Phytomedicine, Год журнала: 2024, Номер 129, С. 155578 - 155578
Опубликована: Апрель 7, 2024
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Янв. 8, 2024
Abstract Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of intricate mechanisms underlying I/R hinders development effective therapeutic interventions. Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system pathways involved in injury. This review article elucidates signaling, as well complex interplay between and including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-β, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca 2+ -Activin A, Hippo-Yes-associated toll-like receptor 4/toll-interleukine-1 domain-containing adapter-inducing interferon-β, hepatocyte factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, apoptosis, inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, blood-brain barrier damage Our comprehensive analysis reveals that activation canonical promotes organ recovery, while non-canonical exacerbates Moreover, explore novel approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, clinical trials. objective this is provide deeper insights roles its I/R-mediated processes dysfunction, facilitate innovative agents for
Язык: Английский
Процитировано
157
ACS Nano, Год журнала: 2024, Номер 18(3), С. 1820 - 1845
Опубликована: Янв. 9, 2024
The blood–brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, BBB also prevents passage of various forms therapeutic agents, nanocarriers, their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe effective vehicles in neurotheranostics. In this Review, first we introduce anatomical physiological functions BBB. Second, present endogenous exogenous transport mechanisms by NPs cross We report nanomaterials, carriers, cargos, with detailed uptake permeability characteristics. Third, describe effect regulating size, shape, charge, surface ligands affect permeability, can be exploited enhance promote classify typical functionalized nanomaterials developed for crossing. Fourth, provide comprehensive review recent progress functional polymeric applications multimodal bioimaging, therapeutics, drug delivery. Finally, conclude discussing existing directions, future perspectives employing
Язык: Английский
Процитировано
80
Frontiers in Immunology, Год журнала: 2023, Номер 13
Опубликована: Фев. 2, 2023
Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms IS. In particular, early proinflammatory response resulting from overactivation resident microglia infiltration circulating monocytes macrophages brain after cerebral ischemia leads to secondary injury. Microglia are innate immune cells that constantly monitor microenvironment under normal conditions. Once occurs, activated produce dual effects neurotoxicity neuroprotection, balance two determines fate damaged neurons. The activation defined as classical (M1 type) or alternative (M2 type). M1 type secrete pro-inflammatory cytokines neurotoxic mediators exacerbate neuronal damage, while M2 promote a repairing anti-inflammatory response. Fine regulation M1/M2 microglial minimize damage maximize protection has therapeutic value. This review focuses on interaction between other involved IS phenotypic characteristics, mechanism natural plant components regulating IS, providing novel candidate drugs for drug development.
Язык: Английский
Процитировано
75
Advanced Materials, Год журнала: 2024, Номер 36(21)
Опубликована: Март 23, 2024
Abstract Neuroinflammation has emerged as a major concern in ischemic stroke therapy because it exacebates neurological dysfunction and suppresses recovery after ischemia/reperfusion. Fingolimod hydrochloride (FTY720) is an FDA‐approved anti‐inflammatory drug which exhibits potential neuroprotective effects brain parenchyma. However, delivering sufficient amount of FTY720 through the blood–brain barrier into lesions without inducing severe cardiovascular side remains challenging. Here, neutrophil membrane‐camouflaged polyprodrug nanomedicine that can migrate tissues situ release response to elevated levels reactive oxygen species. This delivers 15.2‐fold more significantly reduces risk cardiotoxicity infection compared with intravenously administered free drug. In addition, single‐cell RNA‐sequencing analysis identifies attenuates poststroke inflammation by reprogramming microglia toward phenotypes, realized via modulating Cebpb‐regulated activation NLRP3 inflammasomes secretion CXCL2 chemokine. study offers new insights design fabrication nanomedicines for effective suppression therapy.
Язык: Английский
Процитировано
35
CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(5)
Опубликована: Май 1, 2024
Abstract Aims The molecular mechanism of short‐sleep conditions on cognition remains largely unknown. This research aimed to investigate associations between short sleep, inflammatory biomarkers and cognitive function in the US population (NHANES data 2011–2014) explore cellular mechanisms mice. Methods Systemic immune‐inflammation index (SII) was calculated using blood‐cell based biomarkers. Further, we employed integrated bioinformatics single‐cell transcriptomics (GSE137665) examine how sleep exposure influenced pathways associated with inflammation brain. To signaling biological processes deprivation, carried out enrichment analyses utilizing GO KEGG databases. Results Population results showed that, compared normal group, severe lower ability all four tests. Moreover, a higher SII level correlated scores In mice study, elevated activation pathway observed cell subgroups neurons within deprivation recovery cohorts. Additionally, heightened expression oxidative stress response noted GABAergic during deprivation. Conclusion study contributed understanding influence its mechanisms.
Язык: Английский
Процитировано
35
Biomolecules, Год журнала: 2024, Номер 14(3), С. 305 - 305
Опубликована: Март 4, 2024
The majority of approved therapies for many diseases are developed to target their underlying pathophysiology. Understanding disease pathophysiology has thus proven vital the successful development clinically useful medications. Stroke is generally accepted as leading cause adult disability globally and ischemic stroke accounts most common form two main types. Despite its health socioeconomic burden, there still minimal availability effective pharmacological treatment. In this review, we take an in-depth look at etiology stroke, including molecular cellular changes. This followed by a highlight drugs, therapies, complementary medicines that or undergoing clinical trials treatment management stroke. We also identify unexplored potential targets in pathogenesis can be exploited increase pool anti-stroke neuroprotective agents through de novo drug repurposing.
Язык: Английский
Процитировано
31
ACS Nano, Год журнала: 2024, Номер 18(4), С. 3260 - 3275
Опубликована: Янв. 16, 2024
The ischemic stroke is a major global health concern, with high mortality and disability rates. Unfortunately, there dearth of effective clinical interventions for managing poststroke neuroinflammation blood–brain barrier (BBB) disruption that are crucial the brain injury evolving neurological deficits. By leveraging pathological progression an stroke, we developed M2 microglia-targeting lipid nanoparticle (termed MLNP) approach can selectively deliver mRNA encoding phenotype-switching interleukin-10 (mIL-10) to brain, creating beneficial feedback loop drives microglial polarization toward protective phenotypes augments homing mIL-10-loaded MLNPs (mIL-10@MLNPs) regions. In transient middle cerebral artery occlusion (MCAO) mouse model our findings demonstrate intravenously injected mIL-10@MLNPs induce IL-10 production enhance microglia. resulting positive reinforces resolution neuroinflammation, restores impaired BBB, prevents neuronal apoptosis after stroke. Using permanent distal MCAO neuroprotective effects have been further validated by attenuation sensorimotor cognitive Furthermore, mRNA-based targeted therapy has great potential extend therapeutic time window at least up 72 h poststroke. This study depicts simple versatile LNP platform selective delivery therapeutics lesions, showcasing promising addressing associated conditions.
Язык: Английский
Процитировано
29
Scientific Reports, Год журнала: 2024, Номер 14(1)
Опубликована: Март 4, 2024
Abstract Arterial occlusion-induced ischemic stroke (IS) is a highly frequent subtype. Nuclear factor erythroid 2-related 2 (NRF2) transcription that modulates antioxidant genes. Its role in IS still unelucidated. The current study focused on constructing transient middle cerebral artery occlusion (tMCAO) model for investigating the NRF2-related mechanism underlying ischemia/reperfusion (I/R) injury. Each male C57BL/6 mouse was injected with/with no specific NRF2 activator post-tMCAO. Changes blood–brain barrier (BBB)-associated molecule levels were analyzed using western-blotting, PCR, immunohistochemistry, and immunofluorescence analysis. within I/R decreased at 24-h post-ischemia. activation improved brain edema, infarct volume, neurological deficits after MCAO/R. Similarly, sulforaphane (SFN) prevented down-regulated tight junction proteins occludin zonula occludens 1 (ZO-1) reduced up-regulated aquaporin 4 (AQP4) matrix metalloproteinase 9 (MMP9) tMCAO. Collectively, exerted critical effect preserving BBB integrity modulating ferroptosis inflammation. Because related to injury regulation following I/R, this provides potential therapeutic target throws light clinically treating IS.
Язык: Английский
Процитировано
24
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Март 8, 2024
Background There is a growing acknowledgment of the potential influence antioxidative effects resulting from dietary decisions on occurrence stroke. The objective this study was to elucidate correlation between composite antioxidant index (CDAI) and incidence stroke in general population United States. Methods We gathered cross-sectional data encompassing 40,320 participants National Health Nutrition Examination Survey (NHANES) spanning years 1999 2018. Employing weighted multivariate logistic regression, we assessed CDAI stroke, while also investigating nonlinear relationships through restricted cubic spline (RCS) regression. Further, intake components were then incorporated into predictive nomogram model, subsequently evaluated for its discriminatory prowess risk assessment using receiver operating characteristic (ROC) curve. Results Post-adjustment confounding variables, found that higher score associated with decreased odds ratio (OR) [95% CI] associating prevalence 0.96 [0.94-0.98] (P< 0.001). Moreover, adjusted OR across ascending quartiles stood at 0.90 [0.74-1.09], 0.74 [0.60-0.91], 0.61 [0.50-0.76] compared reference quartile, respectively. RCS analysis indicated yet negative constructed based antioxidants, exhibited significant capacity risk, boasting an area under curve (AUC) 77.4% (76.3%–78.5%). Conclusion Our investigation ascertained relationship within broader American population. However, given inherent limitations design, further comprehensive research imperative establish causative nature association.
Язык: Английский
Процитировано
24
Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)
Опубликована: Март 13, 2024
Abstract Tissue-resident macrophages play an important role in the local maintenance of homeostasis and immune surveillance. In central nervous system (CNS), brain are anatomically divided into parenchymal microglia non-parenchymal border-associated (BAMs). Among these cell populations, have been well-studied for their roles during development as well health disease. BAMs, mostly located choroid plexus, meningeal perivascular spaces, now gaining increased attention due to advancements multi-omics technologies genetic methodologies. Research on BAMs over past decade has focused ontogeny, immunophenotypes, involvement various CNS diseases, potential therapeutic targets. Unlike microglia, display mixed origins distinct self-renewal capacity. believed regulate neuroimmune responses associated with barriers contribute immune-mediated neuropathology. Notably, observed function diverse cerebral pathologies, including Alzheimer’s disease, Parkinson’s multiple sclerosis, ischemic stroke, gliomas. The elucidation heterogeneity functions neuroinflammation is mesmerizing, since it may shed light precision medicine that emphasizes deep insights programming cues unique microenvironment. this review, we delve latest findings covering aspects like origins, capacity, adaptability, implications different disorders.
Язык: Английский
Процитировано
20