Artificial transcriptional factor

BACKGROUND: Sevoflurane (Sevo) preconditioning and postconditioning play a protective role against injury induced by hepatic ischemia/reperfusion (I/R). At the same time, the involvement of macrophage infiltration in this process and the precise mechanisms are unclear. Here, we designed this research to elucidate the protective effects of Sevo against hepatic I/R injury and the molecules involved. METHODS: The alleviating effect of Sevo on the liver injury was analyzed by liver function analysis, hematoxylin and eosin staining, Masson trichrome staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling, western blot analysis and an enzyme-linked immunosorbent assay...

Embryonic stem-like cells (ES-like cells) are promising for medical research and clinical applications. Traditional methods involve "Yamanaka" transcription (OSKM) to derive these cells from somatic cells in vitro. Recently, a novel approach has emerged, obtaining ES-like cells from spermatogonia stem cells (SSCs) in a time-related process without adding artificial additives to cell cultures, like transcription factors or small molecules such as pten or p53 inhibitors. This study aims to investigate the role of the Nanog in the conversion of SSCs to pluripotent stem cells through both in silico analysis and in vitro experiments...

Understanding the influence of cis-regulatory elements on gene regulation poses numerous challenges given complexities stemming from variations in transcription factor (TF) binding, chromatin accessibility, structural constraints, and cell-type differences. This review discusses the role of gene regulatory networks in enhancing understanding of transcriptional regulation and covers construction methods ranging from expression-based approaches to supervised machine learning. Additionally, key experimental methods, including MPRAs and CRISPR-Cas9-based screening, which have significantly contributed to understanding TF binding preferences and cis-regulatory element functions, are explored...

Current technologies for upregulation of endogenous genes use targeted artificial transcriptional activators but stable gene activation requires persistent expression of these synthetic factors. Although general "hit-and-run" strategies exist for inducing long-term silencing of endogenous genes using targeted artificial transcriptional repressors, to our knowledge no equivalent approach for gene activation has been described to date. Here we show stable gene activation can be achieved by harnessing endogenous transcription factors ( EndoTF s) that are normally expressed in human cells...

BACKGROUND: APOL1 high-risk variants contribute to kidney disease among African-ancestry individuals. We sought to describe cell-specific APOL1 variants-induced pathways using two mouse models. METHODS: We characterized bacterial artificial chromosome (BAC)/APOL1 transgenic mice crossed with HIV-associated nephropathy (HIVAN) Tg26 mice and BAC/APOL1 transgenic mice given interferon-γ. RESULTS: Both mouse models showed more severe glomerular disease in APOL1-G1 compared to APOL1-G0 mice...

BACKGROUND: Based on the bioinformatics prediction, this study investigates the correlation between aberrant transcription factor Frizzled 5 (FZD5) expression and the establishment of non-small cell lung cancer (NSCLC). METHODS: A mouse model with regard to primary NSCLC was encouraged by intraperitoneal injection of urethane. Lentivirus-based FZD5 silencing was then administrated to examine its role in tumorigenesis in the mouse lung. Silencing of FZD5 was induced in two NSCLC cell lines to examine its function in the malignant behavior pertaining to cells in vitro ...

INTRODUCTION: The 2023 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, themed "Disrupting Prostate Cancer Research: Challenge Accepted," was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023. METHODS: The 2023 marked the 10th Annual CHPCA Meeting, a discussion-oriented scientific think-tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care...

Targeting "undruggable" targets with intrinsically disordered structures is of great significance for the treatment of disease. The transcription factor c-Myc controls global gene expression and is an attractive therapeutic target for multiple types of cancers. However, due to the lack of defined ligand binding pockets, targeted c-Myc have thus far been unsuccessful. Herein, to address the dilemma of lacking ligands, an efficient and high throughput aptamer screening strategy is established, named polystyrene microwell plate-based systematic evolution of ligands by exponential enrichment (microwell-SELEX), and identify the specific aptamer (MA9C1) against c-Myc...

Aspartame, a widely used artificial sweetener, is present in many food products and beverages worldwide. It has been linked to potential neurotoxicity and developmental defects. However, its teratogenic effect on embryonic development and the underlying potential mechanisms need to be elucidated. We investigated the concentration- and time-dependent effects of aspartame on zebrafish development and teratogenicity. We focused on the role of sirtuin 1 (SIRT1) and Forkhead-box transcription factor (FOXO), two proteins that play key roles in neurodevelopment...

Novel strategies employing mechano-transducing materials eliciting biological outcomes have recently emerged for controlling cellular behaviour. Targeted cellular responses are achieved by manipulating physical, chemical, or biochemical modification of material properties. Advances in techniques such as nanopatterning, chemical modification, biochemical molecule embedding, force-tuneable materials, and artificial extracellular matrices are helping understand cellular mechanotransduction. Collectively, these strategies manipulate cellular sensing and regulate signalling cascades including focal adhesions, YAP-TAZ transcription factors, and multiple osteogenic pathways...

Transcription factors (TFs) are crucial epigenetic regulators, which enable cells to dynamically adjust gene expression in response to environmental signals. Computational procedures like digital genomic footprinting on chromatin accessibility assays such as ATACseq can be used to identify bound TFs in a genome-wide scale. This method utilizes short regions of low accessibility signals due to steric hindrance of DNA bound proteins, called footprints (FPs), which are combined with motif databases for TF identification...

BACKGROUND: The number of patients with type 1 diabetes rises rapidly around the world in recent years. Maternal diabetes has a detrimental effect on reproductive outcomes due to decreased oocyte quality. However, the strategies to improve the oocyte quality and artificial reproductive technology (ART) efficiency of infertile females suffering from diabetes have not been fully studied. In this study, we aimed to examine the effects of nicotinamide mononucleotide (NMN) on oocyte maturation of mouse with type 1 diabetes mouse and explore the underlying mechanisms of NMN's effect...

In response to nutrient deprivation, bacteria activate a conserved stress response pathway called the stringent response (SR). During SR activation in Caulobacter crescentus , SpoT synthesizes the secondary messengers guanosine 5'-diphosphate 3'-diphosphate and guanosine 5'-triphosphate 3'-diphosphate (collectively known as (p)ppGpp), which affect transcription by binding RNA polymerase (RNAP) to down-regulate anabolic genes. (p)ppGpp also impacts the expression of anabolic genes by controlling the levels and activities of their transcriptional regulators...

Benzylisoquinoline alkaloids (BIAs) produced in opium poppy have been evidenced to heal patients suffering from various diseases. They, therefore, hold an integral position in the herbal drug industry. Despite the adoption of several approaches for the large-scale production of BIAs, opium poppy remains the only platform in this purpose. The only disadvantage associated with producing BIAs in the plant is their small quantity. Thus, recruiting strategies that boost their levels is deemed necessary. All the methods which have been employed so far are just able to enhance a maximum of two BIAs...

BACKGROUND: Artificial intelligence (AI) technology has made breakthroughs in spinal cord neural injury and restoration in recent years. It has a positive impact on clinical treatment. This study explores AI research's progress and hotspots in spinal cord neural injury and restoration. It also analyzes research shortcomings related to this area and proposes potential solutions. METHODS: We used CiteSpace 6.1.R6 and VOSviewer 1.6.19 to research WOS articles on AI research in spinal cord neural injury and restoration...

Feeding behavior is critical for insect survival and fitness. Most researchers have explored the molecular basis of feeding behaviors by identifying and elucidating the function of olfactory receptors (ORs) and gustatory receptors (GRs). Other types of genes, such as transcription factors, have rarely been investigated, and little is known about their potential roles. The silkworm (Bombyx mori) is a well-studied monophagic insect which primarily feeds on mulberry leaves, but the genetic basis of its monophagy is still not understood...

The production of androst-4-ene-3,17-dione (AD) by the steroidal microbial cell factory requires transcription factors (TFs) to participate in metabolic regulation. However, microbial cell factory lacks effective TFs that can respond to AD in its metabolic pathway. Additionally, finding and obtaining natural TFs that specifically respond to AD is a complex and onerous task. In this study, we devised an artificial TF that responds to AD, termed AdT, based on structure-guided molecular dynamics (MD) simulation...

Seed storability has a significant impact on seed vitality and is a crucial genetic factor in maintaining seed value during storage. In this study, RNA sequencing was used to analyze the seed transcriptomes of two rice thermo-sensitive genic male sterile (TGMS) lines, S1146S (storage-tolerant) and SD26S (storage-susceptible), with 0 and 7 days of artificial accelerated aging treatment. In total, 2658 and 1523 differentially expressed genes (DEGs) were identified in S1146S and SD26S, respectively. Among these DEGs, 729 (G1) exhibited similar regulation patterns in both lines, while 1924 DEGs (G2) were specific to S1146S, 789 DEGs (G3) were specific to SD26S, and 5 DEGs (G4) were specific to contrary differential expression levels...

OBJECTIVES: This study aimed to reveal critical genes regulating peri-implantitis during its development and construct a diagnostic model by using random forest (RF) and artificial neural network (ANN). METHODS: GSE-33774, GSE106090, and GSE57631 datasets were obtained from the GEO database. The GSE33774 and GSE106090 datasets were analyzed for differential expression and functional enrichment. The protein-protein interaction networks (PPI) and RF screened vital genes...

Many diseases emerge from dysregulated cellular signaling, and drugs are often designed to target specific signaling proteins. Off-target effects are, however, common and may ultimately result in failed clinical trials. Here we develop a computer model of the cell's transcriptional response to drugs for improved understanding of their mechanisms of action. The model is based on ensembles of artificial neural networks and simultaneously infers drug-target interactions and their downstream effects on intracellular signaling...