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https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#1
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28817808/ppar%C3%AE-agonist-stimulated-angiogenesis-by-improving-endothelial-precursor-cell-function-via-a-nlrp3-inflammasome-pathway
#2
Yaping Deng, Xue Han, Zheng Yao, Yuannan Sun, Jiawen Yu, Jian Cai, Guofei Ren, Guojun Jiang, Feng Han
BACKGROUND: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators-activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28811274/hypoxia-in-combination-with-muscle-contraction-improves-insulin-action-and-glucose-metabolism-in-human-skeletal-muscle-via-the-hif-1%C3%AE-pathway
#3
Sven W Görgens, Tim Benninghoff, Kristin Eckardt, Christian Springer, Alexandra Chadt, Anita Melior, Jakob Wefers, Andrea Cramer, Jørgen Jensen, Kåre I Birkeland, Christian A Drevon, Hadi Al-Hasani, Jürgen Eckel
Skeletal muscle insulin resistance is the hallmark of type 2 diabetes, and develops long before the onset of the disease. It is well accepted that physical activity improves glycemic control but the knowledge on underlying mechanisms mediating the beneficial effects remains incomplete. Exercise is accompanied by a decrease in intramuscular oxygen levels resulting in induction of HIF-1α. HIF-1α is a master regulator of gene expression and might play an important role in skeletal muscle function and metabolism...
August 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28800542/digitoflavone-dg-attenuates-lps-induced-acute-lung-injury-through-reducing-oxidative-stress-and-inflammatory-response-dependent-on-the-suppression-of-txnip-nlrp3-and-nf-%C3%AE%C2%BAb
#4
Min Meng
Acute lung injury is a severe disease with a high rate of mortality. Digitoflavone (DG) was suggested to possess bioactivities to reduce oxidative stress, inflammation and to regulate apoptosis. In our study, the normal saline, a low dose of DG (12.5mg/kg), a medium dose of DG (25mg/kg) and a high dose of DG (50mg/kg) were administered to male C57BL/6 mice by gavage. And then, the mice were intratracheally injected with either normal saline or lipopolysaccharide (LPS). We found that DG ameliorated LPS-induced lung injury and platelets activation, accompanied with reduced CD41 expression and neutrophil platelet aggregates (NPAs)...
August 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28797239/nutrient-supply-affects-the-mrna-expression-profile-of-the-porcine-skeletal-muscle
#5
Tainã Figueiredo Cardoso, Raquel Quintanilla, Joan Tibau, Marta Gil, Emilio Mármol-Sánchez, Olga González-Rodríguez, Rayner González-Prendes, Marcel Amills
BACKGROUND: The genetic basis of muscle fat deposition in pigs is not well known. So far, we have only identified a limited number of genes involved in the absorption, transport, storage and catabolism of lipids. Such information is crucial to interpret, from a biological perspective, the results of genome-wide association analyses for intramuscular fat content and composition traits. Herewith, we have investigated how the ingestion of food changes gene expression in the gluteus medius muscle of Duroc pigs...
August 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28790925/nlrp3-inflammasome-as-a-molecular-marker-in-diabetic-cardiomyopathy
#6
REVIEW
Beibei Luo, Feng Huang, Yanli Liu, Yiying Liang, Zhe Wei, Honghong Ke, Zhiyu Zeng, Weiqiang Huang, Yan He
Diabetic cardiomyopathy (DCM), a common consequence of longstanding diabetes mellitus, is initiated by death of cardiomyocyte. Hyperglycemia-induced reactive oxygen species (ROS) overproduction is a major contributor of the chronic low-grade inflammation that characterizes as the DCM. ROS may promote the activation of nucleotide-binding oligomerization domain like receptor (NLR) pyrin domain containing 3 (NLRP3) inflammasome, a novel regulator of inflammation and cell death, by nuclear factor-kB (NF-κB) and thioredoxin interacting/inhibiting protein (TXNIP)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28765935/fbw7-increases-the-chemosensitivity-of-pancreatic-cancer-cells-to-gemcitabine-through-upregulation-of-ent1
#7
Qiangsheng Hu, Yi Qin, Bo Zhang, Chen Liang, Shunrong Ji, Si Shi, Wenyan Xu, Jinfeng Xiang, Dingkong Liang, Quanxing Ni, Xianjun Yu, Jin Xu
F-box and WD repeat domain-containing 7 (FBW7) has been characterized as a tumor suppressor, and its mutation or decreased expression has been observed in many types of human cancers. Our recent studies have uncovered that in pancreatic cancer, the KRAS mutation decreased FBW7 expression through phosphorylation and subsequent ubiquitination. Moreover, FBW7 inhibited aerobic glycolysis in pancreatic cancer via induction of thioredoxin-interacting protein (TXNIP), a mitochondrial localized tumor suppressor. The roles of FBW7 in anti-apoptosis and drug resistance via proteosomal degradation of myeloid cell leukemia-1 (MCL-1), which is an anti-apoptotic factor have been reported...
July 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28764817/the-rpmi-1640-vitamin-mixture-promotes-bovine-blastocyst-development-in-vitro-and-downregulates-gene-expression-of-txnip-with-epigenetic-modification-of-associated-histones
#8
S Ikeda, M Sugimoto, S Kume
Diverse environmental conditions surrounding preimplantation embryos, including available nutrients, affect their metabolism and development in both short- and long-term manner. Thioredoxin-interacting protein (TXNIP) is a possible marker for preimplantation stress that is implicated in in vitro fertilization- (IVF) induced long-term DOHaD effects. B vitamins, as participants in one-carbon metabolism, may affect preimplantation embryos by epigenetic alterations of metabolically and developmentally important genes...
August 2, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28761062/t2diacod-a-gene-atlas-of-type-2-diabetes-mellitus-associated-complex-disorders
#9
Jyoti Rani, Inna Mittal, Atreyi Pramanik, Namita Singh, Namita Dube, Smriti Sharma, Bhanwar Lal Puniya, Muthukurussi Varieth Raghunandanan, Ahmed Mobeen, Srinivasan Ramachandran
We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus. They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression. The database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28755477/thioredoxin-interacting-protein-induced-%C3%AE-synuclein-accumulation-via-inhibition-of-autophagic-flux-implications-for-parkinson-s-disease
#10
Cun-Jin Su, Yu Feng, Teng-Teng Liu, Xu Liu, Jun-Jie Bao, Ai-Ming Shi, Duan-Min Hu, Tong Liu, Yun-Li Yu
AIMS: Thioredoxin-interacting protein (TXNIP) is associated with activation of oxidative stress through inhibition of thioredoxin (Trx). However, some evidences point out that TXNIP acts as a scaffolding protein in signaling complex independent of cellular redox regulation. The autophagy-lysosomal pathway plays important roles in the clearance of misfolded proteins and dysfunctional organelles. Lysosomal dysfunction has been involved in several neurodegenerative disorders including Parkinson's disease (PD)...
July 29, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#11
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28712392/-protection-of-rho-associated-protein-kinase-inhibitor-y-27632-in-mrl-lpr-mice
#12
Yuanyuan Wang, Xiaoyun Jia, Qiyi Wang, Ming Ye, Yang Lu, Jiajia Zhang, Sheng Chen, Yanglei Li, Junying Wu, Changhao Xie
Objective To investigate the immunological effect of Rho-associated protein kinase inhibitor Y-27632 on MRL/lpr mice and explore its underlying mechanisms. Methods The study collected 10 wild-type C57BL/6 mice as normal controls and 20 MRL/lpr mice that were randomly assigned to MRL/lpr group and 5 mg/kg Y-27632-treated MRL/lpr group, with 10 mice in each group. Superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), interleukin 6 (IL-6), IL-1β and tumor necrosis factor α (TNF-α) in the serum or spleen were detected by ELISA...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28700004/dexmedetomidine-protects-against-renal-ischemia-and-reperfusion-injury-by-inhibiting-the-p38-mapk-txnip-signaling-activation-in-streptozotocin-induced-diabetic-rats
#13
Xiao Yeda, Lei Shaoqing, Huang Yayi, Zhao Bo, Wang Huaxin, Cao Hong, Xia Zhongyuan
Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion...
June 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28694028/the-pivotal-role-of-extracellular-signal-regulated-kinase-in-gap-junction-mediated-regulation-of-txnip
#14
Shan Gao, Xiling Zhang, Kun Gao, Zhen Zhang, Yanru Huang, Ryuichi Yoda, Jian Yao
Gap junctions (GJs) play a major role in the control of cell structure, function, and metabolism. However, the molecular mechanisms involved are still poorly understood. Given that thioredoxin-interacting protein (TXNIP) regulates a broad range of cellular processes, we tested the possible involvement of TXNIP. Disruption of GJs with several chemical GJ inhibitors or connexin43 (Cx43) siRNA potently suppressed TXNIP, which was preceded by an activation of extracellular signal-regulated kinase (ERK). Inhibition of ERK or its upstream kinase with chemical inhibitors prevented the reduction of TXNIP...
July 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28669627/endogenous-hydrogen-sulfide-mediated-mapk-inhibition-preserves-endothelial-function-through-txnip-signaling
#15
Danyang Tian, Jinghui Dong, Sheng Jin, Xu Teng, Yuming Wu
Mounting evidence demonstrated deficient cystathionine-γ-lyase (CSE)/H2S implicated the development of cardiovascular disease. The present study aimed to evaluating the favorable action of CSE derived H2S on endothelial function in CSE(-/-) mice. CSE(-/-) mice exhibited attenuated endothelium-dependent relaxations, coupled with reduction of endothelial nitric oxide synthase (eNOS) phosphorylation at site of Ser1177, increase of thioredoxin interacting protein (TXNIP) level and MAPK phosphorylation, which were corrected by sodium hydrosulfide chronic treatment for 8 weeks...
June 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28661427/deletion-of-txnip-mitigates-high-fat-diet-impaired-angiogenesis-and-prevents-inflammation-in-a-mouse-model-of-critical-limb-ischemia
#16
Sally L Elshaer, Islam N Mohamed, Maha Coucha, Sara Altantawi, Wael Eldahshan, Megan L Bartasi, Ahmed Y Shanab, Renee Lorys, Azza B El-Remessy
BACKGROUND: Previous work demonstrated that high-fat diet (HFD) triggered thioredoxin-interacting protein (TXNIP) and that silencing TXNIP prevents diabetes-impaired vascular recovery. Here, we examine the impact of genetic deletion of TXNIP on HFD-impaired vascular recovery using hind limb ischemia model. METHODS: Wild type mice (WT, C57Bl/6) and TXNIP knockout mice (TKO) were fed either normal chow diet (WT-ND and TKO-ND) or 60% high-fat diet (WT-HFD and TKO-HFD)...
June 29, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28651973/1-25-oh-2d3-disrupts-glucose-metabolism-in-prostate-cancer-cells-leading-to-a-truncation-of-the-tca-cycle-and-inhibition-of-txnip-expression
#17
Mohamed A Abu El Maaty, Hamed Alborzinia, Shehryar J Khan, Michael Büttner, Stefan Wölfl
Prostate cell metabolism exhibits distinct profiles pre- and post-malignancy. The malignant metabolic shift converts prostate cells from "citrate-producing" to "citrate-oxidizing" cells, thereby enhancing glucose metabolism, a phenotype that contrasts classical tumoral Warburg metabolism. An on-line biosensor chip system (BIONAS 2500) was used to monitor metabolic changes (glycolysis and respiration) in response to the putative anti-cancer nutraceutical 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], in different prostate cancer (PCa) cell lines (LNCaP, VCaP, DU145 and PC3)...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#18
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28606928/mtor-controls-chrebp-transcriptional-activity-and-pancreatic-%C3%AE-cell-survival-under-diabetic-stress
#19
Gia Cac Chau, Dong Uk Im, Tong Mook Kang, Jeong Mo Bae, Won Kim, Suhkneung Pyo, Eun-Yi Moon, Sung Hee Um
Impaired nutrient sensing and dysregulated glucose homeostasis are common in diabetes. However, how nutrient-sensitive signaling components control glucose homeostasis and β cell survival under diabetic stress is not well understood. Here, we show that mice lacking the core nutrient-sensitive signaling component mammalian target of rapamycin (mTOR) in β cells exhibit reduced β cell mass and smaller islets. mTOR deficiency leads to a severe reduction in β cell survival and increased mitochondrial oxidative stress in chemical-induced diabetes...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28606927/mtorc-in-%C3%AE-cells-more-than-only-recognizing-comestibles
#20
Kathrin Maedler, Amin Ardestani
The pathways regulating pancreatic β cell survival in diabetes are poorly understood. Here, Chau et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201701085) demonstrate that mTOR regulates the apoptotic machinery through binding to the ChREBP-Mlx complex to suppress TXNIP, thereby protecting pancreatic β cells in the diabetic setting by inhibiting oxidative stress and mitochondrial dysfunction.
July 3, 2017: Journal of Cell Biology
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