Infant mice fed soy-based formulas exhibit alterations in anxiety-like behaviours and the 5-HT system.

Genistein (GEN) is a phytoestrogen with oestrogen-like activity found in many plants. Classified as an endocrine disruptor, GEN is potentially hazardous, particularly during developmental stages. It induces alterations in anxious behaviour, fertility, and energy metabolism, alongside modifications in specific brain circuits.

A transgene with enhanced therapeutic potential for the preclinical development of gene therapy to treat mucopolysaccharidosis type IVB.

Mucopolysaccharidosis type IVB (MPSIVB) is a lysosomal storage disorder caused by β-galactosidase (β-GAL) deficiency characterized by severe skeletal and neurological alterations without approved treatments. To develop hematopoietic stem progenitor cell (HSPC) gene therapy (GT) for MPSIVB, we designed lentiviral vectors (LVs) encoding human β-GAL to achieve supraphysiological release of the therapeutic enzyme in human HSPCs and metabolic correction of diseased cells. Transduced HSPCs displayed proper colony formation, proliferation, and differentiation capacity, but their progeny failed to release the enzyme at supraphysiological levels.

Transcriptomic analysis of BM-MSCs identified EGR1 as a transcription factor to fully exploit their therapeutic potential.

Bone marrow-mesenchymal stromal cells (BM-MSCs) are key components of the BM niche, where they regulate hematopoietic stem progenitor cell (HSPC) homeostasis by direct contact and secreting soluble factors. BM-MSCs also protect the BM niche from excessive inflammation by releasing anti-inflammatory factors and modulating immune cell activity. Thanks to these properties, BM-MSCs were successfully employed in pre-clinical HSPC transplantation models, increasing the rate of HSPC engraftment, accelerating the hematological reconstitution, and reducing the risk of graft failure.

Hereditary breast and ovarian cancer: from genes to molecular targeted therapies.

Hereditary familial tumors constitute 10-15% of all malignancies and present opportunities for the identification of therapeutic approaches against specific germline genetic defects. Hereditary breast and ovarian cancer (HBOC) syndrome, which is linked to the pathogenic mutations of the breast cancer 1 () and breast cancer 2 () genes, is an important research model for personalized therapeutic approaches for specific germline mutations. HBOC is characterized by multiple cases of breast and ovarian carcinoma in association with other tumors (prostate, pancreas and stomach carcinoma) within the same family branch, a young age of onset (<36 years), bilaterality and an autosomal dominant pattern of inheritance.

MPSI Manifestations and Treatment Outcome: Skeletal Focus.

Mucopolysaccharidosis type I (MPSI) (OMIM #252800) is an autosomal recessive disorder caused by pathogenic variants in the gene encoding for the lysosomal alpha-L-iduronidase enzyme. The deficiency of this enzyme causes systemic accumulation of glycosaminoglycans (GAGs). Although disease manifestations are typically not apparent at birth, they can present early in life, are progressive, and include a wide spectrum of phenotypic findings.

Perinatal exposure to tributyltin affects feeding behavior and expression of hypothalamic neuropeptide Y in the paraventricular nucleus of adult mice.

Organotins such as tributyltin chloride (TBT), are highly diffused environmental pollutants, which act as metabolism disrupting chemicals, i.e. may interfere with fat tissue differentiation, as well as with neuroendocrine circuits, thus impairing the control of energetic balance.

Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro.

Background: Mesenchymal stem cells (MSCs) have been used therapeutically in equine medicine. MSCs release extracellular vesicles (EVs), which affect cell processes by inhibiting cell apoptosis and regulating inflammation. To date, little is known about equine EVs and their regenerative properties.

Recurrent NF1 gene variants and their genotype/phenotype correlations in patients with Neurofibromatosis type I.

Neurofibromatosis type I, a genetic condition due to pathogenic variants in the NF1 gene, is burdened by a high rate of complications, including neoplasms, which increase morbidity and mortality for the disease. We retrospectively re-evaluated the NF1 gene variants found in the period 2000-2019 and we studied for genotype/phenotype correlations of disease complications and neoplasms 34 variants, which were shared by at least two unrelated families (range 2-11) for a total 141 of probands and 21 relatives affected by Neurofibromatosis type I. Recurrent variants could be ascribed to the most common mutational mechanisms (C to T transition, microsatellite slippage, non-homologous recombination).

Early Postnatal Genistein Administration Affects Mice Metabolism and Reproduction in a Sexually Dimorphic Way.

The phytoestrogen genistein (GEN) may interfere with permanent morphological changes in the brain circuits sensitive to estrogen. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on some physiological and reproductive parameters. Mice of both sexes from PND1 to PND8 were treated with GEN (50 mg/kg body weight, comparable to the exposure level in babies fed with soy-based formulas).

Hypothalamic Expression of Neuropeptide Y (NPY) and Pro-OpioMelanoCortin (POMC) in Adult Male Mice Is Affected by Chronic Exposure to Endocrine Disruptors.

In the arcuate nucleus, neuropeptide Y (NPY) neurons, increase food intake and decrease energy expenditure, and control the activity of pro-opiomelanocortin (POMC) neurons, that decrease food intake and increase energy expenditure. Both systems project to other hypothalamic nuclei such as the paraventricular and dorsomedial hypothalamic nuclei. Endocrine disrupting chemicals (EDCs) are environmental contaminants that alter the endocrine system causing adverse health effects in an intact organism or its progeny.

COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence.

Background: Homocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID-19 infection. The purpose of this review was to analyze the correlation between the prevalence of MTHFR C677 T gene polymorphism and COVID-19 incidence and mortality worldwide.

Methods: Data regarding MTHFR C677 T gene mutation were obtained from the interrogation of the Genome Aggregation Database (genomAD), which is publicly available from the web"https://gnomad.

Role of Expanded Mesenchymal Stromal Cells in Determining Hematopoietic Stem Cell Transplantation Outcome.

Overall, the human organism requires the production of ∼1 trillion new blood cells per day. Such goal is achieved via hematopoiesis occurring within the bone marrow (BM) under the tight regulation of hematopoietic stem and progenitor cell (HSPC) homeostasis made by the BM microenvironment. The BM niche is defined by the close interactions of HSPCs and non-hematopoietic cells of different origin, which control the maintenance of HSPCs and orchestrate hematopoiesis in response to the body's requirements.

Clinical application of lung ultrasound score on COVID-19 setting: a regional experience in Southern Italy.

Objective: We aimed to assess the correlation between LUS Soldati proposed score and clinical presentation, course of disease and the possible need of ventilation support/intensive care.

Patients And Methods: All consecutive patients with laboratory confirmed SARS-CoV-2 infection and hospitalized in two COVID Centers were enrolled. All patients performed blood gas analysis and lung ultrasound (LUS) at admission.

X-ray quasi-periodic eruptions from two previously quiescent galaxies.

Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either serendipitously or in archival data, with emission lines in their optical spectra classifying their nuclei as hosting an actively accreting supermassive black hole.

Detection of large-scale X-ray bubbles in the Milky Way halo.

The halo of the Milky Way provides a laboratory to study the properties of the shocked hot gas that is predicted by models of galaxy formation. There is observational evidence of energy injection into the halo from past activity in the nucleus of the Milky Way; however, the origin of this energy (star formation or supermassive-black-hole activity) is uncertain, and the causal connection between nuclear structures and large-scale features has not been established unequivocally. Here we report soft-X-ray-emitting bubbles that extend approximately 14 kiloparsecs above and below the Galactic centre and include a structure in the southern sky analogous to the North Polar Spur.

Liquid biopsy with cell free DNA: new horizons for prostate cancer.

Although prostate cancer (PCa) is one of the most common tumors in European males, the only minimally invasive diagnostic tool in PCa setup is the determination of PSA in serum. Cell-free DNA (cfDNA) has been demonstrated to be helpful for PCa diagnosis but has not yet been integrated into the clinical setting. This review aims to provide a systematic update of cfDNA and its fragmentation patterns in PCa reported in literature published over the last twenty years.

Biomarkers associated with COVID-19 disease progression.

The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment.

Neonatal combination therapy improves some of the clinical manifestations in the Mucopolysaccharidosis type I murine model.

Mucopolysaccharidosis type I (MPS-I), a lysosomal storage disorder caused by a deficiency of alpha-L-iduronidase enzyme, results in the progressive accumulation of glycosaminoglycans and consequent multiorgan dysfunction. Despite the effectiveness of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) in correcting clinical manifestations related to visceral organs, complete improvement of musculoskeletal and neurocognitive defects remains an unmet challenge and provides an impact on patients' quality of life. We tested the therapeutic efficacy of combining HSCT and ERT in the neonatal period.

Insights into Genetic Susceptibility to Melanoma by Gene Panel Testing: Potential Pathogenic Variants in ACD, and .

The contribution of recently established or candidate susceptibility genes to melanoma missing heritability has yet to be determined. Multigene panel testing could increase diagnostic yield and better define the role of candidate genes. We characterized 273 and negative probands through a custom-designed targeted gene panel that included and Co-segregation, loss of heterozygosity (LOH)/protein expression analysis, and splicing characterization were performed to improve variant classification.

Clinical, pathological and dermoscopic phenotype of MITF p.E318K carrier cutaneous melanoma patients.

Background: The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined.

Immunohistochemical mismatch repair proteins expression as a tool to predict the melanoma immunotherapy response.

In difference to other solid malignancies, the identification of biomarkers for the prediction of malignant melanoma (MM) response to immunotherapy is limited. The aim of the current study was to evaluate the immunohistochemical (IHC) expression of MMR proteins in a cohort of MM metastatic patients receiving anti PD-1 treatments. The therapeutic response of patients was also retrospectively assessed.

Postnatal genistein administration selectively abolishes sexual dimorphism in specific hypothalamic dopaminergic system in mice.

As demonstrated in previous studies, early postnatal genistein (GEN) administration to mice pups of both sexes, at doses similar to that of infant soy-based formulas, may affect the development of some steroid-sensitive neuronal circuits (i.e. nitrergic and vasopressinergic systems), causing irreversible alterations in adults.

Quick assessment of cell-free DNA in seminal fluid and fragment size for early non-invasive prostate cancer diagnosis.

Background: Liquid biopsy consists in the quantification and qualification of circulating cell-free DNA (cfDNA) and tumor-derived DNA (ctDNA) for cancer recognition. Recently, the characterization of seminal cfDNA (scfDNA) has been reported as a possible biomarker for prostate cancer (PCa) diagnosis.

Methods: Thirty patients with histologically proven PCa, 33 with benign prostate hyperplasia (BPH) and 21 healthy controls were enrolled.