Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(4), P. 534 - 544

Published: Jan. 2, 2024

Abstract Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated a chitosan/glucose polymer to produce responsive oral nanoformulation. This formulation pH responsive, insoluble in acidic environments and shows increased absorption human duodenum explants Caenorhabditis elegans at neutral pH. The sensitive glucosidase enzymes trigger release. It found that the distributes liver mice rats after administration promotes dose-dependent reduction blood glucose without promoting hypoglycaemia or weight gain diabetic rodents. Non-diabetic baboons also show glucose. No biochemical haematological toxicity adverse events were observed mice, non-human primates. demonstrates orally control episodes.

Language: Английский

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Alzheimer’s Disease Treatment: The Search for a Breakthrough

Medicina, Journal Year: 2023, Volume and Issue: 59(6), P. 1084 - 1084

Published: June 4, 2023

As the search for modalities to cure Alzheimer's disease (AD) has made slow progress, research now turned innovative pathways involving neural and peripheral inflammation neuro-regeneration. Widely used AD treatments provide only symptomatic relief without changing course. The recently FDA-approved anti-amyloid drugs, aducanumab lecanemab, have demonstrated unclear real-world efficacy with a substantial side effect profile. Interest is growing in targeting early stages of before irreversible pathologic changes so that cognitive function neuronal viability can be preserved. Neuroinflammation fundamental feature involves complex relationships among cerebral immune cells pro-inflammatory cytokines, which could altered pharmacologically by therapy. Here, we an overview manipulations attempted pre-clinical experiments. These include inhibition microglial receptors, attenuation enhancement toxin-clearing autophagy. In addition, modulation microbiome-brain-gut axis, dietary changes, increased mental physical exercise are under evaluation as ways optimize brain health. scientific medical communities work together, new solutions may on horizon or halt progression.

Language: Английский

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Nanoligomers targeting NF-κB and NLRP3 reduce neuroinflammation and improve cognitive function with aging and tauopathy

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: July 27, 2024

Abstract Neuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer’s disease, which is characterized by the aggregation of pathological tau. One major driver both age- tau-associated neuroinflammation NF-κB NLRP3 signaling axis. However, current treatments targeting or may have adverse/systemic effects, most not been clinically translatable. In this study, we tested efficacy a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically for reducing improving old (aged 19 months) wildtype mice, rTg4510 tau pathology mice 2 months). We found that 4 weeks NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles improved cognitive-behavioral mice. These effects Nanoligomers were also associated with glial cell activation pathology, favorable changes transcriptome signatures glia-associated inflammation (reduced) neuronal health (increased), positive systemic effects. Collectively, our results provide basis future translational studies brain, perhaps using Nanoligomers, inhibit improve neurodegeneration.

Language: Английский

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Associations of liver dysfunction with incident dementia, cognition, and brain structure: A prospective cohort study of 431 699 adults

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 168(1), P. 26 - 38

Published: Oct. 13, 2023

Abstract The relationship between liver dysfunction and dementia has been researched extensively but remains poorly understood. In this study, we investigate the longitudinal cross‐sectional associations function diseases risk of incident dementia, impaired cognition, brain structure abnormalities using Cox proportion hazard model linear regression model. 431 699 participants with a mean 8.65 (standard deviation [SD] 2.61) years follow‐up were included from UK Biobank; 5542 all‐cause (ACD), 2427 Alzheimer's disease (AD), 1282 vascular (VaD) cases documented. We observed that per SD decreases in alanine transaminase (ALT; ratio [HR], 0.917; P FDR <0.001) increases aspartate aminotransferase (AST; HR, 1.048; = 0.010), AST to ALT (HR, 1.195; <0.001), gamma‐glutamyl transpeptidase (GGT; 1.066; alcoholic (ALD; 2.872; fibrosis cirrhosis 2.285; 0.002), being significantly associated higher ACD. Restricted cubic spline models identified strong U‐shaped association Alb ACD ( nonlinear <0.05). Worse cognition was positively correlated AST, ratio, direct bilirubin (DBil), GGT; negatively ALT, Alb, total (TBil); ALD Moreover, changes GGT, altered cortical subcortical regions, including hippocampus, amygdala, thalamus, pallidum, fusiform sensitivity analysis, metabolic dysfunction‐associated steatotic (MASLD) changes. Our findings provide substantial evidence may be an important factor for dementia. Early intervention unhealthy help prevent cognitive impairment incidence.

Language: Английский

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Nanoligomers targeting NF-κB and NLRP3 reduce neuroinflammation and improve cognitive function with aging and tauopathy

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

Published: Feb. 7, 2024

ABSTRACT Neuroinflammation contributes to impaired cognitive function in brain aging and neurodegenerative disorders like Alzheimer’s disease, which is characterized by the aggregation of pathological tau. One major driver both age- tau-associated neuroinflammation NF-κB NLRP3 signaling axis. However, current treatments targeting or may have adverse/systemic effects, most not been clinically translatable. In this study, we tested efficacy a novel, nucleic acid therapeutic (Nanoligomer) cocktail specifically for reducing improving old (aged 19 months) wildtype mice, rTg4510 tau pathology mice 2 months). We found that 4 weeks NF-κB/NLRP3-targeting Nanoligomer treatment strongly reduced neuro-inflammatory cytokine profiles improved cognitive-behavioral mice. These effects Nanoligomers were also associated with glial cell activation pathology, favorable changes transcriptome signatures glia-associated inflammation (reduced) neuronal health (increased), positive systemic effects. Collectively, our results provide basis future translational studies brain, perhaps using Nanoligomers, inhibit improve neurodegeneration.

Language: Английский

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Liver function and Alzheimer's brain pathologies: A longitudinal study

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: 12(1), P. 100012 - 100012

Published: Jan. 1, 2025

The neuropathological links underlying the association between changes in liver function and AD have not yet been clearly elucidated. We aimed to examine relationship markers longitudinal Alzheimer's disease (AD) core pathologies. Data from Korean Brain Aging Study for Early Diagnosis Prediction of Disease, a cohort study initiated 2014, were utilized. Community memory clinic setting. Three hundred forty-seven older adults. Participants underwent baseline 2-year follow-up evaluations, including assessments various brain imaging techniques, such as amyloid tau PET, FDG-PET, MRI). Liver indicators [alanine aminotransferase (ALT), aspartate (AST), total bilirubin] examined exposure variables. Higher ALT levels associated with greater increase beta-amyloid deposition over 2 years [β = 0.166, Bonferroni-corrected P (P findings suggest possible link lower accumulation pathologies brain. These results also support possibility that liver-brain axis could be potential target therapeutic or preventive strategies against AD.

Language: Английский

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BENEFICIOS Y RETOS DE LA INTEGRACIÓN DE LA NANOTECNOLOGÍA EN LA MEDICINA: UNA REVISIÓN SISTEMÁTICA

MOMENTO, Journal Year: 2025, Volume and Issue: 70, P. 59 - 76

Published: Jan. 30, 2025

La medicina nanotecnológica ha propiciado progresos importantes, proporcionando soluciones revolucionarias para el diagnóstico y tratamiento de enfermedades, aunque aún existen retos, como asegurar su seguridad escalabilidad. Esta revisión metódica examina las últimas aplicaciones la nanotecnología en personalizada, centrándose habilidad elaborar tratamientos acuerdo con particularidades cada individuo. Las nanopartículas se distinguen por incrementar exactitud administración medicamentos, disminuyendo los efectos adversos, particularmente terapias cáncer. Adicionalmente, tecnologías tales biosensores dispositivos imagen a nanoescala mejoran diagnósticos, aumentando oportunidades éxito ámbito clínico. En regeneración e ingeniería tejidos, nanomateriales, al replicar matriz extracelular, promueven celular creación órganos sintéticos. No obstante, todavía persisten preocupaciones respecto biocompatibilidad estos materiales, dado que no entendido completamente interacción sistemas biológicos ni posibles impactos futuro. producción supervisión calidad nanomateriales son costosas técnicamente complicadas, lo obstaculiza accesibilidad Además, ausencia normativas definidas demora puesta marcha estas innovaciones. solo aspira reunir éxitos fundamentales, sino también impulsar propagación del saber América Latina, donde acceso datos científicos especializados es restringido, impactando alumnos investigadores. Con más estudios sobre interacciones biológicas normalización procesos, podría establecerse un instrumento cambio medicina, mejorando potenciando salud pública región.

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Albumin Promotes the Absorption of Pb in the Intestine: A Possible Pathway Linking to the High Absorption of Pb in Adolescence

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

High blood lead (Pb) levels have long been a significant environmental issue affecting the health and development of adolescents. However, main reasons behind this phenomenon, especially absorption transportation processes Pb in intestine, not elucidated, which is major barrier to reducing human body, In study, we explored intestinal process rats different ages at environmentally relevant concentrations. The results indicated that albumin serves as crucial mediating role gradually decreasing with age (aging). Next, experiments induced senescence addition confirmed binding facilitates Pb. Furthermore, low-protein diet can reduce by approximately 50%, possibly due decrease synthesis resulting from reduced raw materials. Collectively, these findings reveal potential for high adolescents, elucidate influence on transportation, provide an alternative pathway regulating adolescents ambient

Language: Английский

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Data‐driven discovery of midlife cardiometabolic profile associated with incident early‐onset and late‐onset dementia

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Cardiometabolic risk factors have been associated with the of late-onset dementia. However, evidence regarding early-onset dementia was inconsistent, and impact clustered cardiometabolic unclear. We aimed to investigate associations profiles incident Among 289 494 UK Biobank participants, cluster analysis built on 12 common markers. Analyses were performed those aged <65 years at baseline (n = 249 870) for ≥65 end follow-up 191 213) During a median 14.1 years, 279 cases 3167 documented. five clusters identified (cluster 1 [obesity-dyslipidemia pattern], 2 [high blood pressure 3 liver enzymes 4 [inflammation pattern] 5 [relatively healthy pattern]), significantly higher risks both dementia; however, estimate (hazard ratio 2.58, 95% CI 1.61-4.14) larger than that (1.36, 1.09-1.71). Cluster 1.39, 1.13-1.72). No significant interactions observed between apolipoprotein E ε4 genotype. patterns characterised by relatively high enzyme levels or systemic inflammation increased Identification high-risk subgroups according distinct might help develop more precise strategies prevention regardless (APOE) status.

Language: Английский

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Hepatopancreatic metabolic disorders and their implications in the development of Alzheimer's disease and vascular dementia

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102250 - 102250

Published: Feb. 26, 2024

Language: Английский

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