The 2024 Nobel Prize in Physiology or Medicine: microRNA Takes Center Stage.

The Journal Editorial Board Members would like to congratulate Victor Ambros and Gary Ruvkun, who were jointly awarded the 2024 Nobel Prize in Physiology or Medicine for their groundbreaking discovery of microRNAs and the role of microRNAs in post-transcriptional gene regulation, uncovering a previously unknown layer of gene control in eukaryotes [...

Dodecanedioic acid prevents and reverses metabolic-associated liver disease and obesity and ameliorates liver fibrosis in a rodent model of diet-induced obesity.

Dodecanedioic acid (DC12) is a dicarboxylic acid present in protective polymers of fruit and leaves. We explored the effects of DC12 on metabolic dysfunction-associated steatohepatitis (MASH) and obesity. DC12 supplementation (100 mg/kg/day) was added to a high-fat diet (HFD) for 8 weeks in rodents to assess its impact on obesity and MASH prevention.

Incidence of Acute Pulmonary Edema Before and After the Systematic Use of Ultrasound B-Lines.

Introduction: Acute pulmonary edema (APE) due to fluid overload is considered the most feared complication in hemodialysis patients. Various diagnostic tests have been proposed to assess the fluid status in patients with end-stage kidney failure (ESKF); among these, lung ultrasound (measuring the number of B-lines) is emerging as a promising tool to identify pulmonary congestion in this patient population.

Methods: We compared the incidence of APE before and after the implementation of lung ultrasound as a routine practice in our unit.

Lipid metabolism in MASLD and MASH: From mechanism to the clinic.

Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is recognised as a metabolic disease characterised by excess intrahepatic lipid accumulation due to lipid overflow and synthesis, alongside impaired oxidation and/or export of these lipids. But where do these lipids come from? The main pathways related to hepatic lipid accumulation are lipogenesis and excess fatty acid transport to the liver (due to increased lipolysis, adipose tissue insulin resistance, as well as excess dietary fatty acid intake, in particular of saturated fatty acids). Not only triglycerides but also other lipids are secreted by the liver and are associated with a worse histological profile in MASH, as shown by lipidomics.

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.

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.

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.

Possible role of bone turnover markers in the diagnosis of adult hypophosphatasia.

Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment.

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.

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.

Automated Approach for Enhancing Fetal Head Station Assessment in Labor with Transperineal Ultrasound.

Rationale And Objectives: Accurate assessment of fetal head station (FHS) is crucial during labor management to reduce the risk of complications and plan the mode of delivery. Although digital vaginal examination (DVE) has been associated with inaccuracies in FHS assessment, ultrasound (US) evaluation remains dependent on sonographer expertise. This study aimed at investigating the reliability and accuracy of an automatic approach to assess the FHS during labor with transperineal US (TPU).

Non-Invasive Diagnostic Approaches for Kidney Disease: The Role of Electronic Nose Systems.

Kidney diseases are a group of conditions related to the functioning of kidneys, which are in turn unable to properly filter waste and excessive fluids from the blood, resulting in the presence of dangerous levels of electrolytes, fluids, and waste substances in the human body, possibly leading to significant health effects. At the same time, the toxins amassing in the organism can lead to significant changes in breath composition, resulting in halitosis with peculiar features like the popular ammonia breath. Starting from this evidence, scientists have started to work on systems that can detect the presence of kidney diseases using a minimally invasive approach, minimizing the burden to the individuals, albeit providing clinicians with useful information about the disease's presence or its main related features.

New Insight into the Role of Vitamin D in the Stroke Risk: A Meta-Analysis of Stratified Data by 25(OH)D Levels.

Mendelian Randomization (MR) studies have emerged as a powerful tool for investigating causal relationships between modifiable risk factors and clinical outcomes, using genetic variants as instrumental variables. In the context of vitamin D research, MR is a promising approach to elucidate the effects of vitamin D on various health outcomes, including adverse cardiovascular events. However, the validity of MR analyses relies heavily on the strength of the genetic associations found.

Enhancing the Anticancer Activity of Attenuated by Cell Wall Functionalization with "Clickable" Doxorubicin.

Among bacteria used as anticancer vaccines, attenuated (Lm) stands out, because it spreads from one infected cancer cell to the next, induces a strong adaptive immune response, and is suitable for repeated injection cycles. Here, we use click chemistry to functionalize the Lm cell wall and turn the bacterium into an "intelligent carrier" of the chemotherapeutic drug doxorubicin. Doxorubicin-loaded Lm retains most of its biological properties and, compared to the control fluorophore-functionalized bacteria, shows enhanced cytotoxicity against melanoma cells both in vitro and in a xenograft model in zebrafish.