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Enrique Luengo Izaskun Buendia Cristina Fernndez‐Mendívil Paula Trigo‐Alonso Pilar Negredo Patrycja Michalska Borja Hernndez‐García Cristina Snchez‐Ramos Juan A. Bernal Tsuneya Ikezu Rafael Len Manuela G. Lpez 《Journal of pineal research》2019,67(1)
Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTauP301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTauP301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD. 相似文献
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Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep
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Flavio Torres Alejandro González‐Candia Camilo Montt Germán Ebensperger Magdalena Chubretovic María Serón‐Ferré Roberto V. Reyes Aníbal J. Llanos Emilio A. Herrera 《Journal of pineal research》2015,58(3):362-373
Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN. 相似文献
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Willy Baccaglini Felipe A. Glina Cristiano Linck Pazeto Luis G. Medina Fernando Korkes Wanderley M. Bernardo Rene Sotelo Sidney Glina Giancarlo Marra Marco Moschini Xavier Cathelineau Rafael Sanchez-Salas 《Clinical genitourinary cancer》2021,19(1):3-11.e1
This meta-analysis focuses on the accuracy of upgrading to clinically significant prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsy (MRI-TB) versus systematic biopsy (SB). We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Literatura Latino Americana em Ciências da Saúde databases through January 2020 for comparative, retrospective/prospective, paired-cohort, and randomized clinical trials with paired comparisons. The population consisted of patients with low-risk PCa in active surveillance with at least 1 index lesion on imaging. We evaluated the quality of evidence by using the Quality Assessment of Diagnostic Accuracy Studies-2 score. Group comparisons considered the differences between the area under the curve summary receiver operating characteristic curve in a 2-tailed method. We also compared the positive predictive value of the best single method (MRI-TB or SB) and the referral study test (combined biopsy, a combination of MRI-TB and SB). The meta-analysis included 6 studies enrolling 741 patients. The pooled sensitivity for the 2 groups was 0.79 (95% confidence interval, 0.74-0.83; I2 = 75%) and 0.67 (95% confidence interval, 0.63-0.74; I2 = 55.4%), respectively. The area under the curve for the MRI-TB and SB groups were 0.99 and 0.92 (P < .001), respectively. The positive predictive value for the MRI-TB and combined biopsy groups were similar. The accumulated evidence suggests better results for MRI-TB compared with SB. Therefore, use of MRI-TB alone may be preferable in patients in active surveillance harboring low-risk PCa. 相似文献
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Del Lama Rafael Silva Candido Raquel Mariana Chiari-Correia Natália Santana Nogueira-Barbosa Marcello Henrique de Azevedo-Marques Paulo Mazzoncini Tinós Renato 《Journal of digital imaging》2022,35(3):446-458
Journal of Digital Imaging - Vertebral Compression Fracture (VCF) occurs when the vertebral body partially collapses under the action of compressive forces. Non-traumatic VCFs can be secondary to... 相似文献
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Miguel A. Sanz Pau Montesinos Haesook T. Kim Guillermo J. Ruiz-Argüelles María S. Undurraga María R. Uriarte Lem Martínez Rafael H. Jacomo Homero Gutiérrez-Aguirre Raul A. M. Melo Rosane Bittencourt Ricardo Pasquini Katia Pagnano Evandro M. Fagundes Edo Vellenga Alexandra Holowiecka Ana J. González-Huerta Pascual Fernández Javier De la Serna Salut Brunet Elena De Lisa José González-Campos José M. Ribera Isabel Krsnik Arnold Ganser Nancy Berliner Raul C. Ribeiro Francesco Lo-Coco Bob L?wenberg Eduardo M. Rego 《Annals of hematology》2015,94(8):1347-1356
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