An immunosenescent CD8+ T cell subset in patients with axial Spondyloarthritis and Psoriatic Arthritis links spontaneous motility to telomere shortening and dysfunction.

Objective: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies (GWAS) and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells, along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA).

Methods: Peripheral blood CD8+ and CD4+ T cells were isolated from r-axSpA (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79).

The GLP-1R agonist semaglutide reshapes pancreatic cancer associated fibroblasts reducing collagen proline hydroxylation and favoring T lymphocyte infiltration.

Background: Metabolic syndrome represents a pancreatic ductal adenocarcinoma (PDAC) risk factor. Metabolic alterations favor PDAC onset, which occurs early upon dysmetabolism. Pancreatic neoplastic lesions evolve within a dense desmoplastic stroma, consisting in abundant extracellular matrix settled by cancer associated fibroblasts (CAFs).

Inflammation promotes stomach epithelial defense by stimulating the secretion of antimicrobial peptides in the mucus.

The mucus serves as a protective barrier in the gastrointestinal tract against microbial attacks. While its role extends beyond merely being a physical barrier, the extent of its active bactericidal properties remains unclear, and the mechanisms regulating these properties are not yet understood. We propose that inflammation induces epithelial cells to secrete antimicrobial peptides, transforming mucus into an active bactericidal agent.

To Erase or Not to Erase: Non-Canonical Catalytic Functions and Non-Catalytic Functions of Members of Histone Lysine Demethylase Families.

Histone lysine demethylases (KDMs) play an essential role in biological processes such as transcription regulation, RNA maturation, transposable element control, and genome damage sensing and repair. In most cases, their action requires catalytic activities, but non-catalytic functions have also been shown in some KDMs. Indeed, some strictly KDM-related proteins and some KDM isoforms do not act as histone demethylase but show other enzymatic activities or relevant non-enzymatic functions in different cell types.

Modulating the skin mycobiome-bacteriome and treating seborrheic dermatitis with a probiotic-enriched oily suspension.

Seborrheic dermatitis (SD) affects 2-5% of the global population, with imbalances in the skin microbiome implicated in its development. This study assessed the impact of an oily suspension containing Lactobacillus crispatus P17631 and Lacticaseibacillus paracasei I1688 (termed EUTOPLAC) on SD symptoms and the skin mycobiome-bacteriome modulation. 25 SD patients were treated with EUTOPLAC for a week.

Dbx2, an Aging-Related Homeobox Gene, Inhibits the Proliferation of Adult Neural Progenitors.

In the adult mouse brain, the subventricular zone (SVZ) underlying the lateral ventricles harbours a population of quiescent neural stem cells, which can be activated (aNSCs) to initiate proliferation and generate a neurogenic lineage consisting of transit amplifying progenitors (TAPs), neuroblasts (NBs) and newborn neurons. This process is markedly reduced during aging. Recent studies suggest that the aged SVZ niche decreases the pool of proliferating neural/stem progenitor cells (NSPCs), and hence adult neurogenesis, by causing transcriptomic changes that promote NSC quiescence.

H3 Lysine 4 Methylation Is Required for Full Activation of Genes Involved in α-Ketoglutarate Availability in the Nucleus of Yeast Cells after Diauxic Shift.

We show that in the metabolic diauxic shift is associated with a H3 lysine 4 tri-methylation (H3K4me3) increase which involves a significant fraction of transcriptionally induced genes which are required for the metabolic changes, suggesting a role for histone methylation in their transcriptional regulation. We show that histone H3K4me3 around the start site correlates with transcriptional induction in some of these genes. Among the methylation-induced genes are and , which regulate the nuclear availability of α-ketoglutarate, which, as a cofactor for Jhd2 demethylase, regulates H3K4 tri-methylation.

A truncated and catalytically inactive isoform of KDM5B histone demethylase accumulates in breast cancer cells and regulates H3K4 tri-methylation and gene expression.

KDM5B histone demethylase is overexpressed in many cancers and plays an ambivalent role in oncogenesis, depending on the specific context. This ambivalence could be explained by the expression of KDM5B protein isoforms with diverse functional roles, which could be present at different levels in various cancer cell lines. We show here that one of these isoforms, namely KDM5B-NTT, accumulates in breast cancer cell lines due to remarkable protein stability relative to the canonical PLU-1 isoform, which shows a much faster turnover.

Simulated Microgravity Modulates Focal Adhesion Gene Expression in Human Neural Stem Progenitor Cells.

We analyzed the morphology and the transcriptomic changes of human neural stem progenitor cells (hNSPCs) grown on laminin in adherent culture conditions and subjected to simulated microgravity for different times in a random positioning machine apparatus. Low-cell-density cultures exposed to simulated microgravity for 24 h showed cell aggregate formation and significant modulation of several genes involved in focal adhesion, cytoskeleton regulation, and cell cycle control. These effects were much more limited in hNSPCs cultured at high density in the same conditions.

GZMK CD8 T effector memory cells are associated with CD15 neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome.

CD8 T cells are a major prognostic determinant in solid tumors, including colorectal cancer (CRC). However, understanding how the interplay between different immune cells impacts on clinical outcome is still in its infancy. Here, we describe that the interaction of tumor infiltrating neutrophils expressing high levels of CD15 with CD8 T effector memory cells (T) correlates with tumor progression.

The RNA helicase DDX5 cooperates with EHMT2 to sustain alveolar rhabdomyosarcoma growth.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. The alveolar fusion positive subtype (FP-RMS) is the most aggressive and is mainly caused by the expression of PAX3/7-FOXO1 oncoproteins, which are challenging pharmacological targets. Here, we show that the DEAD box RNA helicase 5 (DDX5) is overexpressed in alveolar RMS cells and that its depletion and pharmacological inhibition decrease FP-RMS viability and slow tumor growth in xenograft models.

An integrative in-silico analysis discloses a novel molecular subset of colorectal cancer possibly eligible for immune checkpoint immunotherapy.

Background: Historically, the molecular classification of colorectal cancer (CRC) was based on the global genomic status, which identified microsatellite instability in mismatch repair (MMR) deficient CRC, and chromosomal instability in MMR proficient CRC. With the introduction of immune checkpoint inhibitors, the microsatellite and chromosomal instability classification regained momentum as the microsatellite instability condition predicted sensitivity to immune checkpoint inhibitors, possibly due to both high tumor mutation burden (TMB) and high levels of infiltrating lymphocytes. Conversely, proficient MMR CRC are mostly resistant to immunotherapy.

Corrigendum: The Role of Histone Lysine Methylation in the Response of Mammalian Cells to Ionizing Radiation.

[This corrects the article DOI: 10.3389/fgene.2021.

DNMT3A epigenetically regulates key microRNAs involved in epithelial-to-mesenchymal transition in prostate cancer.

Epithelial-to-mesenchymal transition (EMT) is involved in prostate cancer (PCa) metastatic progression, and its plasticity suggests epigenetic implications. Deregulation of DNA methyltransferases (DNMTs) and several microRNAs (miRNAs) plays a relevant role in EMT, but their interplay has not been clarified yet. In this study, we provide evidence that DNMT3A interaction with several miRNAs has a central role in an ex vivo EMT PCa model obtained via exposure of PC3 cells to conditioned media from cancer-associated fibroblasts.

A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.

MYCN drives aggressive behavior and refractoriness to chemotherapy, in several tumors. Since MYCN inactivation in clinical settings is not achievable, alternative vulnerabilities of MYCN-driven tumors need to be explored to identify more effective and less toxic therapies. We previously demonstrated that PARP inhibitors enhance MYCN-induced replication stress and promote mitotic catastrophe, counteracted by CHK1.

An Overview of the Computational Models Dealing with the Regulatory ceRNA Mechanism and ceRNA Deregulation in Cancer.

Pools of RNA molecules can act as competing endogenous RNAs (ceRNAs) and indirectly alter their expression levels by competitively binding shared microRNAs. This ceRNA cross talk yields an additional posttranscriptional regulatory layer, which plays key roles in both physiological and pathological processes. MicroRNAs can act as decoys by binding multiple RNAs, as well as RNAs can act as ceRNAs by competing for binding multiple microRNAs, leading to many cross talk interactions that could favor significant large-scale effects in spite of the weakness of single interactions.

The Role of Histone Lysine Methylation in the Response of Mammalian Cells to Ionizing Radiation.

Eukaryotic genomes are wrapped around nucleosomes and organized into different levels of chromatin structure. Chromatin organization has a crucial role in regulating all cellular processes involving DNA-protein interactions, such as DNA transcription, replication, recombination and repair. Histone post-translational modifications (HPTMs) have a prominent role in chromatin regulation, acting as a sophisticated molecular code, which is interpreted by HPTM-specific effectors.

Biallelic variants in cause a severe neurodevelopmental disorder with microcephaly, bilateral cataract, epilepsy and simplified gyration.

Background: Next-generation sequencing, combined with international pooling of cases, has impressively enhanced the discovery of genes responsible for Mendelian neurodevelopmental disorders, particularly in individuals affected by clinically undiagnosed diseases. To date, biallelic missense variants in gene, encoding a Krüppel-type zinc-finger protein, have been reported in three families with non-syndromic intellectual disability.

Methods: Here, we describe five individuals from four unrelated families with an undiagnosed neurodevelopmental disorder in which we performed exome sequencing, on a combination of trio-based (4 subjects) or single probands (1 subject).