RESUMO
Gold nanorods (AuNRs) have been considered highly compelling materials for early cancer diagnosis and have aroused a burgeoning fascination among the biomedical sectors. By leveraging the versatile tunable optical properties of AuNRs, herein, we have developed a novel tumor-targeted dual-modal nanoprobe (FFA) that exhibits excellent bioluminescence and photoacoustic imaging performance for early tumor diagnosis. FFA has been synthesized by anchoring the recombinant bioluminescent firefly luciferase protein (Fluc) on the folate-conjugated AuNRs via the PEG linker. TEM images and UV-vis studies confirm the nanorod morphology and successful conjugation of the biomolecules to AuNRs. The nanoprobe FFA relies on the ability of the folate module to target the folate receptor-positive tumor cells actively, and simultaneously, the Fluc module facilitates excellent bioluminescent properties in physiological conditions. The success of chemical engineering in the present study enables stronger bioluminescent signals in the folate receptor-positive cells (Skov3, Hela, and MCF-7) than in folate receptor-negative cells (A549, 293T, MCF-10A, and HepG2). Additionally, the AuNRs induced strong photoacoustic conversion performance, enhancing the resolution of tumor imaging. No apparent toxicity was detected at the cellular and mouse tissue levels, manifesting the biocompatibility nature of the nanoprobe. Prompted by the positive merits of FFA, the in vivo animal studies were performed, and a notable enhancement was observed in the bioluminescent/photoacoustic intensity of the nanoprobe in the tumor region compared to that in the folate-blocking region. Therefore, this synergistic dual-modal bioluminescent and photoacoustic imaging platform holds great potential as a tumor-targeted contrast agent for early tumor diagnosis with high-performance imaging information.
Assuntos
Meios de Contraste , Ouro , Medições Luminescentes , Nanotubos , Técnicas Fotoacústicas , Técnicas Fotoacústicas/métodos , Humanos , Nanotubos/química , Ouro/química , Animais , Meios de Contraste/química , Camundongos , Camundongos Nus , Imagem Óptica , Neoplasias/diagnóstico por imagem , Feminino , Luciferases/química , Luciferases/metabolismoRESUMO
BACKGROUND: Epilepsy is a chronic neurological disease characterized by repeated and unprovoked epileptic seizures. Developing disease-modifying therapies (DMTs) has become important in epilepsy studies. Notably, focusing on iron metabolism and ferroptosis might be a strategy of DMTs for epilepsy. Blocking the acid-sensing ion channel 1a (ASIC1a) has been reported to protect the brain from ischemic injury by reducing the toxicity of [Ca2+ ]i . However, whether inhibiting ASIC1a could exert neuroprotective effects and become a novel target for DMTs, such as rescuing the ferroptosis following epilepsy, remains unknown. METHODS: In our study, we explored the changes in ferroptosis-related indices, including glutathione peroxidase (GPx) enzyme activity and levels of glutathione (GSH), iron accumulation, lipid degradation products-malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) by collecting peripheral blood samples from adult patients with epilepsy. Meanwhile, we observed alterations in ASIC1a protein expression and mitochondrial microstructure in the epileptogenic foci of patients with drug-resistant epilepsy. Next, we accessed the expression and function changes of ASIC1a and measured the ferroptosis-related indices in the in vitro 0-Mg2+ model of epilepsy with primary cultured neurons. Subsequently, we examined whether blocking ASIC1a could play a neuroprotective role by inhibiting ferroptosis in epileptic neurons. RESULTS: Our study first reported significant changes in ferroptosis-related indices, including reduced GPx enzyme activity, decreased levels of GSH, iron accumulation, elevated MDA and 4-HNE, and representative mitochondrial crinkling in adult patients with epilepsy, especially in epileptogenic foci. Furthermore, we found that inhibiting ASIC1a could produce an inhibitory effect similar to ferroptosis inhibitor Fer-1, alleviate oxidative stress response, and decrease [Ca2+ ]i overload by inhibiting the overexpressed ASIC1a in the in vitro epilepsy model induced by 0-Mg2+ . CONCLUSION: Inhibiting ASIC1a has potent neuroprotective effects via alleviating [Ca2+ ]i overload and regulating ferroptosis on the models of epilepsy and may act as a promising intervention in DMTs.
Assuntos
Epilepsia , Ferroptose , Fármacos Neuroprotetores , Humanos , Canais Iônicos Sensíveis a Ácido/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Epilepsia/tratamento farmacológico , Ferro/metabolismoRESUMO
OBJECTIVE: This study aimed to estimate the temporal trend of osteoarthritis (OA) burden in China by age, sex, and joint sites from 1990 to 2019 and predict the long-term trend over the next 25 years. METHODS: Using data from the Global Burden of Disease Study 2019, we estimated incident cases, prevalent cases, disability-adjusted life years (DALYs) of OA, and DALYs of OA attributed to high body mass index (BMI), as well as corresponding age-standardized rates (ASRs) for aforementioned indicies. Estimated annual percentage change (EAPC) and Nordpred age-period-cohort model were used to describe temporal trend changes and predict future disease burden. RESULTS: From 1990 to 2019, the ASR of OA incidence increased from 472.53 per 100,000 to 509.84 per 100,000 people (EAPC: 0.36, 95% confidence interval [CI] 0.29-0.44); the ASR of OA prevalence increased from 5,880.58 per 100,000 to 6,330.06 per 100,000 people (EAPC 0.35, 95% CI 0.28-0.42); the ASR of OA DALYs increased from 206.38 per 100,000 to 224.78 per 100,000 people (EAPC 0.40, 95% CI 0.32-0.48). The ASR of OA DALYs attributed to high BMI increased rapidly, especially in men and patients with hip OA. Projections suggest an increasing trend in the incidence, prevalence, and DALYs of OA from 2019 to 2044, with the prevalent cases and DALYs of OA in China expected to increase by approximately 1.5 times over the next 25 years. CONCLUSION: The disease burden of OA has increased in China over the past 30 years and is expected to continue rising over the next 25 years.