Maternal Salivary miR-423-5p Is Linked to Neonatal Outcomes and Periodontal Status in Cardiovascular-High-Risk Pregnancies.

Periodontal disease (PD) during pregnancy may trigger systemic inflammation, increasing the risk of developing cardiometabolic disease (CMD). As a consequence, PD may result in the activation of cellular and molecular pathways, affecting the disease course and pregnancy outcome. Although microRNAs (miRNAs) are considered ideal biomarkers for many diseases, few studies have investigated salivary miRNAs and their role in pregnancy or neonatal outcomes.

Systematic epigenome editing captures the context-dependent instructive function of chromatin modifications.

Chromatin modifications are linked with regulating patterns of gene expression, but their causal role and context-dependent impact on transcription remains unresolved. Here we develop a modular epigenome editing platform that programs nine key chromatin modifications, or combinations thereof, to precise loci in living cells. We couple this with single-cell readouts to systematically quantitate the magnitude and heterogeneity of transcriptional responses elicited by each specific chromatin modification.

Metabolic disorders affecting the liver and heart: Therapeutic efficacy of miRNA-based therapies?

Liver and heart disease are major causes of death worldwide. It is known that metabolic alteration causing type 2 diabetes (T2D) and Nonalcoholic fatty liver (NAFLD) coupled with a derangement in lipid homeostasis, may exacerbate hepatic and cardiovascular diseases. Some pharmacological treatments can mitigate organ dysfunctions but the important side effects limit their efficacy leading often to deterioration of the tissues.

Vaccination against influenza viruses reduces infection, not hospitalization or death, from respiratory COVID-19: A systematic review and meta-analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and has brought a huge burden in terms of human lives. Strict social distance and influenza vaccination have been recommended to avoid co-infections between influenza viruses and SARS-CoV-2. Scattered reports suggested a protective effect of influenza vaccine on COVID-19 development and severity.

The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions.

Interleukin-10 (IL-10) is a pleiotropic cytokine that has a fundamental role in modulating inflammation and in maintaining cell homeostasis. It primarily acts as an anti-inflammatory cytokine, protecting the body from an uncontrolled immune response, mostly through the Jak1/Tyk2 and STAT3 signaling pathway. On the other hand, IL-10 can also have immunostimulating functions under certain conditions.

Esrrb guides naive pluripotent cells through the formative transcriptional programme.

During embryonic development, naive pluripotent epiblast cells transit to a formative state. The formative epiblast cells form a polarized epithelium, exhibit distinct transcriptional and epigenetic profiles and acquire competence to differentiate into all somatic and germline lineages. However, we have limited understanding of how the transition to a formative state is molecularly controlled.

Extracts and Associated Carotenoid Fucoxanthin Downregulate Pro-Angiogenic Mediators on Prostate Cancer and Endothelial Cells.

The exploration of natural preventive molecules for nutraceutical and pharmaceutical use has recently increased. In this scenario, marine microorganisms represent an underestimated source of bioactive products endowed with beneficial effects on health that include anti-oxidant, anti-inflammatory, differentiating, anti-tumor, and anti-angiogenic activities. Here, we tested the potential chemopreventive and anti-angiogenic activities of an extract from the marine coastal diatom Sarno and Zingone () on prostate cancer (PCa) and endothelial cells.

Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy.

Objective: Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the assessment of the effects of exogenous IL-10 on SARS-CoV-2-specific-response using a whole-blood platform.

Methods: Two cohorts were evaluated: in "study population A", plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized "COVID-19 patients" and 29 "NO COVID-19 controls" all unvaccinated.

Overcoming Resistance to Checkpoint Inhibitors: Natural Killer Cells in Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatments over the last 10 years, with even increasing indications in many neoplasms. Non-small cell lung cancer (NSCLC) is considered highly immunogenic, and ICIs have found a wide set of applications in this area, in both early and advanced lines of treatment, significantly changing the prognosis of these patients. Unfortunately, not all patients can benefit from the treatment, and resistance to ICIs can develop at any time.

Epigenetic inheritance is gated by naïve pluripotency and Dppa2.

Environmental factors can trigger cellular responses that propagate across mitosis or even generations. Perturbations to the epigenome could underpin such acquired changes, however, the extent and contexts in which modified chromatin states confer heritable memory in mammals is unclear. Here, we exploit a precision epigenetic editing strategy and forced Xist activity to programme de novo heterochromatin domains (epialleles) at endogenous loci and track their inheritance in a developmental model.

Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis.

Angiotensin-converting enzyme 2 (ACE2) is a receptor for the spike protein of SARS-COV-2 that allows viral binding and entry and is expressed on the surface of several pulmonary and non-pulmonary cell types, with induction of a "cytokine storm" upon binding. Other cell types present the receptor and can be infected, including cardiac, renal, intestinal, and endothelial cells. High ACE2 levels protect from inflammation.

TIMP1 and TIMP2 Downregulate TGFβ Induced Decidual-like Phenotype in Natural Killer Cells.

Natural Killer (NK) cells have been found to be anergic, exhausted and pro-angiogenic in cancers. NK cell from healthy donors, exposed to TGFβ, acquire the CD56CD9CD49a decidual-like-phenotype, together with decreased levels of NKG2D activation marker, increased levels of TIM-3 exhaustion marker, similar to cancer-associated NK cells. Tissue inhibitors of metalloproteases (TIMPs) exert dual roles in cancer.

Genome-Scale CRISPR Screening for Regulators of Cell Fate Transitions.

Knockout CRISPR screening enables the unbiased discovery of genes with a functional role in almost any cellular or molecular process of interest. The approach couples a genome-scale library of guide RNA (gRNA), the Cas9 endonuclease, and a faithful phenotypic read-out to systematically identify candidate genes via their loss-of-function effect. Here we provide a detailed description of the CRISPR screen protocol and outline how to apply it to decipher the gene networks that underlie developmental cell fate decisions.

CLIC1 Protein Accumulates in Circulating Monocyte Membrane during Neurodegeneration.

Pathologies that lead to neurodegeneration in the central nervous system (CNS) represent a major contemporary medical challenge. Neurodegenerative processes, like those that occur in Alzheimer's disease (AD) are progressive, and at the moment, they are unstoppable. Not only is an adequate therapy missing but diagnosis is also extremely complicated.

Repurposed Biguanide Drugs in Glioblastoma Exert Antiproliferative Effects via the Inhibition of Intracellular Chloride Channel 1 Activity.

The lack of in-depth knowledge about the molecular determinants of glioblastoma (GBM) occurrence and progression, combined with few effective and BBB crossing-targeted compounds represents a major challenge for the discovery of novel and efficacious drugs for GBM. Among relevant molecular factors controlling the aggressive behavior of GBM, chloride intracellular channel 1 (CLIC1) represents an emerging prognostic and predictive biomarker, as well as a promising therapeutic target. CLIC1 is a metamorphic protein, co-existing as both soluble cytoplasmic and membrane-associated conformers, with the latter acting as chloride selective ion channel.

Mutual Influence of ROS, pH, and CLIC1 Membrane Protein in the Regulation of G-S Phase Progression in Human Glioblastoma Stem Cells.

Glioblastoma (GB) is the most lethal, aggressive, and diffuse brain tumor. The main challenge for successful treatment is targeting the cancer stem cell (CSC) subpopulation responsible for tumor origin, progression, and recurrence. Chloride Intracellular Channel 1 (CLIC1), highly expressed in CSCs, is constitutively present in the plasma membrane where it is associated with chloride ion permeability.

Molecular Mechanism of DNA Topoisomerase I-Dependent rDNA Silencing: Sir2p Recruitment at Ribosomal Genes.

Saccharomyces cerevisiae sir2Δ or top1Δ mutants exhibit similar phenotypes involving ribosomal DNA, including (i) loss of transcriptional silencing, resulting in non-coding RNA hyperproduction from cryptic RNA polymerase II promoters; (ii) alterations in recombination; and (iii) a general increase in histone acetylation. Given the distinct enzymatic activities of Sir2 and Top1 proteins, a histone deacetylase and a DNA topoisomerase, respectively, we investigated whether genetic and/or physical interactions between the two proteins could explain the shared ribosomal RNA genes (rDNA) phenotypes. We employed an approach of complementing top1Δ cells with yeast, human, truncated, and chimeric yeast/human TOP1 constructs and of assessing the extent of non-coding RNA silencing and histone H4K16 deacetylation.