Clinical and laboratory significance of soluble claudin-5 and VEGF in ovarian cancer DOI Creative Commons
Н. Е. Кушлинский,

S. Kulikova,

Frol A. Gugnin

et al.

Advances in molecular oncology, Journal Year: 2025, Volume and Issue: 12(1), P. 67 - 75

Published: April 15, 2025

Introduction. Claudin 5 is belongs to a family of transmembrane proteins mediating formation tight junctions between cells, maintenance cell polarity in epithelial and endothelial layers, regulation membrane permeability, control signal transduction inside the cells. Results small number studies show that vascular growth factor (VEGF) also affects junctions, particular through claudin expression. In addition their physiological functions, VEGF play an important role pathogenesis various diseases including malignant neoplasms. Aim. To study levels serum patients with ovarian cancer evaluate clinical significance. Materials methods. total, 123 (median age 54 years) 32 group healthy women were examined. measured prior treatment using Human CLDN5 (Claudin 5) ELISA Kit (Elabscience, China) Immunoassay (Quantikine®, R&D Systems, uSA) accordance manufacturer’s instructions. Statistical analysis obtained data was performed GraphPad Prizm v. 10 software. The values compared correlations quantified nonparametric Mann–Whitney, Kruskal–Wallis tests Spearman’s rank correlation coefficient. Overall survival analyzed Kaplan–Meier method. Results. found 97 % 94 women. Median (1st quartile (Q1) – 3rd (Q3)) level 0.77 (0.48–1.17) ng/mL, 0.95 (0.43–1.77) mg/mL. ROC informational value showed unsatisfactory diagnostic accuracy model (area under curve (AuC) 0.613 (95 confidence interval (CI) 0.513–0.713); p = 0.049): for median threshold ng/mL assay had sensitivity 50 specificity 60 %. all women; (Q1–Q3) 45.6 (13.3–89.09) pg/mL statistically significantly lower than cancer: 274.7 (199.0–472.5). good (AuC 0.942 CI 0.886–0.997); <0.0001) which allows use as criterion. best results (71 100 %, respectively) at 226.2 pg/mL. Serum are associated progression. However, not significant prognostic markers this disease. Conclusion. higher positively correlate each other. Additionally, has relatively characteristics group. presence distant metastases points potential tumor research stage, these cannot be recommended or criteria require further study.

Language: Английский

Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood–Brain Barrier DOI Creative Commons
Gabriella Schiera, Carlo Maria Di Liegro,

Giuseppe Schirò

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 150 - 150

Published: Jan. 12, 2024

The blood-brain barrier (BBB) is a fundamental structure that protects the composition of brain by determining which ions, metabolites, and nutrients are allowed to enter from blood or leave it towards circulation. BBB structurally composed layer capillary endothelial cells (BCECs) bound each other through tight junctions (TJs). However, its development as well maintenance properties controlled contact BCECs: pericytes, glial cells, even neurons themselves. Astrocytes seem, in particular, have very important role controlling most BBB. Here, we will focus on these latter since comprehension their roles physiology has been continuously expanding, including ability participate neurotransmission complex functions such learning memory. Accordingly, pathological conditions alter astrocytic can BBB's integrity, thus compromising many activities. In this review, also refer different kinds vitro models used study properties, evidencing modifications under conditions.

Language: Английский

Citations

37

Brain stars take the lead during critical periods of early postnatal brain development: relevance of astrocytes in health and mental disorders DOI Creative Commons

Eugenia Vivi,

Barbara Di Benedetto

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(9), P. 2821 - 2833

Published: March 29, 2024

In the brain, astrocytes regulate shape and functions of synaptic vascular compartments through a variety released factors membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to onset severe pathologies. Clinical pre-clinical studies show alterations in cell number, morphology, molecular makeup astrocyte-dependent processes different affected regions neurodevelopmental (ND) neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate mature during critical period early postnatal time window elevated glia-dependent regulation proper balance between synapse formation/elimination, which is pivotal refining connectivity. Therefore, any intrinsic and/or extrinsic altering these may result an aberrant remodeling mental The peculiar bridging position further allows them "compute" state consequently secrete bloodstream, serve as diagnostic biomarkers distinct healthy or disease conditions. Here, we collect recent advancements regarding astrogenesis astrocyte-mediated neuronal network periods focusing elimination. We then propose alternative hypotheses for involvement aberrancies ND NP light well-known differential prevalence certain disorders males females, also discuss putative sex-dependent influences events. From translational perspective, understanding age- astrocyte-specific functional changes help identify cellular (dys)functions health disease, favouring development tools selection tailored treatment options male/female patients.

Language: Английский

Citations

26

Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models DOI Open Access
Sarah E. Brandl, Markus Reindl

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12699 - 12699

Published: Aug. 11, 2023

The blood-brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, barrier forms neurovascular unit. Upon neuroinflammation, this becomes leaky, allowing molecules cells to enter potentially harm tissue of system. Despite significance animal models in research, they may not always adequately reflect human pathophysiology. Therefore, are needed. This review will provide an overview terms both health disease. It describe all key elements vitro explore how different compositions can be utilized effectively model a variety neuroinflammatory conditions. Furthermore, it existing types that used basic research study respective pathologies thus far.

Language: Английский

Citations

29

Tight junctions DOI Creative Commons

María S. Balda,

Karl Matter

Current Biology, Journal Year: 2023, Volume and Issue: 33(21), P. R1135 - R1140

Published: Nov. 1, 2023

Language: Английский

Citations

24

Lab-on-a-chip models of the blood–brain barrier: evolution, problems, perspectives DOI
Mária A. Deli, Gergő Porkoláb, András Kincses

et al.

Lab on a Chip, Journal Year: 2024, Volume and Issue: 24(5), P. 1030 - 1063

Published: Jan. 1, 2024

A great progress has been made in the development and use of lab-on-a-chip devices to model study blood–brain barrier (BBB) last decade.

Language: Английский

Citations

10

Permeability Benchmarking: Guidelines for Comparing in Silico, in Vitro, and in Vivo Measurements DOI Creative Commons
Christian Jorgensen, Raleigh M. Linville, Ian Galea

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Permeability is a measure of the degree to which cells can transport molecules across biological barriers. Units permeability are distance per unit time (typically cm/s), where accurate measurements needed define drug delivery in homeostasis and model dysfunction occurring during disease. This perspective offers set community-led guidelines benchmark data multidisciplinary approaches different contexts. First, we lay out analytical framework for three methodologies calculate permeability: silico assays using either transition-based counting or inhomogeneous-solubility diffusion approaches, vitro cultured 2D 3D geometries, vivo utilizing situ brain perfusion multiple time-point regression analysis. Then, demonstrate systematic benchmarking both vivo, depicting ways each sensitive choices assay design. Finally, outline seven recommendations best practices underscore significance tailored driving advancements research development. Our exploration encompasses discussion "generic" tissue-specific barriers, including blood–brain barrier (BBB), major hurdle therapeutic agents into brain. By addressing challenges reconciling simulated with experimental assays, aim provide insights essential optimizing accuracy reliability modeling.

Language: Английский

Citations

1

CLDN5: From structure and regulation to roles in tumors and other diseases beyond CNS disorders DOI Creative Commons

Ling Yao,

Xinxin Kang,

Ying Yi

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 200, P. 107075 - 107075

Published: Jan. 19, 2024

Language: Английский

Citations

7

Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders DOI Creative Commons
Duraisamy Kempuraj,

Kirk D. Dourvetakis,

Jessica R. Cohen

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 25, 2024

Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism disease pathogenesis is not understood, certain biomarkers provide valuable insight into pathogenesis, severity, progression therapeutic efficacy. These markers can be used to assess pathophysiological status brain including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, blood-brain barrier (BBB) disruption. Damage or derangements tight junction (TJ), adherens (AdJ), gap (GJ) components BBB lead increased permeability neuroinflammation various disorders disorders. Thus, neuroinflammatory evaluated blood, cerebrospinal fluid (CSF), tissues determine neurological progression, responsiveness. Chronic common age-related Alzheimer's (AD), Parkinson's (PD), dementia. Neurotrauma/traumatic injury (TBI) also leads acute chronic responses. The expression some may altered many years even decades before onset In this review, we discuss neuroinflammation, neurodegeneration associated with disorders, especially those neurovascular pathologies. CSF, tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane 119 (TMEM119), aquaporin, endothelin-1, platelet-derived growth factor receptor beta (PDGFRβ) are important markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding neurotherapeutics. Integration these clinical practice could potentially enhance early diagnosis, monitor improve outcomes.

Language: Английский

Citations

5

Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication DOI Creative Commons
Pedro N. Bernardino, Audrey Luo, Peter M. Andrew

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2023, Volume and Issue: 388(2), P. 301 - 312

Published: Oct. 12, 2023

Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses are associated with persistent neuroinflammation spontaneous recurrent (SRS), also known as acquired epilepsy. Blood-brain barrier (BBB) impairment has recently been proposed pathogenic mechanism linking OP intoxication to chronic adverse neurologic outcomes. In this review, we briefly describe the cellular molecular components of BBB, review evidence altered BBB integrity following intoxication, discuss potential mechanisms by which may promote dysfunction. We highlight complex interplay between dysfunction suggests positive feedforward interaction. Lastly, examine research from diverse models disease states suggest loss contribute epileptogenic processes. Collectively, literature identifies convergent justifies further mechanistic into how causes its role in pathogenesis SRS potentially other long-term sequelae. Such is critical for evaluating stabilization neuroprotective strategy mitigating OP-induced epilepsy possibly seizure disorders etiologies. SIGNIFICANCE STATEMENT: Clinical preclinical studies support link blood-brain epileptogenesis; however, causal relationship difficult prove. Mechanistic delineate relationships provide novel insights resulting organophosphate non-OP neurological conditions such cognitive impairment.

Language: Английский

Citations

12

Neurons enhance blood–brain barrier function via upregulating claudin-5 and VE-cadherin expression due to glial cell line-derived neurotrophic factor secretion DOI Creative Commons
Lu Yang, Zijin Lin,

Ruijing Mu

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: May 29, 2024

Blood–brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an in vitro triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, neuroblastoma SH-SY5Y cells. Co-culture markedly enhanced claudin-5 VE-cadherin expression hCMEC/D3 accompanied by increased transendothelial electrical resistance decreased permeability. Conditioned medium (CM) (S-CM), (U-CM), (US-CM) also promoted expression. Glial cell line-derived neurotrophic factor (GDNF) levels S-CM US-CM were significantly higher than CMs U-CM. Both GDNF upregulated expression, which attenuated anti-GDNF antibody signaling inhibitors. via the PI3K/AKT/FOXO1 MAPK/ERK pathways. Meanwhile, activating PI3K/AKT/ETS1 MAPK/ERK/ETS1 signaling. The roles integrity validated using brain-specific Gdnf silencing mice. developed was successfully applied predict In conclusion, neurons enhance upregulating through secretion established may be used drugs’

Language: Английский

Citations

4