Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies.

Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death.

Real-time morphometric analysis of targeted therapy for neuroblastoma cells in monolayer and 3D hydrogels using digital holographic microscopy.

High-risk neuroblastoma (HR-NB) patient treatment is currently insufficient and challenging due to its high clinical, morphological, and genetic heterogeneity as well as the scarcity of available samples for research. We used a gelatin- and silk fibroin-based hydrogel system with cross-linked vitronectin (VN) as an artificial biomimetic three-dimensional (3D) environment to mirror aggressive neuroblastoma (NB) tumors and tested long-term cell response to Cilengitide (CLG). Based on our previous studies and others using the integrin inhibitor CLG as a potential mechanotherapy drug, we show that CLG caused cell detachment in monolayer cultures of -amplified SK-N-BE (2) and -mutated SH-SY5Y human neuroblastoma cell lines.

Overexpression of Glyoxalase 2 in Human Breast Cancer Cells: Implications for Cell Proliferation and Doxorubicin Resistance.

Glyoxalase 2 (Glo2) is an enzyme of the glyoxalase system whose pathway parallels glycolysis and which aims to remove methylglyoxal (MGO). This study analyzed the possible additional roles of the Glo2 enzyme in breast cancer (MCF7) and non-cancer (HDF) cell lines, investigating its presence at the nuclear level and its potential involvement in cell proliferation and chemotherapy resistance. The results revealed that Glo2 is overexpressed in cancer cells, and its expression is higher during the proliferative (S and G2/M) phases of the cell cycle.

Risk of cancer development associated with disease-modifying therapies for multiple sclerosis: study protocol for a systematic review and meta-analysis of randomised and non-randomised studies.

Background: The association between cancer and multiple sclerosis has long been investigated. Several studies and reviews have examined the risk of cancer among patients with multiple sclerosis treated with disease-modifying therapies (DMTs) but with conflicting results. This study will aim to investigate the association between DMTs for multiple sclerosis and subsequent cancer risk using research synthesis methods.

Adherence Patterns and Health Outcomes in Spanish Young Women Participating in a Virtual-Guided HIIT Program: Insights from the Randomized Controlled WISE Trial.

Background/objectives: A notable decline in physical activity from late adolescence to early adulthood affects young women especially. This study aimed to investigate adherence to an unsupervised virtual-guided high-intensity interval training (HIIT) exercise program among young women in Spain.

Methods: A total of 106 participants were recruited and randomized to the Women's Involvement in Steady Exercise (WISE) trial exercise program, administered remotely via a mobile app, and a control group.

Unveiling the Ro60-Ro52 complex.

The coexistence within a subcellular complex of inter-cellular proteins Ro60, responsible for preserving ncRNA quality, and Ro52, involved in intracellular proteolysis, has been a subject of ongoing debate. Employing molecular docking in tandem with experimental methods like Quartz Crystal Microbalance with Dissipation (QCM-D), Proximity Ligation Assay (PLA), and Indirect Immunofluorescence (IIF), we reveal the presence of Ro60 associating with Ro52 within the cytoplasm. This result unveils the formation of a weak transient complex with a K ≈ (3.

is a lineage-specific gene and a tumor suppressor in neuroblastoma.

Neuroblastoma is a childhood developmental cancer; however, its embryonic origins remain poorly understood. Moreover, in-depth studies of early tumor-driving events are limited because of the lack of appropriate models. Herein, we analyzed RNA sequencing data obtained from human neuroblastoma samples and found that loss of expression of trunk neural crest-enriched gene associates with advanced disease and worse outcome.

SMAD4 promotes somatic-germline contact during murine oocyte growth.

Development of the mammalian oocyte requires physical contact with the surrounding granulosa cells of the follicle, which provide it with essential nutrients and regulatory signals. This contact is achieved through specialized filopodia, termed transzonal projections (TZPs), that extend from the granulosa cells to the oocyte surface. Transforming growth factor (TGFβ) family ligands produced by the oocyte increase the number of TZPs, but how they do so is unknown.

Decoding -ITD Sarcomas: Case Report of a Rare Pediatric Tumor With Challenges in Diagnosis.

Sarcomas characterized by gene alterations, are a distinct clinico-pathological group of high-grade tumors, that represent 5% of small round cell tumors without or fusion. Diverse genetic alterations characterize this group, including gene fusion being the most common alteration and less frequently internal tandem duplications (ITDs). We present a compelling case of a 3-year-old girl diagnosed with a high-grade nasoethmoidal sarcoma exhibiting -ITD.

Physical activity to reduce the burden of frailty after menopause: effectiveness and adherence rate of a resource saving exercise plan.

Objective: Frailty may be increased by menopause. Physical activity has been proposed to reduce frailty, but poor adherence and cost limit effectiveness. We aimed to investigate both the effectiveness against the frailty burden and the adherence rate of a multicomponent physical activity scheme partially managed by the participating women themselves.

Mitochondrial dysfunction in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients.

Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene.

Association between anxiety and frailty in postmenopausal women.

Objective: To explore the association between anxiety and frailty in community-dwelling postmenopausal women.

Methods: This was a cross-sectional study in which 390 postmenopausal women (aged 60-83 years) who were attending a comprehensive care program were surveyed between January 2018 and February 2020. Each participant was administered a validated Spanish version of the Hospital Anxiety and Depression Scale (HADS) to assess their anxiety status.

Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women.

Objective: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) and genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women.

Methods: A cross-sectional study was performed in which we selected five SNPs, three in the gene and two in the .

Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations.

Objectives: To investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness, and reproducibility.

Study Design And Setting: We evaluated a random sample of health economic evaluations indexed in MEDLINE during 2019. We included articles written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years, and/or disability-adjusted life years.

Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making.

Exacerbated response to oxidative stress in the Retinitis Pigmentosa Cerkl mouse model triggers retinal degeneration pathways upon acute light stress.

The retina is particularly vulnerable to genetic and environmental alterations that generate oxidative stress and cause cellular damage in photoreceptors and other retinal neurons, eventually leading to cell death. CERKL (CERamide Kinase-Like) mutations cause Retinitis Pigmentosa and Cone-Rod Dystrophy in humans, two disorders characterized by photoreceptor degeneration and progressive vision loss. CERKL is a resilience gene against oxidative stress, and its overexpression protects cells from oxidative stress-induced apoptosis.

Digital image analysis workflows for evaluation of cell behavior and tumor microenvironment to aid therapeutic assessment in high-risk neuroblastoma.

Digital pathology and artificial intelligence are promising emerging tools in precision oncology as they provide more robust and reproducible analysis of histologic, morphologic and topologic characteristics of tumor cells and the surrounding microenvironment. This study aims to develop digital image analysis workflows for therapeutic assessment in preclinical in vivo models. For this purpose, we generated pipelines that enable automatic detection and quantification of vitronectin and αvβ3 in heterotopic high-risk neuroblastoma xenografts, demonstrating that digital analysis workflows can be used to provide robust detection of vitronectin secretion and αvβ3 expression by malignant neuroblasts and to evaluate the possibility of combining traditional chemotherapy (etoposide) with extracellular matrix-targeted therapies (cilengitide).

Cardiovascular complications of diabetes: role of non-coding RNAs in the crosstalk between immune and cardiovascular systems.

Diabetes mellitus, a group of metabolic disorders characterized by high levels of blood glucose caused by insulin defect or impairment, is a major risk factor for cardiovascular diseases and related mortality. Patients with diabetes experience a state of chronic or intermittent hyperglycemia resulting in damage to the vasculature, leading to micro- and macro-vascular diseases. These conditions are associated with low-grade chronic inflammation and accelerated atherosclerosis.

Myopericarditis Associated with the Novavax COVID-19 Vaccine (NVX-CoV2373): A Retrospective Analysis of Individual Case Safety Reports from VigiBase.

Background: Myocarditis and pericarditis have been associated most notably with mRNA vaccines, but the association with a recently authorized adjuvated vaccine (NVX-CoV2373) is controversial.

Objective: The aim was to analyze the cases of myocarditis and pericarditis in association with NVX-CoV2373 reported to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase), applying disproportionality analyses.

Patients And Methods: The main characteristics of the ICSRs reporting myopericarditis with NVX-CoV2373 have been summarized.

Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness.

The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study the interactions of tumor cells and the tumor microenvironment (TME), which play a crucial role in tumor initiation, progression and metastasis.