ACLY inhibition promotes tumour immunity and suppresses liver cancer.

Immunosuppressive tumour microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) (MASH-HCC). Although immune cell metabolism influences effector function, the effect of tumour metabolism on immunogenicity is less understood. ATP citrate lyase (ACLY) links substrate availability and mitochondrial metabolism with lipid biosynthesis and gene regulation.

Effect of immune checkpoint inhibitor therapy on biventricular mechanics in cancer patients over a short-term follow-up: a systematic review.

Background: Immune checkpoint inhibitors (ICI) have demonstrated a survival benefit in various cancer types. A few numbers of imaging studies have recently measured myocardial strain parameters in cancer patients before and after ICI treatment, reporting not univocal results. This systematic review has been primarily designed to summarize the main findings of these studies and to examine the overall effect of ICI therapy on biventricular mechanics in cancer patients.

MicroRNA-mediated PTEN downregulation as a novel non-genetic mechanism of acquired resistance to PI3Kα inhibitors of head & neck squamous cell carcinoma.

Aims: Head and neck squamous cell carcinomas (HNSCCs) frequently harbor alterations in the PI3K signalling axis and, particularly, in the PIK3CA gene. The promising rationale of using PI3K inhibitors for the treatment of HNSCC has, however, clashed with the spontaneous development of resistance over time.

Methods: To identify valuable targets for overcoming acquired resistance to PI3Kα inhibitors in HNSCC, we performed microRNA profiling on a cohort of HNSCC PDXs that were treated with alpelisib, including both responsive and resistant tumors.

Effect of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) on Left Ventricular Mechanics in Patients Without Overt Cardiac Disease: A Systematic Review and Meta-Analysis.

Over the last two decades, a fair number of echocardiographic studies have investigated the influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on myocardial strain and strain rate parameters assessed by speckle tracking echocardiography (STE) in individuals without overt heart disease, reporting not univocal results. We aimed at analyzing the main findings of these studies. All studies examining conventional echoDoppler parameters by transthoracic echocardiography (TTE) and left ventricular (LV) mechanics [LV-global longitudinal strain (GLS), LV-global strain rate in systole (GSRs), in early diastole (GSRe) and late diastole (GSRl)] by STE in MASLD patients without known heart disease vs.

Salsalate improves the anti-tumor efficacy of lenvatinib in MASH-driven hepatocellular carcinoma.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a growing cause of hepatocellular carcinoma (HCC) worldwide. The complex microenvironment of these tumors, characterized by metabolic dysfunction, hypoxia, steatosis, and fibrosis, limits the effectiveness of standard-of-care therapies, such as the multi-tyrosine kinase inhibitor lenvatinib (LEN). Salsalate (SAL), is a rheumatoid arthritis therapy that enhances fatty acid oxidation and reduces lipogenesis, fibrosis and cell proliferation pathways.

Does Preliminary Chest Shape Assessment Improve the Prognostic Risk Stratification of Individuals with Mitral Annular Disjunction? A Case Report and Narrative Review.

Mitral annular disjunction (MAD), a mitral annular abnormality involving the whole mitral valve annulus circumference, commonly detected in individuals with mitral valve prolapse (MVP), has been recently recognized as a potential risk factor for malignant ventricular arrhythmias (VAs) and sudden cardiac death. Recent evidence indicates that a multimodality imaging assessment comprehensive of echocardiography, cardiac magnetic resonance (CMR), and cardiac computed tomography angiography (CCTA) may improve MAD detection. To date, no previous author has considered the potential influence of chest wall conformation on MAD presence.

Shared molecular, cellular, and environmental hallmarks in cardiovascular disease and cancer: Any place for drug repurposing?

Cancer and cardiovascular disease (CVD) are the 2 biggest killers worldwide. Specific treatments have been developed for the 2 diseases. However, mutual therapeutic targets should be considered because of the overlap of cellular and molecular mechanisms.

CircPVT1 weakens miR-33a-5p unleashing the c-MYC/GLS1 metabolic axis in breast cancer.

Background: Altered metabolism is one of the cancer hallmarks. The role of circRNAs in cancer metabolism is poorly studied. Specifically, the impact of circPVT1, a well-known oncogenic circRNA on triple negative breast cancer metabolism is mechanistically underexplored.

The Prevalence, Pathophysiological Role and Determinants of Mitral Annular Disjunction Among Patients with Mitral Valve Prolapse: A Systematic Review.

Over the last two decades, a number of imaging studies have evaluated the characteristics and clinical implications of mitral annular disjunction (MAD) among patients with mitral valve prolapse (MVP). The present systematic review has been primarily designed to summarize the main findings of these studies and to examine the overall impact of MAD in MVP patients. All imaging studies assessing the prevalence, pathophysiological role and determinants of MAD in MVP individuals, selected from the PubMed and EMBASE databases, were included.

Echocardiographic Assessment of Cardiac Structure and Function of Centenarians: A Systematic Review.

During the last two decades, a limited number of studies have provided echocardiographic details regarding the cardiac structure and function of individuals aged ≥100 years. These studies analyzed limited sample sizes of centenarians using different methodologies. The present systematic review was primarily designed to summarize the main findings of these studies and to examine the overall influence of extremely advanced age on cardiac structure and function.

Could Pulsed Wave Tissue Doppler Imaging Solve the Diagnostic Dilemma of Right Atrial Masses and Pseudomasses? A Case Series and Literature Review.

Even if rarely detected, right atrial (RA) masses represent a diagnostic challenge due to their heterogeneous presentation. Para-physiological RA structures, such as a prominent Eustachian valve, Chiari's network, and lipomatous atrial hypertrophy, may easily be misinterpreted as pathological RA masses, including thrombi, myxomas, and vegetations. Each pathological mass should always be correlated with adequate clinical, anamnestic, and laboratory data.

Echocardiographic Assessment of Biventricular Mechanics of Fetuses and Infants of Gestational Diabetic Mothers: A Systematic Review and Meta-Analysis.

Background: Gestational diabetes mellitus (GDM) is the most common complication in pregnancy, representing a serious risk for the mother and fetus. Identifying new biomarkers to ameliorate the screening and improving GDM diagnosis and treatment is crucial. During the last decade, a few studies have used speckle tracking echocardiography (STE) for assessing the myocardial deformation properties of fetuses (FGDM) and infants (IGDM) of GDM women, providing not univocal results.

A Prospective Monocentric Study of Invasive Breast Carcinoma Diagnosed at 80 Years and Older: Survival Outcomes and Peculiar Challenges.

The lengthening of the lifespan led to an increase in breast cancer (BC) diagnosed in very old age, but the treatment recommendations in this patient group usually lack evidence-based practice. We conducted a prospective observational monocentric study specifically targeting patients diagnosed with invasive BC at 80 years of age or older. We enrolled 88 patients consecutively observed for a new BC diagnosis at 80 years or older.

Metformin Treatment With or Without Mediterranean Diet for the Prevention of Age-Related Diseases in People With Metabolic Syndrome: The MeMeMe Randomized Trial.

Objective: The Metformin and Dietary Restriction to Prevent Age-Related Morbid Events in People With Metabolic Syndrome (MeMeMe) trial tested whether 1,700 mg/day metformin (MET) with or without a Mediterranean diet (MedDiet) intervention could reduce the cumulative incidence of major noncommunicable diseases in people with metabolic syndrome.

Research Design And Methods: A total of 1,442 participants were randomly assigned to one of four interventions: 1) MET (1,700 mg/day) plus MedDiet intervention (MET+MedDiet); 2) placebo plus MedDiet intervention; 3) MET (1,700 mg/day) alone; and 4) placebo alone. Participants were followed up for 3 years on average.

Body weight variability as a predictor of cardiovascular outcomes in type 1 diabetes: A nationwide cohort study.

Aim: Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition.

Materials And Methods: Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years.

Reconsidering the role of depression and common psychiatric disorders as partners in the type 2 diabetes epidemic.

Common psychiatric disorders (CPDs) and depression contribute significantly to the global epidemic of type 2 diabetes (T2D). We postulated a possible pathophysiological mechanism that through Bridge-Symptoms present in depression and CPDs, promotes the establishment of emotional eating, activation of the reward system, onset of overweight and obesity and, ultimately the increased risk of developing T2D. The plausibility of the proposed pathophysiological mechanism is supported by the mechanism of action of drugs such as naltrexone-bupropion currently approved for the treatment of both obesity/overweight with T2D and as separate active pharmaceutical ingredients in drug addiction, but also from initial evidence that is emerging regarding glucagon-like peptide 1 receptor agonists that appear to be effective in the treatment of drug addiction.

Combined TP53 status in tumor-free resection margins and circulating microRNA profiling predicts the risk of locoregional recurrence in head and neck cancer.

Locoregional recurrences represent a frequently unexpected problem in head and neck squamous cell carcinoma (HNSCC). Relapse often (10-30%) occurs in patients with histologically negative resection margins (RMs), probably due to residual tumor cells or hidden pre-cancerous lesions in normal mucosa, both missed by histopathological examination. Therefore, definition of a 'clean' or tumor-negative RM is controversial, demanding for novel approaches to be accurately explored.

Immunosignatures associated with TP53 status and co-mutations classify prognostically head and neck cancer patients.

Background: Immune checkpoint inhibitors (ICIs) are a therapeutic strategy for various cancers although only a subset of patients respond to the therapy. Identifying patients more prone to respond to ICIs may increase the therapeutic benefit and allow studying new approaches for resistant patients.

Methods: We analyzed the TCGA cohort of HNSCC patients in relation to their activation of 26 immune gene expression signatures, as well as their cell type composition, in order to define signaling pathways associated with resistance to ICIs.

Altered Extracellular Vesicle miRNA Profile in Prodromal Alzheimer's Disease.

Extracellular vesicles (EVs) are nanosized vesicles released by almost all body tissues, representing important mediators of cellular communication, and are thus promising candidate biomarkers for neurodegenerative diseases like Alzheimer's disease (AD). The aim of the present study was to isolate total EVs from plasma and characterize their microRNA (miRNA) contents in AD patients. We isolated total EVs from the plasma of all recruited subjects using ExoQuickULTRA exosome precipitation solution (SBI).