Setting a Successful Sorting for Extracellular Vesicle Isolation.

Extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) contain a set of microRNAs with regenerative and anti-inflammatory roles. Therefore, purified MSC-EVs are envisioned as a next-generation therapeutic option for a wide array of diseases. In this protocol, we report the strategy for successfully sorting EVs from the supernatant of adipose-derived MSCs (ASCs), often used in orthopedics regenerative medicine applications.

The development of drug resistance in metastatic tumours under chemotherapy: An evolutionary perspective.

We present a mathematical model of the evolutionary dynamics of a metastatic tumour under chemotherapy, comprising non-local partial differential equations for the phenotype-structured cell populations in the primary tumour and its metastasis. These equations are coupled with a physiologically-based pharmacokinetic model of drug administration and distribution, implementing a realistic delivery schedule. The model is carefully calibrated from the literature, focusing on BRAF-mutated melanoma treated with Dabrafenib as a case study.

From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders.

Neurodegenerative diseases (NDs), like amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD), primarily affect the central nervous system, leading to progressive neuronal loss and motor and cognitive dysfunction. However, recent studies have revealed that muscle tissue also plays a significant role in these diseases. ALS is characterized by severe muscle wasting as a result of motor neuron degeneration, as well as alterations in gene expression, protein aggregation, and oxidative stress.

BRAF and MEK inhibitor targeted therapy in papillary craniopharyngiomas: a cohort study.

Objective: Targeted therapy (TT) with BRAF/MEK inhibitors has emerged as a potential treatment in papillary craniopharyngiomas (PCPs). However, standardized data on large cohorts are lacking. Our study aimed to assess real-life efficacy and safety of BRAF/MEK inhibition in patients with PCPs.

Insights into Dysregulated Neurological Biomarkers in Cancer.

The link between neurodegenerative diseases (NDs) and cancer has generated greater interest in biomedical research, with decades of global studies investigating neurodegenerative biomarkers in cancer to better understand possible connections. Tau, amyloid-β, α-synuclein, SOD1, TDP-43, and other proteins associated with nervous system diseases have also been identified in various types of solid and malignant tumors, suggesting a potential overlap in pathological processes. In this review, we aim to provide an overview of current evidence on the role of these proteins in cancer, specifically examining their effects on cell proliferation, apoptosis, chemoresistance, and tumor progression.

From Nelson's Syndrome to Corticotroph Tumor Progression Speed: An Update.

Since the first description of Nelson syndrome 60 years ago, the way to consider corticotroph pituitary neuroendocrine tumors (PitNETs) after bilateral adrenalectomy has evolved. Today, it is globally acknowledged that only a subset of corticotroph PitNETs is aggressive.After adrenalectomy, corticotroph tumor progression (CTP) occurs in about 30 to 40% of patients during a median follow-up of 10 years.

PIT-EASY survey: validation of the European Pituitary Pathology Group proposal for reporting pituitary neuroendocrine tumors.

The aim of this multicenter prospective survey called PIT-EASY was to assess the relevance of the European Pituitary Pathology Group (EPPG) diagnostic tools for pituitary neuroendocrine tumors (PitNETs) to improve the quality of their histological diagnosis. Each center performed at least 30 histological cases of PitNETs using the EPPG tools and assessed their value using a scorecard with 10 questions. For each center, the histological cases were carried out by pathologists with varying levels of expertise in pituitary pathology defined as junior, intermediate, and expert.

Epigenetics in Alzheimer's Disease: A Critical Overview.

Epigenetic modifications have been implicated in a number of complex diseases as well as being a hallmark of organismal aging. Several reports have indicated an involvement of these changes in Alzheimer's disease (AD) risk and progression, most likely contributing to the dysregulation of AD-related gene expression measured by DNA methylation studies. Given that DNA methylation is tissue-specific and that AD is a brain disorder, the limitation of these studies is the ability to identify clinically useful biomarkers in a proxy tissue, reflective of the tissue of interest, that would be less invasive, more cost-effective, and easily obtainable.

Exploring the Gut Microbiota-Muscle Axis in Duchenne Muscular Dystrophy.

The gut microbiota plays a pivotal role in maintaining the dynamic balance of intestinal epithelial and immune cells, crucial for overall organ homeostasis. Dysfunctions in these intricate relationships can lead to inflammation and contribute to the pathogenesis of various diseases. Recent findings uncovered the existence of a gut-muscle axis, revealing how alterations in the gut microbiota can disrupt regulatory mechanisms in muscular and adipose tissues, triggering immune-mediated inflammation.

Diaphragm reconstruction using a TachoSil patch as alternative to intrasellar packing for small focal diaphragm defects in pituitary surgery: a cohort study.

Background: During pituitary surgery, CSF leaks are often treated by intrasellar packing, using muscle or fat grafts. However, this strategy may interfere with the interpretation of postoperative MRI and may impact the quality of resection in cases of second surgery, due to the existence of additional fibrous tissue. We present an alternative technique, using a diaphragm reconstruction with a heterologous sponge combining fibrinogen and thrombin (TachoSil), applied in selected patients with low-flow CSF leaks.

The human genetic variant rs6190 unveils Foxc1 and Arid5a as novel pro-metabolic targets of the glucocorticoid receptor in muscle.

Genetic variations in the glucocorticoid receptor (GR) gene can impact metabolism. The single nucleotide polymorphism (SNP) rs6190 (p.R23K) has been associated in humans with enhanced metabolic health, but the SNP mechanism of action remains completely unknown.

Flvcr1a deficiency promotes heme-based energy metabolism dysfunction in skeletal muscle.

The definition of cell metabolic profile is essential to ensure skeletal muscle fiber heterogeneity and to achieve a proper equilibrium between the self-renewal and commitment of satellite stem cells. Heme sustains several biological functions, including processes profoundly implicated with cell metabolism. The skeletal muscle is a significant heme-producing body compartment, but the consequences of impaired heme homeostasis on this tissue have been poorly investigated.

Subject-specific finite element head models for skull fracture evaluation-a new tool in forensic pathology.

Post-mortem computed tomography (PMCT) enables the creation of subject-specific 3D head models suitable for quantitative analysis such as finite element analysis (FEA). FEA of proposed traumatic events is an objective and repeatable numerical method for assessing whether an event could cause a skull fracture such as seen at autopsy. FEA of blunt force skull fracture in adults with subject-specific 3D models in forensic pathology remains uninvestigated.

Edaravone: A Novel Possible Drug for Cancer Treatment?

Despite significant advancements in understanding the causes and progression of tumors, cancer remains one of the leading causes of death worldwide. In light of advances in cancer therapy, there has been a growing interest in drug repurposing, which involves exploring new uses for medications that are already approved for clinical use. One such medication is edaravone, which is currently used to manage patients with cerebral infarction and amyotrophic lateral sclerosis.

Prognostic Impact of Hypothalamic Perforation in Adult Patients With Craniopharyngioma: A Cohort Study.

Context: Outcome of craniopharyngioma is related to its locoregional extension, which impacts resectability and the risk of surgical complications. To maximize resection and minimize complications, optic tract localization, temporal lobe extension, and hypothalamic involvement are essential factors for surgical management.

Objective: To assess the outcome of craniopharyngiomas depending on their relation to the hypothalamus location.

Forensic age estimation of the knee by post-mortem DR, CT, and MR imaging: a comparative study.

It is believed by many that reference data for age estimation purposes must be imaging-modality specific. A study from our department has however proven otherwise. We therefore found it interesting to investigate this further by looking at the level of agreement between different imaging modalities.

Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review.

Mounting evidence underscores the intricate interplay between the immune system and skeletal muscles in Duchenne muscular dystrophy (DMD), as well as during regular muscle regeneration. While immune cell infiltration into skeletal muscles stands out as a prominent feature in the disease pathophysiology, a myriad of secondary defects involving metabolic and inflammatory pathways persist, with the key players yet to be fully elucidated. Steroids, currently the sole effective therapy for delaying onset and symptom control, come with adverse side effects, limiting their widespread use.

Evolutionary dynamics of glucose-deprived cancer cells: insights from experimentally informed mathematical modelling.

Glucose is a primary energy source for cancer cells. Several lines of evidence support the idea that monocarboxylate transporters, such as MCT1, elicit metabolic reprogramming of cancer cells in glucose-poor environments, allowing them to re-use lactate, a by-product of glucose metabolism, as an alternative energy source with serious consequences for disease progression. We employ a synergistic experimental and mathematical modelling approach to explore the evolutionary processes at the root of cancer cell adaptation to glucose deprivation, with particular focus on the mechanisms underlying the increase in MCT1 expression observed in glucose-deprived aggressive cancer cells.