Purinergic signaling in the modulation of redox biology

Redox Biology, Journal Year: 2021, Volume and Issue: 47, P. 102137 - 102137

Published: Sept. 22, 2021

Purinergic signaling is a cell communication pathway mediated by extracellular nucleotides and nucleosides. Tri- diphosphonucleotides are released in physiological pathological circumstances activating purinergic type 2 receptors (P2 receptors): P2X ion channels P2Y G protein-coupled receptors. The activation of these triggers the production reactive oxygen nitrogen species alters antioxidant defenses, modulating redox biology cells. P2 controlled ecto-enzymes named ectonucleotidases, E-NTPDase1/CD39 ecto-5'-nucleotidase/CD73) being most relevant. first enzyme hydrolyzes adenosine triphosphate (ATP) diphosphate (ADP) into monophosphate (AMP), second catalyzes hydrolysis AMP to adenosine. activity enzymes diminished oxidative stress. Adenosine actives P1 G-coupled that, general, promote maintenance hemostasis decreasing (ROS) increase enzymes. Intracellular purine metabolism can also contribute ROS generation via xanthine oxidase activity, which converts hypoxanthine xanthine, finally, uric acid. In this review, we describe mechanisms modulated how may be affected disturbances homeostasis

Language: Английский

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Pulmonary fibrosis from molecular mechanisms to therapeutic interventions: lessons from post-COVID-19 patients

Biochemical Pharmacology, Journal Year: 2021, Volume and Issue: 193, P. 114812 - 114812

Published: Oct. 21, 2021

Language: Английский

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An Insight into Recent Advances on Platelet Function in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6022 - 6022

Published: May 27, 2022

Platelets play a variety of roles in vascular biology and are best recognized as primary hemostasis thrombosis mediators. have large number receptors secretory molecules that required for platelet functionality. Upon activation, platelets release multiple substances the ability to influence both physiological pathophysiological processes including inflammation, tissue regeneration repair, cancer progression, spreading. The involvement progression seriousness disorders other than is still being discovered, especially areas inflammation immunological response. This review represents an integrated summary recent advances on function pathophysiology connects hemostasis, response health disease suggests antiplatelet treatment might be used more only thrombosis.

Language: Английский

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N-Cadherin Targeted Melanin Nanoparticles Reverse the Endothelial–Mesenchymal Transition in Vascular Endothelial Cells to Potentially Slow the Progression of Atherosclerosis and Cancer

ACS Nano, Journal Year: 2024, Volume and Issue: 18(11), P. 8229 - 8247

Published: March 1, 2024

Endothelial–mesenchymal transition (EndoMT) of vascular endothelial cells has recently been considered as a key player in the early progression variety and nonvascular diseases, including atherosclerosis, cancer, organ fibrosis. However, current strategies attempting to identify pharmacological inhibitors block regulatory pathways EndoMT suffer from poor selectivity, unwanted side effects, heterogeneous response with different origins. Furthermore, focus on preventing EndoMT, leaving that have already undergone unresolved. Here, we report design simple but powerful nanoparticle system (i.e., N-cadherin targeted melanin nanoparticles) convert cytokine-activated, mesenchymal-like back their original phenotype. We term this process "Reversed EndoMT" (R-EndoMT). R-EndoMT allows impaired barriers recover quiescence intactness, significantly reduced leukocyte cancer cell adhesion transmigration, which could potentially stop atheromatous plaque formation metastasis stages. is achieved types originating arteries, veins, capillaries, independent activating cytokines. reveal nanoparticles reverse by downregulating an dependent RhoA activation pathway. Overall, approach offers prospect treat multiple EndoMT-associated diseases designing phenotypical cells.

Language: Английский

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Comorbidities in COPD: Current and Future Treatment Challenges

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(3), P. 743 - 743

Published: Jan. 27, 2024

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition, primarily characterized by the presence of limited airflow, due to abnormalities airways and/or alveoli, that often coexists with other chronic diseases such as cancer, cardiovascular diseases, and metabolic disorders. Comorbidities are known pose challenge in assessment effective management COPD also acknowledged have an important health economic burden. Local systemic inflammation been proposed having potential role explaining association between these comorbidities. Considering number patients expected rise, understanding mechanisms linking its comorbidities may help identify new targets for therapeutic purposes based on multi-dimensional assessments.

Language: Английский

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TGF-β in Cancer: Metabolic Driver of the Tolerogenic Crosstalk in the Tumor Microenvironment

Cancers, Journal Year: 2021, Volume and Issue: 13(3), P. 401 - 401

Published: Jan. 22, 2021

Overcoming tumor immunosuppression still represents one ambitious achievement for cancer immunotherapy. Of note, the cytokine TGF-β contributes to immune evasion in multiple types, by feeding establishment of a tolerogenic environment host. Indeed, it fosters expansion and accumulation immunosuppressive regulatory cell populations within microenvironment (TME), where also activates resident stromal cells enhances angiogenesis programs. More recently, has turned out as key metabolic adjuster tumors orchestrating pathways TME. In this review, we will scrutinize TGF-β-mediated crosstalk TME, with primary focus on

Language: Английский

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SUMO-Targeted Ubiquitin Ligases and Their Functions in Maintaining Genome Stability

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(10), P. 5391 - 5391

Published: May 20, 2021

Small ubiquitin-like modifier (SUMO)-targeted E3 ubiquitin ligases (STUbLs) are specialized enzymes that recognize SUMOylated proteins and attach to them. They therefore connect the cellular SUMOylation ubiquitination circuits. STUbLs participate in diverse molecular processes span cell cycle regulated events, including DNA repair, replication, mitosis, transcription. operate during unperturbed conditions response challenges, such as genotoxic stress. These modify their target substrates by catalyzing chains form different linkages, resulting proteolytic or non-proteolytic outcomes. Often, function compartmentalized environments, nuclear envelope kinetochore, actively aid relocalization of damaged stalled replication forks promote repair fork restart. Furthermore, reside same vicinity SUMO proteases deubiquitinases (DUBs), providing spatiotemporal control targets. In this review, we focus on mechanisms which help maintain genome stability across species.

Language: Английский

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Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(17), P. 11415 - 11432

Published: Aug. 26, 2022

Acriflavine (ACF) has been known for years as an antibacterial drug. The identification of key oncogenic mechanisms brought, in recent years, a significant increase studies on ACF multipurpose drug that would improve the prognosis cancer patients. interferes with expression hypoxia inducible factor, thus acting metastatic niches tumors and significantly enhancing effects other anticancer therapies. It recognized most potent HIF-1 inhibitor out 336 drugs approved by FDA. This work presents up-to-date knowledge about action its related prodrug systems context SARS-CoV-2 inhibitory properties. explains multitask nature this suggests ACF's coronavirus. Other reports ACF-based potential antiviral are also described.

Language: Английский

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Targeting tumor vasculature to improve antitumor activity of T cells armed ex vivo with T cell engaging bispecific antibody

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(3), P. e006680 - e006680

Published: March 1, 2023

Success of T cell immunotherapy hinges on the tumor microenvironment (TME), and abnormal vasculature is a hallmark most solid tumors associated with immune evasion. The efficacy engaging bispecific antibody (BsAb) treatment relies successful trafficking cytolytic activity cells in tumors. Normalization using vascular endothelial growth factor (VEGF) blockades could improve BsAb-based immunotherapy.Anti-human VEGF (bevacizumab, BVZ) or anti-mouse VEGFR2 (DC101) was used as blockade, ex vivo armed (EATs) carrying anti-GD2, anti-HER2, anti-glypican3 (GPC3) IgG-(L)-scFv platformed BsAb were used. BsAb-driven intratumoral infiltration antitumor response evaluated cancer line-derived xenografts (CDXs) patient-derived (PDXs) carried out BALB-Rag2-/-IL-2R-γc-KO (BRG) mice. expression human lines analyzed by flow cytometry, levels mouse serum measured Quantikine ELISA Kit. Tumor infiltrating lymphocytes (TILs) cytometry bioluminescence; both TILs studied immunohistochemistry.VEGF increased seeding density vitro. BVZ significantly reduced DC101 high venules (HEVs) TME substantially enhanced (2.1-8.1 fold) into neuroblastoma osteosarcoma xenografts, which preferential for CD8(+) versus CD4(+) TILs, leading to superior effects multiple CDX PDX models without added toxicities.VEGF blockade specific antibodies against HEVs cytotoxic improving therapeutic EAT strategies preclinical models, supporting clinical investigation further enhance immunotherapies.

Language: Английский

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Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2258 - 2258

Published: April 12, 2023

Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence increasing. occurs through a multi-step cascade where cells spread from the primary tumor site to brain. The extravasation blood–brain barrier (BBB) critical step in brain metastasis. During extravasation, circulating roll along endothelium (BE), adhere it, then induce alterations endothelial transmigrate BBB enter Rolling adhesion are generally mediated by selectins molecules induced inflammatory mediators, while proteolytic enzymes, including matrix metalloproteinase, transmigration factors, chemokines. However, molecular mechanisms mediating not yet fully understood. A better understanding these essential as it may serve basis for development therapeutic strategies prevention or treatment metastases. In this review, we summarize events that occur during three types most likely develop metastasis: breast cancer, melanoma, lung cancer. Common driving different tumors discussed.

Language: Английский

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