ONC201-Derived Tetrahydropyridopyrimidindiones as Powerful ClpP Protease Activators to Tackle Diffuse Midline Glioma.

Pediatric diffuse intrinsic pontine glioma (DIPG), classified under diffuse midline glioma, is a deadly tumor, with no effective treatments. The human mitochondrial protease ClpP is a potential DIPG therapeutic target, and this study describes the synthesis of two new series of tetrahydropyridopyrimidindiones (THPPDs) as ClpP activators. Among the tested compounds, we have identified (THX6) that shows a strong ClpP activation (EC = 1.

KATP Channel Inhibitors Reduce Cell Proliferation Through Upregulation of H3K27ac in Diffuse Intrinsic Pontine Glioma: A Functional Expression Investigation.

Background: Diffuse intrinsic pontine glioma [DIPG] is a fatal pediatric disease characterized by a post-translational modification, a replacement of lysine by methionine in position 27 of the N-terminal [H3K27M] tail of histone 3 isoform-1 [H3.1] or histone 3 isoform-3 [H3.3], respectively, expressed in the DIPG-36 and DIPG-50 cells.

Novel silver(I) complexes with fenamates: Insights into synthesis, spectral characterization, and bioactivity.

Six new Ag(I) ions complexes with N-phenylanthranilic, mefenamic, and niflumic acids have been synthesized. Three of them are binary complexes with the [Ag(L)] formula (where L represents N-phenylanthranilate (nfa), mefenamate (mfa), or niflumate (nif) ions), and the other three complexes are ternary with the formula [Ag(L)(phen)]⋅nHO (where phen - 1,10-phenanthroline). The complexes were characterized by elemental analysis, differential scanning calorimetry (DSC), X-ray fluorescence, powder X-ray diffraction, and single-crystal X-ray structure analysis.

Recognizing Distress in Cancer Patients in Day Hospital, by Trained Nurses vs. Non-Trained Nurses: A Pilot Study.

: Psychological distress impacts 35-40% of cancer patients, significantly affecting their quality of life, treatment adherence, and relationships with healthcare professionals. Given this, there is a critical need to enhance nursing competencies to effectively monitor and address psychological distress. Previous studies have highlighted discrepancies in capabilities based on nurses' training status, emphasizing trained nurses' critical role in providing appropriate psycho-social referrals.

Analytical interference of Burosumab therapy on intact fibroblast growth factor 23 (iFGF23) measurements using an immunoassay: preliminary evaluation.

Our study evaluated the possible interference of Burosumab (human recombinant monoclonal antibody directed against N-terminal domain of FGF23) on the immunoassay of intact FGF23 (iFGF23) with the Liaison XL. The analytical method uses three different antibodies, one of which directed against the N-terminal portion of FGF23. The evaluation of the method accuracy involved the fully automated execution of a dilution test on EDTA plasma from 5 subjects who had not received any monoclonal antibody (mAb), 20 EDTA plasma from patients treated with Burosumab, and 2 EDTA plasma from subjects who had not received any mAb in witch an adequate volume of Burosumab had been added in vitro.

-Adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as Fluorescent Probes to Detect Microglia Activation through the Imaging of Cannabinoid Receptor Subtype 2 (CB2R).

Cannabinoid receptor subtype 2 (CB2R) is emerging as a pivotal biomarker to identify the first steps of inflammation-based diseases such as cancer and neurodegeneration. There is an urgent need to find specific probes that may result in green and safe alternatives to the commonly used radiative technologies, to deepen the knowledge of the CB2R pathways impacting the onset of the above-mentioned pathologies. Therefore, based on one of the CB2R pharmacophores, we developed a class of fluorescent -adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives spanning from the green to the near-infrared (NIR) regions of the light spectrum.

Pediatric Diffuse Midline Glioma H3K27-Altered: From Developmental Origins to Therapeutic Challenges.

Diffuse intrinsic pontine glioma (DIPG), now referred to as diffuse midline glioma (DMG), is a highly aggressive pediatric cancer primarily affecting children aged 4 to 9 years old. Despite the research and clinical trials conducted to identify a possible treatment for DIPG, no effective drug is currently available. These tumors often affect deep midline brain structures in young children, suggesting a connection to early brain development's epigenetic regulation targets, possibly affecting neural progenitor functions and differentiation.

Fluorescent imaging probes for in vivo ovarian cancer targeted detection and surgery.

Ovarian cancer is the most lethal gynecological cancer, with a survival rate of approximately 40% at five years from the diagno. The first-line treatment consists of cytoreductive surgery combined with chemotherapy (platinum- and taxane-based drugs). To date, the main prognostic factor is related to the complete surgical resection of tumor lesions, including occult micrometastases.

Harmaline to Human Mitochondrial Caseinolytic Serine Protease Activation for Pediatric Diffuse Intrinsic Pontine Glioma Treatment.

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect on stabilizing symptoms.

A further pocket or conformational plasticity by mapping COX-1 catalytic site through modified-mofezolac structure-inhibitory activity relationships and their antiplatelet behavior.

Cyclooxygenase enzymes have distinct roles in cardiovascular, neurological, and neurodegenerative disease. They are differently expressed in different type of cancers. Specific and selective COXs inhibitors are needed to be used alone or in combo-therapies.

Donor specific anti-HLA antibodies in hematopoietic stem cell transplantation. Single Center prospective evaluation and desensitization strategies employed.

Background: In the setting of mismatched-hematopoietic stem cells transplantation, the detection of antibodies directed against donor-specific HLA allele(s) or antigen(s) (DSA) represents a barrier for engraftment. It is thus necessary to plan an immunosuppressive strategy, or to select an alternative donor. This prospective study aimed at evaluating the efficacy of our strategy for testing DSAs and the efficacy of the desensitization strategy (DS) employed between November 2017 and November 2020.

Tetrazole and oxadiazole derivatives as bioisosteres of tariquidar and elacridar: New potent P-gp modulators acting as MDR reversers.

New 2,5- and 1,5-disubstituted tetrazoles, and 2,5-disubstituted-1,3,4-oxadiazoles were synthesized as tariquidar and elacridar derivatives and studied as multidrug resistance (MDR) reversers. Their behaviour on the three ABC transporters P-gp, MRP1 and BCRP was investigated. All compounds inhibited the P-gp transport activity in MDCK-MDR1 cells overexpressing P-gp, showing EC values even in the low nanomolar range (compounds 15, 22).

-Terphenylamines, Acting as Selective COX-1 Inhibitors, Block Microglia Inflammatory Response and Exert Neuroprotective Activity.

Inhibition of cyclooxygenase-2 (COX-2) has been extensively studied as an approach to reduce proinflammatory markers in acute brain diseases, but the anti-neuroinflammatory role of cyclooxygenase-1 (COX-1) inhibition has been rather neglected. We report that -terphenylamine derivatives are selective COX-1 inhibitors, able to block microglia inflammatory response and elicit a neuroprotective effect. These compounds were synthesized via a three-component reaction of chalcones, β-ketoesters, and primary amines, followed by hydrolysis/decarboxylation of the ester group.

Zoledronic Acid Blocks Overactive Kir6.1/SUR2-Dependent K Channels in Skeletal Muscle and Osteoblasts in a Murine Model of Cantú Syndrome.

Cantú syndrome (CS) is caused by the gain of function mutations in the and genes encoding, respectively, for the sulfonylureas receptor type 2 (SUR2) and the inwardly rectifier potassium channel 6.1 (Kir6.1) of the ATP-sensitive potassium (KATP) channels.

The multiple combination of Paclitaxel, Ramucirumab and Elacridar reverses the paclitaxel-mediated resistance in gastric cancer cell lines.

Introduction: Paclitaxel (PTX) interferes with microtubule architecture by binding to β-tubulin, thereby blocking progression at the G2/M phase and inducing apoptosis. This study aimed to investigate molecular processes underlying PTX-mediated resistance in gastric cancer (GC) cells.

Methods: PTX-mediated resistance involves many processes, and in this work some of the factors involved in the resistance mechanism were identified by comparing two GC lines with PTX induced resistance to their sensitive counterparts.

Olive Mill Wastewater Fermented with Microbial Pools as a New Potential Functional Beverage.

Olive mill wastewater (OMWW) represents a by-product but also a source of biologically active compounds, and their recycling is a relevant strategy to recover income and to reduce environmental impact. The objective of the present study was to obtain a new functional beverage with a health-promoting effect starting from OMWW. Fresh OMWW were pre-treated through filtration and/or microfiltration and subjected to fermentation using strains belonging to , and .

Cancer Cure and Consequences on Survivorship Care: Position Paper from the Italian Alliance Against Cancer (ACC) Survivorship Care Working Group.

A multidisciplinary panel of experts and cancer patients developed a position paper to highlight recent evidence on "cancer cure" (ie, the possibility of achieving the same life expectancy as the general population) and discuss the consequences of this concept on follow-up and rehabilitation strategies. The aim is to inform clinicians, patients, and health-care policy makers about strategies of survivorship care for cured cancer patients and consequences impacting patient lives, spurring public health authorities and research organizations to implement resources to the purpose. Two identifiable, measurable, and reproducible indicators of cancer cure are presented.

Outcomes of Locally Advanced Rectal Cancer Patients Treated with Total Neoadjuvant Treatment: A Meta-Anaysis of Randomized Controlled Trials.

Background & Aims: Determining outcomes using the total neoadjuvant therapy (TNT) in patients with local advanced rectal cancer is important for stratifying patients according to expected outcomes in future studies in the era of treatment combination. The present meta-analysis estimated the pathological complete response, disease-free survival, and overall survival probabilities of rectal cancer patients and identified predictors of outcomes.

Methods: Studies reporting pathological complete response rate and time-dependent outcomes (progression or death) after total neoadjuvant treatment of locally advanced rectal cancer (LARC) were identified in MEDLINE through January 2022.

Science and visual Arts: Binomial or Dichotomy? A Pilot study in Systemic Lupus Erythematosus patients.

Scientific literature demonstrated the impairment in cognitive/executive functions and pragmatic language in SLE patients, potentially involving also asymptomatic subjects. The present study focuses on the assessment in an SLE cohort of emotional intelligence, which is an ability regulated by the network of the executive functions, cognitive abilities involved in the initiation, planning, organization, and regulation of achievement-oriented behaviors: with emotional. Thus, emotional intelligence, defined as the ability to reason with emotions, was evaluated in a SLE cohort diagnosed according to the 1997 American College of Rheumatology criteria.

Simultaneous monitoring of SARS-CoV-2 and bacterial profiles from the air of hospital environments with COVID-19-affected patients.

Unlabelled: The SARS-CoV-2 presence and the bacterial community profile in air samples collected at the Intensive Care Unit (ICU) of the Operational Unit of Infectious Diseases of Santa Caterina Novella Hospital in Galatina (Lecce, Italy) have been evaluated in this study. Air samplings were performed in different rooms of the ICU ward with and without COVID-19 patients. No sample was found positive to SARS-CoV-2, according to Allplex 2019-nCoV Assay.

Compositional Data Analysis of 16S rRNA Gene Sequencing Results from Hospital Airborne Microbiome Samples.

The compositional analysis of 16S rRNA gene sequencing datasets is applied to characterize the bacterial structure of airborne samples collected in different locations of a hospital infection disease department hosting COVID-19 patients, as well as to investigate the relationships among bacterial taxa at the genus and species level. The exploration of the centered log-ratio transformed data by the principal component analysis via the singular value decomposition has shown that the collected samples segregated with an observable separation depending on the monitoring location. More specifically, two main sample clusters were identified with regards to bacterial genera (species), consisting of samples mostly collected in rooms with and without COVID-19 patients, respectively.