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https://www.readbyqxmd.com/read/29235250/discovery-and-mechanistic-elucidation-of-a-class-of-pdi-inhibitors-for-the-treatment-of-glioblastoma
#1
Anahita Kyani, Shuzo Tamura, Suhui Yang, Andrea Shergalis, Soma Somanta, Yuting Kuang, Mats Ljungman, Nouri Neamati
Protein disulfide isomerase (PDI) is overexpressed in glioblastoma, the most aggressive form of brain cancer, and folds nascent proteins responsible for the progression and spread of the disease. Herein, we describe a novel, nanomolar PDI inhibitor, pyrimidotriazinedione 35G8, that is toxic in a panel of human glioblastoma cell lines. We performed a medium throughput 20,000-compound screen of a diverse subset of 1,000,000 compounds to identify cytotoxic small molecules. Cytotoxic compounds were screened for PDI inhibition, and, from the screen, 35G8 emerged as the most cytotoxic inhibitor of PDI...
December 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29230270/activation-of-nlrp3-inflammasome-by-advanced-glycation-end-products-promotes-pancreatic-islet-damage
#2
Xiang Kong, Ai-Ling Lu, Xin-Ming Yao, Qiang Hua, Xiao-Yong Li, Li Qin, Hong-Mei Zhang, Guang-Xun Meng, Qing Su
Accumulation of advanced glycation end products (AGEs) contributes to ageing and age-related diseases, especially type 2 diabetes. The NLRP3 inflammasome, as a vital component of the innate immune system, is implicated in the pathogenesis of type 2 diabetes. However, the role of the NLRP3 inflammasome in AGE-induced pancreatic islet damage remains largely unclear. Results showed that administration of AGEs (120 mg/kg for 6 weeks) in C57BL/6J mice induced an abnormal response to glucose (as measured by glucose tolerance and insulin release), pancreatic β-cell ultrastructural lesion, and cell death...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29218237/increased-mir-21a-provides-metabolic-advantages-through-suppression-of-fbp1-expression-in-non-small-cell-lung-cancer-cells
#3
Qingchun Dai, Na Li, Xiaohong Zhou
Lung cancer is the most common solid tumor and the leading cause of cancer-related mortality worldwide. miR-21 is one of the most commonly observed aberrant miRNAs in human cancers. However, the biological roles of miR-21 in glucose metabolism of non-small cell lung cancer (NSCLC) cells remain unknown. In the present study, our findings demonstrated that miR-21 promoted glucose uptake and increased TXNIP expression. miR-21 increased lactate generation and decreased oxygen consumption in NSCLC cells. Moreover, we found that miR-21 promoted glycolysis and decreased OXPHOS...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29203232/thioredoxin-interacting-protein-deficiency-ameliorates-diabetic-retinal-angiogenesis
#4
Jialiang Duan, Chunyang Du, Yonghong Shi, Danyan Liu, Jingxue Ma
Diabetic retinopathy is the leading cause of blindness among working-aged adults around the world. Hyperglycemia and intraocular vascular endothelial growth factor (VEGF) over-accumulation are essential for the progression of diabetic retinopathy, which eventually results in proliferative diabetic retinopathy, characterized by pathologic angiogenesis and impaired vision. Thioredoxin-interacting protein (TXNIP) was highly induced in retinal endothelial cells under diabetic conditions. However, the role of TXNIP in diabetes-associated retinal angiogenesis remains elusive...
December 1, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29180214/thioredoxin-1-attenuates-sepsis-induced-cardiomyopathy-after-cecal-ligation-and-puncture-in-mice
#5
Rickesha L Wilson, Vaithinathan Selvaraju, Rajesh Lakshmanan, Mahesh Thirunavukkarasu, Jacob Campbell, David W McFadden, Nilanjana Maulik
BACKGROUND: Sepsis is a leading cause of mortality among patients in intensive care units across the USA. Thioredoxin-1 (Trx-1) is an essential 12 kDa cytosolic protein that, apart from maintaining the cellular redox state, possesses multifunctional properties. In this study, we explored the possibility of controlling adverse myocardial depression by overexpression of Trx-1 in a mouse model of severe sepsis. METHODS: Adult C57BL/6J and Trx-1Tg/+ mice were divided into wild-type sham (WTS), wild-type cecal ligation and puncture (WTCLP), Trx-1Tg/+sham (Trx-1Tg/+S), and Trx-1Tg/+CLP groups...
December 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29169424/-sodium-hydrosulfide-attenuates-myocardial-injury-through-activating-thioredoxin-system-in-diabetic-rats
#6
Qiang Jia, Rui Yang, Xiaofen Liu, Qiyi Wang, Haoyu Lu, Shanfeng Ma
Objective To investigate the effect of exogenous hydrogen sulfide from sodium hydrosulfide (NaHS) on cardiac thioredoxin (Trx) system in diabetic rats. Methods Male Sprague-Dawley rats were randomly divided into a normal group, a diabetic group, and three NaHS (14, 28 and 56 μmol/kg) treatment groups, with 6 rats in each group. Type 1 diabetes was induced in the groups by a single intraperitoneal (i.p.) injection of streptozotocin. At the fifth week after modeling, the NaHS treatment groups were injected (i...
October 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29169415/-over-expression-of-thioredoxin-interacting-protein-promotes-apoptosis-of-min6-cells-via-activating-p38mapk-pathway
#7
Wenzhen Deng, Yang Li, Yanjun Jia, Liang Tang, Qirui He, Dongfang Liu
Objective To investigate the effect of thioredoxin interacting protein (TXNIP) over-expression on the apoptosis of MIN6 β-cells and the mechanism involved. Methods Lentivirus carrying TXNIP gene was used to infect MIN6 β-cells in logarithmic growth phase, and the infection efficiency was evaluated by fluorescence microscope and Western blotting. Then MIN6 β-cells were divided into three groups: control group, empty lentivirus vector (LV-GFP) group and TXNIP over-expression (LV-GFP-TXNIP) group. CCK-8 assay was used to detect cell proliferation...
October 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29164275/dna-methylation-markers-associated-with-type-2-diabetes-fasting-glucose-and-hba1c-levels-a-systematic-review-and-replication-in-a-case-control-sample-of-the-lifelines-study
#8
Eliza Walaszczyk, Mirjam Luijten, Annemieke M W Spijkerman, Marc J Bonder, Helen L Lutgers, Harold Snieder, Bruce H R Wolffenbuttel, Jana V van Vliet-Ostaptchouk
AIMS/HYPOTHESIS: Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study. METHODS: We performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results...
November 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/29156529/alpinetin-improved-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-nafld-through-improving-oxidative-stress-inflammatory-response-and-lipid-metabolism
#9
Yong Zhou, Yin-Lu Ding, Jian-Liang Zhang, Peng Zhang, Jin-Qing Wang, Zhao-Hua Li
The non-alcoholic fatty liver disease (NAFLD) has become a serious medical problem and an increasing threat to public health. It is characterized by the abnormal fat accumulation in liver without excessive alcohol intake. The concurrent NAFLD might up-regulate the risk of chronic kidney disease as well as the mortality rate. Though various drugs have been investigated to attenuate NAFLD, further study is still necessary to find new therapeutic strategy and to reveal the underlying molecular mechanism. In the present study, NAFLD animal models were induced by feeding with high fat (HF) diet for 8 weeks...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29110407/acupuncture-inhibits-txnip-associated-oxidative-stress-and-inflammation-to-attenuate-cognitive-impairment-in-vascular-dementia-rats
#10
Si-Qi Du, Xue-Rui Wang, Wen Zhu, Yang Ye, Jing-Wen Yang, Si-Ming Ma, Cai-Shuo Ji, Cun-Zhi Liu
AIMS: Oxidative stress and inflammation have been implicated in the pathogenesis of vascular dementia (VD). Thioredoxin-interacting protein (TXNIP) plays a vital role in oxidative stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation. There is evidence that acupuncture has an antioxidative and neuroprotective effect in VD. In this study, we investigated whether acupuncture can attenuate cognitive impairment via inhibiting TXNIP-associated oxidative stress and inflammation in VD rats...
November 6, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29101219/mir-204-controls-glucagon-like-peptide-1-receptor-expression-and-agonist-function
#11
SeongHo Jo, Junqin Chen, Guanlan Xu, Truman B Grayson, Lance A Thielen, Anath Shalev
Glucagon-like peptide 1 receptor (GLP1R) agonists are widely used to treat diabetes. However, their function is dependent on adequate GLP1R expression, which is downregulated in diabetes. GLP1R is highly expressed on pancreatic beta cells and activation by endogenous incretin or GLP1R agonists increases cAMP generation, which stimulates glucose-induced beta cell insulin secretion and helps maintain glucose homeostasis. We now have discovered that the highly beta cell-enriched microRNA, miR-204, directly targets the 3'UTR of GLP1R and thereby downregulates its expression in the beta-cell-derived rat INS-1 cell line and primary mouse and human islets...
November 3, 2017: Diabetes
https://www.readbyqxmd.com/read/29077742/dna-methylation-and-gene-expression-of-txnip-in-adult-offspring-of-women-with-diabetes-in-pregnancy
#12
Azadeh Houshmand-Oeregaard, Line Hjort, Louise Kelstrup, Ninna S Hansen, Christa Broholm, Linn Gillberg, Tine D Clausen, Elisabeth R Mathiesen, Peter Damm, Allan Vaag
BACKGROUND: Fetal exposure to maternal diabetes increases the risk of type 2 diabetes (T2DM), possibly mediated by epigenetic mechanisms. Low blood TXNIP DNA methylation has been associated with elevated glucose levels and risk of T2DM, and increased skeletal muscle TXNIP gene expression was reported in subjects with impaired glucose metabolism or T2DM. Subcutaneous adipose tissue (SAT) and skeletal muscle play a key role in the control of whole body glucose metabolism and insulin action...
2017: PloS One
https://www.readbyqxmd.com/read/29055014/protein-acyltransferase-dhhc3-regulates-breast-tumor-growth-oxidative-stress-and-senescence
#13
Martin E Hemler, Chandan Sharma, Hong-Xing Wang, Qinglin Li, Konstantin Knoblich, Emily S Reisenbichler, Andrea L Richardson
DHHC-type protein acyltransferases may regulate the localization, stability and/or activity of their substrates. In this study, we show that the protein palmitoyltransferase DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlated with diminished patient survival in breast cancer and six other human cancer types. ZDHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduced the sizes of both the primary tumor and metastatic lung colonies. Gene array data and fluorescence dye assays documented increased oxidative stress and senescence in ZDHHC3-ablated cells...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29054699/silymarin-attenuated-paraquat-induced-cytotoxicity-in-macrophage-by-regulating-trx-txnip-complex-inhibiting-nlrp3-inflammasome-activation-and-apoptosis
#14
Zhenning Liu, Mingli Sun, Yu Wang, Lichun Zhang, Hang Zhao, Min Zhao
Oxidative stress and inflammation are involved in paraquat-induced cytotoxicity. Silymarin can exert a potent antioxidative and anti-inflammatory effect in various pathophysiological processes. The aim of this current study is to explore the protective effect and potential mechanism of silymarin in paraquat-induced macrophage injury. Cells were pretreated with different doses of silymarin for 3h before exposure to paraquat. At 24h after exposure to paraquat, the paraquat-induced cytotoxicity to macrophage was measured via the MTT assay and LDH release...
October 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29040017/aralia-elata-miq-seem-extract-decreases-o-glcnac-transferase-expression-and-retinal-cell-death-in-diabetic-mice
#15
Yoon Sook Kim, Minjun Kim, Mee Young Choi, Dong Hoon Lee, Gu Seob Roh, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Ki Hun Park, Seong-Jae Kim, Ji-Myong Yoo, Wan Sung Choi
Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice. AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes. Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting...
October 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29031535/baicalin-protects-aml-12-cells-from-lipotoxicity-via-the-suppression-of-er-stress-and-txnip-nlrp3-inflammasome-activation
#16
Junli Zhang, Haiming Zhang, Xiaoling Deng, Yuping Zhang, Keshu Xu
Baicalin (BA) is an active flavonoid compound originating from the root of Scutellaria baicalensis Georgi that has been reported to exert anti-inflammation and anti-oxidant effects in liver diseases with a long history. However, its protective and regulatory mechanisms on palmitic acid (PA) induced hepatocyte lipotoxicity remain elusive. In the present work, we investigated the cytoprotective effects of BA in AML-12 hepatocytes against lipotoxicity by inhibiting ER stress, oxidative stress and apoptosis. Our results demonstrated that ER stress was induced by 400 μM PA in AML-12 cells with elevated expression of ER stress marker IRE1α hyperphosphorylation...
October 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29031534/salidroside-alleviates-high-glucose-induced-oxidative-stress-and-extracellular-matrix-accumulation-in-rat-glomerular-mesangial-cells-by-the-txnip-nlrp3-inflammasome-pathway
#17
Shiying Wang, Xinxin Zhao, Suxia Yang, Baoping Chen, Jun Shi
Diabetic nephropathy (DN) is a metabolic disease characterized by mesangial cell proliferation and extracellular matrix (ECM) accumulation. Salidroside (SAL) is the major ingredient in Rhodiola rosea and possesses beneficial effects on DN. This study aimed to evaluate the effect of SAL on high glucose (HG)-induced oxidative stress and ECM accumulation and the underlying mechanism. Rat glomerular mesangial cells HBZY-1 were induced by high glucose (HG) in the presence or absence of SAL. Cell proliferation was measured by CCK-8 assay...
October 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28988346/lipid-environment-induces-er-stress-txnip-expression-and-inflammation-in-immune-cells-of-individuals-with-type-2-diabetes
#18
Anaïs Szpigel, Isabelle Hainault, Aurélie Carlier, Nicolas Venteclef, Anne-Françoise Batto, Eric Hajduch, Catherine Bernard, Alain Ktorza, Jean-François Gautier, Pascal Ferré, Olivier Bourron, Fabienne Foufelle
AIMS/HYPOTHESIS: Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation...
October 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28980863/addition-of-exogenous-sodium-palmitate-increases-the-iapp-insulin-mrna-ratio-via-gpr40-in-human-endoc-%C3%AE-h1-cells
#19
Camilla Krizhanovskii, Rikard G Fred, Marie E Oskarsson, Gunilla T Westermark, Nils Welsh
BACKGROUND: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human β-cells. METHODS: EndoC-βH1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA expression and secretion were determined using real-time qPCR/ELISA. Pharmacological activators and/or inhibitors and RNAi were used to determine the underlying mechanisms...
August 2017: Upsala Journal of Medical Sciences
https://www.readbyqxmd.com/read/28966753/short-term-high-dose-of-quercetin-and-resveratrol-alters-aging-markers-in-human-kidney-cells
#20
Fatemeh Abharzanjani, Mohammad Afshar, Mina Hemmati, Maryam Moossavi
BACKGROUND: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. METHODS: Human embryonic kidney cell (HEK-293) was cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 100 mM (18 mg/L) for 24 h. The cells were treated with resveratrol (2...
2017: International Journal of Preventive Medicine
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