Hereditary Breast Cancer: Comprehensive Risk Assessment and Prevention Strategies.

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity and penetrance of the disease.

promoter hypermethylation and Lynch Syndrome: When to test for constitutional epimutations of gene?

Lynch syndrome is a genetic condition predisposing to cancer, particularly colorectal cancer and endometrial cancer, due to germline mutations in MisMatch Repair genes. More rarely, Lynch syndrome is the result of a constitutional promoter methylation. This review summarizes the current knowledge about the role of this epigenetic mechanism in the Lynch syndrome.

Low dose TamOxifen and LifestylE changes for bReast cANcer prevention (TOLERANT study): Study protocol of a randomized phase II biomarker trial in women at increased risk for breast cancer.

Background: Breast Cancer (BC) prevention strategies range from lifestyle changes such as increasing physical activity and reducing body weight to preventive drugs like tamoxifen, known to reduce BC incidence in high-risk women. Sex Hormone Binding Globulin (SHBG) is related to BC risk due to its ability to bind circulating estradiol at high affinity and to regulate estradiol action. A study protocol is presented based on the assessment of the effect of different interventions such as tamoxifen at 10 mg every other day (LDT), intermittent caloric restriction (ICR) two days per week, lifestyle intervention (LI, step counter use) and their combination on the modulation of SHBG and several other biomarkers associated to BC.

Coffee and Microbiota: A Narrative Review.

Coffee is one of the most widely consumed beverages in the world, which has important repercussions on the health of the individual, mainly because of certain compounds it contains. Coffee consumption exerts significant influences on the entire body, including the gastrointestinal tract, where a central role is played by the gut microbiota. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of the microbiota has proven to be of fundamental importance for the development of new therapeutic strategies.

Prothrombin time predicts steroid response in severe alcohol-related hepatitis.

Background And Aims: Alcohol-related hepatitis (AH) is the most severe form of acute alcohol-related liver disease. Maddrey's discriminant function ≥32 defines the severe form of AH, which is associated with a high mortality. Steroid therapy represents the main medical treatment that may reduce short-term mortality.

Germline pathogenic variants in metaplastic breast cancer patients and the emerging role of the BRCA1 gene.

Metaplastic breast cancer (MpBC) is a rare, aggressive breast cancer (BC) histotype. Scarce information is available about MpBC genetic predisposition. Previous studies, mainly consisting of case reports, retrospective reviews and others on target therapies, pointed to a possible involvement of the BRCA1 gene in increasing MpBC risk, without ever confirming it.

An Unenhanced Breast MRI Protocol Based on Diffusion-Weighted Imaging: A Retrospective Single-Center Study on High-Risk Population for Breast Cancer.

Purpose: This study aimed to investigate the use of contrast-free magnetic resonance imaging (MRI) as an innovative screening method for detecting breast cancer in high-risk asymptomatic women. Specifically, the researchers evaluated the diagnostic performance of diffusion-weighted imaging (DWI) in this population.

Methods: MR images from asymptomatic women, carriers of a germline mutation in either the BRCA1 or BRCA2 gene, collected in a single center from January 2019 to December 2021 were retrospectively evaluated.

Metaplastic breast cancer: an all-round multidisciplinary consensus.

Metaplastic breast cancer (MpBC) is a rare and aggressive histologic subtype of breast cancer (BC) characterized by the presence of at least two cellular types, commonly epithelial and mesenchymal components. Despite growing evidence that MpBC is a unique entity, it has long been treated as a variant of nonspecial type (NST) BC. MpBC typically shows the phenotype of triple-negative breast cancer (TNBC), but compared to NST-TNBC, it is a relatively chemorefractory tumor associated with worse outcomes.

Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship.

There is much evidence confirming the crucial role played by the gut microbiota in modulating the immune system in the onset of autoimmune diseases. In this article, we focus on the relationship between alterations in the microbiome and the onset of diabetes mellitus type 1 and LADA, in light of the latest evidence. We will then look at both how the role of the gut microbiota appears to be increasingly crucial in the pathogenesis of these disorders and how this aspect may be instrumental in the development of new potential therapeutic strategies that modulate the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation.

The transcriptional profile of adipose-derived stromal cells (ASC) mirrors the whitening of adipose tissue with age.

Multipotent stem cells persist within the stromal vascular fraction (SVF) of adipose tissue during adulthood. These cells, commonly referred to as adipose-derived stromal cells (ASC), have been extensively investigated over the past years as a promising therapeutic tool based on their regenerative and immunomodulatory properties. However, how ASC might mirror the age-related alteration of the fat they reside in remains unclear.

Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants.

Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. Mutations in LMNA gene, encoding for lamin A/C, account for 10% of familial DCM. LMNA-related cardiomyopathies are characterized by heterogeneous clinical manifestations that vary from a predominantly structural heart disease, mainly mild-to-moderate left ventricular (LV) dilatation associated or not with conduction system abnormalities, to highly pro-arrhythmic profiles where sudden cardiac death (SCD) occurs as the first manifestation of disease in an apparently normal heart.

Corrigendum: Exome Sequencing in BRCA1-2 Candidate Familias: The Contribution of Other Cancer Susceptibility Genes.

[This corrects the article DOI: 10.3389/fonc.2021.

Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells.

Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing of time over the course of adult life, and their combination at midlife is strongly related to increased vulnerability to diseases; however, the causal connection between them remains largely unclear. By combining multi-omics and functional analyses of adipose-derived stromal cells established from young (1 month) and midlife (12 months) mice, we show that an increase in expression of interferon regulatory factor 7 (IRF7) during adult life drives major metabolic changes, which include impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched-chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the 'sterile' activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age.

Distinct pattern of lymphoid neoplasms characterizations according to the WHO classification (2016) and prevalence of associated Epstein-Barr virus infection in Nigeria population.

Background: The present study aimed to classify lymphoid neoplasms according to the latest World Health Organization (WHO) classification and outlining the distribution in Nigeria of different entities. Additionally, the study describes the prevalence of lymphoid neoplasms associated with Epstein-Barr virus (EBV) infection in the Nigerian population.

Methods: We collected 152 formalin-fixed paraffin-embedded (FFPE) tissues diagnosed as lymphoma from 2008 to 2018, coming from three different institutions located within three geopolitical zone in Nigeria.

Exome sequencing in BRCA1-2 candidate familias: the contribution of other cancer susceptibility genes.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is a condition in which the risk of breast and ovarian cancer is higher than in the general population. The prevalent pathogenesis is attributable to inactivating variants of the highly penetrant genes, however, other cancer susceptibility genes may also be involved. By Exome Sequencing (WES) we analyzed a series of 200 individuals selected for genetic testing in genes according to the updated National Comprehensive Cancer Network (NCCN) guidelines.

Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles.

magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents.

Simple and Rapid Non-Enzymatic Procedure Allows the Isolation of Structurally Preserved Connective Tissue Micro-Fragments Enriched with SVF.

The stromal vascular fraction (SVF) consists of a heterogeneous population of stem and stromal cells, generally obtained from adipose tissue by enzymatic digestion. For human cell-based therapies, mechanical process methods to obtain SVF represent an advantageous approach because they have fewer regulatory restrictions for their clinical use. The aim of this study was to characterize a novel commercial system for obtaining SVF from adipose tissue by a mechanical approach without substantial manipulations.

Artificial dermal substitutes for tissue regeneration: comparison of the clinical outcomes and histological findings of two templates.

Objective: Artificial dermal substitutes (DSs) are fundamental in physiological wound healing to ensure consistent and enduring wound closure and provide a suitable scaffold to repair tissue. We compared the clinical and histological features of two DSs, Pelnac and Integra, in the treatment of traumatic and iatrogenic skin defects.

Methods: This prospective observational study involved 71 randomly selected patients from our hospital.

Comparative technical analysis of lipoaspirate mechanical processing devices.

Fat grafting is a well-established procedure in reconstructive, aesthetic, and regenerative medicine, in particular due to the presence in the adipose tissue of a high concentration of mesenchymal stem cells. The need to reduce fat processing times, for an immediate clinical use and regulatory restrictions on the degree of manipulation of human tissues, has led to the development of numerous devices for the mechanical, nonenzymatic processing of adipose tissue. The aim of this study is to describe the state of the art of mechanical devices used for fat processing, performing a technical analysis of the currently commercially available devices.

Colloidal polymer-coated Zn-doped iron oxide nanoparticles with high relaxivity and specific absorption rate for efficient magnetic resonance imaging and magnetic hyperthermia.

Colloidally stable nanoparticles-based magnetic agents endowed with very high relaxivity and specific absorption rate are extremely desirable for efficient magnetic resonance imaging and magnetic hyperthermia, respectively. Here, we report a water dispersible magnetic agent consisting of zinc-doped superparamagnetic iron oxide nanoparticles (i.e.

In Vitro Characterization of Adipose Stem Cells Non-Enzymatically Extracted from the Thigh and Abdomen.

Autologous fat grafting is a surgical technique in which adipose tissue is transferred from one area of the body to another, in order to reconstruct or regenerate damaged or injured tissues. Before reinjection, adipose tissue needs to be purified from blood and cellular debris to avoid inflammation and preserve the graft viability. To perform this purification, different enzymatic and mechanical methods can be used.

A Correlative Imaging Study of in vivo and ex vivo Biodistribution of Solid Lipid Nanoparticles.

Purpose: Solid lipid nanoparticles are largely used in biomedical research and are characterized by high stability and biocompatibility and are also able to improve the stability of various loaded molecules. In vitro studies demonstrated that these nanoparticles are low cytotoxic, while in vivo studies proved their efficiency as nanocarriers for molecules characterized by a low bioavailability. However, to our knowledge, no data on the systemic biodistribution and organ accumulation of solid lipid nanoparticles in itself are presently available.

Fast and Sensitive Detection of Paramagnetic Species Using Coupled Charge and Spin Dynamics in Strongly Fluorescent Nanodiamonds.

Sensing of a few unpaired electron spins, such as in metal ions and radicals, is a useful but difficult task in nanoscale physics, biology, and chemistry. Single negatively charged nitrogen-vacancy (NV) centers in diamond offer high sensitivity and spatial resolution in the optical detection of weak magnetic fields produced by a spin bath but often require long acquisition times on the order of seconds. Here, we present an approach based on coupled spin and charge dynamics in dense NV ensembles in strongly fluorescent nanodiamonds (NDs) to sense external magnetic dipoles.

Light Entrains Diurnal Changes in Insulin Sensitivity of Skeletal Muscle via Ventromedial Hypothalamic Neurons.

Loss of synchrony between geophysical time and insulin action predisposes to metabolic diseases. Yet the brain and peripheral pathways linking proper insulin effect to diurnal changes in light-dark and feeding-fasting inputs are poorly understood. Here, we show that the insulin sensitivity of several metabolically relevant tissues fluctuates during the 24 h period.

Easy formulation of liposomal doxorubicin modified with a bombesin peptide analogue for selective targeting of GRP receptors overexpressed by cancer cells.

The article concerns the obtainment of liposomal doxorubicin (Dox) in which liposomes are externally modified with a targeting peptide able to drive the formulation in a selective way on membrane receptors overexpressed in tumors. We developed a kit composed by three different vials: (A) a vial containing a sterile, translucent, red dispersion of the liposomal doxorubicin drug (Doxil®), (B) a vial filled with a lyophilized powder of a modified phospholipid with a reactive function (DSPE-Peg-maleimide), and (C) a vial containing a 1-9 bombesin peptide analogue (Cys-BN-AA1) chemically modified to react in stoichiometric ratio respect to DSPE-Peg-maleimide. The chosen peptide is a stable analogue antagonist of the wild-type 1-9 bombesin peptide; it is very stable in serum; maintains high specificity, with nanomolar affinity, towards gastrin release peptide receptors (GRPRs indicated also as BB2); and is overexpressed in some cancer cells.