Interleukin-6 transcripts up-regulation in lymph nodes from unicentric and multicentric Castleman disease.

Introduction: Castleman disease (CD) represents a spectrum of heterogeneous lymphoproliferative disorders sharing peculiar histopathological features, clinically subdivided into unicentric CD (UCD) and multicentric CD (MCD) and presenting with variable inflammatory symptoms. Interleukin (IL)-6 and other cytokines play a major role in mediating CD inflammatory manifestations. Although the local microenvironment seems to be among the major sources of hypercytokinemia, the precise cellular origin of IL-6 production in CD is still debated.

Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation.

Cerebral cavernous malformation (CCM) is a neurovascular disease with symptoms such as strokes, hemorrhages and neurological deficits. With surgery being the only treatment strategy, understanding the molecular mechanisms of CCM is crucial in finding alternative therapeutic options for CCM. Neutrophil extracellular traps (NETs) were recently reported in CCM, and NETs were shown to have positive or negative effects in different disease contexts.

HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.

Senescent cells are commonly detected in tumors after chemo and radiotherapy, leading to a characteristic cellular phenotype that resists apoptotic cell death. In this study, we used multiple melanoma cell lines, molecular markers, and therapies to investigate the key role of the BCL-2 family proteins in the survival of senescent cells. We first used BH3 profiling to assess changes in apoptotic priming upon senescence induction.

LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8 T cell responsiveness.

The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone.

Tumor microenvironment of Burkitt lymphoma: different immune signatures with different clinical behavior.

Burkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform.

Extracellular vesicles secreted by cumulus cells contain microRNAs that are potential regulatory factors of mouse oocyte developmental competence.

The role of cumulus cells (CCs) in the acquisition of oocyte developmental competence is not yet fully understood. In a previous study, we matured cumulus-denuded fully-grown mouse oocytes to metaphase II (MII) on a feeder layer of CCs (FL-CCs) isolated from developmentally competent (FL-SN-CCs) or incompetent (FL-NSN-CCs) SN (surrounded nucleolus) or NSN (not surrounding nucleolus) oocytes, respectively. We observed that oocytes cultured on the former could develop into blastocysts, while those matured on the latter arrested at the 2-cell stage.

Discovery of YAP1/TAZ pathway inhibitors through phenotypic screening with potent anti-tumor activity via blockade of Rho-GTPase signaling.

This study describes the identification and target deconvolution of small molecule inhibitors of oncogenic Yes-associated protein (YAP1)/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay.

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.

Morphomics via next-generation electron microscopy.

The living body is composed of innumerable fine and complex structures. Although these structures have been studied in the past, a vast amount of information pertaining to them still remains unknown. When attempting to observe these ultra-structures, the use of electron microscopy (EM) has become indispensable.

Cell stretching activates an ATM mechano-transduction pathway that remodels cytoskeleton and chromatin.

Ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) DNA damage response (DDR) kinases contain elastic domains. ATM also responds to reactive oxygen species (ROS) and ATR to nuclear mechanical stress. Mre11 mediates ATM activation following DNA damage; ATM mutations cause ataxia telangiectasia (A-T).

Position paper of the Italian association of medical oncology on health disparities among transgender and gender-diverse people: the Assisi recommendations.

Transgender and gender-diverse individuals experience substantial health disparities across the cancer care continuum. Despite well recognized unique healthcare needs, there are barriers in accessing cancer prevention and treatment services, influenced by disadvantages in key social-economic determinants of health which result in worse clinical outcomes, as compared to the general population. The Italian Association of Medical Oncology (AIOM) acknowledges the critical relevance of this issue.

Mechanisms controlling the mechanical properties of the nuclei.

The mechanical properties of the nucleus influence different cellular and nuclear functions and have relevant implications for several human diseases. The nucleus protects genetic information while acting as a mechano-sensory hub in response to internal and external forces. Cells have evolved mechano-transduction signaling to respond to physical cellular and nuclear perturbations and adopted a multitude of molecular pathways to maintain nuclear shape stability and prevent morphological abnormalities of the nucleus.

Cancer care in transgender and gender-diverse persons: results from two national surveys among providers and health service users by the Italian Association of Medical Oncology.

Background: Transgender and gender-diverse (TGD) population represents an underserved group across the cancer care continuum. To assess the perspective of both oncology health care providers (OHPs) and TGD individuals in Italy, we conducted two national surveys: one among 2407 OHPs about their attitudes, knowledge and behavior toward TGD patients, and one among TGD persons about their health needs, experiences and barriers encountered in the use of health services across the cancer continuum.

Materials And Methods: The surveys were self-compiled web-based computer-aided web interview, conducted in Italy within the 'OncoGender-Promoting Inclusion in Oncology' project, led by the Italian national cancer society [Associazione Italiana di Oncologia Medica (AIOM)]-associated researchers.

Direct observation of motor protein stepping in living cells using MINFLUX.

Dynamic measurements of molecular machines can provide invaluable insights into their mechanism, but these measurements have been challenging in living cells. Here, we developed live-cell tracking of single fluorophores with nanometer spatial and millisecond temporal resolution in two and three dimensions using the recently introduced super-resolution technique MINFLUX. Using this approach, we resolved the precise stepping motion of the motor protein kinesin-1 as it walked on microtubules in living cells.

Identification of 2-Aminoacyl-1,3,4-thiadiazoles as Prostaglandin E and Leukotriene Biosynthesis Inhibitors.

The application of a multi-step scientific workflow revealed an unprecedented class of PGE/leukotriene biosynthesis inhibitors with activity. Specifically, starting from a combinatorial virtual library of ∼4.2 × 10 molecules, a small set of compounds was identified for the synthesis.

ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen.

ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). ATM prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis after ATM loss. Here, we report that ATM controls the early transcriptional response to estrogens.

Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer.

The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei.

CHD8 suppression impacts on histone H3 lysine 36 trimethylation and alters RNA alternative splicing.

Disruptive mutations in the chromodomain helicase DNA-binding protein 8 gene (CHD8) have been recurrently associated with autism spectrum disorders (ASDs). Here we investigated how chromatin reacts to CHD8 suppression by analyzing a panel of histone modifications in induced pluripotent stem cell-derived neural progenitors. CHD8 suppression led to significant reduction (47.

Corrigendum: The use of progeroid DNA repair-deficient mice for assessing anti-aging compounds, illustrating the benefits of nicotinamide riboside.

[This corrects the article DOI: 10.3389/fragi.2022.

Characterization of Mitochondrial Alterations in Aicardi-Goutières Patients Mutated in and Genes.

Aicardi-Goutières syndrome (AGS) is a rare encephalopathy characterized by neurological and immunological features. Mitochondrial dysfunctions may lead to mitochondrial DNA (mtDNA) release and consequent immune system activation. We investigated the role of mitochondria and mtDNA in AGS pathogenesis by studying patients mutated in and genes.

Association between SARS-CoV-2 RNAemia and dysregulated immune response in acutely ill hospitalized COVID-19 patients.

Severe/critical COVID-19 is associated with immune dysregulation and plasmatic SARS-CoV-2 detection (i.e. RNAemia).

The use of progeroid DNA repair-deficient mice for assessing anti-aging compounds, illustrating the benefits of nicotinamide riboside.

Despite efficient repair, DNA damage inevitably accumulates with time affecting proper cell function and viability, thereby driving systemic aging. Interventions that either prevent DNA damage or enhance DNA repair are thus likely to extend health- and lifespan across species. However, effective genome-protecting compounds are largely lacking.