Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.

Objective: Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).

Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson's disease patients mutated in TMEM175.

Parkinson's disease (PD) represents one of the most frequent neurodegenerative disorders for which clinically useful biomarkers remain to be identified and validated. Here, we adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in plasma and in dermal fibroblasts of PD patients carrying mutations in TMEM175 gene. We revealed a wide dysregulation of lysosome, autophagy, and mitochondrial pathways in these patients, supporting a role of this channel in regulating these cellular processes.

Advances in Molecular Mechanisms and Therapeutic Strategies in Colorectal Cancer: A New Era of Precision Medicine.

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide [...

New Challenges in Bladder Cancer Diagnosis: How Biosensing Tools Can Lead to Population Screening Opportunities.

Bladder cancer is one of the most common cancers worldwide. Despite its high incidence, cystoscopy remains the currently used diagnostic gold standard, although it is invasive, expensive and has low sensitivity. As a result, the cancer diagnosis is mostly late, as it occurs following the presence of hematuria in urine, and population screening is not allowed.

A Maternal Loss-of-Function Variant in KHDC3L Gene Causes a Range of Adverse Pregnancy Outcomes: A Case Report.

Background: The KHDC3L gene encodes a component of the subcortical maternal complex (SCMC). Biallelic mutations in this gene cause 5%-10% of biparental hydatidiform moles (BiHM), and a few maternal deletions in KHDC3L have been identified in women with recurrent pregnancy loss (RPL).

Method: In this study, we had a patient with a history of 10 pregnancy or neonatal losses, including spontaneous abortions, neonatal deaths, and molar pregnancy.

Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.

Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

A decision-making tool for navigating extracellular vesicle research and product development.

Due to their intercellular communication properties and involvement in a wide range of biological processes, extracellular vesicles (EVs) are increasingly being studied and exploited for different applications. Nevertheless, their complex nature and heterogeneity, as well as the challenges related to their purification and characterization procedures, require a cautious assessment of the qualitative and quantitative parameters that need to be monitored. This translates into a multitude of choices and putative solutions that any EV researcher must confront in both research and translational environments.

Brain and behavioural anomalies caused by haploinsufficiency are corrected by vitamin B12.

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes in brain metabolism might contribute to these phenotypes, as many of the deleted genes are involved in metabolic processes, but this is unknown.

, but Not Rutin, Inhibits Survival, Migration, Invasion, and Vasculogenic Mimicry of Glioblastoma Cells.

Glioblastoma (GBM) is the most aggressive type of brain tumor, characterized by poor outcome and limited therapeutic options. During tumor progression, GBM may undergo the process of vasculogenic mimicry (VM), consisting of the formation of vascular-like structures which further promote tumor aggressiveness and malignancy. The resulting resistance to anti-angiogenetic therapies urges the identification of new compounds targeting VM.

Building pangenome graphs.

Pangenome graphs can represent all variation between multiple reference genomes, but current approaches to build them exclude complex sequences or are based upon a single reference. In response, we developed the PanGenome Graph Builder, a pipeline for constructing pangenome graphs without bias or exclusion. The PanGenome Graph Builder uses all-to-all alignments to build a variation graph in which we can identify variation, measure conservation, detect recombination events and infer phylogenetic relationships.

Glucose impacts onto the reciprocal reprogramming between mammary adipocytes and cancer cells.

An established hallmark of cancer cells is metabolic reprogramming, largely consisting in the exacerbated glucose uptake. Adipocytes in the tumor microenvironment contribute toward breast cancer (BC) progression and are highly responsive to metabolic fluctuations. Metabolic conditions characterizing obesity and/or diabetes associate with increased BC incidence and mortality.

Dormancy and awakening of cancer cells: the extracellular vesicle-mediated cross-talk between Dr. Jekill and Mr. Hyde.

Cancer cell dormancy is a reversible process whereby cancer cells enter a quiescent state characterized by cell cycle arrest, inhibition of cell migration and invasion, and increased chemoresistance. Because of its reversibility and resistance to treatment, dormancy is a key process to study, monitor, and interfere with, in order to prevent tumor recurrence and metastasis and improve the prognosis of cancer patients. However, to achieve this goal, further studies are needed to elucidate the mechanisms underlying this complex and dynamic dual process.

Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.

Background: Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person.

Protocol for characterizing non-genetic heterogeneity and expression dynamics of surface proteins in mouse muscle stem cells using flow cytometry.

Here, we present a protocol for investigating the non-genetic heterogeneity of membrane proteins expression within murine muscle stem cell (MuSC) population isolated from injured skeletal muscles. We describe a protocol that employs flow cytometry technology to detect variations in membrane CRIPTO protein levels and ensure measurements standardization. We detail steps for muscle digestion, bulk muscle cell staining, and phenotypic analysis.

A novel iPSC-based model of ICF syndrome subtype 2 recapitulates the molecular phenotype of ZBTB24 deficiency.

Immunodeficiency, Centromeric instability and Facial anomalies (ICF) syndrome is a rare genetic disorder characterized by variable immunodeficiency. More than half of the affected individuals show mild to severe intellectual disability at early onset. This disorder is genetically heterogeneous and is the causative gene of the subtype 2, accounting for about 30% of the ICF cases.

A 3D Pancreatic Cancer Model with Integrated Optical Sensors for Noninvasive Metabolism Monitoring and Drug Screening.

A distinct feature of pancreatic ductal adenocarcinoma (PDAC) is a prominent tumor microenvironment (TME) with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology and treatment resistance. The dynamic crosstalk between cancer cells and the dense stromal compartment leads to spatially and temporally heterogeneous metabolic alterations, such as acidic pH that contributes to drug resistance in PDAC. Thus, monitoring the extracellular pH metabolic fluctuations within the TME is crucial to predict and to quantify anticancer drug efficacy.

PlGF and VEGF-A/PlGF Heterodimer are Crucial for Recruitment and Activation of Immune Cells During Choroid Neovascularization.

Purpose: Recruitment and activation of inflammatory cells, such as retinal microglia/macrophages, in the subretinal space contribute significantly to the pathogenesis of age-related macular degeneration (AMD). This study aims to explore the functional role of vascular endothelial growth factor (VEGF-A), placental growth factor (PlGF) and VEGF-A/PlGF heterodimer in immune homeostasis and activation during pathological laser-induced choroidal neovascularization (CNV).

Methods: To investigate these roles, we utilized the PlGF-DE knockin (KI) mouse model, which is the full functional knockout (KO) of PlGF.