Towards advanced regenerative therapeutics to tackle cardio-cerebrovascular diseases

American Heart Journal Plus Cardiology Research and Practice, Journal Year: 2025, Volume and Issue: 53, P. 100520 - 100520

Published: March 1, 2025

The development of vascularized organoids as novel modelling tools the human cardio-cerebrovascular system for preclinical research has become an essential platform studying tissues/organs personalized therapeutics during recent decades. Organ-on-chip technology is promising investigating physiological in vitro responses drug screening and advanced disease models. Vascularized tissue/organ-on-a-chip benefits every step discovery pipeline a tool with close genome relevance to investigate systems biology. Simultaneously, cardio-cerebrovascular-on-chip-integrated microfluidic serves alternative animal (patho-)physiological processes blood vessels embryonic disease. Integrated next-generation techniques, such three-dimensional bioprinting both cells matrix, may enable organoid-on-chip-based therapeutics.

Language: Английский

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Responsive nanoparticles synergize with Curcumin to break the “reactive oxygen Species-Neuroinflammation” vicious cycle, enhancing traumatic brain injury outcomes

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 5, 2025

Traumatic brain injury (TBI) disrupts oxygen homeostasis in the brain, leading to excessive reactive species (ROS) production and dysregulated antioxidant mechanisms, which fail clear excess ROS. This ROS overload promotes expression of pro-inflammatory genes, releasing cytokines chemokines creating a vicious "ROS-neuroinflammation" cycle, making it essential break this cycle for effective TBI treatment. In study, we developed cysteine-alanine-glutamine-lysine (CAQK) peptide-modified nanoparticles (C-PPS/C) co-delivery curcumin (Cur) modulate oxidative neuroinflammatory disturbances after TBI. mice, C-PPS/C accumulated injured regions, where poly (propylene sulfide)120 scavenged ROS, reducing stress, while Cur release further suppressed inflammation. broke protecting blood-brain barrier (BBB), acute edema, promoting long-term neurological recovery. Further investigation showed that inhibited NF-κB pathway, gene mitigating inflammation, suggesting promising approach

Language: Английский

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Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 9, 2024

Abstract Ischemic stroke is the result of a permanent or transient occlusion brain artery, leading to irreversible tissue injury and long-term sequelae. Despite ongoing advancements in revascularization techniques, remains second cause death worldwide. A comprehensive understanding complex interconnected mechanisms, along with endogenous mediators that modulate responses essential for development effective interventions. Our study investigates cortistatin, neuropeptide extensively distributed immune central nervous systems, known its immunomodulatory properties. With neuroinflammation peripheral deregulation as key pathological features ischemia, cortistatin emerges promising therapeutic candidate. To this aim, we evaluated potential effect well-established middle cerebral artery (MCAO) preclinical model. findings indicate administration at 24 hours post-stroke significantly reduces neurological damage enhances recovery. Importantly, cortistatin-induced neuroprotection was multitargeted, it modulated glial reactivity astrocytic scar formation, facilitated blood-brain barrier recovery, regulated local systemic dysfunction. Surprisingly, immediate early time points proved be not beneficial even detrimental. These results emphasize importance spatio-temporal dynamics pathology develop innovative strategies. Premature interruption certain neuroinflammatory processes might inadvertently compromise neuroprotective mechanisms. In summary, our highlights novel pleiotropic approach against ischemic stroke, offering new treatment options patients whom intervention unsuccessful. Graphical abstract

Language: Английский

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Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke

Pharmacological Research, Journal Year: 2024, Volume and Issue: 210, P. 107501 - 107501

Published: Nov. 7, 2024

Ischemic stroke is the result of a permanent or transient occlusion brain artery, leading to irreversible tissue injury and long-term sequelae. Despite ongoing advancements in revascularization techniques, remains second cause death worldwide. A comprehensive understanding complex interconnected mechanisms, along with endogenous mediators that modulate responses essential for development effective interventions. Our study investigates cortistatin, neuropeptide extensively distributed immune central nervous systems, known its immunomodulatory properties. With neuroinflammation peripheral deregulation as key pathological features ischemia, cortistatin emerges promising therapeutic candidate. To this aim, we evaluated potential effect well-established middle cerebral artery (MCAO) preclinical model. findings indicated administration at 24 h post-stroke significantly reduced neurological damage enhanced recovery. Importantly, cortistatin-induced neuroprotection was multitargeted, it modulated glial reactivity astrocytic scar formation, facilitated blood-brain barrier recovery, regulated local systemic dysfunction. Surprisingly, immediate early time points proved be not beneficial even detrimental. These results emphasize importance spatio-temporal dynamics pathology develop innovative strategies appropriate windows. Premature interruption certain neuroinflammatory processes might inadvertently compromise neuroprotective mechanisms. In summary, our highlights novel pleiotropic approach against ischemic stroke, offering new treatment options patients who undergo intervention but unsuccessful

Language: Английский

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