Increased interleukin-6 levels are associated with atrioventricular conduction delay in severe COVID-19 patients.

Background: Severely ill patients with coronavirus disease 2019 (COVID-19) show an increased risk of new-onset atrioventricular blocks (AVBs), associated with high rates of short-term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)-6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL-6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID-19.

CRISPR/Cas9 Ablation of Integrated HIV-1 Accumulates Proviral DNA Circles with Reformed Long Terminal Repeats.

Gene editing may be used to excise the human immunodeficiency virus type 1 (HIV-1) provirus from the host cell genome, possibly eradicating the infection. Here, using cells acutely or latently infected by HIV-1 and treated with long terminal repeat (LTR)-targeting CRISPR/Cas9, we show that the excised HIV-1 provirus persists for a few weeks and may rearrange in circular molecules. Although circular proviral DNA is naturally formed during HIV-1 replication, we observed that gene editing might increase proviral DNA circles with restored LTRs.

Multicolor Immunofluorescence Staining of Paraffin-Embedded Human Bone Marrow Sections.

Immunofluorescence is an indispensable method for the identification, localization and study of the expression of target antigens in formalin-fixed, paraffin-embedded (FFPE) tissue sections of human bone marrow. However, the procedure shows technical limitations because of the chemical and physical treatments required for sample processing before imaging. Here we describe a revisited protocol to obtain high-resolution images of human bone marrow trephine biopsies, improving the antigen-antibody recognition and preserving the morphology and the architecture of the bone marrow microenvironment.

Mesangiogenic Progenitor Cells and musculoskeletal tissue regeneration: differences between adipose-derived and bone marrow-derived cells?

Mesangiogenic Progenitor cells (MPCs) have been isolated from human bone marrow mononuclear cells (hBM-MNCs) and attracted particular attention for their ability to efficiently differentiate into exponentially growing mesenchymal stromal cells (MSCs) and toward endothelial lineage, suggesting the term "mesangiogenic". Coupling mesengenesis and angiogenis, MPCs has been hypothesized retaining a great tissue regenerative potential in musculoskeletal tissues regeneration. Bone marrow and adipose tissue (AT) represent most promising adult multipotent cell sources attempting to repair bone and cartilage, with controversial results regarding advantages applying BM- or AT-derived cells.

Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder.

Treatment-resistance is a frequent condition for obsessive-compulsive disorder (OCD). Over the past decades, a lot of effort has been made to address this issue, and several augmentation strategies of serotonergic drugs have been investigated. Antidopaminergic drugs are considered the first choice as augmentation strategy for treatment-resistant OCD patients, but they seem to work only for a subset of patients, and none of them have been officially approved for OCD.

High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow.

Hematopoiesis is hosted, supported and regulated by a special bone marrow (BM) microenvironment known as "niche." BM niches have been classified based on micro-anatomic distance from the bone surface into "endosteal" and "central" niches. Whilst different blood vessels have been found in both BM niches in mice, our knowledge of the human BM architecture is much more limited.

Effects of ultrasound and selenium on human neurons in vitro.

As the effects of ultrasound on human brain functions might bear therapeutic potential, in this study, we examined the effects of diagnostic, i.e. non-thermal, ultrasound, on morphology, networking, and metabolic activity of SH- SY5Y human neurons in culture, as well as on the expression of GAP-43, Hsp90 and VEGF proteins, with and without selenium in the culture medium.

Cell differentiation in cardiac myxomas: confocal microscopy and gene expression analysis after laser capture microdissection.

Cardiac myxomas are rare tumors with a heterogeneous cell population including properly neoplastic (lepidic), endothelial and smooth muscle cells. The assessment of neoplastic (lepidic) cell differentiation pattern is rather difficult using conventional light microscopy immunohistochemistry and/or whole tissue extracts for mRNA analyses. In a preliminary study, we investigated 20 formalin-fixed and paraffin-embedded cardiac myxomas by means of conventional immunohistochemistry; in 10/20 cases, cell differentiation was also analyzed by real-time RT-PCR after laser capture microdissection of the neoplastic cells, whereas calretinin and endothelial antigen CD31 immunoreactivity was localized in 4/10 cases by double immunofluorescence confocal microscopy.

Treatment with Allogenic Mesenchymal Stromal Cells in a Murine Model of Systemic Lupus Erythematosus.

Objective: Pre-clinical and uncontrolled studies in patients with systemic lupus erythematosus (SLE) showed that mesenchymal stromal cells (MSCs) have a potential therapeutic role in refractory cases. The optimal therapeutic strategy in these patients remain to be elucidated. Our aim was to test the hypothesis that repeated administrations of 1×10/kg body weight of allogenic MSCs, that is a significantly lower dosage with respect to the fixed 1×10 MSC used in animal models, can be effective in improving the clinical course of a murine SLE model.

Mutations Are Common in Thymic Epithelial Tumors But Not in Hematological Malignancies.

Background: Mutation of general transcription factor IIi (GTF2I) (chromosome 7 c.74146970T>A) is common in thymic epithelial tumors and is a candidate driver aberration for cancer growth. To our knowledge, this mutation has not been described in other diseases.

Melanocortin Receptor-4 and Glioblastoma Cells: Effects of the Selective Antagonist ML00253764 Alone and in Combination with Temozolomide In Vitro and In Vivo.

Currently, no description of melanocortin receptor-4 (MC4R) expression or activity is available in human cancer cells, including glioblastoma (GBM). The aim of this study is to evaluate the presence of MC4Rs in GBM cells and the selective inhibition of their activity through the MC4R antagonist ML00253764 alone and in association with temozolomide in vitro and in vivo. MC4R genotyping and gene expression were performed on human GBM cells (U-87 and U-118) with real-time PCR.

Human adult mesangiogenic progenitor cells reveal an early angiogenic potential, which is lost after mesengenic differentiation.

Background: Mesangiogenic progenitor cells (MPCs) have shown the ability to differentiate in-vitro toward mesenchymal stromal cells (MSCs) as well as angiogenic potential. MPCs have so far been described in detail as progenitors of the mesodermal lineage and appear to be of great significance in tissue regeneration and in hemopoietic niche regulation. On the contrary, information regarding the MPC angiogenic process is still incomplete and requires further clarification.

Nanotopography Induced Human Bone Marrow (MPCs) to (MSCs) Transition.

(MPCs) are a very peculiar population of cells present in the human adult bone marrow, only recently discovered and characterized. Owing to their differentiation potential, MPCs can be considered progenitors for mesenchymal stromal cells (MSCs), and for this reason they potentially represent a promising cell population to apply for skeletal tissue regeneration applications. Here, we evaluate the effects of surface nanotopography on MPCs, considering the possibility that this specific physical stimulus alone can trigger MPC differentiation toward the mesenchymal lineage.

Is chondroitin sulfate responsible for the biological effects attributed to the GC protein-derived Macrophage Activating Factor (GcMAF)?

We hypothesize that a plasma glycosaminoglycan, chondroitin sulfate, may be responsible for the biological and clinical effects attributed to the Gc protein-derived Macrophage Activating Factor (GcMAF), a protein that is extracted from human blood. Thus, Gc protein binds chondroitin sulfate on the cell surface and such an interaction may occur also in blood, colostrum and milk. This interpretation would solve the inconsistencies encountered in explaining the effects of GcMAF in vitro and in vivo.

Human mesenchymal stromal cell-enhanced osteogenic differentiation by contact interaction with polyethylene terephthalate nanogratings.

Among the very large number of polymeric materials that have been proposed in the field of orthopedics, polyethylene terephthalate (PET) is one of the most attractive thanks to its flexibility, thermal resistance, mechanical strength and durability. Several studies have been proposed that interface nano- or micro-structured surfaces with mesenchymal stromal cells (MSCs), demonstrating the potential of this technology for promoting osteogenesis. All these studies were carried out on biomaterials other than PET, which remains almost uninvestigated in terms of cell shaping, alignment and differentiation.