The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels.

Well-differentiated/dedifferentiated liposarcomas (WD/DDLPSs) account for ∼60% of all liposarcomas. They have a poor prognosis due to limited therapeutic options. WD/DDLPSs are characterized by aberrant expression of mouse double minute 2 (MDM2), which forms G-quadruplexes (G4s) in its promoter.

The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels.

Well-differentiated/dedifferentiated liposarcomas (WD/DDLPSs) account for ∼60% of all liposarcomas. They have a poor prognosis due to limited therapeutic options. WD/DDLPSs are characterized by aberrant expression of mouse double minute 2 (MDM2), which forms G-quadruplexes (G4s) in its promoter.

Targeted allele-specific knockdown human recombinant ferritin nanoparticles for personalized treatment of Crouzon syndrome.

Crouzon syndrome is a rare genetic craniofacial malformation caused by heterozygous gain-of-function mutations in the gene. The resulting constitutive activation of the FGFR2 signaling causes the premature osteogenic differentiation of calvarial mesenchymal stromal cells in skull sutures, leading to early suture ossification. Craniectomy is the gold standard treatment, being invasive and burdened by complications.

Preeclampsia biomarkers (sFlt-1/PlGF) dynamics are not disrupted by SARS-CoV-2 infection during pregnancy in a hypertensive disorder SARS-CoV-2 vaccinated cohort.

Objectives: To analyze maternal and perinatal outcomes and serum levels of the preeclampsia (PE) biomarkers sFlt-1 and PlGF in pregnant women with hypertensive disorders vaccinated against SARS-CoV-2, with or without confirmed COVID-19 during pregnancy.

Methods: Multicenter (two-center) prospective cohort study secondary analysis. The cohort comprised pregnant women with hypertensive disorders who received SARS-CoV-2 vaccination, assessed from August 2021 to December 2022.

Characterizing oxidative stress induced by Aβ oligomers and the protective role of carnosine in primary mixed glia cultures.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. A critical aspect of AD pathology is represented by oxidative stress, which significantly contributes to neuronal damage and death. Microglia and astrocytes, the primary glial cells in the brain, are crucial for managing oxidative stress and supporting neuronal function.

The B-cells paradigm in systemic sclerosis: an update on pathophysiology and B-cell-targeted therapies.

Systemic sclerosis (SSc) is considered a rare autoimmune disease in which there are alterations of both the innate and adaptive immune response resulting in the production of autoantibodies. Abnormalities of the immune system compromise the normal function of blood vessels leading to a vasculopathy manifested by Raynaud's phenomenon, an early sign of SSc . As a consequence of this reactive picture, the disease can evolve leading to tissue fibrosis.

Development and characterization of new carnosine-loaded liposomal formulations.

Carnosine is an endogenous dipeptide characterized by a multimodal mechanism of action. However, its clinical potential is limited by serum and cytosolic carnosinases, which significantly reduce its bioavailability. Based on that, different research groups have worked on the development of new strategies able not only to prevent its rapid metabolization but also to improve its distribution and specific targeting.

Taming Mass Gaps with Anti-de Sitter Space.

Anti-de Sitter space acts as an infrared cutoff for asymptotically free theories, allowing interpolation between a weakly coupled small-sized regime and a strongly coupled flat-space regime. We scrutinize the interpolation for theories in two dimensions from the perspective of boundary conformal theories. We show that the appearance of a singlet marginal operator destabilizes a gapless phase existing at a small size, triggering a boundary renormalization group flow to a gapped phase that smoothly connects to flat space.

Unveiling the human fetal-maternal interface during the first trimester: biophysical knowledge and gaps.

The intricate interplay between the developing placenta and fetal-maternal interactions is critical for pregnancy outcomes. Despite advancements, gaps persist in understanding biomechanics, transport processes, and blood circulation parameters, all of which are crucial for safe pregnancies. Moreover, the complexity of fetal-maternal interactions led to conflicting data and methodological variations.

Efficacy of tailor-made notched music training for primary tinnitus: A systematic review and meta-analysis.

Objective: We systematically reviewed and meta-analyzed the efficacy of Tailor-Made Notched Music Training (TMNMT) for primary subjective tinnitus in adults. The main goal was to evaluate TMNMT's impact on tinnitus symptoms.

Methods: Following PRISMA guidelines, we included randomized and non-randomized trials.

Presentation and progression of MPO-ANCA interstitial lung disease.

The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate.

Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopment disorder that is typically characterized by debilitating episodic attacks of hemiplegia, seizures, and intellectual disability. Over 85% of individuals with AHC have a de novo missense variant in ATP1A3 encoding the catalytic α3 subunit of neuronal NaK ATPases. The remainder of the patients are genetically unexplained.

The Anti-Cancer Activity of the Naturally Occurring Dipeptide Carnosine: Potential for Breast Cancer.

Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine, possessing a multimodal pharmacodynamic profile that includes anti-inflammatory and anti-oxidant activities. Carnosine has also shown its ability to modulate cell proliferation, cell cycle arrest, apoptosis, and even glycolytic energy metabolism, all processes playing a key role in the context of cancer. Cancer is one of the most dreaded diseases of the 20th and 21st centuries.

Muscle fibrosis as a prognostic biomarker in facioscapulohumeral muscular dystrophy: a retrospective cohort study.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in FSHD patients, increase the need for reliable biomarkers. Muscle magnetic resonance imaging (MRI) studies showed that the appearance of STIR-positive (STIR+) lesions in FSHD muscles represents an initial stage of muscle damage, preceding irreversible adipose changes.

A Catalog of Coding Sequence Variations in Salivary Proteins' Genes Occurring during Recent Human Evolution.

Saliva houses over 2000 proteins and peptides with poorly clarified functions, including proline-rich proteins, statherin, P-B peptides, histatins, cystatins, and amylases. Their genes are poorly conserved across related species, reflecting an evolutionary adaptation. We searched the nucleotide substitutions fixed in these salivary proteins' gene loci in modern humans compared with ancient hominins.

The Tuscany Regional Network for rare diseases: from European Reference Networks' experience to registry based organisation and management model for rare diseases.

Background: In the European Union, a disease is defined as rare when it affects fewer than 1 in 2000 people. Currently, there are up to 8000 described rare diseases (RDs), collectively affecting 30 million people in the European Union. In 2004 Tuscany region (Italy) established a Regional Network of hospital units to ensure highly specialised medical care in the field of RDs.

The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms.

Carnosine is a naturally occurring endogenous dipeptide composed by the ligation of β-alanine and L-histidine performed particularly by tissues with an increased oxidative metabolism such as muscles and brain. In the last 50 years different studies have assessed the role and function of carnosine through numerous , , and clinical studies, demonstrating the multimodal mechanism of action of this dipeptide that includes anti-aggregant, antioxidant, and anti-inflammatory activities. In particular its activity has been investigated in experimental models of cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and neurodegenerative disorders, such as cerebral ischemia and Alzheimer's disease (AD).

Gap Junctions and Connexins in Microglia-Related Oxidative Stress and Neuroinflammation: Perspectives for Drug Discovery.

Microglia represent the immune system of the brain. Their role is central in two phenomena, neuroinflammation and oxidative stress, which are at the roots of different pathologies related to the central nervous system (CNS). In order to maintain the homeostasis of the brain and re-establish the equilibrium after a threatening imbalance, microglia communicate with each other and other cells within the CNS by receiving specific signals through membrane-bound receptors and then releasing neurotrophic factors into either the extracellular or directly into the cytoplasm of nearby cells, such as astrocytes and neurons.

Anti-RuvBL1/2 Autoantibodies Detection in a Patient with Overlap Systemic Sclerosis and Polymyositis.

Anti-RuvBL1/2 autoantibodies have recently been detected in patients with systemic sclerosis (SSc) and scleromyositis overlap syndromes. These autoantibodies exhibit a distinct speckled pattern in an indirect immunofluorescent assay on Hep-2 cells. We report the case of a 48 year old man with facial changes, Raynaud's phenomenon, puffy fingers, and muscle pain.

Role of biomarkers (sFlt-1/PlGF) in cases of COVID-19 for distinguishing preeclampsia and guiding clinical management.

Objectives: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS).

Study Design: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed.