The Protective Effects of Mogroside V Against Neuronal Damages by Attenuating Mitochondrial Dysfunction via Upregulating Sirtuin3.

Mitochondrial dysfunction and oxidative stress are thought to play a dominant role in the pathogenesis of Parkinson's disease (PD). Mogroside V (MV), extracted from Siraitia grosvenorii, exhibits antioxidant-like activities. The aim of this study was to investigate the function of MV in neuroprotection in PD and to reveal its mechanism of action. To that end, we firstly set up mice models of PD with unilateral striatum injection of 0.25 mg/kg rotenone (Rot) and co-treated with 2.5 mg/kg, 5 mg/kg, and 10 mg/kg MV by gavage. Results showed that Rot-induced motor impairments and dopaminergic neuronal damage were reversed by treatment of 10 mg/kg MV. Then, we established cellular models of PD using Rot-treated SH-SY5Y cells, which were divided into six groups, including control, Rot, and co-enzyme Q10 (CQ10), as well as MV groups, MV25, MV50, and MV100 treated with 25 µM, 50 µM, and 100 µM MV doses, respectively. Results demonstrated that MV effectively attenuates Rot neurotoxicity through a ROS-related intrinsic mitochondrial pathway. MV reduced overproduction of reactive oxygen species (ROS), recovered the mitochondrial membrane potential (MMP), and increased the oxygen consumption rate and adenosine triphosphate (ATP) production in a dose-dependent manner. Hence, treatment with MV led to a reduction in the number of apoptotic cells, as reflected by Annexin-V/propidium iodide co-staining using flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. In addition, the Sirtuin3 (SIRT3) protein level and activity were decreased upon exposure to Rot both in substantia nigra (SN) of mice and SH-SY5Y cells. SIRT3 impairment hyperacetylated a key mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2). MV alleviates SIRT3 and SOD2 molecular changes. However, after successfully inhibiting SIRT3 by its specific inhibitor 3-1H-1, 2, 3-triazol-4-yl pyridine (3TYP), MV was not able to reduce ROS levels, reverse abnormal MMP, or decrease apoptotic cells. Motor impairments and dopaminergic neuronal injury in the SN were alleviated with the oral administration of MV in Rot-treated PD mice, indicating a relationship between protection against defective motility and preservation of dopaminergic neurons. Therefore, we conclude that MV can alleviate Rot-induced neurotoxicity in a PD model, and that SIRT3 may be an important regulator in the protection of MV.

1,2-Dimyristoyl-sn-glycero-3-phosphocholine promotes the adhesion of nanoparticles to bio-membranes and transport in rat brain.

1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) coated on the surface of superparamagnetic iron oxide nanoparticles (SPIONs) has advantages in neurotherapy and drug delivery. In this study, the surface of polyvinylpyrrolidone (PVP)-SPIONs was modified with DMPC, then PVP-SPIONs and DMPC/PVP-SPIONs were co-incubated with rat adrenal pheochromocytoma (PC-12) cells to observe the effect of DMPC on the distribution of SPIONs in cells, and further PVP-SPIONs and DMPC/PVP-SPIONs were implanted into the substantia nigra of Sprague-Dawley (SD) rats by stereotaxic injection, and the brain tissues were removed at both twenty-four hours and seven days after injection. The distribution and transport of nanoparticles in the substantia nigra in vivo were explored in these different time periods. The results show that DMPC/PVP-SPIONs were effectively distributed on the membranes of axons, as well as dendritic and myelin sheaths. The attachment of nanoparticles to bio-membranes in the brain could result from similar phospholipid structures of DMPC and the membranes. In addition, DMPC/PVP-SPIONs were transported in the brain faster than those without DMPC. In vitro experiments found that DMPC/PVP-SPIONs enter cells more easily. These characteristics of iron oxide nanoparticles that are modified by phospholipids lead to potential applications in drug delivery or activating neuron membrane channels.

Correction to: miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1.

PURPOSE: Whether autophagy plays a key role in thyroxine-induced cardiomyocyte hypertrophy, and whether the role of autophagy in thyroxine-induced cardiomyocyte hypertrophy is related to targeting of Beclin-1 by miR-762 remains unclear. This research focused on testing these two hypotheses. Importantly, the results of this study will help us better understand the molecular mechanisms of thyroxine-induced cardiomyocyte hypertrophy. METHODS: In vivo and in vitro, RT-PCR, western blot, and dual luciferase reporter assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, Masson staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. RESULTS: Our results showed that in vivo, serum TT3, TT4, and heart rate were significantly upregulated in the T4 group compared with the control group. Moreover, the surface area of cardiomyocytes was significantly increased in the T4 group, and the structural disorder was accompanied by obvious hyperplasia of collagen fibers. The expression of ANP, and ß-MHC was significantly upregulated in the T4 group. In addition, LC3 II/LC3 I, Beclin-1 and the count of autophagic vacuoles were significantly upregulated, but miR-762 was significantly downregulated in the T4 group compared to the control group. Subsequently, a dual luciferase reporter assay suggested that Beclin-1 was the target gene of miR-762. In vitro, the results for the T3 group were consistent with the results for the T4 group. Furthermore, cardiomyocyte hypertrophy and autophagic activity were attenuated in the T3 + miR-762 mimic group compared with the T3 group. In contrast, cardiomyocyte hypertrophy and autophagic activity were aggravated in the T3 + miR-762 inhibitor group compared with the T3 group. CONCLUSIONS: miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1.

[Automatic detection and classification of atrial fibrillation using RR intervals and multi-eigenvalue].

Atrial fibrillation (AF) is a common arrhythmia disease. Detection of atrial fibrillation based on electrocardiogram (ECG) is of great significance for clinical diagnosis. Due to the non-linearity and complexity of ECG signals, the procedure to manually diagnose the ECG signals takes a lot of time and is prone to errors. In order to overcome the above problems, a feature extraction method based on RR interval is proposed in this paper. The discrete degree of RR interval is described with the robust coefficient of variation (RCV), the distribution shape of RR interval is described with the skewness parameter (SKP), and the complexity of RR interval is described with the Lempel-Ziv complexity (LZC). Finally, the feature vectors of RCV, SKP, and LZC are input into the support vector machine (SVM) classifier model to achieve automatic classification and detection of atrial fibrillation. To verify the validity and practicability of the proposed method, the MIT-BIH atrial fibrillation database was used to verify the data. The final classification results show that the sensitivity is 95.81%, the specificity is 96.48%, the accuracy is 96.09%, and the specificity of 95.16% is achieved in the MIT-BIH normal sinus rhythm database. The experimental results show that the proposed method is an effective classification method for atrial fibrillation.

Insulin-producing acinar cells in adult human pancreas.

OBJECTIVE: The aim of this study was to characterize cells expressing insulin and amylase in adult human pancreas. METHODS: We applied serial section and immunohistochemistry to pancreas samples from 5 adult nondiabetic subjects (2 men and 3 women;mean age, 65.8 years; random plasma glucose level, 5.1 mM). Cells expressing insulin and amylase were captured by immunofluorescence and confocal miscroscopy. RESULTS: We found a widespread occurrence of insulin-producing cells in exocrine acini and amylase-reactive acinar cells in well-formed islets. The insulin-producing cells in exocrine acini predominantly formed single and double cell units though cell clusters, and islands occurred. Acini containing insulin-producing cells outnumbered the islets with a factor of approximately 5. Confocal microscopy and double immunostaining identified acinar A-cells coexpressing both amylase and insulin. CONCLUSIONS: The acinar A-cells represent a distinct category of pancreatic cell populations and might be possible endogenous progenitors of insulin-producing cells in normal and abnormal metabolic homeostasis.