A Historical Review of Brain Drug Delivery

Pharmaceutics, Год журнала: 2022, Номер 14(6), С. 1283 - 1283

Опубликована: Июнь 16, 2022

The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a for syphilis, salvarsan, did not enter brain, due to presence blood–brain barrier (BBB). Owing restricted transport across BBB, FDA-approved drugs CNS have been generally limited lipid-soluble small molecules. Drugs do cross BBB can be re-engineered on endogenous carrier-mediated and receptor-mediated systems, which were identified during 1970s–1980s. By 1990s, multitude technologies emerged, including trans-cranial delivery, CSF disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, biologics. advantages limitations each these are critically reviewed.

Язык: Английский

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Potential Impact of Prosthetic Biomaterials on the Periodontium: A Comprehensive Review

Molecules, Год журнала: 2023, Номер 28(3), С. 1075 - 1075

Опубликована: Янв. 20, 2023

The success of a prosthetic treatment is closely related to the periodontal health individual. aim this article was review and present importance restorative materials on condition periodontium, changes that occur in composition subgingival microbiota levels inflammatory markers gingival crevicular fluid. Articles influence different proinflammatory cytokines were searched for using keywords "prosthetic biomaterials", "fixed prosthesis", "periodontal health", "subgingival microbiota", biomarkers" "gingival fluid" PubMed/Medline, Science Direct, Scopus Google Scholar. type material used prosthesis fabrication together with poor marginal internal fit can result microbiota, as well increased accumulation retention dentobacterial plaque, thus favoring development disease failure. Biological have helped understand response tissues main purpose improving their clinical application patients who need them. Metal-free ceramic prostheses induce lower regardless method; however, use CAD/CAM systems recommended fabrication. In addition, it presumed metal-ceramic cause producing more dysbiotic biofilm higher prevalence periodontopathogenic bacteria, which may further favor deterioration.

Язык: Английский

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Systems-level computational modeling in ischemic stroke: from cells to patients

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Июль 2, 2024

Ischemic stroke, a significant threat to human life and health, refers class of conditions where brain tissue damage is induced following decreased cerebral blood flow. The incidence ischemic stroke has been steadily increasing globally, its disease mechanisms are highly complex involve multitude biological at various scales from genes all the way body system that can affect onset, progression, treatment, prognosis. To complement conventional experimental research methods, computational systems biology modeling integrate describe pathogenic across multiple help identify emergent modulatory principles drive progression recovery. In addition, by running virtual experiments trials in computers, these models efficiently predict evaluate outcomes different treatment methods thereby assist clinical decision-making. this review, we summarize current application systems-level field multiscale mechanism-based, physics-based omics-based perspectives discuss how modeling-driven frameworks deliver insights for future drug development.

Язык: Английский

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Digging into the Role of Inflammatory Biomarkers in Sudden Sensorineural Hearing Loss Diagnosis and Prognosis: A Systematic Review and Meta-Analysis

Medicina, Год журнала: 2022, Номер 58(7), С. 963 - 963

Опубликована: Июль 20, 2022

Background and Objectives: Sudden Sensorineural Hearing Loss (SSNHL) is a quite common clinical finding in otolaryngology. Most cases are classified as idiopathic there dearth of information on factors able to predict the response treatment hearing recovery. The main aim this systematic review meta-analysis was assess critically discuss role circulating inflammatory biomarkers SSNHL. Materials Methods: A search conducted English literature published between 1 January 2009 7 July 2022 Pubmed, Scopus, Web Science, ScienceDirect, Cochrane following PRISMA guidelines. Results: total 256 titles were retrieved from search. After full-text screening application inclusion/exclusion criteria, 13 articles included. Twelve out thirteen studies reported significant differences values SSNHL patients, which Tumor Necrosis Factor alpha (TNF-α) C-reactive Protein (CRP) most analyzed. Our for CRP’s mean groups vs. controls showed significantly higher CRP levels with pooled overall difference 1.07; confidence interval (CI) at 95%: 0.03; 2.11. For TNF-α, discordant results found: three patients controls, whereas other investigations lower (overall 1.97; 95% CI: −0.90; 4.84). high between-study heterogeneity found. Conclusions: This pointed that, although exists growing field circulatory identification SSNHL, low quality evidence. resulted be than while TNF-α more heterogeneous behavior. data herein needs confirmed well-designed prospective multicenter randomized studies, objective improving outcome thereby reducing social burden loss.

Язык: Английский

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Selected Mediators of Inflammation in Patients with Acute Ischemic Stroke

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(18), С. 10614 - 10614

Опубликована: Сен. 13, 2022

During a stroke, series of biochemical and metabolic changes occur which eventually lead to the death cells by necrosis or apoptosis. This is multi-stage process involving oxidative stress an inflammatory response from first signs occlusion blood vessel until late stages regeneration healing ischemic tissues. The purpose research was assess concentration pro-inflammatory cytokines IL-6 TNF-α in serum patients with stroke (AIS) investigate their role as new markers predicting functional prognosis after thrombolytic therapy. researches have shown that concentrations measured biomarkers were higher compared control group. Serum levels THF-α before initiation intravenous thrombolysis lower subgroup favourable result (mRS: 0−2 pts) group unfavourable 3−6 pts). A positive correlation found between AIS during <4.5 h on one day onset means increases increase concentration. It has also been acute phase seventh days, onset, associated poorer early treated thrombolysis. relationship level subacute severity neurological deficit. investigated may be prognostic factor treatment AIS.

Язык: Английский

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Inflammatory markers and the risk of idiopathic sudden sensorineural hearing loss: A Mendelian randomization study

Frontiers in Neurology, Год журнала: 2023, Номер 14

Опубликована: Фев. 22, 2023

Background Observational studies suggest that inflammatory markers may increase the risk of idiopathic sudden sensorineural hearing loss (ISSHL). However, causal relationship between two has not been established. We sought to assess possible effect several genetically predicted and ISSHL by Mendelian random (MR) analysis. Methods extracted single nucleotide polymorphisms (SNPs) associated with C-reactive protein (CRP), Tumor necrosis factor-α (TNF-α), fibrinogen from abstract data European Individual Large genome-wide association (GWAS). Genetic for were obtained FinnGen study ( n = 196,592). Effect estimates assessed using inverse variance weighting (IVW) as primary method. Sensitivity analyses performed weighted median, MR-Egger, MR-PRESSO evaluate heterogeneity pleiotropy. Results In random-effects IVW approach, there was a significant genetic susceptibility CRP levels (OR 1.23, 95% CI 1.02–1.49, P 0.03). contrast, TNF-α risked factors 1.14, 0.88–1.49, 0.30; OR 0.74, 0.07–7.96, 1.05, 0.88–1.25, 0.59). All above results consistent after validation different randomization methods sensitivity analyses. Conclusion This provides evidence is factor ISSHL, while do Introduction.

Язык: Английский

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Circulating PIWI-Interacting RNAs in Acute Ischemic Stroke Patients

Non-coding RNA Research, Год журнала: 2025, Номер 11, С. 294 - 302

Опубликована: Янв. 15, 2025

Язык: Английский

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Predicting the risk of ischemic stroke in patients with atrial fibrillation using heterogeneous drug–protein–disease network-based deep learning

APL Bioengineering, Год журнала: 2025, Номер 9(2)

Опубликована: Апрель 3, 2025

Current risk assessment models for predicting ischemic stroke (IS) in patients with atrial fibrillation (AF) often fail to account the effects of medications and complex interactions between drugs, proteins, diseases. We developed an interpretable deep learning model, AF-Biological-IS-Path (ABioSPath), predict one-year IS AF by integrating drug–protein–disease pathways real-world clinical data. Using a heterogeneous multilayer network, ABioSPath identifies mechanisms drug actions propagation comorbid By combining mechanistic patient-specific characteristics, model provides individualized assessments potential molecular involved. utilized electronic health record data from 7859 patients, collected January 2008 December 2009 across 43 hospitals Hong Kong. outperformed baseline all evaluation metrics, achieving AUROC 0.7815 (95% CI: 0.7346–0.8283), positive predictive value 0.430, negative 0.870, sensitivity 0.500, specificity 0.885, average precision 0.409, Brier score 0.195. Cohort-level analysis identified key such as CRP, REN, PTGS2, within most common pathways. Individual-level further highlighted importance PIK3/Akt cytokine chemokine signaling risks associated less-studied drugs like prochlorperazine maleate. offers robust, data-driven approach prediction, requiring only routinely without need costly biomarkers. Beyond IS, has applications screening other diseases, enhancing patient care, providing insights development.

Язык: Английский

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Research progress on the mechanism of action and clinical application of remote ischemic post-conditioning for acute ischemic stroke

Clinical Neurology and Neurosurgery, Год журнала: 2024, Номер 244, С. 108397 - 108397

Опубликована: Июнь 23, 2024

Язык: Английский

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Tumor Necrosis Factor (TNF)-α-Stimulated Gene 6 (TSG-6): A Promising Immunomodulatory Target in Acute Neurodegenerative Diseases

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 1162 - 1162

Опубликована: Янв. 6, 2023

Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), the first soluble chemokine-binding protein to be identified in mammals, inhibits chemotaxis and transendothelial migration of neutrophils attenuates inflammatory response dendritic cells, macrophages, monocytes, T cells. This immunoregulatory is a pivotal mediator therapeutic efficacy mesenchymal stem/stromal cells (MSC) diverse pathological conditions, including neuroinflammation. However, TSG-6 also constitutively expressed some tissues, such as brain spinal cord, generally upregulated inflammation monocytes/macrophages, astrocytes, vascular smooth muscle fibroblasts. Due its ability modulate sterile inflammation, exerts protective effects degenerative diseases, disorders. Emerging evidence provides insights into potential use peripheral diagnostic and/or prognostic biomarker, especially context ischemic stroke, whereby pathobiological relevance this has been demonstrated patients. Thus, review, we will discuss most recent data on involvement neurodegenerative particularly focusing relevant anti-inflammatory immunomodulatory functions. Furthermore, examine suggesting novel opportunities that can afforded by modulating TSG-6-related pathways neuropathological contexts and, notably, stroke.

Язык: Английский

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