The evaluation of type I interferon score in dermatomyositis, a systematic review and a meta-analysis.

Dermatomyositis (DM) is a rare autoimmune systemic disorder manifesting with typical skin rashes and proximal muscle weakness. A specific clinical DM subset is characterized by the presence of the anti-melanoma differentiation-associated protein 5 (MDA5) autoantibodies. These patients are usually burdened by a severe clinical phenotype exhibiting a poor prognosis.

Peptides inhibiting the assembly of monomeric human l-lactate dehydrogenase into catalytically active homotetramer decrease the synthesis of lactate in cultured cells.

The energetic metabolism of cancer cells relies on a substantial commitment of pyruvate to the catalytic action of lactate-generating dehydrogenases. This coupling mainly depends on lactate dehydrogenase A (LDH-A), which is overexpressed in different types of cancers, and therefore represents an appealing therapeutic target. Taking into account that the activity of LDHs is exclusively exerted by their tetrameric forms, it was recently shown that peptides perturbing the monomers-to-tetramer assembly inhibit human LDH-A (hLDH-A).

Unlocking the full potential of rare disease drug development: exploring the not-for-profit sector's contributions to drug development and access.

This commentary provides a comprehensive overview of the challenges and opportunities in the field of drug development for rare diseases and especially of gene therapy products for ultra-rare diseases. It discusses the limited market size, reimbursement and scientific complexities that deter pharmaceutical investment in this field. Highlighting the pivotal role of charitable organizations like Fondazione Telethon, it showcases their efforts in funding research and ensuring access to innovative therapies.

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis.

Polyacrylic-Coated Solid Nanoparticles Increase the Aquaporin Permeability to Hydrogen Peroxide.

Aquaporins (AQPs) allow the diffusion of hydrogen peroxide (HO) and act as ROS scavenging systems, which are important for controlling the redox state of cells. Recently, cerium oxide nanoparticles were found to increase the water and HO permeability by modulating AQPs. To further analyze the action of nanoparticles (NPs) on AQP, we examined the effect of the NPs presenting different core compositions (CeO, GdO, FeO, and TiO), hydrodynamic sizes, and surface functionalization.

Identification and structural characterization of a pathogenic ARSA missense variant in two consanguineous families from Jammu and Kashmir (India) with late infantile metachromatic leukodystrophy.

Background: Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder caused by a deficiency of Arylsulfatase A (ARSA) enzyme activity. Its clinical manifestations include progressive motor and cognitive decline. ARSA gene mutations are frequent in MLD.

Effect of nanofibers as reinforcement on resin-based dental materials: A systematic review of in vitro studies.

This systematic review provides an update on the effect of nanofibers as reinforcement on resin-based dental materials. A bibliographic search was conducted in MEDLINEPubMed, Embase, Web of Science, Scopus, BVS (LILACS, BBO e IBECS), Cochrane, LIVIVO, and gray literature (BDTD) to identify relevant articles up to May 2021. In vitro studies that evaluated and compared the mechanical properties of nanofibers resin-based composite materials, were eligible.

Asparagine and Glutamine Deprivation Alters Ionizing Radiation Response, Migration and Adhesion of a p53 Colorectal Cancer Cell Line.

Colorectal cancer (CRC) is the most prominent form of colon cancer for both incidence (38.7 per 100,000 people) and mortality (13.9 per 100,000 people).

Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial.

Osteoarthritis (OA) is a common, debilitating, chronic disease with no disease-modifying drug approved to date. We discovered LNA043-a derivative of angiopoietin-like 3 (ANGPTL3)-as a potent chondrogenesis inducer using a phenotypic screen with human mesenchymal stem cells. We show that LNA043 promotes chondrogenesis and cartilage matrix synthesis in vitro and regenerates hyaline articular cartilage in preclinical OA and cartilage injury models in vivo.

Test-retest reliability of wireless inertial-sensor derived measurements of knee joint kinematics.

Advances in sensor technology have provided an opportunity to measure gait characteristics using body-worn inertial measurement units (IMUs). Whilst research investigating the validity of IMUs in reporting gait characteristics is extensive, research investigating the reliability of IMUs is limited. This study aimed to investigate the inter-session reliability of wireless IMU derived measures of gait (i.

An Automatic Foot and Shank IMU Synchronization Algorithm: Proof-of-concept.

When using wearable sensors for measurement and analysis of human performance, it is often necessary to integrate and synchronise data from separate sensor systems. This paper describes a synchronization technique between IMUs attached to the shanks and insoles attached at the feet and aims to solve the need to compute the ankle joint angle, which relies on synchronized sensor data. This will additionally enable concurrent analysis using gait kinematic and kinetic features.

Case Report: Heterozygous Germline Variant in Additional to Biallelic Pathogenic Variants in a Patient With Ribosomopathy Shwachman-Diamond Syndrome.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive ribosomopathy mainly characterized by exocrine pancreatic insufficiency, skeletal alterations, neutropenia, and a relevant risk of hematological transformation. At least 90% of SDS patients have pathogenic variants in the first gene associated with the disease with very low allelic heterogeneity; three variants, derived from events of genetic conversion between and its pseudogene, , provided the alleles observed in about 62% of SDS patients. We performed a reanalysis of the available WES files of a group of SDS patients with biallelic pathogenic variants, studying the results by next bioinformatic and protein structural analysis.

Structural Aspects of Type II Asparaginase in Complex with Its Secondary Product L-Glutamate.

Bacterial L-asparaginases are amidohydrolases (EC 3.5.1.

Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago.

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder, affecting 1:5000 individuals worldwide. All the genes associated to the disease (ENG, ACVRL1, SMAD4, GDF2) belong to the TGF-β/BMPs signaling pathway. We found 19 HHT unrelated families, coming from a Northern Italy region and sharing the ACVRL1 in-frame deletion c.

A Targeted Catalytic Nanobody (T-CAN) with Asparaginolytic Activity.

L-asparaginase is an amidohydrolase (EC 3.5.1.

Side-by-Side Comparison of uPAR-Targeting Optical Imaging Antibodies and Antibody Fragments for Fluorescence-Guided Surgery of Solid Tumors.

Purpose: Radical resection is paramount for curative oncological surgery. Fluorescence-guided surgery (FGS) aids in intraoperative identification of tumor-positive resection margins. This study aims to assess the feasibility of urokinase plasminogen activator receptor (uPAR) targeting antibody fragments for FGS in a direct comparison with their parent IgG in various relevant in vivo models.

Revealing Escherichia coli type II L-asparaginase active site flexible loop in its open, ligand-free conformation.

Since 1993, when the structure of Escherichia coli type II L-asparaginase (EcAII) in complex with L-aspartate was firstly reported, many structures of the wild type and mutated enzyme have been deposited in the Protein Data Bank. None of them report the full structure of the monomer in its ligand-free, open conformation, mainly because of the high dynamic and flexibility of the active site flexible loop. Here we report for the first time the structure of EcAII wild type in its open conformation comprising, for at least one protomer, clear electron density for the active site flexible loop (PDB ID: 6YZI).

LANCL1 binds abscisic acid and stimulates glucose transport and mitochondrial respiration in muscle cells via the AMPK/PGC-1α/Sirt1 pathway.

Objective: Abscisic acid (ABA) is a plant hormone also present and active in animals. In mammals, ABA regulates blood glucose levels by stimulating insulin-independent glucose uptake and metabolism in adipocytes and myocytes through its receptor LANCL2. The objective of this study was to investigate whether another member of the LANCL protein family, LANCL1, also behaves as an ABA receptor and, if so, which functional effects are mediated by LANCL1.

The Potential of a Bioactive, Pre-reacted, Glass-Ionomer Filler Resin Composite to Inhibit the Demineralization of Enamel in Vitro.

Clinical Relevance: A prereacted, glass-ionomer filler fluoride-containing resin composite had lower remineralization potential than glass-ionomer cements but was able to inhibit enamel demineralization; thus, it may be an option for restoring dental surfaces for patients at high risk of caries.

Summary: Evidence is lacking on the use of surface prereacted glass-ionomer filler resin composites to inhibit demineralization and that simulate real clinical conditions. The present laboratory study evaluated the potential of such composites to prevent demineralization and quantified fluoride (F) and other ions released from restorative materials after a dynamic pH-cycling regimen applied to the tooth material interface in vitro.

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues.

Auto-antibodies are classically associated with autoimmune diseases, where they are an integral part of diagnostic panels. However, recent evidence is accumulating on the presence of auto-antibodies against single or selected panels of auto-antigens in many types of cancer. Auto-antibodies might initially represent an epiphenomenon derived from the inflammatory environment induced by the tumor.

In Vitro Evaluation of Desensitizing Agents Containing Bioactive Scaffolds of Nanofibers on Dentin Remineralization.

This study evaluated the effect of the incorporation of bioactive nanofibers in desensitizing agents on dentin permeability. Sixty disks of dentin were randomly distributed in four groups ( = 15). Distribution was based on the desensitizing agents, fluoride varnish and self-etching adhesive, and the presence of nanofibers: C (self-etching adhesive Clearfil SE Bond), CN (Clearfil SE Bond with 1% nanofiber), D (Duraphat varnish), and DN (Duraphat varnish with 1% nanofiber).

In Silico Identification of SOX1 Post-Translational Modifications Highlights a Shared Protein Motif.

The transcription factor SOX1 is a key regulator of neural stem cell development, acting to keep neural stem cells (NSCs) in an undifferentiated state. Postnatal expression of Sox1 is typically confined to the central nervous system (CNS), however, its expression in non-neural tissues has recently been implicated in tumorigenesis. The mechanism through which SOX1 may exert its function is not fully understood, and studies have mainly focused on changes in SOX1 expression at a transcriptional level, while its post-translational regulation remains undetermined.