model-for-molecular-stratification-with-interpretability-based-on-the-pathway-pathway-interaction-network
#20
JOURNAL ARTICLE
Teng Ma, Jianxin Wang
MOTIVATION: Studying the molecular heterogeneity of cancer is essential for achieving personalized therapy. At the same time, understanding the biological processes that drive cancer development can lead to the identification of valuable therapeutic targets. Therefore, achieving accurate and interpretable clinical predictions requires paramount attention to thoroughly characterizing patients at both the molecular and biological pathway levels. RESULTS: Here, we present GraphPath, a biological knowledge-driven graph neural network with multi-head self-attention mechanism that implements the pathway-pathway interaction network...
March 26, 2024: Bioinformatics
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