Modeling gene regulation

OBJECTIVES: To evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells' phenotypic, genomic, and transcriptomic heterogeneity. METHODS: MIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively...

Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors. Here, we report that breast cancer brain metastasis stromal cell interactions in 3D cocultures induce therapeutic resistance to HER2-targeting agents, particularly to the small molecule inhibitor of HER2/EGFR neratinib...

One of the primary concerns for the survival of the human species is the growing demand for food brought on by an increasing global population. New developments in genome-editing technology present promising opportunities for the growth of wholesome and prolific farm animals. Genome editing in large animals is used for a variety of purposes, including biotechnology to improve food production, animal health, and pest management, as well as the development of animal models for fundamental research and biomedicine...

In skeletal muscle, Na+ ,K+ -ATPase (NKA), a heterodimeric (α/β) P-type ATPase, has an essential role in maintenance of Na+ and K+ homeostasis, excitability, and contractility. AMP-activated protein kinase (AMPK), an energy sensor, increases the membrane abundance and activity of NKA in L6 myotubes, but its potential role in regulation of NKA content in skeletal muscle, which determines maximum capacity for Na+ and K+ transport, has not been clearly delineated. We examined whether energy stress and/or AMPK affect expression of NKA subunits in rat L6 and primary human myotubes...

BACKGROUND: Traditional bandages, gauze, and cotton balls are increasingly insufficient for addressing complex war injuries characterized by severe bleeding and diverse wound conditions. The giant salamander, a species of high medical value, secretes a unique mucus when stimulated, which has potential applications in wound care. MATERIALS: Giant salamander skin mucus gel dressing wrapped with bone marrow mesenchymal stem cells (BMSCs-GSSM-gel) was prepared and validated...

OBJECTIVE: To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. METHODS: High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression...

OBJECTIVE: To explore the role of zinc finger protein 36(ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. METHODS: ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36 -deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed...

OBJECTIVE: To investigate the changes of mitochondrial respiratory function during myocardial fibrosis in mice with myocardial infarction (MI) and its correlation with the increase of glycolytic flux. METHODS: Forty C57BL/6N mice were randomized into two equal groups to receive sham operation or ligation of the left anterior descending coronary artery to induce acute MI. At 28 days after the operation, 5 mice from each group were euthanized and left ventricular tissue samples were collected for transcriptomic sequencing...

BACKGROUND: This study was performed to determine the biological processes in which NKX2-1 is involved and thus its role in the development of lung squamous cell carcinoma (LUSC) toward improving the prognosis and treatment of LUSC. METHODS: Raw RNA sequencing (RNA-seq) data of LUSC from The Cancer Genome Atlas (TCGA) were used in bioinformatics analysis to characterize NKX2-1 expression levels in tumor and normal tissues. Survival analysis of Kaplan-Meier curve, the time-dependent receiver operating characteristic (ROC) curve, and a nomogram were used to analyze the prognosis value of NKX2-1 for LUSC in terms of overall survival (OS) and progression-free survival (PFS)...

Waterborne transmission of the bacterium Legionella pneumophila has emerged as a major cause of severe nosocomial infections of major public health impact. The major route of transmission involves the uptake of aerosolized bacteria, often from the contaminated hot water systems of large buildings. Public health regulations aimed at controlling the mesophilic pathogen are generally concerned with acute pasteurization and maintaining high temperatures at the heating systems and throughout the plumbing of hot water systems, but L...

BACKGROUND: Diabetic kidney disease (DKD) is one of diabetic complications, which has become the leading cause of end-stage kidney disease. In addition to angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker(ACEI/ARB) and sodium-glucose cotransporter-2 inhibitor (SGLT2i), traditional Chinese medicine (TCM) is an effective alternative treatment for DKD. In this study, the effect of Qufeng Tongluo (QFTL) decoction in decreasing proteinuria has been observed and its mechanism has been explored based on autophagy regulation in podocyte...

OBJECTIVE: This study aims to explore the mechanism of action of Yixintai in treating chronic ischemic heart failure by combining bioinformatics and experimental validation. MATERIALS AND METHODS: Five potential drugs for treating heart failure were obtained from Yixintai (YXT) through early mass spectrometry detection. The targets of YXT for treating heart failure were obtained by a search of online databases. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted on the common targets using the DAVID database...

Nowadays, effective prognostic models for esophageal cancer (ESCA) are still lacking. Long noncoding RNAs (lncRNAs) are commonly utilized as indicators for diagnosing cancer and forecasting patient outcomes. Cuproptosis is regulated by multiple genes and is crucial to the progression of ESCA. However, it is not yet clear what role the cuproptosis-associated lncRNAs (CuALs) play in ESCA. To tackle this problem, a prognostic signature incorporating three CuALs was created. This signature was constructed by the use of the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression...

The angiotensin-converting enzyme (ACE) gene ( ACE ) insertion/deletion ( I/D ) polymorphism raises the possibility of personalising ACE inhibitor therapy to optimise its efficiency and reduce side effects in genetically distinct subgroups. However, the extent of its influence among these subgroups is unknown. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of the ACE I/D polymorphism on haemodynamic parameters in humans undergoing antihypertensive therapy...

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease worldwide and lack of research on the diagnostic utility of mitochondrial regulators in NAFLD. Mitochondrial dysfunction plays a pivotal role in the development and progression of NAFLD, especially oxidative stress and acidity β-oxidative overload. Thus, we aimed to identify and validate a panel of mitochondrial gene expression biomarkers for detection of NAFLD. METHODS: We selected the GSE89632 dataset and identified key mitochondrial regulators by intersecting DEGs, WGCNA modules, and MRGs...

The biological function and prognostic value of efferocytosis in cancer remains unclear. In this study, we systematically analysed the expression profiles and genetic variations of 50 efferocytosis-related regulator genes in 33 cancer types. Using data from The Cancer Genome Atlas, we established an efferocytosis potential index (EPI) model to represent the efferocytosis level in each cancer type. The relationship between the EPI and prognosis, immune-related molecules, specific pathways, and drug sensitivity was determined...

BACKGROUND: Gout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed. METHODS: For the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database...

Methamphetamine use disorder (MUD) is a neuropsychiatric disorder characterized by binge drug taking episodes, intervals of abstinence, and relapses to drug use even during treatment. MUD has been modeled in rodents and investigators are attempting to identify its molecular bases. Preclinical experiments have shown that different schedules of methamphetamine self-administration can cause diverse transcriptional changes in the dorsal striatum of Sprague-Dawley rats. In the present review, we present data on differentially expressed genes (DEGs) identified in the rat striatum following methamphetamine intake...

Background: Uterine Corpus Endometrial Carcinoma (UCEC) is the most common type of cancer that develops in the uterus, specifically originating from the endometrium, the inner lining of the uterus. Programmed cell death (PCD) is a highly regulated process that eliminates damaged, aged, or unwanted cells in the body. Dysregulation of PCD pathways can contribute to the formation and progression of various cancers, including UCEC. Methods: Fourteen PCD pathways (autophagy-dependent cell death, alkaliptosis, apoptosis, cuproptosis, entotic cell death, ferroptosis, immunogenic cell death, lysosome-dependent cell death, MPT-driven necrosis, necroptosis, netotic cell death, oxeiptosis, parthanatos, and pyroptosis) were involved in building a prognostic signature...

BACKGROUND: Cis -regulatory elements (CREs) play crucial roles in regulating gene expression during erythroid cell differentiation. Genome-wide erythroid-specific CREs have not been characterized in chicken erythroid cells, which is an organism model used to study epigenetic regulation during erythropoiesis. METHODS: Analysis of public genome-wide accessibility (ATAC-seq) maps, along with transcription factor (TF) motif analysis, CTCF, and RNA Pol II occupancy, as well as transcriptome analysis in fibroblasts and erythroid HD3 cells, were used to characterize erythroid-specific CREs...