Exploring the crosstalk between endothelial cells, immune cells, and immune checkpoints in the tumor microenvironment: new insights and therapeutic implications

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 4, 2023

Abstract The tumor microenvironment (TME) is a highly intricate milieu, comprising multitude of components, including immune cells and stromal cells, that exert profound influence on initiation progression. Within the TME, angiogenesis predominantly orchestrated by endothelial (ECs), which foster proliferation metastasis malignant cells. interplay between with ECs complex can either bolster or hinder system. Thus, comprehensive understanding crosstalk essential to advance development immunotherapeutic interventions. Despite recent progress, underlying molecular mechanisms govern remain elusive. Nevertheless, immunomodulatory function has emerged as pivotal determinant response. In light this, study relationship checkpoints garnered considerable attention in field immunotherapy. By targeting specific pathways signaling molecules associated novel strategies may be devised enhance efficacy current treatments. this vein, we sought elucidate ECs, ultimate goal identifying therapeutic targets charting new avenues for

Language: Английский

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Endothelial cells in tumor microenvironment: insights and perspectives

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 15, 2024

The tumor microenvironment is a highly complex and dynamic mixture of cell types, including tumor, immune endothelial cells (ECs), soluble factors (cytokines, chemokines, growth factors), blood vessels extracellular matrix. Within this network, ECs are not only relevant for controlling fluidity permeability, orchestrating angiogenesis but also regulating the antitumor response. Lining luminal side vessels, check passage molecules into compartment, regulate cellular transmigration, interact with both circulating pathogens innate adaptive cells. Thus, they represent first-line defense system that participates in responses. Tumor-associated involved T priming, activation, proliferation by acting as semi-professional antigen presenting targeting may assist improving functions. Moreover, tumor-associated contribute to development at site tertiary lymphoid structures, which have recently been associated enhanced response checkpoint inhibitors (ICI). When compared normal ECs, abnormal terms phenotype, genetic expression profile, They characterized high proliferative potential ability activate immunosuppressive mechanisms support progression metastatic dissemination. A complete phenotypic functional characterization could be helpful clarify their role within identify EC specific drug targets improve cancer therapy. emerging therapeutic strategies based on combination anti-angiogenic treatments immunotherapy strategies, ICI, CAR bispecific antibodies aim impact block same time increase recruitment activation effector tumor.

Language: Английский

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Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 13, 2024

Abstract Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With outbreak coronavirus disease 19 worldwide, has increased correspondingly. Comprehending pathophysiology underlying molecular mechanisms may thus be essential developing therapeutic strategies reducing mortality. To facilitate further understanding its pathogenesis exploring novel therapeutics, this review provides comprehensive information from presents therapeutics. We first describe that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance oxidative stress. Next, we summarize signaling pathways related above four aspects pathophysiology, along latest research progress. Finally, discuss emerging show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies mesenchymal stromal cell highlighting pathophysiological basis influences on signal transduction for their use.

Language: Английский

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Targeting endothelial permeability in the EPR effect

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 361, P. 212 - 235

Published: Aug. 8, 2023

Language: Английский

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Anti-inflammatory potential of platinum nanozymes: mechanisms and perspectives

Nanoscale, Journal Year: 2023, Volume and Issue: 15(35), P. 14284 - 14300

Published: Jan. 1, 2023

PtNPs hold great potential as anti-inflammatory agents, regulating the ROS-mediated recruitment and activation of immune system components.

Language: Английский

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Shedding light on the molecular and regulatory mechanisms of TLR4 signaling in endothelial cells under physiological and inflamed conditions

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 24, 2023

Toll-like receptor 4 (TLR4) are part of the innate immune system. They capable recognizing pathogen-associated molecular patterns (PAMPS) microbes, and damage-associated (DAMPs) damaged tissues. Activation TLR4 initiates downstream signaling pathways that trigger secretion cytokines, type I interferons, other pro-inflammatory mediators necessary for an immediate response. However, systemic release proteins is a powerful driver acute chronic inflammatory responses. Over past decades, immense progress has been made in clarifying regulatory mechanisms inflammation. most common strategies used to study rely on genetic manipulation or treatment with agonists such as lipopolysaccharide (LPS) derived from outer membrane Gram-negative bacteria, which often associated generation irreversible phenotypes target cells unintended cytotoxicity crosstalk due off-target pleiotropic effects. Here, optogenetics offers alternative strategy control monitor cellular unprecedented spatiotemporally precise, dose-dependent, non-invasive manner. This review provides overview structure, function its fundamental role endothelial under physiological conditions, well advances modulation strategies.

Language: Английский

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Translational nanorobotics breaking through biological membranes

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

In the dynamic realm of translational nanorobotics, endeavor to develop nanorobots carrying therapeutics in rational vivo applications necessitates a profound understanding biological landscape human body and its complexity. Within this landscape, membranes stand as critical barriers successful delivery therapeutic cargo target site. Their crossing is not only challenge for nanorobotics but also pivotal criterion clinical success therapeutic-carrying nanorobots. Nevertheless, despite their urgency, strategies membrane remain relatively underrepresented scientific literature, signaling an opportunity further research innovation. This review focuses on with various propulsion mechanisms from chemical physical hybrid mechanisms, it identifies describes four essential that represent needed be crossed journey applications. First entry point into blood stream, which skin or mucosa intravenous injection; next exit bloodstream across endothelium site; cell through plasma and, finally, escape lysosome, otherwise destroys cargo. The discusses design challenges inherent translating nanorobot technologies real-world provides overview documented crossings. aim underscore need interdisciplinary collaborations between chemists, materials scientists biologists vital domain has potential revolutionize field precision medicine.

Language: Английский

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Novel composite bone cement modulates inflammatory response in vitro

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 14, 2025

1. To evaluate the anti-inflammatory properties of enoxaparin sodium polymethylmethacrylate bone cement within indirect co-culture model comprising endothelial cells and macrophages. 2. investigate impacts inflammatory factors IL-6 IL-10 on macrophage M2 polarisation cell apoptosis. An system macrophages was established by utilizing 1 µg/mL lipopolysaccharide (LPS) to trigger an response model. The experiment categorized into 4 groups: blank control group, LPS-indicated PMMA + LPS ES-PMMA group. Flow cytometry performed ascertain apoptosis rate trend in system. Meanwhile, ELISA, Western blotting, immunofluorescence were adopted measure expression levels Interleukin-6(IL-6), Tumour Necrosis Factor-α(TNF-α), Intercellular Cell Adhesion Molecule (ICAM), Interleukin-10(IL-10) supernatants. In detection two typical proteins, CD86 CD206, it observed that level protein, which indicates M1 polarisation, elevated LPS-induced group comparison (**P < 0.01). found be down-regulated (*P 0.05). contrast, CD206 M2-polarisation, compared (***P 0.001). Conversely, this up-regulated IL-6, TNF-α, IL-10, ICAM investigated culture supernatants using Elisa assay. results showed had higher 0.001), while lower Additionally, aforementioned cytokines 0.01 or *P 0.05) Blot revealed 0.001) with Compared all three proteins 0.05 **P 0.01), whereas protein shown have fluorescence intensity diminished reduced relative enhanced terms detection, considerably when rose noticeably (1) system, fulfills functions impeding factor promoting IL-10. (2) facilitates declines a (3) can modify local environment modulating factors, is potentially valuable for application cement-related surgery.

Language: Английский

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Capillary leak and endothelial permeability in critically ill patients: a current overview

Intensive Care Medicine Experimental, Journal Year: 2023, Volume and Issue: 11(1)

Published: Dec. 20, 2023

Abstract Capillary leak syndrome (CLS) represents a phenotype of increased fluid extravasation, resulting in intravascular hypovolemia, extravascular edema formation and ultimately hypoperfusion. While endothelial permeability is an evolutionary preserved physiological process needed to sustain life, excessive leak—often caused by systemic inflammation—can have detrimental effects on patients’ outcomes. This article delves into the current understanding CLS pathophysiology, diagnosis potential treatments. Systemic inflammation leading compromise cell interactions through various signaling cues (e.g., angiopoietin–Tie2 pathway), shedding glycocalyx collectively contribute manifestation CLS. subsequently leads seepage protein-rich interstitial space. Recent insights importance sub-glycocalyx space preserving lymphatic flow are highlighted for in-depth understanding. no established diagnostic criteria exist frequently diagnosed clinical characteristics only, we highlight more objective serological (non)-invasive measurements that hint towards phenotype. currently available treatment options limited, further review resuscitation experimental approaches target permeability. Despite improved efforts develop uniform criteria, associate consequences these delineate options. Graphical

Language: Английский

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Research Progress and Molecular Mechanisms of Endothelial Cells Inflammation in Vascular-Related Diseases

Journal of Inflammation Research, Journal Year: 2023, Volume and Issue: Volume 16, P. 3593 - 3617

Published: Aug. 1, 2023

Endothelial cells (ECs) are widely distributed inside the vascular network, forming a vital barrier between bloodstream and walls of blood vessels. These versatile serve myriad functions, including regulation tension management hemostasis thrombosis. Inflammation constitutes cascade biological responses incited by biological, chemical, or physical stimuli. While inflammation is inherently protective mechanism, dysregulated can precipitate host pathologies. ECs play critical role in genesis progression inflammation, which has been implicated etiology numerous disorders, such as atherosclerosis, cardiovascular diseases, respiratory diabetes mellitus, sepsis. Upon activation, secrete potent inflammatory mediators that elicit both innate adaptive immune reactions, culminating inflammation. To date, no comprehensive nuanced account research progress concerning vascular-related maladies exists. Consequently, this review endeavors to synthesize contributions processes, delineate molecular signaling pathways involved regulation, categorize consolidate various models treatment strategies for diseases. It our aspiration furnishes cogent experimental evidence supporting established link endothelial pathologies, offers theoretical foundation clinical investigations, imparts valuable insights development therapeutic agents targeting these

Language: Английский

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