Bioorthogonal Janus microparticles for photothermal and chemo-therapy.

Bioorthogonal chemistry, recognized as a highly efficient tool in chemical biology, has shown significant value in cancer treatment. The primary objective is to develop efficient delivery strategies to achieve enhanced bioorthogonal drug treatment for tumors. Here, Janus microparticles (JMs) loaded with cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) triggers are reported.

Exploring oncogenic roles and clinical significance of EZH2: focus on non-canonical activities.

The enhancer of zeste homolog 2 (EZH2) is a catalytic component of Polycomb repressive complex 2 (PRC2) mediating the methylation of histone 3 lysine 27 (H3K27me3) and hence the epigenetic repression of target genes, known as canonical function. Growing evidence indicates that EZH2 has non-canonical roles that are exerted as PRC2-dependent and PRC2-independent methylation of non-histone proteins, and methyltransferase-independent interactions of EZH2 with various proteins contributing to gene expression regulation and alterations in the protein stability. is frequently mutated and/or its expression is deregulated in various cancer types.

Epigenetic Mechanisms Driving Adaptation in Tropical and Subtropical Plants: Insights and Future Directions.

Epigenetic mechanisms, including DNA methylation, histone modifications, and Noncoding RNAs, play a critical role in enabling plants to adapt to environmental changes without altering their DNA sequence. These processes dynamically regulate gene expression in response to diverse stressors, making them essential for plant resilience under changing global conditions. This review synthesises research on tropical and subtropical plants-species naturally exposed to extreme temperatures, salinity, drought, and other stressors-while drawing parallels with similar mechanisms observed in arid and temperate ecosystems.

Epigenetic Role of Long Non-coding RNAs in Multiple Myeloma.

Purpose Of The Review: This review aims to explore the pivotal role of long non-coding RNAs (lncRNAs) as epigenetic regulators in the pathogenesis of multiple myeloma (MM). Additionally, we have portrayed the dual role of lncRNAs in the epigenetic landscape of MM pathobiology.

Recent Findings: In MM, lncRNAs are pivotal for proliferation, progression, and drug resistance by acting as miRNA sponges, regulating mRNA activity through microRNA recognition elements (MREs).

AAVR Expression is Essential for AAV Vector Transduction in Sensory Hair Cells.

Adeno-associated virus (AAV) vectors are a leading platform for gene therapy. Recently, AAV-mediated gene therapy in the inner ear has progressed from laboratory use to clinical trials, but the lower transduction rates in outer hair cells (OHCs) in the organ of Corti and in vestibular hair cells in adult mice still pose a challenge. OHCs are particularly vulnerable to inner ear insults.

Role of NEAT1 and HOTAIR long non-coding RNAs in Behcet's Disease pathogenesis and their correlation with target inflammatory cytokines.

Background: Recent studies have highlighted the potential role of several long non-coding RNAs (lncRNAs) in the pathogenesis of Behçet's disease (BD). This study investigated the expression profiles of lncRNA NEAT1 and lncRNA HOTAIR, and their target cytokine genes, IL-6 and TNF-α, in active and inactive BD patients.

Methods: This cross-sectional study was conducted on peripheral blood mononuclear cells (PBMCs) obtained from 25 BD patients and 25 age-sex-matched healthy controls (HCs).

Evaluation of circ_0002232 and circ-vimentin gene expressions as valuable biomarkers in acute myeloid leukemia patients.

Background And Aim: Acute myeloid leukemia (AML) is a remarkably complex malignancy; with considerable genetic, epigenetic, and phenotypic heterogenicity. Circ-RNAs are a novel class of non-coding RNA. They may influence leukemia development and offer exciting possibilities for targeted AML diagnosis and therapy.

Chronic viral mimicry induction following p53 loss promotes immune evasion.

Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through 'viral mimicry' responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood.

The effect of exercise and physical activity on skeletal muscle epigenetics and metabolic adaptations.

Physical activity (PA) and exercise elicit adaptations and physiological responses in skeletal muscle, which are advantageous for preserving health and minimizing chronic illnesses. The complicated atmosphere of the exercise response can be attributed to hereditary and environmental variables. The primary cause of these adaptations and physiological responses is the transcriptional reactions that follow exercise, whether endurance- (ET) or resistance- training (RT).

Value of the combination of intraepithelial tumor-infiltrating lymphocyte density and the heterogeneity of density as a prognostic marker in stage III colorectal cancers.

Tumor-infiltrating lymphocyte (TIL) density is both a prognostic and a predictive factor in colorectal cancer (CRC). Whether the heterogeneity of TIL density across the tumor plays an important role in the clinical outcome of CRC is not well known. Adjuvant chemotherapy-treated patients with stage III CRC were analyzed for survival according to TIL density and density heterogeneity, which were determined on CD8-immunostained slides using a machine learning method and by calculating the Simpson evenness index, respectively.

An appropriate DNA input for bisulfite conversion reveals LINE-1 and Alu hypermethylation in tissues and circulating cell-free DNA from cancers.

The autonomous and active Long-Interspersed Element-1 (LINE-1, L1) and the non-autonomous Alu retrotransposon elements, contributing to 30% of the human genome, are the most abundant repeated sequences. With more than 90% of their sequences being methylated in normal cells, these elements undeniably contribute to the global DNA methylation level and constitute a major part of circulating-cell-free DNA (cfDNA). So far, the hypomethylation status of LINE-1 and Alu in cellular and extracellular DNA has long been considered a prevailing hallmark of ageing-related diseases and cancer.

Epigenetic Modifications as Novel Therapeutic Strategies of Cancer Chemoprevention by Phytochemicals.

Purpose: Epigenetic modifications, such as aberrant DNA methylation, histone alterations, non-coding RNA remodeling, and modulation of transcription factors, are pivotal in the pathogenesis of diverse malignancies. Reactive oxygen species (ROS) have the capacity to impact these epigenetic mechanisms, including DNA methylation, throughout the different stages of cancer development. Therefore, the aim of this review is to address the impact of.

Oral cancer immunology: state of the art and future perspectives.

Oral cancer is a multifactorial disease involving genetic, epigenetic, and environmental factors. The literature indicates that inflammatory cells at the advancing front of the tumor induce a host immune response, preventing the spread of the tumor. However, cancer cells adopt various continued strategies to circumvent this immune surveillance.

The protein cargo of extracellular vesicles correlates with the epigenetic aging clock of exercise sensitive DNAmFitAge.

Extracellular vesicles (EVs) are implicated in inter-organ communication, which becomes particularly relevant during aging and exercise. DNA methylation-based aging clocks reflect lifestyle and environmental factors, while regular exercise is known to induce adaptive responses, including epigenetic adaptations. Twenty individuals with High-fitness (aged 57.

Conserved features of recombination control in vertebrates.

A recent study in PLOS Biology on the epigenetic recombination regulator PRDM9 in salmonid fish reveals that its function has been preserved across vertebrates for hundreds of millions of years, with rapidly evolving DNA-binding domains being a defining attribute.

Lysine acetylation and its role in the pathophysiology of acute pancreatitis.

Acute pancreatitis (AP) represents a severe inflammatory condition of the exocrine pancreas, precipitating systemic organ dysfunction and potential failure. The global prevalence of acute pancreatitis is on an ascending trajectory. The condition carries a significant mortality rate during acute episodes.

Mitotic block and epigenetic repression underlie neurodevelopmental defects and neurobehavioral deficits in congenital heart disease.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease associated with microcephaly and poor neurodevelopmental outcomes. Here we show that the Ohia HLHS mouse model, with mutations in Sap130, a chromatin modifier, and Pcdha9, a cell adhesion protein, also exhibits microcephaly associated with mitotic block and increased apoptosis leading to impaired cortical neurogenesis. Transcriptome profiling, DNA methylation, and Sap130 ChIPseq analyses all demonstrate dysregulation of genes associated with autism and cognitive impairment.

A genome-wide survey of DNA methylation reveals hyper-methylation regulates after-ripening and dormancy of recalcitrant Panax notoginseng seeds.

DNA methylation plays a crucial role in regulating fruit ripening and seed development. It remains unknown about the dynamic characteristics of DNA methylation and its regulation mechanisms in morpho-physiological dormancy (MPD)-typed seeds with recalcitrant characteristics. The Panax notoginseng seeds are defined by the MPD and are characterized by a strong sensitivity to dehydration during the after-ripening process.

Defining ortholog-specific UHRF1 inhibition by STELLA for cancer therapy.

UHRF1 maintains DNA methylation by recruiting DNA methyltransferases to chromatin. In mouse, these dynamics are potently antagonized by a natural UHRF1 inhibitory protein STELLA, while the comparable effects of its human ortholog are insufficiently characterized, especially in cancer cells. Herein, we demonstrate that human STELLA (hSTELLA) is inadequate, while mouse STELLA (mSTELLA) is fully proficient in inhibiting the abnormal DNA methylation and oncogenic functions of UHRF1 in human cancer cells.

High-resolution whole-genome DNA methylation revealed unique signatures of painful diabetic neuropathy.

The aim of this work was to describe the DNA methylation signature and to identify genes associated with neuropathic pain in type 2 diabetes mellitus. We analyzed two independent diabetic neuropathy cohorts: PROPGER consisting of 72 painful and 67 painless patients recruited at the German Diabetes Center in Düsseldorf (DE), and PROPENG comprising 27 painful and 65 painless diabetic neuropathy patients recruited at the University of Manchester (UK). Genome-wide methylation data was generated using Illumina Infinium Methylation EPIC v1.

Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.

Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80 liver-associated macrophages.

Delivery of an mRNA formulated with lipid nanoparticles (LNPs) induces robust humoral and cell-mediated branches of the immune response. Depending on the LNP formula, mRNA encoding proteins can be detected in the liver upon intramuscular administration of mRNA/LNP in mice. This study investigated the impact of mRNA/LNP administration on liver-associated macrophages at the transcriptomic and epigenetic levels in a mouse model.

The immunological landscape of primary biliary cholangitis: Mechanisms and therapeutic prospects.

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease characterized by the progressive destruction of intrahepatic bile ducts, leading to fibrosis, and potentially cirrhosis. PBC has been considered a prototypical autoimmune condition, given the presence of specific autoantibodies and the immune response against well-defined mitochondrial autoantigens. Further evidence supports the interaction of immunogenetic and environmental factors in the aetiology of PBC.