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https://www.readbyqxmd.com/read/29223072/alteration-of-autophagy-related-proteins-in-peripheral-blood-mononuclear-cells-of-patients-with-parkinson-s-disease
#1
Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6)...
November 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29222553/ghrelin-attenuates-retinal-neuronal-autophagy-and-apoptosis-in-an-experimental-rat-glaucoma-model
#2
Ke Zhu, Meng-Lu Zhang, Shu-Ting Liu, Xue-Yan Li, Shu-Min Zhong, Fang Li, Ge-Zhi Xu, Zhongfeng Wang, Yanying Miao
Purpose: Ghrelin, a natural ligand for the growth hormone secretagogue receptor type 1a (GHSR-1a), may protect retinal neurons against glaucomatous injury. We therefore characterized the underlying mechanism of the ghrelin/GHSR-1a-mediated neuroprotection with a rat chronic intraocular hypertension (COH) model. Methods: The rat COH model was produced by blocking episcleral veins. A combination of immunohistochemistry, Western blot, TUNEL assay, and retrograde labeling of retinal ganglion cells (RGCs) was used...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29219657/the-levels-of-mutant-k-ras-and-mutant-n-ras-are-rapidly-reduced-in-a-beclin1-atg5-dependent-fashion-by-the-irreversible-erbb1-2-4-inhibitor-neratinib
#3
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Cindy Sander, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate...
December 8, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29219022/effectiveness-of-radiofrequency-hyperthermia-for-treating-cartilage-in-guinea-pigs-with-primary-osteoarthritis
#4
Kenji Takahashi, Hiroshi Nakamura, Hitoshi Ozawa, Sanshiro Hashimoto, Norio Iijima, Shimpei Higo, Hiroshi Watanabe, Yusuke Mochizuki, Shinro Takai
Objective Autophagy was reported to be essential for maintaining chondrocyte function, and reduced autophagy leads to osteoarthritis (OA). Previous studies showed involvement of heat shock stress in the control of autophagy in cells. This study sought to investigate the effect of hyperthermia on the expression of autophagy-related proteins in articular cartilage and the progression of naturally occurring OA in Hartley guinea pigs. Design Radiofrequency pulses of 13.56 MHz were applied to the animals' knees for 20 minutes to induce hyperthermia...
January 2018: Cartilage
https://www.readbyqxmd.com/read/29218081/tetramethylpyrazine-phosphate-and-borneol-combination-therapy-synergistically-attenuated-ischemia-reperfusion-injury-of-the-hypothalamus-and-striatum-via-regulation-of-apoptosis-and-autophagy-in-a-rat-model
#5
Bin Yu, Ming Ruan, Tao Liang, Shi-Wen Huang, Sheng-Jin Liu, Hai-Bo Cheng, Xiang-Chun Shen
The combination of tetramethylpyrazine (TMP) and borneol (BO) has shown promise for treatment of cerebral ischemia in clinical and experimental studies. However, the mechanism for the synergistic effect of these compounds is unclear. In this study, global cerebral ischemia-reperfusion (GCIR) was induced in rats that were subsequently treated with tetramethylpyrazine phosphate (TMPP) (13.3 mg/kg), BO (0.16 g/kg), or the combination TMPP + BO. Neuronal ultrastructure and intracellular calcium [Ca2+]i levels were evaluated in hypothalamus and striatum...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29216769/zinc-prevents-mitochondrial-superoxide-generation-by-inducing-mitophagy-in-the-setting-of-hypoxia-reoxygenation-in-cardiac-cells
#6
Xiyun Bian, Tianming Teng, Huanhuan Zhao, Jiangyu Qin, Zhen Qiao, Yuemin Sun, Zhiqiang Liun, Zhelong Xu
Zinc plays a role in autophagy and protects cardiac cells from ischemia/reperfusion injury. This study aimed to test if zinc can induce mitophagy leading to attenuation of mitochondrial superoxide generation in the setting of hypoxia/reoxygenation (H/R) in cardiac cells. H9c2 cells were subjected to 4 h hypoxia followed by 2 h reoxygenation. Under normoxic conditions, treatments of cells with ZnCl2 increased both the LC3-II/LC3-I ratio and GFP-LC3 puncta, implying that zinc induces autophagy. Further experiments showed that endogenous zinc is required for the autophagy induced by starvation and rapamycin...
December 7, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29212196/juglanin-inhibits-lung-cancer-by-regulation-of-apoptosis-ros-and-autophagy-induction
#7
Liang Chen, Ya-Qiong Xiong, Jing Xu, Ji-Peng Wang, Zi-Li Meng, Yong-Qing Hong
Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare, exerting suppressive activity against cancer cell progression in vitro and in vivo. Juglanin administration causes apoptosis and reactive oxygen species (ROS) in different types of cells through regulating various signaling pathways. In our study, the effects of juglanin on non-small cell lung cancer were investigated. A significant role of juglanin in suppressing lung cancer growth was observed. Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29197632/crosstalk-between-autophagy-and-oxidative-stress-regulates-proteolysis-in-the-diaphragm-during-mechanical-ventilation
#8
Ashley J Smuder, Kurt J Sollanek, W Bradley Nelson, Kisuk Min, Erin E Talbert, Andreas N Kavazis, Matthew B Hudson, Marco Sandri, Hazel H Szeto, Scott K Powers
Mechanical ventilation (MV) results in the rapid development of ventilator-induced diaphragm dysfunction (VIDD). While the mechanisms responsible for VIDD are not fully understood, recent data reveal that prolonged MV activates autophagy in the diaphragm, which may occur as a result of increased cellular reactive oxygen species (ROS) production. Therefore, we tested the hypothesis that 1) accelerated autophagy is a key contributor to VIDD; and that 2) oxidative stress is required to increase the expression of autophagy genes in the diaphragm...
November 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29190916/coenzyme-q10-inhibits-the-activation-of-pancreatic-stellate-cells-through-pi3k-akt-mtor-signaling-pathway
#9
Ran Xue, Jing Yang, Jing Wu, Qinghua Meng, Jianyu Hao
Aim: Pancreatic stellate cells (PSCs) have a vital role in pancreatic fibrosis accompanied by pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Any agents which can affect the activation of PSCs could become potential candidates for treatment strategies in PDAC and CP. Our aim was to explore the effect of Coenzyme Q10 (CoQ10) in the process of PSCs activation. Methods: Isolated PSCs from C57BL/6 mice were treated with various dosages of CoQ10 (1, 10, and 100μM) and different time (24h, 48h, and 72 h)...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29186197/fingolimod-suppresses-neuronal-autophagy-through-the-mtor-p70s6k-pathway-and-alleviates-ischemic-brain-damage-in-mice
#10
Xiao Li, Ming-Huan Wang, Chuan Qin, Wen-Hui Fan, Dai-Shi Tian, Jun-Li Liu
The bioactive, signaling lipid, sphingosine-1-phosphate (S1P), and its analog, fingolimod (FTY720), have previously shown neuroprotective effects against ischemic brain injury. However, the underlying mechanisms have not yet been fully clarified. The roles of autophagy in ischemic stroke are being increasingly recognized. In the present study, we sought to determine whether the S1P pathway is involved in neuronal autophagy and investigate its possible mechanisms following stroke. Interestingly, we found that FTY720 significantly attenuates infarct volumes and reduces neuronal apoptosis on days 1 and 3 post stroke, accompanied by amelioration of functional deficits...
2017: PloS One
https://www.readbyqxmd.com/read/29164558/rapamycin-facilitates-fracture-healing-through-inducing-cell-autophagy-and-suppressing-cell-apoptosis-in-bone-tissues
#11
Z-Y Yin, J Yin, Y-F Huo, J Yu, L-X Sheng, Y-F Dong
OBJECTIVE: To investigate the changes in cell autophagy and the molecular mechanism of rapamycin affecting the fracture healing. MATERIAL AND METHODS: Sprague-Dawley (SD) rats were used to establish the right femoral shaft fracture models, and then underwent immunofluorescence assay to detect the autophagy level in bone tissues. After model establishment, SD rats were divided into two groups, the control group and the rapamycin group (1 mg/kg/d). Respectively, at the 2nd, 4th, and 6th week, rats were randomly selected from each group for X-ray and Micro-computed tomography (Micro-CT) examinations to determine callus growth, immunofluorescence assay to detect the protein expression of light chain 3 II (LC3 II), immunohistochemistry to evaluate the autophagy level through detecting the expression of Beclin1 in rats, Western blotting assay to detect cell apoptosis in tissues, hematoxylin and eosin staining (HE staining) to evaluate the osteoblastic activity through count of osteoblast in bone tissue at the end of fracture, and measure the expression of vascular endothelial growth factors (VEGF)...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29163826/hdac-inhibitors-enhance-neratinib-activity-and-when-combined-enhance-the-actions-of-an-anti-pd-1-immunomodulatory-antibody-in-vivo
#12
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Paul Dent
Patients whose NSCLC tumors become afatinib resistant presently have few effective therapeutic options to extend their survival. Afatinib resistant NSCLC cells were sensitive to clinically relevant concentrations of the irreversible pan-HER inhibitor neratinib, but not by the first generation ERBB1/2/4 inhibitor lapatinib. In multiple afatinib resistant NSCLC clones, HDAC inhibitors reduced the expression of ERBB1/3/4, but activated c-SRC, which resulted in higher total levels of ERBB1/3 phosphorylation. Neratinib also rapidly reduced the expression of ERBB1/2/3/4, c-MET and of mutant K-/N-RAS; K-RAS co-localized with phosphorylated ATG13 and with cathepsin B in vesicles...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163157/a-dual-role-of-p53-in-regulating-colistin-induced-autophagy-in-pc-12-cells
#13
Ziyin Lu, Chunli Chen, Zhiyong Wu, Yusong Miao, Ishfaq Muhammad, Liangjun Ding, Erjie Tian, Wanjun Hu, Huilin Ni, Rui Li, Bo Wang, Jichang Li
This study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by real-time PCR and western blot, fluorescence/immunofluorescence microscopy, and electron microscopy. The results showed that silencing of p53 leads to down-regulation of Atg5 and beclin1 for 12 h while up-regulation at 24 h and up-regulation of p62 noted...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29157832/pachymic-acid-promotes-induction-of-autophagy-related-to-igf-1-signaling-pathway-in-wi-38-cells
#14
Su-Gyeong Lee, Moon-Moo Kim
BACKGROUND: The insulin-like growth factor 1 (IGF-1) signaling pathway has spotlighted as a mechanism to elucidate aging associated with autophagy in recent years. Therefore, we have tried to screen an effective compound capable of inducing autophagy to delay aging process. PURPOSE: The aim of this study is to investigate whether pachymic acid, a main compound in Poria cocos, induces autophagy in the aged cells. METHODS: The aging of young cells was induced by treatment with IGF-1 at 50 ng/ml three times every two days...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29156523/cancer-associated-%C3%AF-broblasts-confer-cisplatin-resistance-of-tongue-cancer-via-autophagy-activation
#15
Juan-Kun Liao, Bin Zhou, Xiu-Mei Zhuang, Pei-Lin Zhuang, Da-Ming Zhang, Wei-Liang Chen
Cancer-associated fibroblasts (CAFs) play important roles in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC). However, effect of CAFs on chemotherapy resistance of TSCC remains largely obscure. Here, we cultured the matched primary CAFs and normal fibroblasts (NFs) pairs and detected their roles in cisplatin sensitivity of TSCC, as well as autophagy-related protein LC3 and Beclin1 expressions. During exposure to cisplatin, TSCC with CAFs group exhibited significantly increased cell viability and IC50, but reduced apoptosis than that with NFs group...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#16
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29145153/the-pro-apoptosis-effect-of-sinomenine-in-renal-carcinoma-via-inducing-autophagy-through-inactivating-pi3k-akt-mtor-pathway
#17
Fei Deng, Yue-Xian Ma, Liang Liang, Ping Zhang, Jing Feng
Renal cell carcinoma (RCC) is a heterogeneous histological disease and the most common kidney cancer. The mortality rate of RCC remains high despite the improved treatment. Sinomenine is an isoquinoline extracted from Chinese medicinal plant Sinomenium acutum, famous for its ability to suppress several cancer cell types. Our research aimed to explore the anti-cancer potential of sinomenine in RCC. Results showed that sinomenine reduced the viability by reducing sphere-forming ability and enhancing pro-apoptosis effect in ACHN cells in a dose dependent manner...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136784/the-alternation-of-autophagy-apoptosis-in-cd4-cd25-foxp3-tregs-on-the-developmental-stages-of-atherosclerosis
#18
Yuling Tian, Xiao Liang, Yue Wu
Naturally regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses in atherosclerosis. However, the regulatory mechanism underlying Tregs upon long-term development of atherosclerosis remains unknown. Therefore, in this study, atherosclerotic model was induced in ApoE-/- mice by feeding fat-diet for 10 weeks. Quantification of atherosclerotic lesions was done by calculating the lesion size in the aortic sinus every 2 weeks. The lipid levels and inflammatory mediators were detected in serum sample...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29128104/effects-of-intermedin-on-autophagy-in-cerebral-ischemia-reperfusion-injury
#19
Meng Wang, Jing Wang, Zhengang Liu, Xin Guo, Ning Wang, Nana Jia, Yanshu Zhang, Jie Yuan
OBJECTIVE: This study aimed to evaluate the effects of intermedin (IMD) on autophagy in cerebral ischemia/reperfusion (I/R) injury (CIRI). METHODS: Sixty rats were randomly averaged into four groups: sham, ischemia/reperfusion (I/R), IMD, and 3-methyladenine (3-MA). In the sham group, the right common carotid artery, external carotid artery, and internal carotid artery were detached, and no monofilament was inserted. In the other groups, two hours after cerebral ischemia, the rats were injected through the lateral ventricle with normal saline for I/R group, IMD for the IMD group, and 3-MA for the 3-MA group for 24h...
November 8, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29123982/decreased-grip-strength-muscle-pain-and-atrophy-occur-in-rats-following-long-term-exposure-to-excessive-repetitive-motion
#20
Mitsuhiro Fujiwara, Masahiro Iwata, Takayuki Inoue, Yosuke Aizawa, Natsumi Yoshito, Kazuhiro Hayashi, Shigeyuki Suzuki
Work-related musculoskeletal disorders (WMSD) are caused by the overuse of muscles in the workplace. Performing repetitive tasks is a primary risk factor for the development of WMSD. Many workers in highly repetitive jobs exhibit muscle pain and decline in handgrip strength, yet the mechanisms underlying these dysfunctions are poorly understood. In our study, rats performed voluntary repetitive reaching and grasping tasks (Task group), while Control group rats did not perform these activities. In the Task group, grip strength and forearm flexor withdrawal threshold declined significantly from week 2 to week 6, compared with these values at week 0 (P < 0...
November 2017: FEBS Open Bio
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