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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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Dynamic contrast-enhanced ultrasound (DCE-US) has been proposed as a powerful tool for cancer diagnosis by estimation of perfusion and dispersion parameters reflecting angiogenic vascular changes. This work was aimed at identifying which vascular features are reflected by the estimated perfusion and dispersion parameters through comparison with acoustic angiography (AA). AA is a high-resolution technique that allows quantification of vascular morphology. Three-dimensional AA and 2-D DCE-US bolus acquisitions were used to monitor the growth of fibrosarcoma tumors in nine rats. AA-derived vascular properties were analyzed along with DCE-US perfusion and dispersion to investigate the differences between tumor and control and their evolution in time. AA-derived microvascular density and DCE-US perfusion exhibited good agreement, confirmed by their spatial distributions. No vascular feature was correlated with dispersion. Yet, dispersion provided better cancer classification than perfusion. We therefore hypothesize that dispersion characterizes vessels that are smaller than those visible with AA.  相似文献   
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Changes in resting energy expenditure (REE) of cancer patients vary depending on type of tumor, treatment time point and kind of treatment. Little is known about REE of acute leukemia adult patients after treatment, especially with results related to body weight or fat free mass (FFM). This study aimed to assess changes in REE of acute leukemia adult patients before and after the first remission induction. Evaluation of REE was performed by indirect calorimetry and predicted REE was calculated by Harris-Benedict equation. Weight and height were measured and compared to a control group of healthy individuals. FFM was assessed by bioelectrical impedance for adjusting REE values. We evaluated 18 patients and 26 healthy individuals. At diagnosis, patients presented REE, REE/weight, and REE/FFM higher than the controls. Reductions of REE, REE/weight, and REE/FFM were also observed in patients after the first cycle of chemotherapy. The predicted REE for the patients group showed significant lower value compared with measured REE. Before the first cycle of chemotherapy REE was increased but undergoes a reduction after treatment, reaching values similar to the controls. For predictive Harris-Benedict equation, stress factors should be added to avoid underestimation of REE before and after chemotherapy.  相似文献   
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