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https://www.readbyqxmd.com/read/28938597/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#1
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938583/ppa1-regulates-tumor-malignant-potential-and-clinical-outcome-of-colon-adenocarcinoma-through-jnk-pathways
#2
Ping Wang, Yi Zhou, Qi Mei, Jing Zhao, Liu Huang, Qiang Fu
Colorectal cancer (CRC) represents one of the most prevalent malignancies and the third leading cause of cancer death worldwide. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate, therefore participates in the energy metabolism. Proteomic studies have demonstrated the up-regulated expression of PPA1 in various tumors, however, its expression pattern in CRC hasn't been reported. In the current study, we used RT-qCR, Western Blot and immunohistochemical (IHC) staining to explore the expression of PPA1 in 113 paired colon cancer tissues and adjacent normal tissues, which revealed that PPA1 was correlated with lymph node metastasis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938581/targeting-progastrin-enhances-radiosensitization-of-colorectal-cancer-cells
#3
Aline Kowalski-Chauvel, Valerie Gouaze-Andersson, Alix Vignolle-Vidoni, Caroline Delmas, Christine Toulas, Elizabeth Cohen-Jonathan-Moyal, Catherine Seva
A high percentage of advanced rectal cancers are resistant to radiation. Therefore, increasing the efficacy of radiotherapy by targeting factors involved in radioresistance seems to be an attractive strategy. Here we demonstrated that the pro-hormone progastrin (PG), known to be over-expressed in CRC, and recognized as a pro-oncogenic factor, is a radioresistance factor that can be targeted to sensitize resistant rectal cancers to radiations. First, we observed an increase in PG mRNA expression under irradiation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938400/il-1%C3%AE-inhibits-connexin-43-and-disrupts-decidualization-of-human-endometrial-stromal-cells-through-erk1-2-and-p38-map-kinase
#4
Jie Yu, Sarah L Berga, Wei Zou, D Grace Yook, Joshua C Pan, Aurora Arroyo Andrade, Lijuan Zhao, Neil Sidell, Indrani C Bagchi, Milan K Bagchi, Robert N Taylor
Inflammation can interfere with endometrial receptivity. We examined how IL-1β affects expression of the uterine gap junction protein, Cx43, which is known to be critical for embryonic implantation. We used an in vitro model of human endometrial stromal cells (ESC), Western blotting and a combination of validated, selective kinase inhibitors to evaluate five canonical IL-1β signaling pathways. Cx43 and two other markers of ESC differentiation (prolactin and VEGF) were inhibited predominantly via IL-1β-activated ERK1/2 and p38 MAP kinase cascades...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935193/celastrol-inhibits-hepatitis-c-virus-replication-by-upregulating-heme-oxygenase-1-via-the-jnk-mapk-nrf2-pathway-in-human-hepatoma-cells
#5
Chin-Kai Tseng, Sung-Po Hsu, Chun-Kuang Lin, Yu-Hsuan Wu, Jin-Ching Lee, Kung-Chia Young
BACKGROUND AND PURPOSE: Celastrol, a quinone methide triterpene isolated from the root extracts of Tripterygium wilfordii, can greatly induce the gene expression activity of heme oxygenase-1 (HO-1) to achieve disease prevention and control. HO-1 induction was recently shown to result in anti-HCV activity by inducing type I interferon and inhibiting hepatitis C virus (HCV) NS3/4A protease activity. The aim of the present study is to evaluate the anti-HCV activity of celastrol and characterize its mechanism of inhibition...
September 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28934742/elevated-apoptosis-in-the-liver-of-dairy-cows-with-ketosis
#6
Xiliang Du, Liang Chen, Dan Huang, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Yiwei Zhu, Zhe Wang, Xinwei Li, Guowen Liu
BACKGROUND/AIMS: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. METHODS: The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28933787/blocking-autophagy-enhances-the-apoptotic-effect-of-18%C3%AE-glycyrrhetinic-acid-on-human-sarcoma-cells-via-endoplasmic-reticulum-stress-and-jnk-activation
#7
Shuying Shen, Menglu Zhou, Kangmao Huang, Yizheng Wu, Yan Ma, Jiying Wang, Jianjun Ma, Shunwu Fan
Sarcoma, a rare form of cancer, is unlike the much more common carcinomas as it occurs in a distinct type of tissue. The potent antitumor effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, have been demonstrated in various cancers. However, the effect of GA on human sarcoma, and the underlying mechanisms, remain to be elucidated. In the current study, we show that GA inhibits sarcoma cell proliferation by inducing G0/G1-phase arrest. Exposure to GA resulted in the activation of caspase-3, -8, and -9, indicating that GA induced apoptosis through both extrinsic and intrinsic pathways...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28931802/hepatitis-c-virus-infection-increases-c-jun-n-terminal-kinase-jnk-phosphorylation-and-accentuates-hepatocyte-lipoapoptosis
#8
Hiroko Takaki, Yuko Akazawa, Youko Kido, Mami Morishita, Takuya Honda, Hidetaka Shibata, Satoshi Miuma, Hisamitsu Miyaaki, Naota Taura, Hisayoshi Kondo, Kazuhiko Nakao
BACKGROUND Hepatitis C virus (HCV) infection and metabolic diseases including nonalcoholic steatohepatitis (NASH) exhibit a complex interplay. Although free fatty acid-mediated apoptosis is a prominent feature of NASH, the impact of HCV infection on hepatocyte lipotoxicity has remained largely unexplored. The study aimed at identifying whether infection by HCV affected the apoptotic pathway in hepatocytes during fatty acid assault. MATERIAL AND METHODS OR6 cells, which are derived from human hepatocellular carcinoma Huh-7 cells and harbor a full-length HCV RNA genome replication system, were treated with palmitate...
September 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28931215/berberine-could-inhibit-thyroid-carcinoma-cells-by-inducing-mitochondrial-apoptosis-g0-g1-cell-cycle-arrest-and-suppressing-migration-via-pi3k-akt-and-mapk-signaling-pathways
#9
Liang Li, Xingchun Wang, Rampersad Sharvan, Jingyang Gao, Shen Qu
Berberine, an important natural isoquinoline alkaloid from traditional Chinese medicine, is reported to exhibit multiple pharmacological properties, including anti-microbial, anti-diabetes, anti-obesity, anti-inflammatory and anti-carcinogenic activities. Although studies have shown that a wide range of carcinoma cells could be inhibited by berberine, few studies involved thyroid carcinoma. We therefore examined the effect of berberine on papillary thyroid carcinoma (PTC, the most common subtype) and anaplastic thyroid carcinoma (ATC, the most malignant and aggressive subtype)...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28930674/a-protein-scaffold-coordinates-src-mediated-jnk-activation-in-response-to-metabolic-stress
#10
Shashi Kant, Claire L Standen, Caroline Morel, Dae Young Jung, Jason K Kim, Wojciech Swat, Richard A Flavell, Roger J Davis
Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28928861/down-regulation-of-rps9-inhibits-osteosarcoma-cell-growth-through-inactivation-of-mapk-signaling-pathway
#11
Dong-Dong Cheng, Bin Zhu, Shi-Jie Li, Ting Yuan, Qing-Cheng Yang, Cun-Yi Fan
Objectives: Osteosarcoma is the most common malignant bone tumor in adolescents; however, the mechanisms involved in the pathogenesis and progression of osteosarcoma remain to be elucidated. Researchers have provided valuable insights into the tumorigenesis of Ribosomal protein S9 (RPS9) in some cancers. The purpose of this study was to elucidate the expression, functions, and mechanisms of RPS9 in human osteosarcoma. Methods: The expression of RPS9 in osteosarcoma tissues and cell lines was evaluated by qRT-PCR and western blotting...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928458/agonist-immunotherapy-restores-t-cell-function-following-mek-inhibition-improving-efficacy-in-breast-cancer
#12
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928277/jnk-activation-of-bim-promotes-hepatic-oxidative-stress-steatosis-and-insulin-resistance-in-obesity
#13
Sara A Litwak, Lokman Pang, Sandra Galic, Mariana Igoillo-Esteve, William J Stanley, Jean-Valery Turatsinze, Kim Loh, Helen E Thomas, Arpeeta Sharma, Eric Trepo, Christophe Moreno, Daniel J Gough, Decio L Eizirik, Judy B de Haan, Esteban N Gurzov
The BCL-2 family are crucial regulators of the mitochondrial pathway of apoptosis in normal physiology and disease. Besides their role in cell death, BCL-2 proteins have been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism. It remains unclear, however, whether these proteins have a physiological role in glucose homeostasis and metabolism in vivo Here we report that fat accumulation in the liver increases JNK-dependent BIM expression in hepatocytes. To determine the consequences of hepatic BIM deficiency in diet-induced obesity, we generated liver-specific BIM knockout (BLKO) mice...
September 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28928235/testosterone-protects-high-fat-low-carbohydrate-diet-induced-non-alcoholic-fatty-liver-disease-in-castrated-male-rats-mainly-via-modulating-er-stress
#14
Yue Jia, Jennifer Kuang Yee, Christina Wang, Liana Nikolaenko, Maruja Diaz-Arjonilla, Joshua N Cohen, Samuel W French, Peter Y Liu, YanHe Lue, Wai-Nang Paul Lee, Ronald S Swerdloff
We previously showed that testosterone (T) deficiency enhanced high-fat diet (HFD) induced hepatic steatosis in rats that was independent of insulin resistance, and that T replacement reduced hepatic macrovesicular fat accumulation and inflammation. The present report explores the mechanism of T-protective effects on HFD-induced steatohepatitis. Adult male rats were randomized into four treatment groups for 15 weeks (intact rats on regular chow diet or HFD, and castrated rats on HFD with/without T replacement)...
September 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28927780/effects-of-metformin-on-proliferation-and-apoptosis-of-human-megakaryoblastic-dami-and-meg-01-cells
#15
Xue Liang, Peiyan Kong, Jin Wang, Yulin Xu, Chunfang Gao, Guozhen Guo
Metformin has received increasing attention for its potential anticancer activity against certain human leukemia cells, but its effects on human megakaryoblastic cells are unclear. This study aimed to investigate the effects of metformin on proliferation and apoptosis of human megakaryoblastic cells (Dami and MEG-01) and the underlying molecular mechanisms. CCK8 assay was employed to measure cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Western blot was further employed to measure apoptosis-related proteins...
August 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28926923/involvement-of-mapk-nf-%C3%AE%C2%BAb-signal-transduction-pathways-camellia-japonica-mitigates-inflammation-and-gastric-ulcer
#16
Md Rashedunnabi Akanda, Byung-Yong Park
Gastric ulcer is an important risk factor for human health globally. Camellia japonica (CJ) is a plant of which the fruits are used as traditional phytomedicine for inflammatory and immunomodulatory diseases; however, the underlying molecular mechanism has not been clarified. The present study aimed to investigate the immunopharmacological activities of Camellia japonica and validate its pharmacological targets. To evaluate the protective roles of Camellia japonica on LPS-induced inflammation in RAW 264.7 cells and HCl/EtOH-induced gastric ulcer in mice; we applied 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), nitric oxide (NO), reactive oxygen species (ROS), histopathology, malondialdehyde (MDA), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blot analyses...
September 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28925592/defining-a-microrna-mrna-interaction-map-for-calcineurin-inhibitor-induced-nephrotoxicity
#17
Christopher J Benway, John Iacomini
Calcineurin inhibitors induce nephrotoxicity through poorly understood mechanisms thereby limiting their use in transplantation and other diseases. Here we define a microRNA (miRNA)-messenger RNA (mRNA) interaction map that facilitates exploration into the role of miRNAs in cyclosporine-induced nephrotoxicity (CIN) and the gene pathways they regulate. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we isolated RNAs associated with Argonaute 2 in the RNA-Induced Silencing Complex (RISC) of cyclosporine A (CsA) treated and control human proximal tubule cells and identified mRNAs undergoing active targeting by miRNAs...
September 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28924347/the-mechanisms-of-graphene-based-materials-induced-programmed-cell-death-a-review-of-apoptosis-autophagy-and-programmed-necrosis
#18
REVIEW
Lingling Ou, Shaoqiang Lin, Bin Song, Jia Liu, Renfa Lai, Longquan Shao
Graphene-based materials (GBMs) are widely used in many fields, including biomedicine. To date, much attention had been paid to the potential unexpected toxic effects of GBMs. Here, we review the recent literature regarding the impact of GBMs on programmed cell death (PCD). Apoptosis, autophagy, and programmed necrosis are three major PCDs. Mechanistic studies demonstrated that the mitochondrial pathways and MAPKs (JNK, ERK, and p38)- and TGF-β-related signaling pathways are implicated in GBMs-induced apoptosis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28924007/multiple-signaling-pathways-coordinately-regulate-forgetting-of-olfactory-adaptation-through-control-of-sensory-responses-in-c-elegans
#19
Tomohiro Kitazono, Sayuri Hara-Kuge, Osamu Matsuda, Akitoshi Inoue, Manabi Fujiwara, Takeshi Ishihara
Forgetting memories is important for animals to properly respond to continuously changing environments. To elucidate the mechanisms of forgetting, we used one of the behavioral plasticities of C. elegans hermaphrodite, olfactory adaptation to an attractive odorant, diacetyl, as a simple model of learning. In C. elegans, the TIR-1/JNK-1 pathway accelerates forgetting of olfactory adaptation by facilitating neural secretion from AWC sensory neurons. In this study, to identify the downstream effectors of the TIR-1/JNK-1 pathway, we conducted a genetic screen for suppressors of the gain-of-function mutant of tir-1 (ok1052), which shows excessive forgetting...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923916/critical-role-of-caveolin-1-in-ocular-neovascularization-and-multitargeted-antiangiogenic-effects-of-cavtratin-via-jnk
#20
Yida Jiang, Xianchai Lin, Zhongshu Tang, Chunsik Lee, Geng Tian, Yuxiang Du, Xiangke Yin, Xiangrong Ren, Lijuan Huang, Zhimin Ye, Wei Chen, Fan Zhang, Jia Mi, Zhiqin Gao, Shasha Wang, Qishan Chen, Liying Xing, Bin Wang, Yihai Cao, William C Sessa, Rong Ju, Yizhi Liu, Xuri Li
Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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