A new era of cancer immunotherapy: vaccines and miRNAs

Cancer Immunology Immunotherapy, Год журнала: 2025, Номер 74(5)

Опубликована: Апрель 1, 2025

Язык: Английский

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Aquaporin proteins: A promising frontier for therapeutic intervention in cerebral ischemic injury

Cellular Signalling, Год журнала: 2024, Номер 124, С. 111452 - 111452

Опубликована: Окт. 5, 2024

Язык: Английский

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Microglia Signatures: A Cause or Consequence of Microglia-Related Brain Disorders?

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(20), С. 10951 - 10951

Опубликована: Окт. 11, 2024

Microglia signatures refer to distinct gene expression profiles or patterns of activity that are characteristic microglia. Advances in profiling techniques, such as single-cell RNA sequencing, have allowed us study microglia at a more detailed level and identify unique associated, but not always, with different functional states these cells. Microglial depend on the developmental stage, brain region, specific pathological conditions. By studying signatures, it has been possible gain insights into underlying mechanisms microglial activation begin develop targeted therapies modulate microglia-mediated immune responses CNS. Historically, first two coincide M1 pro-inflammatory M2 anti-inflammatory phenotypes. The one includes upregulation genes CD86, TNF-α, IL-1β, iNOS, while second may involve like CD206, Arg1, Chil3, TGF-β. However, long known many phenotypes exist between M2, likely corresponding signatures. Here, we discuss their association, if any, neurodegenerative pathologies other disorders.

Язык: Английский

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Brain distribution study of [14C]-Riluzole following intranasal administration in mice

International Journal of Pharmaceutics, Год журнала: 2025, Номер 670, С. 125195 - 125195

Опубликована: Янв. 8, 2025

Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery enhance CNS riluzole (RLZ), standard ALS which is subject blood-brain barrier efflux mechanisms. Additionally, impact elacridar (ELC), an pump inhibitor, on IN RLZ bioavailability was examined. To quantify vivo mice, [14C]-RLZ synthesised using optimised one-pot method. yield 21.3 ± 3.4 %, measured by High Performance Liquid Chromatography (HPLC), with specific activity 40.4 3.9 µCi/mg HPLC liquid scintillation counting. synthesis verified proton nuclear magnetic resonance (1H NMR), chromatography-mass spectrometry. (5 mg/kg) produced double maximum brain levels (1.11 0.34 % Injected Dose (ID)/brain) at 30 min as oral mg/kg). The uptake liver reduced half for administration compared administration. Intravenous ELC substantially increased 3.52 0.62 ID/g 60 post-administration, 1.87 0.33 absence inhibitor. However, concentrations were also observed blood. These results indicate that enhances targeting reduces accumulation route. Brain enhanced further ELC, although not selectively or blood observed. Further metabolic research Chromatography-Mass spectrometry (LC-MS) NMR along excretion studies are warranted more comprehensive understanding pharmacokinetics RLZ/ELC. employing suitable animal models crucial RLZ's effects progression, mechanism action, efficacy, side aid development.

Язык: Английский

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Unveiling Acid-Sensing Ion Channels (ASICs) in Neurodegeneration: Implications for Disease Pathogenesis and Therapeutic Strategies

Current Pharmacology Reports, Год журнала: 2025, Номер 11(1)

Опубликована: Март 11, 2025

Язык: Английский

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Revenge Unraveling the Fortress: Exploring Anticancer Drug Resistance Mechanisms in BC for Enhanced Therapeutic Strategies

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104707 - 104707

Опубликована: Март 1, 2025

Язык: Английский

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Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Апрель 9, 2025

Язык: Английский

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Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies

Life, Год журнала: 2025, Номер 15(4), С. 647 - 647

Опубликована: Апрель 14, 2025

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of upper and lower motor neurons, leading to muscle atrophy, paralysis, respiratory failure. This comprehensive review synthesizes current knowledge on ALS pathophysiology, clinical heterogeneity, diagnostic frameworks, evolving therapeutic strategies. Mechanistically, arises from complex interactions between genetic mutations (e.g., in C9orf72, SOD1, TARDBP (TDP-43), FUS) dysregulated cellular pathways, including impaired RNA metabolism, protein misfolding, nucleocytoplasmic transport defects, prion-like propagation toxic aggregates. Phenotypic manifesting as bulbar-, spinal-, or respiratory-onset variants, complicates its early diagnosis, which thus necessitates rigorous application revised El Escorial criteria emerging biomarkers such neurofilament light chain. Clinically, intersects with frontotemporal dementia (FTD) up 50% cases, driven shared TDP-43 pathology C9orf72 hexanucleotide expansions. Epidemiological studies have revealed lifetime risk 1:350, male predominance (1.5:1) peak onset 50 70 years. Disease progression varies widely, median survival 2–4 years post-diagnosis, underscoring urgency for intervention. Approved therapies, riluzole (glutamate modulation), edaravone (antioxidant), tofersen (antisense oligonucleotide), offer modest benefits, while dextromethorphan/quinidine alleviates pseudobulbar affect. Non-pharmacological treatment advances, non-invasive ventilation (NIV), prolong 13 months improve quality life, particularly bulb-involved patients. Multidisciplinary care—integrating physical therapy, support, nutritional management, cognitive assessments—is critical addressing non-motor symptoms dysphagia, spasticity, sleep disturbances). Emerging therapies show promise preclinical models. However, challenges persist translating insights into universally effective treatments. Ethical considerations, euthanasia end-of-life decision-making, further highlight need patient-centered communication palliative

Язык: Английский

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Unravelling the role of Interleukin-12 in Neuroinflammatory mechanisms: Pathogenic pathways linking Neuroinflammation to neuropsychiatric disorders

International Immunopharmacology, Год журнала: 2025, Номер 156, С. 114654 - 114654

Опубликована: Апрель 27, 2025

Язык: Английский

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Netrin-1: Key Insights in Neural Development and Disorders

Tissue and Cell, Год журнала: 2024, Номер 93, С. 102678 - 102678

Опубликована: Дек. 14, 2024

Язык: Английский

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