Development of -(4-(1-Imidazol-1-yl)phenyl)-4-chlorobenzenesulfonamide, a Novel Potent Inhibitor of β-Catenin with Enhanced Antitumor Activity and Metabolic Stability.

The potential as a cancer therapeutic target of the recently reported hotspot binding region close to Lys508 of the β-catenin armadillo repeat domain was not exhaustively explored. In order to get more insight, we synthesized novel -(heterocyclylphenyl)benzenesulfonamides -. The new compounds significantly inhibited Wnt-dependent transcription as well as SW480 and HCT116 cancer cell proliferation.

Long-Term Structural and Functional Assessment of Doyne Honeycomb Retinal Dystrophy following Nanosecond 2RT Laser Treatment: A Case Series.

Introduction: Doyne honeycomb retinal dystrophy (DHRD), or autosomal dominant radial drusen, is a genetic disease caused by pathogenic variants of the epidermal growth factor (EGF)-containing fibulin-like extracellular matrix protein 1 gene and is characterized by the formation of subretinal drusenoid deposits. In a previous study, we reported the short-term beneficial effects of nanosecond laser treatment (2RT) on retinal function in DHRD. The aim of the present report was to describe the findings of a long-term follow-up of retinal structure/function in a small case series of patients with DHRD who underwent 2RT treatment.

4-(3-Phenyl-4-(3,4,5-trimethoxybenzoyl)-1-pyrrol-1-yl)benzenesulfonamide, a Novel Carbonic Anhydrase and Wnt/β-Catenin Signaling Pathway Dual-Targeting Inhibitor with Potent Activity against Multidrug Resistant Cancer Cells.

We synthesized new pyrrole and indole derivatives as human carbonic anhydrase (hCA) inhibitors with the potential to inhibit the Wnt/β-catenin signaling pathway. The presence of both 1-(4-sulfonamidophenyl) and 3-(3,4,5-trimethoxyphenyl) substituents was essential for strong hCA inhibitors. The most potent hCA XII inhibitor ( = 6.

The -Alkylation of Agelastatin A Modulates Its Chemical Reactivity.

Agelastatin A is a marine alkaloid with potent biological activity. To date, at least 17 different strategies have achieved its total synthesis, along with many analogues. The present study focuses on the acidity stability of some -methyl derivatives of agelastatin A.

Novel -(Heterocyclylphenyl)benzensulfonamide Sharing an Unreported Binding Site with T-Cell Factor 4 at the β-Catenin Armadillo Repeats Domain as an Anticancer Agent.

Despite intensive efforts, no inhibitors of the Wnt/β-catenin signaling pathway have been approved so far for the clinical treatment of cancer. We synthesized novel -(heterocyclylphenyl)benzenesulfonamides as β-catenin inhibitors. Compounds - showed strong inhibition of the luciferase activity.

Longitudinal Structure-Function Evaluation in a Patient with -Associated Retinal Dystrophy: Progressive Visual Function Loss with Retinal Remodeling.

Background: Retinal dystrophies related to damaging variants in the cadherin-related family member 1 () gene are rare and phenotypically heterogeneous. Here, we report a longitudinal (three-year) structure-function evaluation of a patient with a -related retinal dystrophy.

Methods: A 14-year-old girl was evaluated between 2019 and 2022.

Induction of Ferroptosis in Glioblastoma and Ovarian Cancers by a New Pyrrole Tubulin Assembly Inhibitor.

We synthesized new aroyl diheterocyclic pyrrole (ARDHEP) that exhibited the hallmarks of ferroptosis. Compound strongly inhibited U-87 MG, OVCAR-3, and MCF-7 cancer cells, induced an increase of cleaved PARP, but was not toxic for normal human primary T lymphocytes at 0.1 μM.

Changes in markers of hepatic steatosis and fibrosis in patients with type 2 diabetes during treatment with glucagon-like peptide-1 receptor agonists. A multicenter retrospective longitudinal study.

Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is common in people with type 2 diabetes (T2D) and can progress to advanced fibrosis and cirrhosis. In this retrospective study, we explored the longitudinal changes in markers of hepatic steatosis and fibrosis during T2D treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs).

Methods: We analysed observational data from six diabetes outpatient clinics.

Effectiveness of Dulaglutide in the Real World and in Special Populations of Type 2 Diabetic Patients.

Context: In randomized controlled trials (RCTs) on type 2 diabetes (T2D) patients, the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-RA) dulaglutide reduced HbA1c and body weight, but generalizability of such findings to real-world T2D patients is challenging.

Objective: We evaluated effectiveness of dulaglutide in routine clinical practice, especially in subgroups of patient that are underrepresented in RCTs.

Design: Retrospective multicenter study.

Effectiveness of dulaglutide vs liraglutide and exenatide once-weekly. A real-world study and meta-analysis of observational studies.

Introduction And Aim: Real-word data on the head-to-head comparisons among glucagon-like peptide-1 receptor agonists (GLP-1RA) are scant. Therefore, we aimed to compare the effectiveness of dulaglutide versus liraglutide and exenatide once weekly (exeOW) in type 2 diabetic (T2D) patients under routine care.

Methods: This was a retrospective, multicenter, real-world study on patients with T2D (aged 18-80) initiating a GLP-1RA between 2010 and 2018 at specialist outpatient clinics.

Trend 2010-2018 in the clinical use of GLP-1 receptor agonists for the treatment of type 2 diabetes in routine clinical practice: an observational study from Northeast Italy.

Aims: Several GLP-1 receptor agonists (GLP-1RA) have become available for the treatment of type 2 diabetes (T2D), and evidence on their beneficial effects has evolved. We evaluated how the clinical phenotype of patients initiating GLP-1RA changed from 2010 to 2018.

Methods: This was a retrospective study conducted at six diabetes outpatient clinics in Northeast Italy.

Advances in the Dereplication of Aroma Precursors from Grape Juice by Pretreatment with Lead Acetate and Combined HILIC- and RP-HPLC Methods.

Glycosidic aroma precursors (GAPs) contribute to the varietal flavor of wine. Researchers have applied various sample preparation and analytical methods in attempts to achieve their separation and identification. However, mass spectrometric methods still fail to unequivocally define their structures.

Minor acetylated metabolites from .

The phenylethanoids rostkovianoside, 6'--acetylcrassifolioside and the flavonoid rutin 3‴-acetate, were isolated from the methanolic extract of the aerial parts of Hayne. The structures of these previously undescribed compounds were elucidated by interpretation of spectroscopic data. The acetylation of rutin was also carried out and four ester derivatives were spectroscopically characterized.

Effects of closed-loop intravenous anesthesia guided by Bispectral Index in adult patients on emergence delirium: a randomized controlled study.

Background: Emergence delirium (ED) is an acute change in cognition after general anesthesia (GA) occurring in operative room, recovery room or in postanesthesia care. The automated propofol-remifentanil titration by Bispectral Index (BIS) (AutoTIVA) avoids period of deep (BIS<40) anesthesia and could potentially decrease the ED. The aim of this study was to evaluate ED in surgical patients under AutoTIVA, manual titration of propofol-remifentanil (ManualTIVA) or volatile BIS-guided GA.

Physiological effects of the open lung approach during laparoscopic cholecystectomy: focus on driving pressure.

Background: During laparoscopy, respiratory mechanics and gas exchange are impaired because of pneumoperitoneum and atelectasis formation. We applied an open lung approach (OLA) consisting in lung recruitment followed by a decremental positive-end expiratory pressure (PEEP) trial to identify the level of PEEP corresponding to the highest compliance of the respiratory system (best PEEP). Our hypothesis was that this approach would improve both lung mechanics and oxygenation without hemodynamic impairment.

Research survey on iridoid and phenylethanoid glycosides among seven populations of Euphrasia rostkoviana Hayne from the Alps.

The traditional use of extracts of Euphrasia rostkoviana to relieve ocular inflammation or infections is well documented and supported by clinical studies. Various classes of chemical compounds such as iridoids, phenylethanoids, flavonoids and hydroxycinnamic acids have been reported. The present work aims to assess the chemical diversity among seven populations of Euphrasia rostkoviana found in northern Italy.

Effect of age on the performance of bispectral and entropy indices during sevoflurane pediatric anesthesia: a pharmacometric study.

Background: Bispectral index (BIS) and entropy monitors have been proposed for use in children, but research has not supported their validity for infants. However, effective monitoring of young children may be even more important than for adults, to aid appropriate anesthetic dosing and reduce the chance of adverse consequences. This prospective study aimed to investigate the relationships between age and the predictive performance of BIS and entropy monitors in measuring the anesthetic drug effects within a pediatric surgery setting.

Reference values for coagulation assessment in full-term newborns.

Background: Most data in the literature report reduced coagulation activities in the first few days of life with respect to adults and the effects of these differences must be considered when diagnosing and treating hemostatic disorders. The management of pediatric population is further complicated by the lack of age-related reference values and by the unreliability of currently-used hemostatic tests, while an accurate interpretation of results is required to reduce the cases of inappropriate investigation. Thromboelastography (TEG®) is a point-of-care test that provides an efficient analysis of the dynamic viscoelastic properties of whole blood that may provide superior evaluation and management of coagulopathies in newborn.

Propofol but not sevoflurane prevents mitochondrial dysfunction and oxidative stress by limiting HIF-1α activation in hepatic ischemia/reperfusion injury.

Mitochondrial dysfunction, reactive oxygen species (ROS) production and oxidative stress during reperfusion are determinant in hepatic ischemia/reperfusion (I/R) injury but may be impacted by different anesthetic agents. Thus, we aimed at comparing the effects of inhaled sevoflurane or intravenous propofol anesthesia on liver mitochondria in a rodent model of hepatic I/R injury. To this, male Wistar rats underwent I/R surgery using sevoflurane or propofol.

Impact of prolonged assisted ventilation on diaphragmatic efficiency: NAVA versus PSV.

Background: Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency.

Continuous spinal analgesia with levobupivacaine for postoperative pain management: Comparison of 0.125% versus 0.0625% in elective total knee and hip replacement: A double-blind randomized study.

Background And Aims: Continuous spinal anesthesia (CSA) has not been widely used for postoperative analgesia, mainly to avoid complications from the subarachnoid injection. Recently, the introduction of low caliber CSA catheters (Spinocath(®)), has allowed to decrease anesthetics doses and volumes with good analgesia and reduced complications. The aim of this present study was to compare two concentrations of levobupivacaine administered through CSA for postoperative pain management after major orthopedic surgery.