Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.

The ADP-ribosyl hydrolases PARG and ARH3 counteract PARP enzymatic activity by removing ADP-ribosylation. PARG and ARH3 activities have a synthetic lethal effect; however, the specific molecular mechanisms underlying this response remain unknown. Here, we show that the PARG and ARH3 synthetic lethality is enhanced further in the presence of DNA alkylating agents, suggesting that the inability to revert ADP-ribosylation primarily affects the repair of alkylated DNA bases.

Evaluation of menstrual blood loss (MBL) by self-perception and pictorial methods and correlation to uterine myometrial pathology.

Purpose: Evaluating menstrual blood loss (MBL) in primary healthcare is challenging. Our study aimed to assess MBL using two methods: self-perception and pictograms (Pictorial Blood Assessment Chart-PBAC and Menstrual Pictogram superabsorbent polymer-c version-MP) in women undergoing transvaginal ultrasound (TVS).

Methods: We enrolled 221 premenopausal women with spontaneous menstruation, no hormonal therapy, and no ongoing pregnancy.

Use of phase angle as an indicator of overtraining in sport and physical training.

The use of bioelectrical impedance analysis (BIA) is now well established in healthcare as an essential support tool for patient management in various clinical settings. Its use in sports is rapidly expanding due to the valuable insights it offers, helping to better structure athletes' diets and training programs, thereby optimizing their performance. In the context of sport, however, there is a consensus regarding the importance of proper interpretation of BIA-derived data, which cannot be limited to mere estimation of body composition.

Warming-up the immune cell engagers (ICEs) era in breast cancer: state of the art and future directions.

The advent of immune checkpoint inhibitors (ICIs) has deeply reshaped the therapeutic algorithm of triple-negative breast cancer (TNBC). However, there is considerable scope for better engagement of the immune system in other BC subtypes. ICIs have paved the way for investigations into emerging immunotherapeutic strategies, such as immune cell engagers (ICEs) that work by promoting efficient tumor cell killing through the redirection of immune system against cancer cells.

Protective effects of olive oil antioxidant phenols on mercury-induced phosphatidylserine externalization in erythrocyte membrane: Insights into scramblase and flippase activity.

In several physiopathological processes, phosphatidylserine (PS), normally sequestered to the inner leaflet of the plasma membrane, becomes exposed to the cell surface. In erythrocytes (RBC), PS externalization is a crucial event for the removal of aged/damaged cells but can also be associated with increased prothrombotic activity. Structurally related olive oil antioxidants, including hydroxytyrosol (HT), are able to significantly reduce the percentage of PS-exposing RBC, when cells are exposed to toxic compounds such as the heavy metal mercury (Hg).

Operator-dependent and operator-independent contrast media minimization strategies to prevent acute kidney injury after percutaneous coronary intervention.

Contrast associated acute kidney injury (CA-AKI) is a major complication of contrast media (CM) exposure following percutaneous coronary intervention (PCI), associated with high rates of morbidity and mortality in both early and late phases. During the past years, several CA-AKI prevention strategies based on CM sparing have been proposed, which differ significantly in terms of methodological features and efficacy. In this review, we propose a new classification of these techniques based on their dependency on operators' management.

Hepatic lipogenesis marked by GCKR-modulated triglycerides increases serum FGF21 in children/teens with obesity.

Aims: Fibroblast growth factor 21 (FGF21) decreases hepatic lipogenesis in animal models, and FGF21 analogues decrease serum triglycerides (TG) in adults in phase-2 trials. On the other hand, serum FGF21 is associated with higher TG in observational studies of people with obesity, raising a sort of paradox. We tested the hypothesis that FGF21 is induced by TG in youth with obesity, as a compensatory mechanism.

Unleashing the potential of extracellular vesicles for ulcerative colitis and Crohn's disease therapy.

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Chromosome alignment and Kif18A action rely on spindle-localized control of Cdk1 activity.

Introduction: During mitosis, chromosome alignment at the mitotic spindle equator grants correct chromosome segregation and proper nuclei formation in daughter cells. The kinesin 8 family member Kif18A plays a crucial role for chromosome alignment by localizing at the kinetochore-microtubule (K-MT) plus ends to dampen MT dynamics and stabilize K-MT attachments. Kif18A action is directly antagonized by the master mitotic kinase cyclin B-dependent kinase 1 (Cdk1) and is promoted by protein phosphatase 1 (PP1).

Cutaneous phosphorylated-synuclein: an early diagnostic biomarker for pure autonomic failure.

Background: Pure autonomic failure (PAF) presents with progressive autonomic failure without other neurological features. Atypical presentations may lead to diagnostic uncertainty. We studied whether cutaneous phosphorylated-alpha-synuclein (p-syn) could distinguish between PAF, multiple system atrophy (MSA) and non-synucleinopathy-related autonomic failure, and examined its relationship with quantitative markers of cardiovascular autonomic failure.

Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study.

Background: Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients' outcomes have not been reported so far.

Patients And Methods: In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy.

Design and functional studies of xylene-based cyclic mimetics of SOCS1 protein.

Peptidomimetics of Suppressors of cytokine signaling 1 (SOCS1) protein demonstrated valid therapeutic potentials as anti-inflammatory agents. Indeed, SOCS1 has a small kinase inhibitory region (KIR) primarily involved in the inhibition of the JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway Herein, on the basis of previous investigations on a potent mimetic of KIR-SOCS1, named PS5, we designed and evaluated the SAR (Structure Activity Relationship) features of two xylene-based macrocycles analogues of PS5. These novel compounds bear thiol-xylene linkages with mono- and bi-cyclic scaffolds: they were in vitro functionally investigated toward JAK2 catalytic domain, as ligands with microscale thermophoresis (MST) and as inhibitors through LC-MS analyses.

Exploring the management of recurrent angioedema caused by different mechanisms.

Purpose Of Review: We aim to explore the most recent insights into the pathogenesis of recurrent angioedema caused by different mechanisms and then focus on the management and treatment approaches available.

Recent Findings: The recently developed DANCE consensus classification identifies five types of angioedema: mast cell-mediated (AE-MC), bradykinin-mediated, because of intrinsic vascular endothelium dysfunction (AE-VE), drug-induced (AE-DI), and due to unknown mechanisms (AE-UNK). These subtypes require different management with treatment choices targeting the main pathogenetic pathways involved in each form.

Anthropometric estimates can predict satisfaction with breast in a population of asymptomatic women.

Background: Several authors hypothesized that normative values of breast related quality of life in asymptomatic populations can be helpful to better understand changes induced by surgery. Breast related quality of life can be associated to breast anthropometry. This study was designed to explore this hypothesis, find relevant correlations and, using machine learning techniques, predict values of satisfaction with breast from easy body measurements.

Chemical characterization of wheat-based waste derived from a pharmaceutical process for its potential valorization.

Introduction: We report the analysis and characterization and the preliminary biological evaluation, of both liquid and solid wastes obtained from the processing of wheat () to produce the most iconic phytostimulin-based pharmaceutical products. The study aims to verify whether the waste can be reused in another process and not destined to its simple destructive disposal.

Methods: In this perspective, we first carried out an in-depth chemical-physical analysis of the waste together with a biocompatibility evaluation to plan the feasible final choice of waste destination.

Enzyme-Assisted Electrochemical Point-of-Care Test for miRNA Detection in Liquid Biopsy.

In the personalized medicine era, affordable and portable devices for quicker cancer monitoring, even in remote areas, are crucial. To address this need, we have developed an enzyme-assisted electrochemical point-of-care (POC) test for application toward liquid biopsy. In particular, miR-200a-5p has been taken into account as the model target due to its correlation for triple negative breast cancer (TNBC) prognosis.

Bifidobacteriaceae diversity in the human microbiome from a large-scale genome-wide analysis.

We performed a large-scale genome-wide analysis aiming to investigate the prevalence and strain-level diversity of Bifidobacteriaceae species in the human microbiome. We considered 9,528 publicly available human metagenomes and integrated them with 1,192 isolate genomes from different sources. The prevalence and abundance of Bifidobacteriaceae species in humans was linked to multiple host characteristics: they were reduced in older people and enriched in populations characterized by Westernized lifestyles with geography-specific patterns.

Constitutive opening of the Kv7.2 pore activation gate causes -developmental encephalopathy.

Pathogenic variants in encoding Kv7.2 voltage-gated potassium channel subunits cause developmental encephalopathies (-encephalopathies), both with and without epilepsy. We herein describe the clinical, in vitro, and in silico features of two encephalopathy-causing variants (A317T, L318V) in Kv7.

The Effect of Parental Caregiving on the Fertility Expectations of Adult Children.

Previous research has highlighted the positive impact of parents on their adult children's fertility plans through childcare, but the association between parental health and fertility expectations remains unclear. Thus, this paper offers a novel perspective on the issue of family support by investigating how caregiving responsibilities toward elderly parents affect adult children's decision to have a child. Using a long panel dataset for Australia, we examine whether adult children changed their fertility expectations after becoming care providers to their parents.

Genistein in focus: pharmacological effects and immune pathway modulation in cancer.

Cancer is a significant global health concern, responsible for mortality and morbidity of individuals. It is characterized by uncontrolled cellular growth, tumor formation, and potential metastasis. The immune system is pivotal in recognizing and eliminating cancerous cells, with immune cells such as T cells, B cells, natural killer cells (NK), and dendritic cells playing critical roles.