Escape of Kdm6a from X chromosome is detrimental to ischemic brains via IRF5 signaling DOI
Conelius Ngwa, Afzal Misrani,

Kanaka Valli Manyam

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Abstract The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our prior research has suggested the escapee genes Kdm6a Kdm5c are involved microglial activation after stroke aged mice. However, underlying mechanisms remain unclear. We hypothesized Kdm6a/5c demethylate H3K27Me3/H3K4Me3 microglia respectively, mediate transcription interferon regulatory factor 5 (IRF5) IRF4, leading to pro-inflammatory responses exacerbated injury. Aged (17–20 months) conditional knockout (CKO) female mice (one allele gene) were subjected a 60-min middle cerebral artery occlusion (MCAO). Gene floxed females (two alleles) males allele) included as controls. Infarct volume behavioral deficits quantified 3 days stroke. Immune including infiltration peripheral leukocytes ischemic brain assessed by flow cytometry. Epigenetic modification IRF5/4 analyzed CUT&RUN assay. demethylation H3K27Me3 kdm6a increased IRF5 transcription; meanwhile Kdm5c demethylated H3K4Me3 repress IRF5. Both Kdm6afl/fl Kdm5cfl/fl had worse outcomes compared fl/y CKO showed more robust expression CD68 microglia, elevated plasma levels IL-1β or TNF-α, concluded IRF5 signaling plays critical mediating deleterious effect Kdm6a; whereas Kdm5c’s independent IRF5.

Language: Английский

Exploring Potential Epigenetic Biomarkers for Colorectal Cancer Metastasis DOI Open Access

Priyadarshana Ajithkumar,

Sai Shyam Vasantharajan,

Sharon Pattison

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 874 - 874

Published: Jan. 10, 2024

Metastatic progression is a complex, multistep process and the leading cause of cancer mortality. There growing evidence that emphasises significance epigenetic modification, specifically DNA methylation histone modifications, in influencing colorectal (CRC) metastasis. Epigenetic modifications influence expression genes involved various cellular processes, including pathways associated with These could contribute to metastatic by enhancing oncogenes silencing tumour suppressor genes. Moreover, specific alterations enable cells acquire invasive characteristics altering cell adhesion, migration, invasion-related pathways. Exploring involvement modification crucial for identifying biomarkers impact prediction metastasis CRC. This review provides summary potential CRC, particularly examines these biomarkers.

Language: Английский

Citations

9
Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension DOI
Ashley Pitzer Mutchler, Alexandria Porcia Haynes, Mohammad Saleem

et al.

Circulation Research, Journal Year: 2025, Volume and Issue: 136(2), P. 232 - 254

Published: Jan. 16, 2025

Access to excess dietary sodium has heightened the risk of cardiovascular diseases, particularly affecting individuals with salt sensitivity blood pressure. Our research indicates that innate antigen-presenting immune cells contribute rapid pressure increases in response intake. Emerging evidence suggests epigenetic reprogramming, subsequent transcriptional and metabolic changes, allows these have a sustained repetitive stimuli. Epigenetic mechanisms also steer T-cell differentiation signaling. Immune respond environmental nutritional cues, such as salt, promoting regulation changes. This article aims identify discuss role system contributing salt-sensitive hypertension.

Language: Английский

Citations

1
The Killer’s Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer DOI Open Access
Marisabel Mecca,

Simona Picerno,

Salvatore Cortellino

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2750 - 2750

Published: Feb. 27, 2024

Inflammation is a key contributor to both the initiation and progression of tumors, it can be triggered by genetic instability within as well lifestyle dietary factors. The inflammatory response plays critical role in epigenetic reprogramming tumor cells, cells that comprise microenvironment. Cells microenvironment acquire phenotype promotes immune evasion, progression, metastasis. We will review mechanisms pathways involved interaction between inflammation, nutrition, limitations current therapies, discuss potential future therapeutic approaches.

Language: Английский

Citations

7
Escape of Kdm6a from X Chromosome Is Detrimental to Ischemic Brains via IRF5 Signaling DOI
Conelius Ngwa, Afzal Misrani,

Kanaka Valli Manyam

et al.

Translational Stroke Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

0
Epigenetic dynamics in meniscus cell migration and its zonal dependency in response to inflammatory conditions DOI Creative Commons

Yize Zhang,

Erjing Zhang,

Catherine K.W. Cheung

et al.

APL Bioengineering, Journal Year: 2025, Volume and Issue: 9(1)

Published: Feb. 20, 2025

Meniscus injuries are challenging to treat due the tissue heterogeneity and limited treatment efficacy. Understanding meniscus cell migration, crucial for healing, remains incomplete, especially its zonal dependency. This study explores how epigenetic mechanisms affect migration under inflammation, focusing on healing implications. Distinct histone modifications chromatin dynamics between inner outer cells were observed during emphasizing need consider these differences in repair strategies. Furthermore, tumor necrosis factor alpha (TNF-α), a proinflammatory cytokine, slows while remain unaffected, indicating response. Interestingly, TNF-α differentially alters modifications, particularly H3K27me3, types. Transcriptome analysis showed significant gene expression changes with more affected than cells. Gene cluster revealed different responses remodeling, extracellular matrix assembly, wound zones. We further identified potential therapeutic targets by using drugs, GSKJ4 (a demethylase inhibitor) C646 acetyltransferase inhibitor), which restored inflammatory conditions, highlighting their treating tears. highlights utility tear injuries. Overall, our findings elucidate intricate interplay along provides insight into enhancing regeneration, may lead improved clinical outcomes patients osteoarthritis.

Language: Английский

Citations

0
Selenalysine as a Chemical Tool for Probing Histone Post-Translational Modifications DOI
S. Martin, Jasmin Mecinović

Bioconjugate Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Post-translational modifications (PTMs) on histones play a crucial role in determining the structure and function of chromatin, thereby regulating eukaryotic gene expression. Histone lysine methylation acetylation are among most widespread biomedically important PTMs, with new chemical tools for their examination high demand. Here, we report first use γ-selenalysine as an efficient mimic enzymatic methylation, acetylation, deacetylation reactions catalyzed by histone methyltransferases, acetyltransferases, deacetylase. We also show that easily accessible selenocysteine cysteine residues can undergo chemo- site-selective alkylation to generate both unmodified modified related γ-thialysine peptides. This dual-modification strategy enables site-specific incorporation two distinct functionalities into peptides, mimicking post-translational commonly found histones. Our research presents novel approach which serves unique handle chemoselective introduction selenalysine, along its methylated acetylated analogues. These designed facilitate study epigenetic proteins human health disease.

Language: Английский

Citations

0
20 years of histone lysine demethylases: From discovery to the clinic and beyond DOI

Zach H. Gray,

M. Honer, Pooja Ghatalia

et al.

Cell, Journal Year: 2025, Volume and Issue: 188(7), P. 1747 - 1783

Published: April 1, 2025

Language: Английский

Citations

0
Epigenetic Control of Alveolar Macrophages: Impact on Lung Health and Disease DOI Creative Commons
Nirmal Parajuli, Kalpana Subedi, Xzaviar Kaymar Solone

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(9), P. 640 - 640

Published: April 25, 2025

Alveolar macrophages (AMs) are immune cells located in the alveoli—the tiny air sacs lungs where gas exchange occurs. Their functions regulated by various epigenetic mechanisms, which essential for both healthy lung function and disease development. In lung’s microenvironment, AMs play critical roles surveillance, pathogen clearance, tissue repair. This review examines how regulation influences AM their involvement diseases. Key such as DNA methylation, histone modifications, non-coding RNAs, regulate gene expression response to environmental signals. lungs, these modifications enable quickly respond inhaled threats. However, when processes malfunction, they could contribute diseases pulmonary fibrosis, COPD, hypertension. By exploring changes affect polarization, plasticity, responses, we can gain deeper insights into role open new avenues treating preventing respiratory conditions. Ultimately, understanding mechanisms within enhances our knowledge of immunology offers potential innovative interventions restore health prevent

Language: Английский

Citations

0
Conjunctival MicroRNA Expression Signature in Primary Sjögren's Syndrome Dry Eye: A NanoString-Based Bioinformatic Analysis DOI Creative Commons
Francesca Giovannetti, Paola Pontecorvi, Francesca Megiorni

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(4), P. 80 - 80

Published: April 29, 2025

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by inflammation and tissue destruction of the salivary lacrimal glands, leading to sicca symptoms. Dysregulation microRNAs (miRNAs), key post-transcriptional regulators, has been implicated in pSS, but their role conjunctival epithelial cells (CECs) remains unclear. This study aimed identify altered miRNA expression patterns CEC from patients with pSS potential involvement pathogenesis. samples were collected six healthy controls (HCs) using nylon-tipped swabs. The was profiled NanoString nCounter system minimal RNA input. Differentially expressed (DE) miRNAs identified via ROSALIND software, bioinformatics tools (miRNet miRTargetLink) applied construct miRNA-centric networks, predict target genes, perform pathway enrichment analysis. We 11 DE compared HCs. Key miRNAs, including hsa-miR-548j-3p hsa-miR-219b-3p, are central immune inflammatory regulation pathways. Pathway analysis highlighted processes such as cell regulation, signaling, glandular damage. Dysregulated modulate targets, like TNFAIP3, IL6R, IFNAR1, IL7, ICOSLG, suggesting underscores biomarkers therapeutic targets pSS-associated dry eye disease. Despite limitations small sample size reliance on silico predictions, our findings provide valuable insights into miRNA-mediated responses inflammation, paving way for future diagnostic advancements.

Language: Английский

Citations

0
How does orthodontic tooth movement influence the dental pulp? RNA‐sequencing on human premolars DOI
Zuodong Zhao, Catia Attanasio, Chen Zong

et al.

International Endodontic Journal, Journal Year: 2024, Volume and Issue: 57(12), P. 1783 - 1801

Published: July 31, 2024

The objective of this study is to analyse the gene expression profile dental pulp (DP) human premolars subjected 7 and 28 days orthodontic force (OF) in vivo by using RNA sequencing. maxillary mandibular DP were additionally compared.

Language: Английский

Citations

3