SART1 modulates poly-(ADP-ribose) chain accumulation and PARP1 chromatin localization.

PARP1 inhibitors (PARPis) are used for treatment of cancers with mutations in or that are deficient in homologous recombination. The identification of modulators of PARP1 activity is critical to understand and overcome resistance to PARPis. We integrated data from three omics-scale screens to discover new regulators of PARP1 activity.

Pursuing Polypharmacology: Benzothiopyranoindoles as G-Quadruplex Stabilizers and Topoisomerase I Inhibitors for Effective Anticancer Strategies.

Here, we explored the benzothiopyranoindole scaffold to develop antiproliferative agents with a polypharmacological profile targeting both G-quadruplex (G4)-structures and Topoisomerase (Topo) I enzyme. In a preliminary optimization phase, compound was selected from an in-house collection as a suitable lead for the rational development of a small library of analogs (-). When assayed in NIH's NCI-60 Human Cancer Cell Line In Vitro Screen Program, compound and its demethylated analogue showed significant antiproliferative/cytotoxic activity.

Urineprint of high-altitude: Insights from analyses of urinary biomarkers and bio-physical-chemical features of extracellular vesicles.

Humans exposed to altitude hypoxia experience dysfunctions of the urinary system. As a non-invasive, easily manageable and informative biological sample, urine represents a relevant matrix for detecting clinical impairments of urinary system, as well as alterations of other systems and extracellular vesicles (EVs) biology during high-altitude expeditions. Nevertheless, gaps exist in the comprehensive assessment of dysfunction, molecular burden and EVs biology due to high-altitude acute exposure.

Precision sampling of discrete sites identified during in-vivo functional testing in the mammalian heart.

Ventricular arrhythmias after myocardial infarction (MI) originate from discrete areas within the MI border zone (BZ), identified during functional electrophysiology tests. Accurate sampling of arrhythmogenic sites for ex-vivo study remains challenging, yet is critical to identify their tissue, cellular and molecular signature. In this study, we developed, validated, and applied a targeted sampling methodology based on individualized 3D prints of the human-sized pig heart.

The cards they're dealt: types of gambling activity, online gambling, and risk of problem gambling in European adolescents.

Objective: This study aims to identify risk factors associated with gambling engagement and the likelihood of problem behavior, distinguishing by type of gambling activity and examining the impact of online gambling.

Methods: Data about 85,420 students aged 16 from 33 countries participating in the 2019 European School Survey Project on Alcohol and Other Drugs (ESPAD) were analyzed through a three-stage sequential probit model, specifically focusing on four types of activity: lotteries, slot machines, cards, and betting. Furthermore, predicted probabilities were calculated for subsamples of students engaging in different types of gambling activities to explore their influence on the likelihood of problem gambling behavior, conditioned on online gambling involvement.

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2).

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS).

Decompression Illness After Technical Diving Session in Mediterranean Sea: Oxidative Stress, Inflammation, and HBO Therapy.

SCUBA diving poses risks due to pressure changes during descent (compression) and ascent (decompression). Decompression sickness (DCS) occurs due to gas bubble formation as the pressure decreases, causing joint pain, numbness, dizziness, or even paralysis and death. Immediate treatment involves 100% oxygen to help eliminate inert gases and hyperbaric oxygen therapy (HBOT), which is essential to reduce gas emboli formation and inflammation, thus improving symptoms.

Discovery of -substituted-2-oxoindolin benzoylhydrazines as c-MET/SMO modulators in EGFRi-resistant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), the leading cause of cancer-related mortality worldwide, poses a formidable challenge due to its heterogeneity and the emergence of resistance to targeted therapies. While initially effective, first- and third-generation EGFR-tyrosine kinase inhibitors (TKIs) often fail to control disease progression, leaving patients with limited treatment options. To address this unmet medical need, we explored the therapeutic potential of multitargeting agents that simultaneously inhibit two key signalling pathways, the mesenchymal-epithelial transition factor (c-MET) and the G protein-coupled receptor Smoothened (SMO), frequently dysregulated in NSCLC.

Different effects of cardiomyocyte contractile activity on transverse and axial tubular system luminal content dynamics.

Background: Efficient excitation-contraction coupling of mammalian ventricular cardiomyocytes depends on the transverse-axial tubular system (TATS), a network of surface membrane invaginations. TATS enables tight coupling of sarcolemmal and sarcoplasmic reticulum membranes, which is essential for rapid Ca-induced Ca release, and uniform contraction upon electrical stimulation. The majority of TATS in healthy ventricular cardiomyocytes is composed of transverse tubules (TT, ∼90 % of TATS in rabbit).

The role of TandemHeart combined with ProtekDuo as right ventricular support device: A simulation approach.

Background And Objective: Right ventricular failure increases short-term mortality in the setting of acute myocardial infarction, cardiogenic shock, advanced left-sided heart failure and pulmonary arterial hypertension. Percutaneous and surgically implanted right ventricular assist devices (RVAD) have been investigated in different clinical settings. The use of the ProtekDuo™ is currently a promising approach due to its features such as groin-free approach leading to early mobilisation, easy percutaneous deployment, compatibility with different pumps and oxygenators, and adaptability to different configurations.

Sex-related differences in vitamin D testing in the Veneto Region, Italy: a retrospective analysis from 2005 to 2016.

Unlabelled: A retrospective analysis was performed to evaluate the frequency of vitamin D blood testing in individuals from the Padua province, Veneto, Italy from 2005 to 2016. A significant increase in the frequency of vitamin D blood tests, particularly in females was observed and in individuals with severe vitamin D deficiency (Class I).

Purpose: Vitamin D deficiency has been linked to negative health outcomes that extend beyond bone-related conditions.

HPLC-MS/MS method for simultaneous analysis of plasma 2-hydroxybutyrate and 2-hydroxyisobutyrate: Development and clinical significance.

Recent studies have identified relationships between diabetes mellitus and short-chain fatty acids, including 2-hydroxybutyrate (2-HB) and 2-hydroxyisobutyrate (2-HiB); 2-HB has been associated to the early stages of insulin resistance, while 2-HiB with the risk and progression of complications of Type 1 diabetes. Their metabolism and pathophysiological role in humans are not fully clarified. The possible association between 2-HB and 2-HiB and diabetes mellitus was investigated with a novel mass spectrometry-based assay, capable of discriminating plasma 2-HiB and 2-HB from their HB isomers.

Regular Exercise Training Induces More Changes on Intestinal Glucose Uptake from Blood and Microbiota Composition in Leaner Compared to Heavier Individuals in Monozygotic Twins Discordant for BMI.

Background/objectives: Obesity impairs intestinal glucose uptake (GU) (intestinal uptake of circulating glucose from blood) and alters gut microbiome. Exercise improves intestinal insulin-stimulated GU and alters microbiome. Genetics influence the risk of obesity and gut microbiome.

The Effect of Acute High-Altitude Exposure on Oral Pathogenic Bacteria and Salivary Oxi-Inflammatory Markers.

The environment can alter the homeostasis of humans and human microbiota. Oral health is influenced by high altitude through symptoms of periodontitis, barodontalgia, dental barotrauma, and a decrease in salivary flow. Microbiota and inflammatory state are connected in the oral cavity.

Triple Therapy in COPD in Real Life: Is It Better to Use Single or Multiple Inhalers?

Today, single-inhaler ICS/LAMA/LABA (SITT) COPD therapies are available. It is unclear whether they are more effective than multiple-device triple therapies (MITT) in improving COPD outcomes. : We retrospectively considered patients on SITT/MITT in 2019/2020 who were prescribed >7 packages of ICS/LABA/LAMA or ICS/LAMA (+LAMA).

Vitamin C in the Management of Thyroid Cancer: A Highway to New Treatment?

Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic setting. Furthermore, oxidative stress is related to more aggressive features of TC.

Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness.

Automatic noise detection for ambulatory electrocardiogram in presence of ventricular arrhythmias through a machine learning approach.

Noise detection in ambulatory electrocardiography is investigated as a machine learning binary classification problem on a set of twelve noise indices. Ten of these noise indices are replicated from relevant scientific literature. Two novel noise indices are also introduced: the electrocardiogram derivative pattern similarity index (edp) and the number of inversions of the signal's slope over a minimum amplitude threshold (inv).

In vitro regenerative effects of a pooled pathogen-reduced lyophilized human cord blood platelet lysate for wound healing applications.

Background: Cord blood platelets, easily obtained from blood units not suitable for hematopoietic stem cell transplantation, represent an abundant source of growth factors for use in wound healing. Although several protocols have been described for platelet lysate production, no standard manufacturing protocol is available. The use of pooled cord blood platelets could thus facilitate standardization.