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https://www.readbyqxmd.com/read/28737825/combination-of-rapamycin-and-garlic-derived-s-allylmercaptocysteine-induces-colon-cancer-cell-apoptosis-and-suppresses-tumor-growth-in-xenograft-nude-mice-through-autophagy-p62-nrf2-pathway
#1
Siying Li, Guang Yang, Xiaosong Zhu, Lin Cheng, Yueyue Sun, Zhongxi Zhao
The natural plant-derived product S-allylmercapto-cysteine (SAMC) has been studied in cancer therapy as a single and combination chemotherapeutic agent. The present study was employed to verify the combination use of SAMC and rapamycin that is the mTOR inhibitor with anticancer ability but has limited efficacy due to drug resistance, and to explore the underlying mechanisms. We combined rapamycin and SAMC for colorectal cancer treatment in the HCT‑116 cancer cells and a xenograft murine model. The in vivo study was established by xenografting HCT‑116 cells in BALB/c nude mice...
July 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28736850/progressive-ataxia-and-palatal-tremor-two-autopsy-cases-of-a-novel-tauopathy
#2
Andrew F Gao, Achinoam Faust-Socher, Maryam Al-Murshed, Marc R Del Bigio, Anthony E Lang, David G Munoz
BACKGROUND: Sporadic progressive ataxia and palatal tremor is a rare syndrome characterized by mid- to late-adult-onset symptomatic palatal tremor and slowly progressive cerebellar ataxia. To date, there has been only one autopsy report, which described a novel 4-repeat tauopathy with hypertrophic olivary degeneration and tau-positive inclusions in olivary neurons and dystrophic neuritic processes termed glomeruloid bodies. We report on 2 additional autopsy cases. METHODS: Sections from selected paraffin-embedded brain regions were stained with hematoxylin and eosin/Luxol fast blue and processed for phosphorylated tau, 3-repeat tau, 4-repeat tau, neurofilament, glial fibrillary acid protein, phosphorylated α-synuclein, phosphorylated TAR DNA-binding protein 43, beta-amyloid, and p62 immunohistochemistry...
July 24, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28734275/low-level-of-autophagy-related-gene-10-atg10-expression-in-the-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#3
Marzieh Shams Nooraei, Ali Noori-Zadeh, Shahram Darabi, Farzad Rajaei, Zohreh Golmohammadi, Hojjat Allah Abbaszadeh
Background: Autophagy is a mechanism disassembling the damaged organelles from the cell. This study attempted to examine the expression of several autophagy-related genes in Parkinson’s disease (PD) rat model. Methods: The male Wistar rats were divided into three groups as control, sham, and lesion. In the latter group, the PD rat model was induced by the injection of 6-hydroxydopamine in the striatum.The behavioral test was conducted one (baseline) and four weeks after the surgery through apomorphine hydrochloride...
July 23, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28734243/caveolin-1-related-autophagy-initiated-by-aldosterone-induced-oxidation-promotes-liver-sinusoidal-endothelial-cells-defenestration
#4
Xiaoying Luo, Dan Wang, Xuan Luo, Xintao Zhu, Guozhen Wang, Zuowei Ning, Yang Li, Xiaoxin Ma, Renqiang Yang, Siyi Jin, Yun Huang, Ying Meng, Xu Li
Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models...
July 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28732797/functional-convergence-of-akt-protein-with-vegfr-1-in-human-endothelial-progenitor-cells-exposed-to-sera-from-patient-with-type-2-diabetes-mellitus
#5
Mehdi Hassanpour, Aysa Rezabakhsh, Reza Rahbarghazi, Alireza Nourazarian, Mohammad Nouri, Çığır Biray Avci, Shahrooz Ghaderi, Neda Alidadyani, Bakiye Goker Bagca, Hesam Saghaei Bagheri
Diabetes mellitus type 2 predisposes patients to various microvascular complications. In the current experiment, the potent role of diabetes mellitus was investigated on the content of VEGFR-1, -2, Tie-1 and -2, and Akt in human endothelial progenitor cells. The gene expression profile of mTOR and Hedgehog signaling pathways were measured by PCR array. The possible crosstalk between RTKs, mTOR and Hedgehog signaling was also studied by bioinformatic analysis. Endothelial progenitor cells were incubated with serum from normal and diabetic for 7days...
July 18, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#6
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28730238/altered-expression-of-mtor-and-autophagy-in-term-normal-human-placentas
#7
Qiu Xia Zhang, Quan Na, Weiwei Song
Mammalian target of rapamycin (mTOR) and autophagy have been implied in trophoblast cells proliferation and invasion. This study investigated whether mTOR and autophagy were involved in placental development and fetal programming. A total of 90 term normal placentas (37-42 gestational weeks) were collected from women who underwent elective cesarean section, with large for gestational age (LGA), fetal growth restriction (FGR), and appropriate for gestational age (AGA) infants (n=30, respectively). Capillary volume density within peripheral villi significantly decreased in the FGR placentas compared with the AGA group (p<0...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28729825/dexmedetomidine-protects-mouse-brain-from-ischemia-reperfusion-injury-via-inhibiting-neuronal-autophagy-through-up-regulating-hif-1%C3%AE
#8
Cong Luo, Ming-Wen Ouyang, Ying-Ying Fang, Shu-Ji Li, Quan Zhou, Jun Fan, Zai-Sheng Qin, Tao Tao
Stroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia is still unknown. In this study, we found that post-conditioning with DEX and DEX+3-methyladenine (3-MA) (autophagy inhibitor) reduced brain infarct size and improved neurological deficits compared with DEX+RAPA (autophagy inducer) 24 h after transient middle cerebral artery artery occlusion (tMCAO) model in mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#9
Luciene Lenhare, Barbara M Crisol, Vagner R R Silva, Carlos K Katashima, André V Cordeiro, Karina D Pereira, Augusto D Luchessi, Adelino S R da Silva, Dennys E Cintra, Leandro P Moura, José R Pauli, Eduardo R Ropelle
Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot. Transcriptomic and phenotypic analysis were also performed by using strains of genetically-diverse BXD mice...
July 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28727070/short-term-heat-stress-causes-altered-intracellular-signaling-in-oxidative-skeletal-muscle
#10
S Ganesan, C M Summers, S C Pearce, N K Gabler, R J Valentine, L H Baumgard, R P Rhoads, J T Selsby
Heat stress (HS) causes morbidities and mortalities, in part by inducing organ-specific injury and dysfunction. Further, HS markedly reduces farm animal productivity, and this is especially true for lean tissue accretion. The purpose of this investigation was to determine the extent to which short-term HS caused muscle dysfunction in skeletal muscle. We have previously found increased free radical injury in skeletal muscle following 24 h of HS. Thus, we hypothesized that HS would lead to apoptosis, autophagy, and decreased mitochondrial content in skeletal muscle...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28724966/acetylation-induced-tdp-43-pathology-is-suppressed-by-an-hsf1-dependent-chaperone-program
#11
Ping Wang, Connor M Wander, Chao-Xing Yuan, Michael S Bereman, Todd J Cohen
TDP-43 pathology marks a spectrum of multisystem proteinopathies including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and sporadic inclusion body myositis. Surprisingly, it has been challenging to recapitulate this pathology, highlighting an incomplete understanding of TDP-43 regulatory mechanisms. Here we provide evidence supporting TDP-43 acetylation as a trigger for disease pathology. Using cultured cells and mouse skeletal muscle, we show that TDP-43 acetylation-mimics promote TDP-43 phosphorylation and ubiquitination, perturb mitochondria, and initiate degenerative inflammatory responses that resemble sporadic inclusion body myositis pathology...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28724916/involvement-of-the-p62-nrf2-signal-transduction-pathway-on-erythrophagocytosis
#12
Inês B Santarino, Michelle S Viegas, Neuza S Domingues, Ana M Ribeiro, Miguel P Soares, Otília V Vieira
Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy effectors. Here, we report that besides recruitment of microtubule-associated protein-1-light chain 3 (LC3), additional autophagy machinery such as sequestosome 1 (p62) is also acquired by single-membrane phagosomes at very early stages of the phagocytic process and that its acquisition is very important to the outcome of the process...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724634/adaptor-protein-p62-promotes-skin-tumor-growth-and-metastasis-and-is-induced-by-uva-radiation
#13
Ashley Sample, Baozhong Zhao, Lei Qiang, Yu-Ying He
Skin cancer is the most common cancer and exposure to ultraviolet (UV) radiation, namely UVA and UVB is the major risk factor for skin cancer development. UVA is significantly less effective in causing direct DNA damage than UVB, but UVA has been shown to increase skin cancer risk. The mechanism by which UVA contributes to skin cancer remains unclear. Here, using RNA-Seq, we show that UVA induces autophagy and lysosomal gene expression, including the autophagy receptor and substrate p62. We found that UVA activates the transcription factor EB (TFEB), a known regulator of autophagy and lysosomal gene expression, which, in turn, induces p62 transcription...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28722333/xiap-inhibitor-embelin-induces-autophagic-and-apoptotic-cell-death-in-human-oral-squamous-cell-carcinoma-cells
#14
You-Jin Lee, Bong-Soo Park, Hae-Ryoun Park, Su-Bin Yu, Hae-Mi Kang, In-Ryoung Kim
Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9-22. Our results showed that Embelin had anticancer activity against the Ca9-22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO...
July 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28722162/cyanidin-suppresses-autophagic-activity-regulating-chondrocyte-hypertrophic-differentiation
#15
Zhen Cao, Song Huang, Ce Dou, Qiang Xiang, Shiwu Dong
Cartilage is a kind of special connective tissue which does not contain neither blood vessels nor lymphatics and nerves. Therefore, the damage in cartilage is difficult to be repaired spontaneously. Constructing tissue engineered cartilage provides a new technique for cartilage repairing. Mesenchymal stem cells (MSCs) possess a unique capability of self-renew and can differentiate into pre-chondrocytes which are frequently applied as seed cells in tissue engineering. However, in regenerated cartilage the chondrocytes derived from MSCs can hardly maintain homeostasis and preferentially present hypertrophic like phenotype...
July 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28720712/regulation-of-the-autophagy-system-during-chronic-contractile-activity-induced-muscle-adaptations
#16
Yuho Kim, David A Hood
Skeletal muscle is adaptable to exercise stimuli via the upregulation of mitochondrial biogenesis, and recent studies have suggested that autophagy also plays a role in exercise-induced muscle adaptations. However, it is still obscure how muscle regulates autophagy over the time course of training adaptations. This study examined the expression of autophagic proteins in skeletal muscle of rats exposed to chronic contractile activity (CCA; 6 h/day, 9V, 10 Hz continuous, 0.1 msec pulse duration) for 1, 3, and 7 days (n = 8/group)...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28717222/fty720-induces-autophagy-associated-apoptosis-in-human-oral-squamous-carcinoma-cells-in-part-through-a-reactive-oxygen-species-mcl-1-dependent-mechanism
#17
Li-Yuan Bai, Chang-Fang Chiu, Shih-Jiuan Chiu, Po-Chen Chu, Jing-Ru Weng
In this study, we interrogated the mechanism by which the immunosuppressant FTY720 mediates anticancer effects in oral squamous cell carcinoma (OSCC) cells. FTY720 differentially suppressed the viability of the OSCC cell lines SCC4, SCC25, and SCC2095 with IC50 values of 6.1, 6.3, and 4.5 μM, respectively. This antiproliferative effect was attributable to the ability of FTY720 to induce caspase-dependent apoptosis. Mechanistic evidence suggests that FTY720-induced apoptosis was associated with its ability to inhibit Akt-NF-κB signaling, to facilitate the proteasomal degradation of the antiapoptotic protein Mcl-1, and to increase reactive oxygen species (ROS) generation...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715869/rapamycin-inhibits-oxidative-nitrosative-stress-and-enhances-angiogenesis-in-high-glucose-treated-human-umbilical-vein-endothelial-cells-role-of-autophagy
#18
Aysa Rezabakhsh, Mahdi Ahmadi, Majid Khaksar, Azadeh Montaseri, Hassan Malekinejad, Reza Rahbarghazi, Alireza Garjani
Chronic hyperglycemia is a potent risk factor of abnormal angiogenesis with various tissue diseases. Autophagy, as an alternative cell response, is mostly generated by a vast array of insults. Applying autophagic response contributes to normal cell retrieval circumstance during various insults. We aimed to show whether stimulation/inhibition of autophagy could reduce or exacerbate oxidative status and angiogenic potential in endothelial cells after exposure to 30mM glucose. HUVECs were incubated with the combined regime of 100nM Rapamycin and 30mM glucose over a period of 72h...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28715145/the-autophagy-receptor-adaptor-p62-is-up-regulated-by-uva-radiation-in-melanocytes-and-in-melanoma-cells
#19
Ashley Sample, Baozhong Zhao, Chunli Wu, Steven Qian, Xianglin Shi, Andrew Aplin, Yu-Ying He
UVA (315-400 nm) is the most abundant in sunlight and is used in indoor tanning beds. However, much remains to be understood about the regulation of the UVA damage response in melanocytes and melanoma. Here we show that UVA, but not the shorter waveband UVB (280-315 nm), up-regulates adaptor protein p62 in an Nrf2- and ROS-dependent manner, suggesting a UVA-specific effect on p62 regulation. UVA-induced p62 up-regulation was inhibited by a mitochondria-targeted antioxidant or Nrf2 knockdown. In addition, p62 knockdown inhibited UVA-induced ROS production and Nrf2 up-regulation...
July 17, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28714954/c9orf72-expansion-disrupts-atm-mediated-chromosomal-break-repair
#20
Callum Walker, Saul Herranz-Martin, Evangelia Karyka, Chunyan Liao, Katherine Lewis, Waheba Elsayed, Vera Lukashchuk, Shih-Chieh Chiang, Swagat Ray, Padraig J Mulcahy, Mateusz Jurga, Ioannis Tsagakis, Tommaso Iannitti, Jayanth Chandran, Ian Coldicott, Kurt J De Vos, Mohamed K Hassan, Adrian Higginbottom, Pamela J Shaw, Guillaume M Hautbergue, Mimoun Azzouz, Sherif F El-Khamisy
Hexanucleotide repeat expansions represent the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which such expansions cause neurodegeneration are poorly understood. We report elevated levels of DNA-RNA hybrids (R-loops) and double strand breaks in rat neurons, human cells and C9orf72 ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signaling and accumulation of protein-linked DNA breaks...
July 17, 2017: Nature Neuroscience
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