Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Язык: Английский

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Applications of hydrogels and nanoparticles in the treatment of traumatic brain injury

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 6, 2025

Traumatic brain injury (TBI) represents a significant global public health issue, with effective management posing numerous challenges. The pathophysiology of TBI is typically categorized into two phases: primary and secondary injuries. Secondary involves pathophysiological mechanisms such as blood-brain barrier (BBB) disruption, mitochondrial dysfunction, oxidative stress, inflammatory responses. Current pharmacological strategies often encounter obstacles in treating effectively, primarily due to challenges BBB penetration, inadequate target site accumulation, off-target toxicity. Versatile hydrogels nanoparticles offer potential solutions these limitations. This review discusses recent progress utilizing for treatment over the past 5 years, highlighting their relevance underlying pathophysiology. Hydrogels demonstrate substantial promise addressing injury, providing broad spectrum future therapeutic opportunities.

Язык: Английский

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Traumatic Brain Injury Recovery with Photobiomodulation: Cellular Mechanisms, Clinical Evidence, and Future Potential

Cells, Год журнала: 2024, Номер 13(5), С. 385 - 385

Опубликована: Фев. 23, 2024

Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI’s heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial dysfunction, oxidative stress, persistent neuroinflammation. The objective of this study analyze transcranial photobiomodulation (PBM), employs specific red near-infrared light wavelengths modulate brain functions, as promising therapy address pathophysiology in single intervention. reviews the feasibility therapy, firstly by synthesizing PBM’s cellular mechanisms with each identified pathophysiological aspect. outcomes human clinical studies are then reviewed. findings support potential for treating TBI, notwithstanding variations parameters such wavelength, power density, dose, source positioning, pulse frequencies. Emerging data indicate that these plays role outcomes. Additionally, new research into effects on electrical properties polymerization dynamics neuronal microstructures, like microtubules tubulins, provides insights future parameter optimization. In summary, PBM represents multifaceted therapeutic intervention TBI vast may be fulfilled optimizing parameters. Future should investigate parameters, possible incorporating artificial intelligence.

Язык: Английский

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The recent two decades of traumatic brain injury: a bibliometric analysis and systematic review

International Journal of Surgery, Год журнала: 2024, Номер unknown

Опубликована: Апрель 11, 2024

Background: Traumatic brain injury (TBI) is a serious public health burden worldwide, with mortality rate of 20%-30%; however, reducing the incidence and rates TBI remains major challenge. This study provides multidimensional analysis to explore potential breakthroughs in over past two decades. Materials Methods: We used bibliometric Latent Dirichlet Allocation (LDA) analyses analyze publications focusing on published between 2003 2022 from Web Science Core Collection (WOSCC) database identify core journals collaborations among countries/regions, institutions, authors, research trends. Results: Over 20 years, 41,545 articles 3,043 were included, 12,916 authors 20,449 institutions across 145 countries/regions. The annual number has increased ten-fold compared previous publications. revealed that high-income countries, especially United States, have significant influence. Collaboration was limited several LDA results indicated hotspots included four main areas: “Clinical finding”, “Molecular mechanism”, “Epidemiology”, “Prognosis”. Epidemiological consistently recent years. Through epidemiological topic analysis, etiology shifted traffic accidents falls demographically aging society. Conclusion: decades, developed rapidly, its epidemiology received increasing attention. Reducing preventive perspective emerging as trend alleviate future social burden; therefore, might bring TBI.

Язык: Английский

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The neuroprotective potential of phytochemicals in traumatic brain injury: mechanistic insights and pharmacological implications

Frontiers in Pharmacology, Год журнала: 2024, Номер 14

Опубликована: Янв. 4, 2024

Traumatic brain injury (TBI) leads to damage, comprising both immediate primary damage and a subsequent cascade of secondary mechanisms. The results in localized while the initiates inflammatory responses, followed by disruption blood-brain barrier, infiltration peripheral blood cells, edema, release various immune mediators, including chemotactic factors interleukins. TBI disrupts molecular signaling, cell structures, functions. In addition physical tissue such as axonal injuries, contusions, haemorrhages, interferes with functioning, impacting cognition, decision-making, memory, attention, speech capabilities. Despite deep understanding pathophysiology TBI, an intensive effort evaluate underlying mechanisms effective therapeutic interventions is imperative manage repercussions TBI. Studies have commenced explore potential employing natural compounds for These are characterized their low toxicity limited interactions conventional drugs. Moreover, many demonstrate capacity target aspects process. While our there urgent need mitigate its consequences. Here, we aimed summarize mechanism action role phytochemicals against progression. This review discusses implications phytonutrients addresses consequences addition, highlighted roles emerging promising candidates intervention highlights neuroprotective mechanistic approach. Furthermore, efforts focused on mechanisms, providing better therapeutics.

Язык: Английский

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Effect of low fibrinogen level on in-hospital mortality and 6-month functional outcome of TBI patients, a single center experience

Neurosurgical Review, Год журнала: 2024, Номер 47(1)

Опубликована: Фев. 28, 2024

Язык: Английский

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Mortality Predictors for Adult Patients with Mild-to-Moderate Traumatic Brain Injury: A Literature Review

Neurology International, Год журнала: 2024, Номер 16(2), С. 406 - 418

Опубликована: Апрель 5, 2024

Traumatic brain injuries (TBIs) represent a significant public health concern, with mild-to-moderate cases comprising substantial portion of incidents. Understanding the predictors mortality among adult patients TBIs is crucial for optimizing clinical management and improving outcomes. This literature review examines existing research to identify analyze in this patient population. Through comprehensive peer-reviewed articles studies, key prognostic factors, such as age, Glasgow Coma Scale (GCS) score, presence intracranial hemorrhage, pupillary reactivity, coexisting medical conditions, are explored. Additionally, investigates role advanced imaging modalities, biomarkers, scoring systems predicting following TBI. By synthesizing findings from diverse aims provide clinicians researchers valuable insights into factors influencing outcomes TBI, thus facilitating more informed decision making targeted interventions practice.

Язык: Английский

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Multifocal motor neuropathy as a mimic of amyotrophic lateral sclerosis: Serum neurofilament light chain as a reliable diagnostic biomarker

Muscle & Nerve, Год журнала: 2024, Номер 69(4), С. 422 - 427

Опубликована: Фев. 9, 2024

Abstract Introduction/Aims The clinical presentation of multifocal motor neuropathy (MMN) may mimic early amyotrophic lateral sclerosis (ALS) with predominant lower neuron (LMN) involvement, posing a diagnostic challenge. Both diseases have specific treatments and prognoses, highlighting the importance diagnosis. aim this study was to assess value serum neurofilament light chain (NfL) in differentiating MMN from LMN dominant ALS. Methods NfL measured n = 37 patients age‐ sex‐matched ALS, determine accuracy. Clinical demographic data were obtained at time sampling. Results Serum concentration significantly compared ALS (mean 20.7 pg/mL vs. 59.4 pg/mL, p < .01). demonstrated good discriminating two groups (AUC 0.985 [95% CI 0.963–1.000], sensitivity 94.6%, specificity 100%, cut‐off 44.00 pg/mL). Discussion could be helpful tool those whom electrophysiological examinations remain inconclusive process.

Язык: Английский

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Bioactive hydrogel synergizes neuroprotection, macrophage polarization, and angiogenesis to improve repair of traumatic brain injury

Materials Today Bio, Год журнала: 2024, Номер 29, С. 101335 - 101335

Опубликована: Ноя. 12, 2024

Traumatic brain injury (TBI) can lead to severe neurotrauma, leading long-term cognitive decline and even death. Massive neuronal loss excessive neuroinflammation are critical issues in the treatment of secondary TBI. To tackle these challenges, we developed a GelMA CSMA hydrogel loaded with Erythropoietin (EPO) Interleukin-4 (IL-4), named GC/I/E. By directly loading EPO, rapid neuroprotection angiogenesis were achieved. Meanwhile, by Mesoporous silica nanoparticles (MSNs) IL-4 (MSN@IL-4), sustained inflammation modulation during was attained.

Язык: Английский

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Exploring Azithromycin’s Neuroprotective Role in Traumatic Brain Injury: Insights into Cognitive and Motor Recovery and Neuroinflammatory Modulation

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 115 - 115

Опубликована: Янв. 16, 2025

Traumatic brain injury (TBI) is a leading cause of mortality worldwide and often results in substantial cognitive, motor, psychological impairments, triggering oxidative stress, neuroinflammation, neurodegeneration. This study examined the neuroprotective effects azithromycin (AZI) TBI. TBI was induced rats using weight-drop method. Subsequently, received daily intraperitoneal (I.P.) dose AZI (150 mg/kg) for 28 days. Behavioral tests (Morris water maze, rotarod, open field tests) were performed to assess cognitive motor functions. Neurochemical analyses included stress markers (GSH, SOD, MDA, catalase), inflammatory cytokines (TNF-α, IL-1β), apoptotic (caspase-3, Bax, Bcl-2), mitochondrial complexes (complex I, II, III, IV, V), transforming growth factor- beta (TGF-β) as neurofilament marker. Histological evaluations focused on neuronal integrity cortex, hippocampus, striatum. Treatment with significantly facilitated function recovery TBI-affected rats. At molecular level, effectively reduced markers, ameliorated neuroinflammation by decreasing TNF-α, IL-1β, apoptosis, differentially modulated complexes. assessments revealed enhanced fewer pathological changes AZI-treated compared untreated controls. shown interfere several pathways involved TBI's pathophysiology. While preclinical are promising, further studies necessary establish long-term safety efficacy clinical setting. research supports potential re-purposing novel treatment strategy related neurodegenerative disorders.

Язык: Английский

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