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1.
J Am Chem Soc ; 146(9): 6252-6265, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38377559

RESUMO

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.


Assuntos
Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio , Antracenos , Linhagem Celular Tumoral
2.
Front Neurol ; 15: 1336385, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356893

RESUMO

Objective: Dementia is a significant public health concern, and mild cognitive impairment (MCI) serves as a transitional stage between normal aging and dementia. Among the various types of MCI, amnestic MCI (aMCI) has been identified as having a higher likelihood of progressing to Alzheimer's dimension. However, limited research has been conducted on the prevalence of aMCI in China. Therefore, the objective of this study is to investigate the prevalence of aMCI, examine its cognitive characteristics, and identify associated risk factors. Methods: In this cross-sectional study, we investigated a sample of 368 older adults aged 60 years and above in the urban communities of Chengdu, China. The participants underwent a battery of neuropsychological assessments, including the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), Auditory Verbal Learning Test (AVLT), Wechsler's Logical Memory Task (LMT), Boston Naming Test (BNT) and Trail Making Test Part A (TMT-A). Social information was collected by standard questionnaire. Multiple logistic regression analysis was utilized to screen for the risk and protective factors of aMCI. Results: The data analysis included 309 subjects with normal cognitive function and 59 with aMCI, resulting in a prevalence of 16.0% for aMCI. The average age of participants was 69.06 ± 7.30 years, with 56.0% being females. After controlling for age, gender and education, the Spearman partial correlation coefficient between various cognitive assessments and aMCI ranged from -0.52 for the long-term delayed recall scores in AVLT to 0.19 for the time-usage scores in TMT-A. The results indicated that all cognitive domains, except for naming scores (after semantic cue of BNT) and error quantity (in TMT-A), showed statistically significant associations with aMCI. Furthermore, the multiple logistic regression analysis revealed that older age (OR = 1.044, 95%CI: 1.002~1.087), lower educational level, and diabetes (OR = 2.450, 95%CI: 1.246~4.818) were risk factors of aMCI. Conclusion: This study found a high prevalence of aMCI among older adults in Chengdu, China. Individuals with aMCI exhibited lower cognitive function in memory, language, and executive domains, with long-term delayed recall showing the strongest association. Clinicians should prioritize individuals with verbal learning and memory difficulties, especially long-term delayed recall, in clinical practice.

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