Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer due to its high heterogeneity that drives tumor aggressiveness. Melanoma plasticity consists of two distinct phenotypic states that co-exist in the tumor niche, the proliferative and the invasive, respectively associated with a high and low expression of MITF, the master regulator of melanocyte lineage. However, despite efforts, melanoma research is still far from exhaustively dissecting this phenomenon.

Qualitative and semi-quantitative ultrasound assessment in delta and Omicron Covid-19 patients: data from high volume reference center.

Objective: to evaluate the efficacy of US, both qualitatively and semi-quantitatively, in the selection of treatment for the Covid-19 patient, using patient triage as the gold standard.

Methods: Patients admitted to the Covid-19 clinic to be treated with monoclonal antibodies (mAb) or retroviral treatment and undergoing lung ultrasound (US) were selected from the radiological data set between December 2021 and May 2022 according to the following inclusion criteria: patients with proven Omicron variant and Delta Covid-19 infection; patients with known Covid-19 vaccination with at least two doses. Lung US (LUS) was performed by experienced radiologists.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

Epidemiology, Clinical Presentation and Treatment of Non-Hepatic Hyperammonemia in ICU COVID-19 Patients.

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data.

Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients over a Year in the Intensive Care Unit.

Background: The benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high-risk procedure for the transmission of SARS-CoV-2 to healthcare workers (HCWs). The present study analyzed the optimal timing of PDT, the clinical outcomes of patients undergoing PDT, and the safety of HCWs performing PDT.

Transglutaminase Type 2 regulates the Wnt/β-catenin pathway in vertebrates.

TG2 is a multifunctional enzyme involved in several cellular processes and has emerging as a potential regulator of gene expression. In this regard, we have recently shown that TG2 is able to activate HSF1, the master transcriptional regulator of the stress-responsive genes; however, its effect on the overall gene expression remains unclear. To address this point, we analyzed, by RNA-seq, the effect of TG2 on the overall transcriptome as well as we characterized the TG2 interactome in the nucleus.

COVID-19 infection: the China and Italy perspectives.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Since its first report in December 2019, despite great efforts made in almost every country worldwide, this disease continues to spread globally, especially in most parts of Europe, Iran, and the United States. Here, we update the recent understanding in clinical characteristics, diagnosis strategies, as well as clinical management of COVID-19 in China as compared to Italy, with the purpose to integrate the China experience with the global efforts to outline references for prevention, basic research, treatment as well as final control of the disease.

Effective Synergy of Sorafenib and Nutrient Shortage in Inducing Melanoma Cell Death through Energy Stress.

Skin melanoma is one of the most aggressive and difficult-to-treat human malignancies, characterized by poor survival rates, thus requiring urgent novel therapeutic approaches. Although metabolic reprogramming has represented so far, a cancer hallmark, accumulating data indicate a high plasticity of cancer cells in modulating cellular metabolism to adapt to a heterogeneous and continuously changing microenvironment, suggesting a novel therapeutic approach for dietary manipulation in cancer therapy. To this aim, we exposed melanoma cells to combined nutrient-restriction/sorafenib.

Genistein antagonizes gliadin-induced CFTR malfunction in models of celiac disease.

In celiac disease (CD), an intolerance to dietary gluten/gliadin, antigenic gliadin peptides trigger an HLA-DQ2/DQ8-restricted adaptive Th1 immune response. Epithelial stress, induced by other non-antigenic gliadin peptides, is required for gliadin to become fully immunogenic. We found that cystic-fibrosis-transmembrane-conductance-regulator (CFTR) acts as membrane receptor for gliadin-derived peptide P31-43, as it binds to CFTR and impairs its channel function.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes.

Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis.

The secretome of human amniotic fluid stem cells (AFSCs) has great potential as a therapeutic agent in regenerative medicine. However, it must be produced in a clinically compliant manner before it can be used in humans. In this study, we developed a means of producing a biologically active secretome from AFSCs that is free of all exogenous molecules.

Glutamate induces autophagy via the two-pore channels in neural cells.

NAADP (nicotinic acid adenine dinucleotide phosphate) has been proposed as a second messenger for glutamate in neuronal and glial cells via the activation of the lysosomal Ca2+ channels TPC1 and TPC2. However, the activities of glutamate that are mediated by NAADP remain unclear. In this study, we evaluated the effect of glutamate on autophagy in astrocytes at physiological, non-toxic concentration.

Modulation of Phenotype and Function of Human CD4CD25 T Regulatory Lymphocytes Mediated by cAMP-Elevating Agents.

We have shown that cholera toxin (CT) and other cyclic AMP (cAMP)-elevating agents induce upregulation of the inhibitory molecule CTLA-4 in human resting CD4 T lymphocytes, which following the treatment acquired suppressive functions. In this study, we evaluated the effect of cAMP-elevating agents on human CD4CD25 T cells, which include the T regulatory cells (Tregs) that play a pivotal role in the maintenance of immunological tolerance. We found that cAMP-elevating agents induce upregulation of CTLA-4 in CD4CD25 and further enhance its expression in CD4CD25 T cells.

Fasting boosts sensitivity of human skin melanoma to cisplatin-induced cell death.

Melanoma is one of leading cause of tumor death worldwide. Anti-cancer strategy includes combination of different chemo-therapeutic agents as well as radiation; however these treatments have limited efficacy and induce significant toxic effects on healthy cells. One of most promising novel therapeutic approach to cancer therapy is the combination of anti-cancer drugs with calorie restriction.

Autophagy in malignant transformation and cancer progression.

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy.

Atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: 96-week analysis results of the MODAT study.

Introduction: The 48-week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB recommended stopping study enrollment but continuing follow-up of enrolled patients. We present the 96-week efficacy analysis.

Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression: 48-week efficacy and safety results.

Objectives: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml.

Methods: A multicentre, randomized, open-label, noninferiority trial.

Ambra1 at the crossroad between autophagy and cell death.

Autophagy is a self-digesting mechanism responsible for the degradation and recycling of most intracellular macromolecules and the removal of damaged organelles by the lysosome. An impressive number of recent studies have provided key information about the regulation of autophagy and its role in cell survival during nutrient depletion and many other stressful situations. In particular, many evidences have highlighted a crucial role of dysregulated autophagy in oncogenesis.

Molecular diagnosis and species identification of imported malaria in returning travellers in Italy.

A new seminested polymerase chain reaction (sn-PCR)-based protocol was developed and used to detect and identify Plasmodium species in 1226 whole-blood samples from patients (872 Italians and 354 foreigners) with at least 1 symptom compatible with clinical malaria. The results were compared with those obtained by microscopy: 187 samples were positive by microscopy for malaria parasites and 196 were positive by sn-PCR. When compared to microscopy, the sn-PCR detected different malaria parasite species in 11 cases.

Regulation of autophagy in mammals and its interplay with apoptosis.

A growing number of publications show that apoptosis induction is often associated with increased autophagy indicating the existence of an interplay between these two important cellular events. The simultaneous activation of both phenomena has been detected not only in experimental settings but also in vivo under physiological and pathological conditions. Despite these studies, the reciprocal influence of the two pathways in vivo has still not been completely understood.

Scavenging of reactive nitrogen species by mycobacterial truncated hemoglobins.

Tuberculosis and leprosy are among the most challenging infectious threats to human health. The ability of mycobacteria to persist in vivo in the presence of reactive nitrogen and oxygen species implies the presence in these bacteria of effective detoxification (pseudoenzymatic) systems. Mycobacterium tuberculosis and Mycobacterium leprae truncated hemoglobins (trHbs) belonging to group I (or N; trHbN) and group II (or O; trHbO) have recently been implicated in the scavenging of nitrogen monoxide (*NO) and peroxynitrite (ONOO-/HOONO).