A Nrf-2 Stimulatory Hydroxylated Cannabidiol Derivative from Hemp ().

A phytochemical analysis of mother liquors obtained from crystallization of CBD from hemp (), guided by LC-MS/MS and molecular networking profiling and completed by isolation and NMR-based characterization of constituents, resulted in the identification of 13 phytocannabinoids. Among them, anhydrocannabimovone (), isolated for the first time as a natural product, and three new hydroxylated CBD analogues (1,2-dihydroxycannabidiol, , 3,4-dehydro-1,2-dihydroxycannabidiol, , and hexocannabitriol, ) were obtained. Hexocannabitriol () potently modulated, in a ROS-independent way, the Nrf2 pathway, outperforming all other cannabinoids obtained in this study and qualifying as a potential new chemopreventive chemotype against cancer and other degenerative diseases.

Treatment-Free Remission in Chronic Myeloid Leukemia Patients Treated With Low-Dose TKIs: A Feasible Option Also in the Real-Life. A Campus CML Study.

Treatment-free remission (TFR) has become a primary therapeutic goal in CML and is also considered feasible by international guidelines. TKIs dose reduction is often used in real-life practice to reduce adverse events, although its impact on TFR is still a matter of debate. This study aimed to explore the attitude of Italian hematologists towards prescribing TKIs at reduced doses and its impact on TFR.

Lung function from school age to adulthood in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the International PCD Cohort and calculated z-scores for forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and FEV/FVC ratio using the Global Lung Function Initiative 2012 references.

Harnessing a Feasible and Versatile Calvarial Suture 2-D Culture System to Study Suture Biology.

As a basic science, craniofacial research embraces multiple facets spanning from molecular regulation of craniofacial development, cell biology/signaling and ultimately translational craniofacial biology. Calvarial sutures coordinate development of the skull, and the premature fusion of one or more, leads to craniosynostosis. Animal models provide significant contributions toward craniofacial biology and clinical/surgical treatments of patients with craniofacial disorders.

Phytochemical profile of Centevita®, a Centella asiatica leaves extract, and isolation of a new oleanane-type saponin.

Centella asiatica is a popular medicinal plant and several phytotherapic products in the market include its extracts as active constituents. A LC-MS guided phytochemical investigation on the commercial C. asiatica leaves extract named Centevita® allowed characterization and quantification of 24 secondary metabolites including 10 polyphenols and 14 ursane- or oleanane-type triterpenoids in the sapogenin or saponin form.

Loss of Detection of sgN Precedes Viral Abridged Replication in COVID-19-Affected Patients-A Target for SARS-CoV-2 Propagation.

The development of prophylactic agents against the SARS-CoV-2 virus is a public health priority in the search for new surrogate markers of active virus replication. Early detection markers are needed to follow disease progression and foresee patient negativization. Subgenomic RNA transcripts (with a focus on sgN) were evaluated in oro/nasopharyngeal swabs from COVID-19-affected patients with an analysis of 315 positive samples using qPCR technology.

Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice.

High-fat diet (HFD) consumption leads to obesity and a chronic state of low-grade inflammation, named metainflammation. Notably, metainflammation contributes to neuroinflammation due to the increased levels of circulating free fatty acids and cytokines. It indicates a strict interplay between peripheral and central counterparts in the pathogenic mechanisms of obesity-related mood disorders.

Genetic Analysis in African American Children Supports Ancestry-Specific Neuroblastoma Susceptibility.

Background: Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease.

Methods: We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs.

Hepatectomy Versus Sorafenib in Advanced Nonmetastatic Hepatocellular Carcinoma: A Real-life Multicentric Weighted Comparison.

Objective: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario.

Background Data: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial.

Methods: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered.

Molecular Diagnostic Outcomes from 700 Cases: What Can We Learn from a Retrospective Analysis of Clinical Exome Sequencing?

Clinical exome sequencing (CES) aids in the diagnosis of rare genetic disorders. Herein, we report the molecular diagnostic yield and spectrum of genetic alterations contributing to disease in 700 pediatric cases analyzed at the Children's Hospital of Philadelphia. The overall diagnostic yield was 23%, with three cases having more than one molecular diagnosis and 2.

Chemical Composition of Green Pea ( L.) Pods Extracts and Their Potential Exploitation as Ingredients in Nutraceutical Formulations.

Agro-industrial wastes contain a large number of important active compounds which can justify their use as innovative ingredients in nutraceutical products. This study aimed to provide a complete analysis of active molecules, namely (poly)phenols in pea pods water-based extracts, through a UHPLC-Q-Orbitrap HRMS methodology. Data showed that 5-caffeoylquinic acid, epicatechin, and hesperidin were the most relevant (poly)phenols found in the assayed extracts, with a mean value of 59.

Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT.

Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119).

HS donating corticosteroids: Design, synthesis and biological evaluation in a murine model of asthma.

Introduction: Hydrogen sulfide (HS) is a fundamental biological endogenous gas-mediator in the respiratory system. It regulates pivotal patho-physiological processes such as oxidative stress, pulmonary circulation, airway tone and inflammation.

Objectives: We herein describe the design and synthesis of molecular hybrids obtained by the condensation of several corticosteroids with different hydrogen sulfide releasing moieties.

OMICS in Chronic Kidney Disease: Focus on Prognosis and Prediction.

Chronic kidney disease (CKD) patients are characterized by a high residual risk for cardiovascular (CV) events and CKD progression. This has prompted the implementation of new prognostic and predictive biomarkers with the aim of mitigating this risk. The 'omics' techniques, namely genomics, proteomics, metabolomics, and transcriptomics, are excellent candidates to provide a better understanding of pathophysiologic mechanisms of disease in CKD, to improve risk stratification of patients with respect to future cardiovascular events, and to identify CKD patients who are likely to respond to a treatment.

Imaging the "Hot Phase" of a Familiar Left-Dominant Arrhythmogenic Cardiomyopathy.

We describe the case of a young man with an initial diagnosis of acute myocarditis that was finally recognized as a familial left-dominant arrhythmogenic cardiomyopathy. The diagnostic process was also based on demonstration, serial cardiac magnetic resonance imaging, and typical patterns of myocardial damage, including features of the disease's inflammatory "hot phase".

HS Donors and Their Use in Medicinal Chemistry.

Hydrogen sulfide (HS) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous HS is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of HS levels has a potential therapeutic value.

Discovery of Bile Acid Derivatives as Potent ACE2 Activators by Virtual Screening and Essential Dynamics.

The angiotensin-converting enzyme II (ACE2) is a key molecular player in the regulation of vessel contraction, inflammation, and reduction of oxidative stress. In addition, ACE2 has assumed a prominent role in the fight against the COVID-19 pandemic-causing virus SARS-CoV-2, as it is the very first receptor in the host of the viral spike protein. The binding of the spike protein to ACE2 triggers a cascade of events that eventually leads the virus to enter the host cell and initiate its life cycle.

Prevalence and associated psychological risk factors of postpartum depression: a cross-sectional study.

This cross-sectional study aimed to evaluate the prevalence of postpartum depression and the associated risk factors in a sample of Italian women at three months after delivery. Eighty women were screened by completing the Edinburgh Postnatal Depression Scale (EPDS). Women with a score ≥10 were evaluated as positive and other variables were detected through the administration of the Postpartum Depression Predictors Inventory.

Long-Term Outcomes With Pharmacological Ovarian Suppression During Chemotherapy in Premenopausal Early Breast Cancer Patients.

Background: Although use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor-positive disease. There are controversial data on its fertility preservation potential.

Methods: The Prevention of Menopause Induced by Chemotherapy: a Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6 (PROMISE-GIM6) trial is a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from October 2003 to January 2008.

Epidemiology and Pattern of Resistance of Gram-Negative Bacteria Isolated from Blood Samples in Hospitalized Patients: A Single Center Retrospective Analysis from Southern Italy.

Background: Blood culturing remains the mainstream tool to inform an appropriate treatment in hospital-acquired bloodstream infections and to diagnose any bacteremia.

Methods: A retrospective investigation on the prevalence of Gram-negative bacteria (GNB) and their resistance in hospitalized patients by age, sex, and units from blood cultures (BCs) was conducted from January 2018 to April 2020 at Sant'Elia hospital, Caltanissetta, southern Italy. We divided the patient age range into four equal intervals.

Hemorrhagic Stroke Induces a Time-Dependent Upregulation of miR-150-5p and miR-181b-5p in the Bloodstream.

To date, the only effective pharmacological treatment for ischemic stroke is limited to the clinical use of recombinant tissue plasminogen activator (rtPA), although endovascular therapy has also emerged as an effective treatment for acute ischemic stroke. Unfortunately, the benefit of this treatment is limited to a 4.5-h time window.