Astrocyte Dysfunction Reflected in Ischemia-Induced Astrocyte-Derived Extracellular Vesicles: A Pilot Study on Acute Ischemic Stroke Patients.

Extracellular vesicles (EVs) secreted by astrocytes (ADEVs) mediate numerous biological processes, providing insights into damage, repair, and protection following ischemic stroke (IS). This pilot study aimed to broaden the current knowledge on the astrocyte response to ischemia by dynamically assessing the aquaporin-4 (AQP4) and glial cell line-derived neurotrophic factor (GDNF) as cargo proteins of these vesicles in eighteen acute IS patients and nine controls. EV proteins were detected by Western blotting and followed 24 h (D1), 7 days (D7), and one month (M1) after symptoms onset.

Extracellular Vesicle-Based Characterization of Stem Cell Phenotype in Glioblastomas.

Glioblastoma (GB) is the most common brain malignancy occurring in adult patients having an extremely low overall survival. Therefore, it is paramount to establish reliable and accurate diagnostic and prognostic markers to guide a personalized and more effective treatment. Molecular characterization of the tumor is the ultimate goal in GB management and comprises, among others, the study of the extracellular vesicles (EVs).

Comparative Analysis of Inflammatory Indexes in Lung Cancer Patients With and Without Brain Metastases.

Introduction Lung cancer is the leading cause of oncological deaths worldwide. Various combined inflammatory indexes, such as the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) have shown associations with pretreatment survival prognosis in patients suffering of lung cancer with or without brain metastases. This study aimed to compare the average values of NLR, PLR, LMR, and SII in healthy patients, patients with lung cancer without any other metastases, and patients with lung cancer and brain metastases.

GFAP as Astrocyte-Derived Extracellular Vesicle Cargo in Acute Ischemic Stroke Patients-A Pilot Study.

The utility of serum glial fibrillary acidic protein (GFAP) in acute ischemic stroke (AIS) has been extensively studied in recent years. Here, we aimed to assess its potential role as a cargo protein of extracellular vesicles (EVs) secreted by astrocytes (ADEVs) in response to brain ischemia. Plasma samples from eighteen AIS patients at 24 h (D1), 7 days (D7), and one month (M1) post-symptoms onset, and nine age, sex, and cardiovascular risk factor-matched healthy controls were obtained to isolate EVs using the Exoquick ULTRA EV kit.

mCRP-Induced Focal Adhesion Kinase-Dependent Monocyte Aggregation and M1 Polarization, Which Was Partially Blocked by the C10M Inhibitor.

Monomeric C-reactive protein (mCRP) has recently been implicated in the abnormal vascular activation associated with development of atherosclerosis, but it may act more specifically through mechanisms perpetuating damaged vessel inflammation and subsequent aggregation and internalization of resident macrophages. Whilst the direct effects of mCRP on endothelial cells have been characterized, the interaction with blood monocytes has, to our knowledge, not been fully defined. Here we showed that mCRP caused a strong aggregation of both U937 cell line and primary peripheral blood monocytes (PBMs) obtained from healthy donors.

Astrocyte Involvement in Blood-Brain Barrier Function: A Critical Update Highlighting Novel, Complex, Neurovascular Interactions.

Neurological disorders have been linked to a defective blood-brain barrier (BBB), with dysfunctions triggered by stage-specific disease mechanisms, some of these being generated through interactions in the neurovascular unit (NVU). Advanced knowledge of molecular and signaling mechanisms in the NVU and the emergence of improved experimental models allow BBB permeability prediction and the development of new brain-targeted therapies. As NVU constituents, astrocytes are the most numerous glial cells, characterized by a heterogeneity that occurs as a result of developmental and context-based gene expression profiles and the differential expression of non-coding ribonucleic acids (RNAs).

Recent Progress in the Identification of Early Transition Biomarkers from Relapsing-Remitting to Progressive Multiple Sclerosis.

Despite extensive research into the pathophysiology of multiple sclerosis (MS) and recent developments in potent disease-modifying therapies (DMTs), two-thirds of relapsing-remitting MS patients transition to progressive MS (PMS). The main pathogenic mechanism in PMS is represented not by inflammation but by neurodegeneration, which leads to irreversible neurological disability. For this reason, this transition represents a critical factor for the long-term prognosis.

Prognostic Factors of Survival in Glioblastoma Multiforme Patients-A Retrospective Study.

Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumor that occurs in adults. In spite of prompt diagnosis and rapidly administered treatment, the survival expectancy is tremendously poor. Extensive research has been performed in order to establish factors to predict the outcome of GBM patients; however, worldwide accepted prognostic markers are still lacking.

Effects of Laser Application on Alveolar Bone Mesenchymal Stem Cells and Osteoblasts: An In Vitro Study.

Unlabelled: Mesenchymal stem cells isolated from the bone marrow have a great differentiation potential, being able to produce many cell lines, including osteoblasts. Osteoblasts have an important role in bone remodeling by actively participating in the maturation and mineralization of the extracellular matrix. The aim of this study was to determine the effect of laser application on the viability and proliferation of osteoblasts.

Dynamic Evaluation of Natural Killer Cells Subpopulations in COVID-19 Patients.

The aim of the study was to evaluate the dynamic changes of the total Natural Killer (NK) cells and different NK subpopulations according to their differentiated expression of CD16/CD56 in COVID-19 patients. Blood samples with EDTA were analyzed on day 1 (admission moment), day 5, and day 10 for the NK subtypes. At least 30,000 singlets were collected for each sample and white blood cells were gated in CD45/SSC and CD16/CD56 dot plots of fresh human blood.

Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients.

Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B and T cells with a secondary long-term reconstruction of the immune system. This study provides evidence of CLD’s immunomodulatory role in peripheral blood mononuclear cells (PBMCs) harvested from 40 patients with untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion from PBMCs isolated by density gradient centrifugation with Ficoll−Paque using xMAP technology on a FlexMap 3D analyzer with a highly sensitive multiplex immunoassay kit.

Primary MSCs for Personalized Medicine: Ethical Challenges, Isolation and Biocompatibility Evaluation of 3D Electrospun and Printed Scaffolds.

Autologous cell therapy uses patients' own cells to deliver precise and ideal treatment through a personalized medicine approach. Isolation of patients' cells from residual tissue extracted during surgery involves specific planning and lab steps. In the present manuscript, a path from isolation to in vitro research with human mesenchymal stem cells (MSCs) obtained from residual bone tissues is described as performed by a medical unit in collaboration with a research center.

The Importance of Small Extracellular Vesicles in the Cerebral Metastatic Process.

Brain metastases represent more than 50% of all cerebral tumors encountered in clinical practice. Recently, there has been increased interest in the study of extracellular vesicles, and the knowledge about exosomes is constantly expanding. Exosomes are drivers for organotropic metastatic spread, playing important roles in the brain metastatic process by increasing the permeability of the blood-brain barrier and preparing the premetastatic niche.

Treatment With Cladribine Selects IFNγ+IL17+ T Cells in RRMS Patients - An Study.

Background: Multiple sclerosis (MS) is an incurable autoimmune disease mediated by a heterogeneous T cell population (CD3+CD161+CXCR3-CCR6+IFNγ-IL17+, CD3+CXCR3+CCR6+IFNγ+IL17+, and CD3+CXCR3+IFNγ+IL17- phenotypes) that infiltrates the central nervous system, eliciting local inflammation, demyelination and neurodegeneration. Cladribine is a lymphocyte-depleting deoxyadenosine analogue recently introduced for MS therapy as a Disease Modifying Drug (DMD). Our aim was to establish a method for the early identification and prediction of cladribine responsiveness among MS patients.

Reviewing the Significance of Blood-Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment.

The disruption of blood-brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the immune attack and later for the CNS self-sustained 'inside-out' demyelination and neurodegeneration processes. This review presents the characteristics of BBB malfunction in MS but mostly highlights current developments regarding the impairment of the neurovascular unit (NVU) and the metabolic and mitochondrial dysfunctions of the BBB's endothelial cells. The hypoxic hypothesis is largely studied and agreed upon recently in the pathologic processes in MS.

The Involvement of Exosomes in Glioblastoma Development, Diagnosis, Prognosis, and Treatment.

Brain tumours are a serious concern among both physicians and patients. The most feared brain tumour is glioblastoma (GBM) due to its heterogeneous histology, substantial invasive capacity, and rapid postsurgical recurrence. Even in cases of early management consisting of surgery, chemo-, and radiotherapy, the prognosis is still poor, with an extremely short survival period.

The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.

Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE.