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Beclin 1

Gang Li, Lei Chen, Kai Chen
BACKGROUND The aim of this study was to use a rat model of femoral fracture healing to study the effects of curcumin on cell autophagy, compared with treatment with 3-methyladenine (3-MA), an inhibitor of autophagy. MATERIAL AND METHODS Thirty-six Sprague-Dawley rats with right mid-femoral fracture were divided into three groups: the curcumin-treated group (N=12) (gavage with curcumin 400 mg/kg/day); the curcumin + 3-MA-treated group (gavage with curcumin 400 mg/kg/day + 3-MA 30 mg/kg/day); and the control group (N=12) (gavage normal saline)...
June 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Feng Jiang, Jin-Yong Zhou, Dan Zhang, Ming-Hao Liu, Yu-Gen Chen
The present study assessed the antitumor effect of artesunate (ART) in vitro and in vivo, as well as its underlying mechanism of action in HCT116 colon cancer cells. An MTT assay, DAPI staining, flow cytometry, western blotting, immunohistochemistry, transmission electron microscopy and TUNEL assay were performed to study the molecular mechanism underlying the antitumor effects of ART in HCT116 colon cancer cells. ART was observed to inhibit proliferation by inducing the apoptosis of HCT116 cells both in vitro and in vivo...
June 1, 2018: International Journal of Molecular Medicine
Meng Zhang, Yong-Ning Deng, Jing-Yi Zhang, Jie Liu, Yan-Bo Li, Hua Su, Qiu-Min Qu
SIRT3 is a class III histone deacetylase that modulates energy metabolism, genomic stability and stress resistance. It has been implicated as a potential therapeutic target in a variety of neurodegenerative diseases, including Parkinson's disease (PD). Our previous study demonstrates that SIRT3 had a neuroprotective effect on a rotenone-induced PD cell model, however, the exact mechanism is unknown. In this study, we investigated the underlying mechanism. We established a SIRT3 stable overexpression cell line using lentivirus infection in SH-SY5Y cells...
April 2018: Aging and Disease
Xiaoru Xin, Mengying Wu, Qiuyu Meng, Chen Wang, Yanan Lu, Yuxin Yang, Xiaonan Li, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Jiao Li, Song Jia, Dongdong Lu
BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. RESULTS: HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer...
June 12, 2018: Molecular Cancer
Yi-Wei Geng, Ya-Lan Wang, Rong Deng, Kai-Li Fu, Yan Deng
OBJECTIVE: To investigate the role of autophagy in the regulatory effect of Shufeng Huoxue Fumula (SFHXF) on the proliferation and melanin metabolism in cultured murine B16 melanoma cells. METHODS: B16 cells were treated with solutions containing 0.12, 0.25, 0.49, 0.98, or 1.96 mg/mL SFHXF preparations, rapamycin (an autophagy inducer), or rapamycin+SFHXF. The changes in the proliferation of B16 cells were assessed using MTT assay, and tyrosinase activity and melanin content in the cells were determined...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Shu-Yu Fang, Jie-Jie Cui, Meng-Jia Gong, Yun He, Jing-Fang Zhang, Yang Bi
OBJECTIVE: To investigate the effects of different concentrations of all-trans retinoic acid (ATRA) on the maturation, differentiation and autophagy of Hepa1-6 cells. MONTHOD: Hepa1-6 cells were treated with 0.1, 1, and 10 µmol/L ATRA, and the changes in the expressions of hepatic specific markers were detected using real-time PCR and Western blotting. Indocyanine green (ICG) and periodic acid-schiff (PAS) staining was used to assess the functional maturation of Hepa1-6 cells, and the cell-cell junction and autophagy were observed under transmission electron microscopy to determine the optimal concentration of ATRA for treatment...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Xin Jiang, Xiaoli Niu, Qingjun Guo, Yanhong Dong, Jing Xu, Nan Yin, Qianqian Qi, Yanqiu Jia, Liwei Gao, Qihui He, Peiyuan Lv
Vascular dementia (VD) is a heterogeneous group of brain disorders in which cognitive impairment is attributed to cerebrovascular pathologies. Autophagy, a self-cannibalization mechanism, has been demonstrated to be involved in VD progression. Molecular hydrogen is known for its powerful anti-oxidative, anti-apoptotic, and anti-inflammatory activities, and it is also involved in autophagy. However, the effects of hydrogen on VD remain unclear. The current study found that hydrogen-rich water (HRW) significantly alleviated spatial learning and memory impairments...
June 7, 2018: Behavioural Brain Research
M Li, G Peng, Q Ye, Y Wang, Y Xiong, R Wang, Z Yang
The mechanisms of autophagy during liver ischemia-reperfusion injury are not completely understood. This study aimed to assess the role of high-mobility group box 1 protein (HMGB1) in autophagy in LO2 cells following anoxia-reoxygenation injury. LO2 cells were pretreated with the HMGB1 inhibitor ammonium glycyrrhizinate (1000 μmol/L) or the HMGB1 agonist recombinant HMGB1 (rHMGB1, 10 ng/mL) at proper concentrations before induction of anoxia-reoxygenation injury. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell viability were evaluated...
June 2018: Transplantation Proceedings
Beyza Vurusaner, Simona Gargiulo, Gabriella Testa, Paola Gamba, Gabriella Leonarduzzi, Giuseppe Poli, Huveyda Basaga
Autophagy has been shown to be stimulated in advanced atherosclerotic plaques by metabolic stress, inflammation and oxidized lipids. The lack of published studies addressing the potential stimulation of pro-survival autophagy by oxysterols, a family of cholesterol oxidation products, has prompted our study. Thus, the goal of the current study is to elucidate the molecular mechanism of the autophagy induced by 27-hydroxycholesterol (27-OH), that is one of the most abundant oxysterols in advanced atherosclerotic lesions, and to assess whether the pro-oxidant effect of the oxysterol is involved in the given response...
May 26, 2018: Redox Biology
Wei-Chung Chiang, Yongjie Wei, Yi-Chun Kuo, Shuguang Wei, Anwu Zhou, Zhongju Zou, Jenna Yehl, Matthew J Ranaghan, Adam Skepner, Joshua A Bittker, José R Perez, Bruce A Posner, Beth Levine
Autophagy, a lysosomal degradation pathway, plays a crucial role in cellular homeostasis, development, immunity, tumor suppression, metabolism, prevention of neurodegeneration and lifespan extension. Thus, pharmacological stimulation of autophagy may be an effective approach for preventing or treating certain human diseases and/or aging. We sought to establish a method for developing new chemical compounds that specifically induce autophagy. To do this, we developed two assays to identify compounds that target a key regulatory node of autophagy induction - specifically, the binding of Bcl-2 (a negative regulator of autophagy) to Beclin 1 (an allosteric modulator of the Beclin 1/VPS34 lipid kinase complex that functions in autophagy initiation)...
June 7, 2018: ACS Chemical Biology
Malihe-Sadat Poormasjedi-Meibod, Maral Mansouri, Mary Fossey, Jordan W Squair, Jie Liu, John H McNeill, Christopher R West
Spinal cord injury (SCI) causes autonomic dysfunction, altered neurohumoral control, profound hemodynamic changes, and an increased risk of heart disease. In this prospective study we investigated the cardiac consequences of chronic experimental SCI in rats by combining cutting edge in vivo techniques (magnetic resonance imaging (MRI) and left-ventricular (LV) pressure-volume catheterization) with histological and molecular assessments. 12 weeks post-SCI, MRI-derived structural indices and in vivo LV catheterization derived functional indices indicated the presence of LV atrophy (LV mass in Control vs...
June 7, 2018: Journal of Neurotrauma
Fang-Hui Li, Tao Li, Jing-Yi Ai, Lei Sun, Zhu Min, Rui Duan, Ling Zhu, Yan-Ying Liu, Timon Cheng-Yi Liu
The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1 H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes...
2018: Frontiers in Physiology
Xingwu Jiang, Weiqiang Lu, Xiaoyang Shen, Quan Wang, Jing Lv, Mingyao Liu, Feixiong Cheng, Zhongming Zhao, Xiufeng Pang
Lung cancer patients treated with tyrosine kinase inhibitors (TKIs) often develop resistance. More effective and safe therapeutic agents are urgently needed to overcome TKI resistance. Here, we propose a medical genetics-based approach to identify indications for over 1,000 US Food and Drug Administration-approved (FDA-approved) drugs with high accuracy. We identified a potentially novel indication for an approved antidepressant drug, sertraline, for the treatment of non-small cell lung cancer (NSCLC). We found that sertraline inhibits the viability of NSCLC cells and shows a synergy with erlotinib...
June 7, 2018: JCI Insight
Tetsuya Takagawa, Atsushi Kitani, Ivan Fuss, Beth Levine, Steven R Brant, Inga Peter, Masaki Tajima, Shiro Nakamura, Warren Strober
The LRRK2/MUC19 gene region constitutes a high-risk genetic locus for the occurrence of both inflammatory bowel diseases (IBDs) and Parkinson's disease. We show that dendritic cells (DCs) from patients with Crohn's disease (CD) and lymphoblastoid cell lines derived from patients without CD but bearing a high-risk allele (rs11564258) at this locus as heterozygotes exhibited increased LRRK2 expression in vitro. To investigate the immunological consequences of this increased LRRK2 expression, we conducted studies in transgenic mice overexpressing Lrrk2 and showed that these mice exhibited more severe colitis induced by dextran sodium sulfate (DSS) than did littermate control animals...
June 6, 2018: Science Translational Medicine
Xiaomu Tan, Sherwin Azad, Xunming Ji
Oxidative stress plays a role in many neurological diseases. Hypoxic preconditioning (HPC) has been proposed as an intervention that protects neurons from damage by altering their response to oxidative stress. The aim of this study was to investigate the mechanisms by which HPC results in neuroprotection in cultured SH-SY5Y cells subjected to oxidative stress to provide a guide for future investigation and targeted interventions. SH-SY5Y cells were subjected to HPC protocols or control conditions. Oxidative stress was induced by H2 O2 ...
January 1, 2018: Cell Transplantation
Shuai Wu, Yunjiao He, Xianxiu Qiu, Wenchao Yang, Wenchao Liu, Xiaohua Li, Yan Li, Han-Ming Shen, Renxiao Wang, Zhenyu Yue, Yanxiang Zhao
The Beclin 1-Vps34 complex, known as "mammalian class III PI3K," plays essential roles in membrane-mediated transport processes including autophagy and endosomal trafficking. Beclin 1 acts as a scaffolding molecule for the complex and readily transits from its metastable homodimeric state to interact with key modulators such as Atg14L or UVRAG and form functionally distinct Atg14L/UVRAG-containing Beclin 1-Vps34 subcomplexes. The Beclin 1-Atg14L/UVRAG interaction relies critically on their coiled-coil domains, but the molecular mechanism remains poorly understood...
June 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hong Qiao, Yong-Bo Wang, Yu-Mei Gao, Li-Li Bi
BACKGROUNDS: Glioma is the most fatal primary brain glioma in central nervous system mainly attributed to its high invasion. Prucalopride, a Serotonin-4 (5-HT4) receptor agonist, has been reported to regulate neurodevelopment. This study aimed to investigate the influence of the Prucalopride on glioma cells and unveil underlying mechanism. METHODS: In this study, glioma cells proliferation was evaluated by Cell counting kit-8 (CCK8). Wound healing and transwell assay were used to test cellular migration and invasion...
June 4, 2018: BMC Neurology
Toshiaki Yoshimoto, Yuji Morine, Chie Takasu, Rui Feng, Tetsuya Ikemoto, Kozo Yoshikawa, Syuichi Iwahashi, Yu Saito, Hideya Kashihara, Masatake Akutagawa, Takahiro Emoto, Yosuke Kinouchi, Mitsuo Shimada
Background: Light emitting-diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro. Methods: Human colon cancer cells (HT-29 or HCT-116) were seeded onto laboratory dishes and irradiated with 465-nm LED at 30 mW/cm2 for 30 minutes...
March 2018: Annals of gastroenterological surgery
Sunderajhan Sekar, Xiaoxin Wu, Thor Friis, Ross Crawford, Indira Prasadam, Yin Xiao
OBJECTIVES: Obesity is a known strong risk factor for the onset of knee osteoarthritis and is often accompanied by dysregulated lipid metabolism with elevated levels of free fatty acids such as saturated fatty acids (SFAs). The purpose of this study was to determine how autophagy varies in chondrocytes in response to predominant SFAs such as lauric, myristic, palmitic, and stearic acids. METHODS: Normal human articular cartilage chondrocytes and C28/I2 chondrocyte cell lines were stimulated with different SFAs in both the absence and presence of interleukin-1β to study the effects of SFA and inflammatory cytokines in mediating the activation of autophagy...
March 20, 2018: Nutrition
Liying Zhan, Yuan Zhang, Wating Su, Qiongxia Zhang, Rong Chen, Bo Zhao, Wei Li, Rui Xue, Zhongyuan Xia, Shaoqing Lei
Patients with diabetes are vulnerable to myocardial ischemia reperfusion (IR) injury, which may also induce acute lung injury (ALI) due to overaccumulation of reactive oxygen species (ROS) and inflammation cytokine in circulation. Despite autophagy plays a significant role in diabetes and pulmonary IR injury, the role of autophagy in ALI secondary to myocardial IR in diabetes remains largely elusive. We aimed to investigate pulmonary autophagy status and its roles in oxidative stress and inflammation reaction in lung tissues from diabetic rats subjected to myocardial IR...
2018: Journal of Diabetes Research
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