TRIM65 regulates innate immune signaling by enhancing K6-linked ubiquitination of IRF3 and its chromatin recruitment.

Viral infection triggers a rapid and effective cellular response primarily mediated by interferon β (IFNβ), which induces an antiviral state through complex signaling cascades. To maintain a robust antiviral response while preventing excessive activation, the induction of IFNβ and downstream signaling are tightly regulated. Members of the tripartite-motif (TRIM) family of E3 ubiquitin (Ub) ligases play crucial roles in modulating these processes.

Impact of porcine brush border membrane enzymes on INFOGEST in vitro digestion model: A step forward to mimic the small intestinal phase.

Brush border membrane (BBM) enzymes greatly affect the bioaccessibility and bioavailability of food nutrients. Despite their physiological importance, a step simulating the final stage of intestinal digestion has not yet been included in the harmonized protocols for in vitro digestion, primarily due to the challenges of replicating the dynamics of intestinal degradation. Herein, we propose an advancement toward a more physiologically relevant method, complementing the harmonized static gastric-duodenal digestion INFOGEST model with the missing small intestinal phase.

Self-assembling nanoparticles for delivery of miR-603 and miR-221 in glioblastoma as a new strategy to overcome resistance to temozolomide.

Glioblastoma (GBM) is a highly aggressive brain cancer with poor clinical outcome. Unfortunately, chemotherapy with temozolomide (TMZ) has a limited efficacy due to resistance mainly attributed to O6-methylguanine methyl transferase (MGMT) activity. Recently, miR-603 and miR-221 have been identified to target MGMT, thus improving the efficacy of temozolomide (TMZ) in the treatment of GBM.

Rapid modulation of interscapular brown adipose tissue mitochondrial activity by ketosis induced by 1,3-butanediol administration to rats.

Some studies indicate that brown adipose tissue (BAT) represents a promising target in the fight against dysmetabolic diseases, with indications suggesting it as a potential target for the effects of ketone bodies. We investigate whether the elevation of plasma levels of the ketone body β-hydroxybutyrate, achieved through the in vivo administration of its precursor 1,3-butanediol (BD) to rats, could impact interscapular BAT (iBAT) mitochondrial biochemistry and functionality. We examined the effects induced by BD within 3 h and after 2 weeks of treatment.

Navigating women's cancer prevention: Two cross-sectional studies to investigate psychosocial antecedents of cervical and breast cancer screening attendance.

Despite population-based cancer screening programmes effectively decreasing mortality, participation rates are unsatisfactory for both cervical and breast screening. This research tested an integrated theory of planned behaviour model applied to cervical cancer screening (CCS; Study 1) and breast cancer screening (BCS; Study 2) attendance. Women residing in Campania (Italy) and belonging to each screening target population joined two independent surveys (Study 1:  = 332,  = 41.

Advancing perioperative optimization in Crohn's disease surgery with machine learning predictions.

This editorial offers commentary on the article which aimed to forecast the likelihood of short-term major postoperative complications (Clavien-Dindo grade ≥ III), including anastomotic fistula, intra-abdominal sepsis, bleeding, and intestinal obstruction within 30 days, as well as prolonged hospital stays following ileocecal resection in patients with Crohn's disease (CD). This prediction relied on a machine learning (ML) model trained on a cohort that integrated a nomogram predictive model derived from logistic regression analysis and a random forest (RF) model. Both the nomogram and RF showed good performance, with the RF model demonstrating superior predictive ability.

Computational journey to unveil organophosphorothioate pesticides' metabolism: A focus on chlorpyrifos and CYP2C19 mutational landscape.

Organophosphorothioates (OPT) are pesticides impacting human, animal and environmental health. They enter the environment worldwide, primarily due to their application as insecticides. OPTs are mainly neurotoxic upon bioactivation and inhibition of brain and serum acetylcholinesterase (AChE).

Brain metabolic profiling of schizophrenia: a path towards a better understanding of the neuropathogenesis of psychosis.

Schizophrenia (SCZ) is a complex psychotic syndrome whose pathogenesis involves countless protagonists, none of which, to date, can fully explain how this disorder develops. In this narrative review, an overview of the biochemical impairment is offered according to several perspectives. Indeed, the metabolic framework behind SCZ dopaminergic hypotheses, glutamate - gamma-amynobutyric acid dysregulation, norepinephrine and serotonin, calcium channel dysfunction is addressed together with the energetic impairment, involving glucose and lipids in SCZ etiopathogenesis, in order to highlight the multilevel pathways affected in this neuropsychiatric disorder.

Effectiveness and Safety of Glecaprevir/Pibrentasvir in Italian Children and Adolescents With Chronic Hepatitis C: A Real-Word, Multicenter Study.

Background & Aims: Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC.

Methods: This prospective, multicentre study involved 11 Italian centres.

The hockey fans in training intervention for men with overweight or obesity: a pragmatic cluster randomised trial.

Background: Obesity disproportionately impacts men's health yet fewer men engage in preventive healthcare. We examined the effectiveness of Hockey Fans in Training (Hockey FIT), a gender-sensitised lifestyle intervention that engages men with overweight/obesity through their passion as fans of a local sports team, on weight change and other health indicators.

Methods: Pragmatic, cluster randomised trial (aged 35-65 years, body mass index ≥ 27 kg/m) within 42 community-based sites in Canada and the United States, randomly assigned (1:1) to intervention (Hockey FIT) or control (wait-list) and stratified by region.

Impact of intravascular ultrasound for coronary bifurcations treated with last generations stents: insights from the BIFURCAT-ULTRA registry.

Background: Bifurcation lesions are associated with higher rates of major adverse cardiovascular events (MACE).

Aim: To investigate the impact of imaging-guided PCI in a real-world population with coronary bifurcation lesions.

Methods: From the ULTRA-BIFURCAT registry, we compared IVUS vs.

Brain and behavioural anomalies caused by haploinsufficiency are corrected by vitamin B12.

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes in brain metabolism might contribute to these phenotypes, as many of the deleted genes are involved in metabolic processes, but this is unknown.

Catheter-Based Renal Denervation for Resistant Arterial Hypertension: 10-Year Real-World Follow-Up Data.

This analysis of real-world data examines the efficacy, safety, and long-term outcomes of renal denervation in hypertensive patients for up to 10 years. Sixty-five consecutive patients underwent renal denervation (RDN) (single operator) for uncontrolled resistant hypertension. Efficacy was defined as the interindividual change of office (OBPM) and ambulatory blood pressure monitoring (ABPM) at 1, 6, 12 months, 2-4 and 5-10 years after RDN.

Diet quality in patients with treatment-resistant schizophrenia: time for improving nutritional recommendations.

Background: Treatment-resistant schizophrenia (TRS) is a severe psychiatric disorder that is associated with a high level of psychotic symptoms and cognitive deficit as well as poor functioning, and an increased risk of mortality for cardiometabolic diseases. Some studies suggest that lifestyle, particularly diet, could represent a risk factor for obesity and its metabolic complications in these patients.

Methods: This cross-sectional study aimed to evaluate diet quality and eating habits in individuals with TRS.

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.

The human gut Bacteroides eggerthii expresses a new galactofuranose-containing lipooligosaccharide with weak immunostimulatory properties.

Lipopolysaccharides (LPS) decorating the cell surface of Gram-negative bacteria exhibit nuanced functionalities linked to their precise structural composition. However, despite their critical role in health and disease, information on the structure and function of LPS from members of the human gut microbiota is still limited. Here, we deciphered the complete structure of the LPS isolated from the human gut bacterium Bacteroides eggerthii 1_2_48FAA.

Myxinidin-analogs able to sequester Fe(III): Metal-based gun to combat Pseudomonas aeruginosa biofilm.

Bacteria have developed a tendency to form biofilms, where bacteria live in organized structures embedded in a self-produced matrix of DNA, proteins, and polysaccharides. Additionally, bacteria need iron(III) as an essential nutrient for bacterial growth and secrete siderophore groups that sequester it from the environment. To design a molecule able both to inhibit the bacteria and to sequester iron, we developed two hydroxamate-based peptides derived from an analog (WMR-4), previously developed in our lab, of the antimicrobial peptide myxinidin.

A Reappraisal on cortical myoclonus and brief Remarks on myoclonus of different Origins.

Myoclonus has multiple clinical manifestations and heterogeneous generators and etiologies, encompassing a spectrum of disorders and even physiological events. This paper, developed from a teaching course conducted by the Neurophysiology Commission of the Italian League against Epilepsy, aims to delineate the main types of myoclonus, identify potential underlying neurological disorders, outline diagnostic procedures, elucidate pathophysiological mechanisms, and discuss appropriate treatments. Neurophysiological techniques play a crucial role in accurately classifying myoclonic phenomena, by means of simple methods such as EEG plus polymyography (EEG + Polymyography), evoked potentials, examination of long-loop reflexes, and often more complex protocols to study intra-cortical inhibition-facilitation In clinical practice, EEG + Polymyography often represents the first step to identify myoclonus, acquire signals for off-line studies and plan the diagnostic work-up.

Opportunities and Challenges of Arginase Inhibitors in Cancer: A Medicinal Chemistry Perspective.

The overexpression of two arginase (ARG) isoforms, ARG1 and ARG2, contributes to the onset of numerous disorders, including cardiovascular and immune-mediated diseases, as well as tumors. To elucidate the specific roles of ARG1 and ARG2 without interfering with their physiological functions, it is crucial to develop effective ARG inhibitors that target only one isoform, while maintaining low toxicity and an adequate pharmacokinetic profile. In this context, we present a comprehensive overview of the different generations of ARG inhibitors.