A5102823895- Drug Transport and Resistance Mechanisms
- Obesity, Physical Activity, Diet
- Estrogen and related hormone effects
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Diet, Metabolism, and Disease
- PARP inhibition in cancer therapy
- Diabetes Management and Research
- DNA Repair Mechanisms
- Cholesterol and Lipid Metabolism
- Adenosine and Purinergic Signaling
- Diabetes and associated disorders
- Hormonal Regulation and Hypertension
- Blood Pressure and Hypertension Studies
- Liver Disease Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Birth, Development, and Health
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cardiovascular Disease and Adiposity
- Metabolism, Diabetes, and Cancer
- Thyroid Disorders and Treatments
- Tryptophan and brain disorders
- Sirtuins and Resveratrol in Medicine
- Pharmacogenetics and Drug Metabolism
- Cancer therapeutics and mechanisms
- Sulfur-Based Synthesis Techniques
Istituti di Ricovero e Cura a Carattere Scientifico
2024
Ospedale Santa Maria della Misericordia di Udine
2018-2024
University of Bologna
2014-2024
University of Milan
2023-2024
Dublin City University
2024
Italian Institute of Technology
2024
GNA University
2024
National Research Council
2024
Istituto delle Scienze Neurologiche di Bologna
2024
University of Udine
2016-2023
OBJECTIVE To evaluate whether the diagnosis of pediatric type 1 diabetes or its acute complications changed during early phase coronavirus disease 2019 (COVID-19) pandemic in Italy. RESEARCH DESIGN AND METHODS This was a cross-sectional, web-based survey all Italian centers to collect diabetes, diabetic ketoacidosis (DKA), and COVID-19 data patients presenting with new-onset established between 20 February 14 April 2020. RESULTS Fifty-three 68 (77.9%) responded. There 23% reduction new cases...
Two dedicated receptors for bile acids (BAs) have been identified, the nuclear hormone receptor farnesoid X (FXR) and G protein-coupled TGR5, which represent attractive targets treatment of metabolic chronic liver diseases. Previous work characterized 6α-ethyl-3α,7α-dihydroxy-5β-cholan-24-oic acid (INT-747), a potent selective FXR agonist, as well 6α-ethyl-23(<i>S</i>)-methyl-3α,7α,12α-trihydroxy-5β-cholan-24-oic (INT-777), TGR5 agonist. Here we characterize...
Abstract Respiratory tract dendritic cells (DCs) are juxtaposed to directly sample inhaled environmental particles. Processing and presentation of these airborne Ags could result in either the development immunity or tolerance. The purpose this study was determine consequences cigarette smoke exposure on DC function mice. We demonstrate that while decreased number DCs lungs, Ag-induced migration regional thoracic lymph nodes unaffected. However, smoking suppressed maturation within as...
Abstract Dendritic cells (DCs) are essential orchestrators of immune responses and represent potential targets for immunomodulation in autoimmune diseases. Human amniotic fluid secretome is abundant immunoregulatory factors, with extracellular vesicles (EVs) being a significant component. However, the impact these EVs on dendritic subsets remain unexplored. In this study, we investigated interaction between highly purified cell derived from stem lines (HAFSC‐EVs). Our results suggest that...
We report on the relationship between structure-pharmacokinetics, metabolism, and therapeutic activity of semisynthetic bile acid analogs, including 6<i>α</i>-ethyl-3<i>α</i>,7<i>α</i>-dihydroxy-5<i>β</i>-cholan-24-oic (a selective farnesoid X receptor [FXR] agonist), 6<i>α</i>-ethyl-23(<i>S</i>)-methyl-3<i>α</i>,7<i>α</i>,12<i>α</i>-trihydroxy-5<i>β</i>-cholan-24-oic specific Takeda G protein–coupled 5 [TGR5] 6<i>α</i>-ethyl-3<i>α</i>,7<i>α</i>-dihydroxy-24-nor-5<i>β</i>-cholan-23-sulfate...
As a continuation of previous efforts in mapping functional hot spots on the bile acid scaffold, we here demonstrate that introduction hydroxy group at C11β position affords high selectivity for FXR. In particular, synthesis and FXR/TGR5 activity novel acids bearing different hydroxylation patterns C ring are reported discussed from structure-activity standpoint. The results obtained led us to discover first derivative endowed with potency FXR receptor,...
Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on possibility triggering synthetic using only small organic molecules (dubbed "fully small-molecule-induced lethality"). We exploited this to target pancreatic cancer, one major unmet needs oncology. discovered dihydroquinolone pyrazoline-based molecule (35d) that...
Pediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship less investigated. We aimed to evaluate sex-related differences on risk factors and preclinical signs target organ damage adolescents overweight/obesity (OW/OB).
Abstract Backgrounds The incidence of Type 1 Diabetes (T1D) in children and adolescents is increasing by 3–4% per year. Children with T1D (CwD) should receive person-centered, specialized treatment from a multidisciplinary team to ensure appropriate care. Italy the first implement countrywide screening program, which will raise need for funding pediatric study aims update organization Italian Centers diabetes Methods In 2022, members 59 following CwD were invited complete an email survey...
Abstract The RAD51-BRCA2 interaction is central to DNA repair through homologous recombination. Emerging evidence indicates RAD51 overexpression and its correlation with chemoresistance in various cancers, suggesting inhibition as a compelling avenue for intervention. We previously showed that combining olaparib (a PARP inhibitor (PARPi)) RS -35d BRCA2-RAD51 inhibitor) was efficient killing pancreatic ductal adenocarcinoma (PDAC) cells. However, impaired cell viability even when administered...
Abstract The class A scavenger receptors (SR-A) MARCO and SR-AI/II are expressed on lung macrophages (MΦs) dendritic cells (DCs) function in innate defenses against inhaled pathogens particles. Increased expression of SR-As the lungs mice an OVA-asthma model suggested additional role modulating responses to allergen. After OVA sensitization aerosol challenge, MARCO-deficient exhibited greater eosinophilic airway inflammation hyperresponsiveness compared with wild-type mice. for simple...
NAD+ has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects homeostasis underpin wide range of diseases, including cancer, metabolic disorders, aging. Although the beneficial effects boosting on mitochondrial fitness, metabolism, lifespan are well established, date, no therapeutic enhancers de novo biosynthesis have been reported. Herein we report discovery...
Pregnane X receptor (PXR) is a master xenobiotic-sensing transcription factor and validated target for immune inflammatory diseases. The identification of chemical probes to investigate the therapeutic relevance still highly desired. In fact, currently available PXR ligands are not selective can exhibit toxicity and/or potential off-target effects. this study, we have identified garcinoic acid as efficient agonist. properties natural molecule specific agonist were demonstrated by screening...
Aim/Hypothesis To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis type 1 diabetes in Italy during COVID-19 pandemic 2020 with DKA 2017-2019. Methods Forty-seven pediatric centers caring for &gt;90% young people recruited 4,237 newly diagnosed children between 2017 and a longitudinal study. Four subperiods were defined based on government-imposed containment measures COVID-19, frequencies severe compared same periods Results Overall, increased from 35.7% (95%CI,...
To assess the prevalence of pre-diabetes phenotypes, i.e., impaired fasting glucose (IFG), tolerance (IGT), increased HbA1c (IA1c), and their association with metabolic profile atherogenic lipid in youths overweight/obesity (OW/OB).This cross-sectional study analyzed data 1549 (5-18 years) OW/OB followed nine Italian centers between 2016 2020. Fasting post-load measurements glucose, insulin, were available. Insulin resistance (IR) was estimated by HOMA-IR insulin sensitivity (IS) reciprocal...
TGR5 is a G-protein-coupled receptor (GPCR) mediating cellular responses to bile acids (BAs). Although some efforts have been devoted generate homology models of and draw structure-activity relationships BAs, none these studies has hitherto described how BAs bind TGR5. Here, we present an integrated computational, chemical, biological approach that instrumental determine the binding mode As result, key residues identified are involved in receptor. Collectively, results provide new hints...