AKRs confer oligodendrocytes resistance to differentiation-stimulated ferroptosis.

Ferroptosis is a recently characterized form of cell death that has gained attention for its roles in both pathological and physiological contexts. The existence of multiple anti-ferroptotic pathways in both neoplastic and healthy cells, along with the critical regulation of iron metabolism involved in lipid peroxides (lipid-ROS) production-the primary mediators of this cell death process-underscores the necessity of precisely controlling or preventing accidental/unwanted ferroptosis. Conversely, dysregulated iron metabolism and alterations in the expression or activity of key anti-ferroptotic components are linked to the development and progression of various human diseases, including multiple sclerosis (MS).

Evolution of fungal tuberculosis necrotizing toxin (TNT) domain-containing enzymes reveals divergent adaptations to enhance NAD cleavage.

Tuberculosis necrotizing toxin (TNT) is a protein domain discovered on the outer membrane of Mycobacterium tuberculosis (Mtb), and the fungal pathogen Aspergillus fumigatus. TNT domains have pure NAD(P) hydrolytic activity, setting them apart from other NAD-cleaving domains such as ADP-ribosyl cyclase and Toll/interleukin-1 receptor homology (TIR) domains which form a wider set of products. Importantly, the Mtb TNT domain has been shown to be involved in immune evasion via depletion of the intracellular NAD pool of macrophages.

Novel Calcium-Binding Motif Stabilizes and Increases the Activity of Ecto-NADase.

Nicotinamide adenine dinucleotide (NAD) is an essential molecule in all kingdoms of life, mediating energy metabolism and cellular signaling. Recently, a new class of highly active fungal surface NADases was discovered. The enzyme from the opportunistic human pathogen was thoroughly characterized.

Identification of structural determinants of nicotinamide phosphoribosyl transferase (NAMPT) activity and substrate selectivity.

NAD homeostasis in mammals requires the salvage of nicotinamide (Nam), which is cleaved from NAD by sirtuins, PARPs, and other NAD-dependent signaling enzymes. Nam phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step in vitamin B3 salvage, whereby Nam reacts with phosphoribosyl pyrophosphate (PRPP) to form nicotinamide mononucleotide. NAMPT has a high affinity towards Nam, which is further enhanced by autophosphorylation of His247.

Factors contributing to medication errors: A descriptive qualitative study of Italian nursing students.

Background: It is estimated that 20-40 % of medication errors (MEs) made by nursing students are not reported, thus creating a gap in learning from mistakes. There is scarce literature on the reasons for the underreporting of MEs made by nursing students.

Objectives: The aim was to analyse the opinions of nursing students about MEs, types and causes and factors that facilitate or discourage ME reporting during clinical training.

The integration of AlphaFold-predicted and crystal structures of human -3-hydroxy-l-proline dehydratase reveals a regulatory catalytic mechanism.

Computational methods for protein structure prediction have made significant strides forward, as evidenced by the last development of the neural network AlphaFold, which outperformed the CASP14 competitors by consistently predicting the structure of target proteins. Here we show an integrated structural investigation that combines the AlphaFold and crystal structures of human -3-Hydroxy-l-proline dehydratase, an enzyme involved in hydroxyproline catabolism and whose structure had never been reported before, identifying a structural element, absent in the AlphaFold model but present in the crystal structure, that was subsequently proved to be functionally relevant. Although the AlphaFold model lacked information on protein oligomerization, the native dimer was reconstructed using template-based and computational approaches.

The balance between NAD biosynthesis and consumption in ageing.

Nicotinamide adenine dinucleotide (NAD) is a vital coenzyme in redox reactions. NAD is also important in cellular signalling as it is consumed by PARPs, SARM1, sirtuins and CD38. Cellular NAD levels regulate several essential processes including DNA repair, immune cell function, senescence, and chromatin remodelling.

Structure of Thermococcus litoralis Δ-pyrroline-2-carboxylate reductase in complex with NADH and L-proline.

L-Hydroxyproline (L-Hyp) is a nonstandard amino acid that is present in certain proteins, in some antibiotics and in the cell-wall components of plants. L-Hyp is the product of the post-translational modification of protein prolines by prolyl hydroxylase enzymes, and the isomers trans-3-hydroxy-L-proline (T3LHyp) and trans-4-hydroxy-L-proline (T4LHyp) are major components of mammalian collagen. T4LHyp follows two distinct degradation pathways in bacteria and mammals, while T3LHyp is metabolized by a two-step metabolic pathway that is conserved in bacteria and mammals, which involves a T3LHyp dehydratase and a Δ-pyrroline-2-carboxylate (Pyr2C) reductase.

Chronomodulated capecitabine and adjuvant radiation in intermediate-risk to high-risk rectal cancer: a phase II study.

Objectives: The aim of this study was to evaluate the feasibility and tolerability of capecitabine administration according to a specific time schedule, combined with adjuvant radiation therapy, in intermediate-risk to high-risk rectal cancer patients treated with an upfront surgery. The primary endpoint was the rate of grade 3 to 4 diarrhea during chemoradiation (CRT).

Materials And Methods: Stage II and III rectal cancer patients received, after total mesorectal excision, 2 cycles of XELOX regimen (oxaliplatin 130 mg/m(2) on day 1; capecitabine 1000 mg/m(2) bid on day 1 to 14, q21), followed by capecitabine (800 mg/m(2) bid daily; 20% dose at 12:00 AM and 80% dose at 12:00 PM) administered continuously during pelvic radiation (total 50.

Feasibility study of biweekly capecitabine, oxaliplatin, and irinotecan in patients with untreated advanced gastric cancer.

Background: Capecitabine in combination with oxaliplatin and irinotecan (COI regimen) is active and well tolerated in metastatic colorectal cancer. Since there is no internationally adopted standard regimen, we have conducted a pilot study of COI in untreated advanced gastric cancer.

Methods: Patients received irinotecan, 180 mg/m2 infused over 90 min on day 1, followed by oxaliplatin, 85 mg/m2 in a 3-hr infusion on day 2, and capecitabine, 1000 mg/m2/day orally twice daily from days 2 to 6 of a biweekly schedule.

Dose finding study of erlotinib combined to capecitabine and irinotecan in pretreated advanced colorectal cancer patients.

Purpose: This study evaluated the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of erlotinib when combined to irinotecan and capecitabine in pre-treated metastatic colorectal cancer patients.

Methods: Five dose level combinations with irinotecan (from 180 to 240 mg/m(2), day 1, q21), capecitabine (1,500-2,000 mg/m(2) per day, days 2-15, q21) and erlotinib (50-150 mg per day, continuously) were planned. Patients were enrolled in cohorts of three, and evaluated for first cycle acute toxicity.

Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits.

The relevance of low folate levels as determinants of cognitive deficits and the usefulness of folate supplementation in the treatment of cognitive deficits was reviewed from the literature. Over 40 papers and book chapters published in English, French, German, Italian and Spanish were examined. This represents those papers published in the international literature in the last 10 years which were identified by various key words including folate, cognition and aging (or ageing).

Inverse relationship between scores on the quality of life questionnaire SF-12 and on the Aging Males' Symptoms scale in Italian men.

Objectives: To analyse the relation between results of the Aging Males' Symptoms (AMS) questionnaire for aging males, and of quality of life (QOL) questionnaire SF-12 and cardiovascular risk factors.

Methods: 1,927 men aged 55-85 years were interviewed by 56 general practitioners. During the interview the men were asked to fill in the AMS scale and the QOL questionnaire SF-12.

Feasibility of sequential therapy with FOLFIRI followed by docetaxel/cisplatin in patients with radically resected gastric adenocarcinoma. A randomized phase III trial.

Objective: Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting.

Methods: 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B).

Capecitabine plus oxaliplatin and irinotecan regimen every other week: a phase I/II study in first-line treatment of metastatic colorectal cancer.

Background: A phase I/II study was performed to determine the safety and activity of a capecitabine plus oxaliplatin and irinotecan (COI) regimen using capecitabine concurrently with oxaliplatin and irinotecan in previously untreated patients with metastatic colorectal cancer.

Patients And Methods: Patients received irinotecan on day 1, oxaliplatin (85 mg/m(2)) on day 2 and capecitabine (1000 mg/m(2) orally twice daily) on days 2-6 of a biweekly schedule. Three dose levels ranging from 150 to 180 mg/m(2) were explored for irinotecan in sequential cohorts of three to six patients.

Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study.

This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX). One hundred and forty-three patients with measurable, non-resectable metastatic colorectal cancer were randomised in a multicentre study to receive TEGAFIRI (UFT 250 mg m(-2) day days 1-14, LV 90 mg day days 1-14, irinotecan 240 mg m(-2) day 1; q21) or TEGAFOX (UFT 250 mg m(-2) day days 1-14, LV 90 mg day days 1-14, oxaliplatin 120 mg m(-2) day 1; q21). Among 143 randomised patients, 141 were analysed (68 received TEGAFIRI and 73 TEGAFOX).

Irinotecan, fluorouracil and folinic acid (FOLFIRI) as effective treatment combination for patients with advanced gastric cancer in poor clinical condition.

Aims And Background: Irinotecan (CPT-11) has been tested as a single agent in several studies, and response rates of 18-23% have been reported in first-line gastric cancer therapy. In the present study we report the safety and efficacy results combining CPT-11 with 5-fluorouracil (5-FU) and folinic acid (FA).

Patients And Methods: Thirty consecutive patients with metastatic gastric cancer, considered in poor clinical condition, were treated with CPT-11 and 5-FU/FA according to the FOLFIRI regimen.

[Determinants of depression in 111 Italian patients with systemic sclerosis].

Background: A high prevalence of depressive symptoms has been described in systemic sclerosis (SSc), but no clear association with organ involvement or objective indices of disease severity has been depicted. To date, no effort has been made to determine the prevalence of depressive symptoms in Italian patients with SSc or to clarify their cause.

Methods: One-hundred-eleven SSc patients were asked to fill in the Beck Depression Inventory (BDI) questionnaire, the scleroderma Health Assessment Questionnaire (sHAQ) and two additional questions assessing the patient's familiar support and the social consequences of the patient's change in physical appearnace.

Dehydroepiandrosterone sulfate (DHEA-S) and Alzheimer's dementia in older subjects.

Objectives And Methods: We investigated the association of serum dehydroepiandrosterone sulfate (DHEA-S) levels with dementia of Alzheimer's type (DAT) and impairment in selected cognitive domains (memory, language, attention and working memory) in 158 patients (75.5+/-6.7 years, 46 men) with first-diagnosed probable DAT and in 158 age- and sex-matched controls.

Capecitabine chemoradiation for rectal cancer after curative surgery.

This study reports the tolerability and feasibility of capecitabine, an oral fluoropyrimidine, chemoradiation as postoperative treatment. Stage II-III rectal cancer patients received 2 cycles of bolus 5-FU (425 mg/m2) and leucovorin (LV) (20 mg/m2) on days 1-5 q3w followed by oral capecitabine (800 mg/m2 bid) continuously during pelvic radiotherapy (total 50.4 Gy).

Alzheimer's disease-associated disability: an ICF approach.

Purpose: The aim of the study is to provide a description of dementia-associated disability in Alzheimer's disease (AD) patients through the International Classification of Functioning, Disability and Health (ICF).

Method: Twenty-six AD patients at different stages of disease participated in the study. Mini Mental State Examination (MMSE) and Global Deterioration Scale (GDS) were used to stage the degree of cognitive impairment and the stage of disease, respectively.

Pathological features as predictors of recurrence after radical resection of gastric cancer.

Background: The aim of this study was to investigate the pattern and timing of recurrence and to determine associated risk factors after radical resection of gastric cancer including D2 dissection.

Methods: A total of 274 patients who had undergone radical resection of gastric cancer with nodal involvement or T3-4 tumour were randomized to receive chemotherapy or no further treatment (control group). Locoregional recurrence and distant metastasis were analysed in a competing risks framework, by estimating the crude cumulative incidence in each group.

Treatment of cancer-related anemia with epoetin alfa: a review.

Erythropoietin (EPO) is a hematopoietic growth hormone that regulates survival, proliferation, and differentiation of erythroid progenitor cells. A reduction in tissue oxygenation stimulates EPO production, through a complex feedback mechanism. Patients with cancer-related anemia have an inadequate EPO response that is further impaired by cancer treatments such as chemotherapy.

Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer.

Aims And Background: As raltitrexed and oxaliplatin (L-OHP) are both effective in the treatment of colorectal cancer but have different mechanisms of action, we studied the antitumoral activity and safety of their combined use in patients with advanced colorectal cancer.

Methods: A 15-min intravenous infusion of raltitrexed (2.5 mg/m2) and a 180-min infusion of oxaliplatin (100 mg/m2) were administered on day 1 every three weeks for a maximum of six cycles.

Efficacy of treatment with irinotecan and oxaliplatin combination in FU-resistant metastatic colorectal cancer patients.

Objectives: As single agents, irinotecan and oxaliplatin are active in colorectal cancer after fluorouracil (FU)-containing regimen failure. Their synergistic activity and non-overlapping toxicity profile are well documented, but more data are needed to explore their exact sequence. The aim of this study was to evaluate the activity and tolerability of irinotecan followed by oxaliplatin in patients with FU-resistant colorectal cancer.