Berardinelli

Due to poor data in literature, we aimed to investigate the respiratory function in a large cohort of naïve Italian adult (≥18 years) SMA patients in a multi-centric cross-sectional study. The following respiratory parameters were considered: forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and need for non-invasive ventilation (NIV). We included 145 treatment-naïve adult patients (SMA2=18, SMA3=125; SMA4=2), 58 females (40 %), with median age at evaluation of 37 years (range 18-72)...

IOX2 is a potent inhibitor of prolyl hydroxylase 2, a key enzyme in the regulation of hypoxia-inducible factor (HIF) and oxygen homeostasis. As such, it can be used to enhance athletic performance and is currently banned by the World Anti-Doping Agency (WADA). Detection of metabolites is critical to demonstrate drug use in doping. However, there is currently little data on IOX2 human metabolism. Our aim was to identify relevant biomarkers of IOX2 use in humans. For this purpose, IOX2 was incubated with 10-donor-pooled human hepatocytes for 3 h, incubates were analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS), and LC-HRMS/MS data were screened with Compound Discoverer (Thermo Scientific) for a comprehensive identification of IOX2 metabolites...

Recently we proposed an isocratic enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the separation and quantitative determination of dextro- (DXM) and levo-methorphan (LVM) and their pharmacologically relevant metabolites, dextrorphan and levorphanol, respectively, in human blood samples. This method was based on the polysaccharide-based chiral column Lux AMP, a specialty column characterized with high stability in mobile phases of pH 11.0 and above. The use of a single-source column is a limitation for any analytical method...

Drug repositioning strategy represents a valid tool to accelerate the pharmacological development through the identification of new applications for already existing compounds. In this view, we aimed at discovering molecules able to trigger telomere-localized DNA damage and tumor cell death. By applying an automated high-content spinning-disk microscopy, we performed a screening aimed at identifying, on a library of 527 drugs, molecules able to negatively affect the expression of TRF2, a key protein in telomere maintenance...

Maintaining the metabolic homeostasis of fatty acids is crucial for human health. Excess fatty acids are stored in lipid droplets (LDs), the primary energy reservoir that helps regulate fat and lipid homeostasis in nearly all cell types. Seipin (BSCL2), a conserved endoplasmic reticulum protein, plays a critical role in LD biogenesis and regulating LD morphology. Pathogenic variants of seipin are associated with multiple human genetic diseases, including Berardinelli-Seip Congenital Generalized Lipodystrophy Type 2 (BSCL2)...

No abstract text is available yet for this article.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal-recessive neurodegenerative disorder caused by mutations in survival motor neuron 1 (SMN1) gene, and consequent loss of function of SMN protein, which results in progressive loss of lower motor neurons, and muscular wasting. Antisense oligonucleotide (ASO) nusinersen (Spinraza®) modulates the pre-mRNA splicing of the SMN2 gene, allowing rebalance of biologically active SMN. It is administered intrathecally via lumbar puncture after removing an equal amount of cerebrospinal fluid (CSF)...

OBJECTIVE: The aim of this study was to provide an overview of the clinical phenotypes associated with 4 SMN2 copies. METHODS: Clinical phenotypes were analyzed in all the patients with 4 SMN2 copies as part of a nationwide effort including all the Italian pediatric and adult reference centers for spinal muscular atrophy (SMA). RESULTS: The cohort includes 169 patients (102 men and 67 women) with confirmed 4 SMN2 copies (mean age at last follow-up = 36...

Epithelial-mesenchymal transition (EMT) changes cell phenotype by affecting immune properties of amniotic epithelial cells (AECs). The present study shows how the response to lipopolysaccharide of cells collected pre- (eAECs) and post-EMT (mAECs) induces changes in their transcriptomics profile. In fact, eAECs mainly upregulate genes involved in antigen-presenting response, whereas mAECs over-express soluble inflammatory mediator transcripts. Consistently, network analysis identifies CIITA and Nrf2 as main drivers of eAECs and mAECs immune response, respectively...

PURPOSE: Evaluate overall survival (OS), RAS, BRAF, and MSI frequencies in patients with metastatic colorectal cancer (mCRC), refractory to chemotherapy, and finally treated with cetuximab. METHODS: A retrospective cohort study to evaluate 211 mCRC patients with wild-type KRAS treated with cetuximab. BRAF V600E, KRAS, NRAS gene mutations, and MSI status were identified using PCR techniques in a population of pre-treated patients who were refractory to fluoropyrimidines, oxaliplatin, and irinotecan...

BACKGROUND: The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. CGL patients experience shortened life expectancy. The plasma lipidomic profile has not been characterized fully in CGL, nor has the extent of dietary intake in its modulation. The present work investigated the plasma lipidomic profile of CGL patients in comparison to eutrophic individuals at the fasted state and after a breakfast meal...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

In the present study an enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the first time for quantitative determination of the recreational drug of abuse methylone and its major metabolites in oral fluid. The simultaneous chemo- and enantioseparation of methylone and its major metabolites was performed on a polysaccharide-based chiral column based on amylose tris(5-chloro-3-methylphenylcarbamate) as chiral selector (Lux i-Amylose-3) with methanol containing 0...

As a consequence of recently implemented legal restrictions on fentanyl analogs, a new generation of acylpiperazine opioids appeared on the illicit drug market. AP-238 was the latest opioid in this series to be notified by the European Early Warning System in 2020 and was involved in an increasing number of acute intoxications. AP-238 metabolism was investigated to provide useful markers of consumption. For the tentative identification of the main phase I metabolites, a pooled human liver microsome assay was performed...

Targets for finished livestock are often determined by expected fat, either subcutaneous or intramuscular. These targets are used frequently to improve eating quality. Lower intramuscular fat, lack of product uniformity, and insufficient tenderness can negatively impact beef acceptability. This study aimed to investigate the differences in gene expression that alter metabolism and intercellular signaling in the muscle and adipose tissue in beef carcasses at different fat endpoints. In this study, longissimus thoracis muscle samples and adipose tissue were collected at harvest, and RNA was extracted and then sequenced using RNAseq...

BACKGROUND AND OBJECTIVE: Severe metabolic complications generally manifest at an early age in Berardinelli - Seip congenital lipodystrophy (BSCL) and their management is especially challenging. Nutritional intervention with low lipid diets is considered by experts to be fundamental in treating the disease when associated with medical therapy, however little is known about the beneficial effects of dietary interventions alone. AIM: To underline the importance of a well-structured low-fat diet in BSCL patients...

Amniotic membrane and amniotic fluid derived cells are regarded as a promising stem cell source for developing regenerative medicine techniques, although they have never been tested on male infertility diseases such as varicocele (VAR). The current study aimed to examine the effects of two distinct cell sources, human Amniotic Fluid Mesenchymal Stromal Cells (hAFMSCs) and amniotic epithelial cells (hAECs), on male fertility outcomes in a rat induced VAR model. To explain cell-dependent enhancement of reproductive outcomes in rats transplanted with hAECs and hAFMSCs, insights on testis morphology, endocannabinoid system (ECS) expression and inflammatory tissue response have been carried out alongside cell homing assessment...

INTRODUCTION: The Performance of Upper Limb version 2.0 (PUL 2.0) is increasingly used in Duchenne Muscular Dystrophy (DMD) to study longitudinal functional changes of motor upper limb function in ambulant and non-ambulant patients. The aim of this study was to evaluate changes in upper limb functions in patients carrying mutations amenable to skipping exons 44, 45, 51 and 53. METHODS: All DMD patients were assessed using the PUL 2.0 for at least 2 years, focusing on 24-month paired visits in those with mutations eligible for skipping exons 44, 45, 51 and 53...

There is high clinical demand for the resolution of tendinopathies, which affect mainly adult individuals and animals. Tendon damage resolution during the adult lifetime is not as effective as in earlier stages where complete restoration of tendon structure and property occurs. However, the molecular mechanisms underlying tendon regeneration remain unknown, limiting the development of targeted therapies. The research aim was to draw a comparative map of molecules that control tenogenesis and to exploit systems biology to model their signaling cascades and physiological paths...