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https://www.readbyqxmd.com/read/29475133/reactive-oxygen-species-promote-tubular-injury-in-diabetic-nephropathy-the-role-of-the-mitochondrial-ros-txnip-nlrp3-biological-axis
#1
Yachun Han, Xiaoxuan Xu, Chengyuan Tang, Peng Gao, Xianghui Chen, Xiaofen Xiong, Ming Yang, Shikun Yang, Xuejing Zhu, Shuguang Yuan, Fuyou Liu, Li Xiao, Yashpal S Kanwar, Lin Sun
NLRP3/IL-1β activation via thioredoxin (TRX)/thioredoxin-interacting protein (TXNIP) following mitochondria ROS (mtROS) overproduction plays a key role in inflammation. However, the involvement of this process in tubular damage in the kidneys of patients with diabetic nephropathy (DN) is unclear. Here, we demonstrated that mtROS overproduction is accompanied by decreases in TRX expression and TXNIP up-regulation. In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice...
February 15, 2018: Redox Biology
https://www.readbyqxmd.com/read/29456721/combined-treatment-with-d-allose-docetaxel-and-radiation-inhibits-the-tumor-growth-in-an-in-vivo-model-of-head-and-neck-cancer
#2
Hiroshi Hoshikawa, Kazuyo Kamitori, Kanako Indo, Terushige Mori, Mizuna Kamata, Tomoko Takahashi, Masaaki Tokuda
The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433676/bioactive-phytochemicals-that-regulate-the-cellular-processes-involved-in-diabetic-nephropathy
#3
REVIEW
Amna Parveen, Mirim Jin, Sun Yeou Kim
BACKGROUND: Owing to the multiple causative factors, the current advances in medication for diabetic nephropathy (DN) do not appear to have improved therapies for patients. Furthermore, use of multiple synthetic medications has shown various adverse effects and ultimately leads to deterioration of the condition. Medicinal plants and their bioactive constituents are considered to be safer and more effective than synthetic medicines against various chronic diseases. Therefore, the use of natural products in the management of DN has been suggested...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29404777/verapamil-inhibits-ser202-thr205-phosphorylation-of-tau-by-blocking-txnip-ros-p38-mapk-pathway
#4
Mariarosa Anna Beatrice Melone, Clemente Dato, Simona Paladino, Cinzia Coppola, Claudia Trebini, Maria Teresa Giordana, Lorena Perrone
PURPOSE: Oxidative stress is a hallmark of Alzheimer's Disease (AD) and promotes tau phosphorylation. Since Thioredoxin Interacting protein (TXNIP), the inhibitor of the anti-oxidant system of Thioredoxin, is up regulated in the hippocampus of AD patients, we investigated whether TXNIP plays a role in promoting tau phosphorylation and whether Verapamil, an inhibitor of TXNIP expression, prevents TXNIP downstream effects. METHODS: We analyzed TXNIP expression and tau phosphorylation in the hippocampus of the 5xFAD mice in the absence and presence of a pharmacological treatment with Verapamil...
February 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29401599/reduced-endothelial-thioredoxin-interacting-protein-protects-arteries-from-damage-induced-by-metabolic-stress-in-vivo
#5
Tatiana Bedarida, Alison Domingues, Stephanie Baron, Chrystophe Ferreira, Francoise Vibert, Charles-Henry Cottart, Jean-Louis Paul, Virginie Escriou, Pascal Bigey, Pascale Gaussem, Teddy Leguillier, Valerie Nivet-Antoine
Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIPfl/fl cdh5cre). Control (TXNIPfl/fl) and TXNIPfl/fl cdh5cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIPfl/fl and TXNIPfl/fl cdh5cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced...
January 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29399631/dna-methylation-as-a-mediator-of-the-association-between-prenatal-adversity-and-risk-factors-for-metabolic-disease-in-adulthood
#6
Elmar W Tobi, Roderick C Slieker, René Luijk, Koen F Dekkers, Aryeh D Stein, Kate M Xu, P Eline Slagboom, Erik W van Zwet, L H Lumey, Bastiaan T Heijmans
Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29394934/ire1%C3%AE-inhibition-decreased-txnip-nlrp3-inflammasome-activation-through-mir-17-5p-after-neonatal-hypoxic-ischemic-brain-injury-in-rats
#7
Di Chen, Brandon J Dixon, Desislava M Doycheva, Bo Li, Yang Zhang, Qin Hu, Yue He, Zongduo Guo, Derek Nowrangi, Jerry Flores, Valery Filippov, John H Zhang, Jiping Tang
BACKGROUND: The endoplasmic reticulum (ER) is responsible for the control of correct protein folding and protein function which is crucial for cell survival. However, under pathological conditions, such as hypoxia-ischemia (HI), there is an accumulation of unfolded proteins thereby triggering the unfolded protein response (UPR) and causing ER stress which is associated with activation of several stress sensor signaling pathways, one of them being the inositol requiring enzyme-1 alpha (IRE1α) signaling pathway...
February 2, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29386025/mirna-23a-cxcr4-regulates-neuropathic-pain-via-directly-targeting-txnip-nlrp3-inflammasome-axis
#8
Zhiqiang Pan, Qun Shan, Pan Gu, Xiao Min Wang, Lydia Wai Tai, Menglan Sun, Xin Luo, Liting Sun, Chi Wai Cheung
BACKGROUND: Chemokine CXC receptor 4 (CXCR4) in spinal glial cells has been implicated in neuropathic pain. However, the regulatory cascades of CXCR4 in neuropathic pain remain elusive. Here, we investigated the functional regulatory role of miRNAs in the pain process and its interplay with CXCR4 and its downstream signaling. METHODS: miRNAs and CXCR4 and its downstream signaling molecules were measured in the spinal cords of mice with sciatic nerve injury via partial sciatic nerve ligation (pSNL)...
January 31, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29378950/k63-ubiquitylation-triggers-proteasomal-degradation-by-seeding-branched-ubiquitin-chains
#9
Fumiaki Ohtake, Hikaru Tsuchiya, Yasushi Saeki, Keiji Tanaka
Different polyubiquitin chain linkages direct substrates toward distinct cellular pathways. K63-linked ubiquitylation is known to regulate proteasome-independent events such as signal transduction, but its function in the context of heterogeneous ubiquitin chains remains unclear. Here, we report that K63 ubiquitylation plays a critical role in proteasome-mediated substrate degradation by serving as a "seed" for K48/K63 branched ubiquitin chains. Quantitative analysis revealed that K48/K63 branched linkages preferentially associate with proteasomes in cells...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29378331/identification-of-the-txnip-ires-and-characterization-of-the-impact-of-regulatory-ires-trans-acting-factors
#10
Sebastian Lampe, Michael Kunze, Anica Scholz, Thilo F Brauß, Sofia Winslow, Stefan Simm, Mario Keller, Juliana Heidler, Ilka Wittig, Bernhard Brüne, Tobias Schmid
Translation is a tightly regulated process and is predominantly controlled at the level of its initiation. Translation initiation mostly occurs in a cap-dependent manner. Under stress conditions when cap-dependent translation is hampered, internal ribosome entry sites (IRESes) allow for cap-independent translation of certain mRNAs. IRES-dependent translation is commonly regulated by RNA-interacting proteins, known as IRES trans-acting factors (ITAFs). In the present study, we found the 5' untranslated region (UTR) of the thioredoxin-interacting protein (TXNIP) mRNA to be bound by the ITAF hnRNPA1...
January 26, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29356688/diabetes-pathogenic-mechanisms-and-potential-new-therapies-based-upon-a-novel-target-called-txnip
#11
Lance Thielen, Anath Shalev
PURPOSE OF REVIEW: Thioredoxin-interacting protein has emerged as a major factor regulating pancreatic β-cell dysfunction and death, key processes in the pathogenesis of type 1 and type 2 diabetes. Accumulating evidence based on basic, preclinical, and retrospective epidemiological research suggests that TXNIP represents a promising therapeutic target for diabetes. The present review is aimed at providing an update regarding these developments. RECENT FINDINGS: TXNIP has been shown to be induced by glucose and increased in diabetes and to promote β-cell apoptosis, whereas TXNIP deletion protected against diabetes...
January 19, 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29339473/identification-of-thioredoxin-interacting-protein-txnip-as-a-downstream-target-for-igf1-action
#12
Karthik Nagaraj, Lena Lapkina-Gendler, Rive Sarfstein, David Gurwitz, Metsada Pasmanik-Chor, Zvi Laron, Shoshana Yakar, Haim Werner
Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29328484/additive-antitumour-effect-of-d%C3%A2-allose-in-combination-with-cisplatin-in-non-small-cell-lung-cancer-cells
#13
Nobuhiro Kanaji, Kazuyo Kamitori, Akram Hossain, Chisato Noguchi, Ayako Katagi, Norimitsu Kadowaki, Masaaki Tokuda
D‑allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D‑allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D‑allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC‑LCD; adenocarcinomas: A549, HI1017, RERF‑LC‑A1 and NCI-H1975) were treated with D‑allose (50 mM) with or without cisplatin (5 µM)...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328429/anthocyanins-inhibit-high-glucose-induced-renal-tubular-cell-apoptosis-caused-by-oxidative-stress-in-db-db-mice
#14
Jinying Wei, Haijiang Wu, Haiqiang Zhang, Fang Li, Shurui Chen, Baohua Hou, Yonghong Shi, Lijuan Zhao, Huijun Duan
Oxidative stress is an important contributory factor resulting the development of kidney injury in patients with diabetes. Numerous in vitro and in vivo studies have suggested that anthocyanins, natural phenols commonly existing in numerous fruits and vegetables, exhibit important antioxidative, anti‑inflammatory and antihyperlipidemic effects; however, their effects and underlying mechanisms on diabetic nephropathy (DN) have not yet been fully determined. In the present study, the regulation of apoptosis metabolism and antioxidative effects exhibited by anthocyanins [grape seed procyanidin (GSPE) and cyanidin‑3‑O‑β‑glucoside chloride (C3G)] were investigated, and the molecular mechanism underlying this process was investigated in vivo and in vitro...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29325019/deep-molecular-phenotypes-link-complex-disorders-and-physiological-insult-to-cpg-methylation
#15
Shaza B Zaghlool, Dennis O Mook-Kanamori, Sara Kader, Nisha Stephan, Anna Halama, Rudolf Engelke, Hina Sarwath, Eman K Al-Dous, Yasmin A Mohamoud, Werner Roemisch-Margl, Jerzy Adamski, Gabi Kastenmüller, Nele Friedrich, Alessia Visconti, Pei-Chien Tsai, Tim Spector, Jordana Bell, Mario Falchi, Annika Wahl, Melanie Waldenberger, Annette Peters, Christian Gieger, Maija Pezer, Gordan Lauc, Johannes Graumann, Joel A Malek, Karsten Suhre
Epigenetic regulation of cellular function provides a mechanism for rapid organismal adaptation to changes in health, lifestyle, and environment. Associations of cytosine-guanine di-nucleotide (CpG) methylation with clinical endpoints that overlap with metabolic phenotypes suggest a regulatory role for these CpG sites in the body's response to disease or environmental stress. We previously identified 20 CpG sites in an epigenome-wide association study (EWAS) with metabolomics that were also associated in recent EWASs with diabetes-, obesity-, and smoking-related endpoints...
January 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29322219/sirt6-mediated-transcriptional-suppression-of-txnip-is-critical-for-pancreatic-beta-cell-function-and-survival-in-mice
#16
Kunhua Qin, Ning Zhang, Zhao Zhang, Michael Nipper, Zhenxin Zhu, Jake Leighton, Kexin Xu, Nicolas Musi, Pei Wang
AIMS/HYPOTHESIS: Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. METHODS: Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system...
January 10, 2018: Diabetologia
https://www.readbyqxmd.com/read/29282201/mondoa-is-an-essential-glucose-responsive-transcription-factor-in-human-pancreatic-beta-cells
#17
Paul Richards, Latif Rachdi, Masaya Oshima, Piero Marchetti, Marco Bugliani, Mathieu Armanet, Catherine Postic, Sandra Guilmeau, Raphael Scharfmann
While the mechanisms by which glucose regulates insulin secretion from pancreatic beta cells are now well described, the way glucose modulates gene expression in such cells needs more understanding. Here, we demonstrate that MondoA, but not its paralogue ChREBP, is the predominant glucose-responsive transcription factor in human pancreatic beta EndoC-βH1 cells and in human islets. In high glucose conditions, MondoA shuttles to the nucleus where it is required for the induction of the glucose-responsive genes ARRDC4 and TXNIP, the latter being a protein strongly linked to beta-cell dysfunction and diabetes...
December 27, 2017: Diabetes
https://www.readbyqxmd.com/read/29278702/hypoxia-potentiates-lps-induced-inflammatory-response-and-increases-cell-death-by-promoting-nlrp3-inflammasome-activation-in-pancreatic-%C3%AE-cells
#18
Cheng Chen, Xiaoqian Ma, Cejun Yang, Wei Nie, Juan Zhang, Hongde Li, Pengfei Rong, Shounan Yi, Wei Wang
Hypoxia and islet inflammation are involved in β-cell failure in type 2 diabetes (T2D). Elevated plasma LPS levels have been verified in patients with T2D, and hypoxia occurs in islets of diabetic mice. Activation of inflammasomes in ischemic or hypoxic conditions was identified in various tissues. Here, we investigated whether hypoxia activates the inflammasome in β cells and the possible mechanisms involved. In mouse insulinoma cell line 6 (MIN6), hypoxia (1% O2) primes the NLRP3 inflammasome along with NF-κB signaling activation...
December 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29248547/dual-role-of-ezh2-in-cutaneous-anaplastic-large-cell-lymphoma-promoting-tumor-cell-survival-and-regulating-tumor-microenvironment
#19
Shengguo Yi, Jingru Sun, Lei Qiu, Wenjing Fu, Anqi Wang, Xiaoqing Liu, Yong Yang, Marshall E Kadin, Ping Tu, Yang Wang
Primary cutaneous anaplastic T cell lymphoma (PCALCL), characterized by the CD30+ anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma (CTCL). Little is known about the mechanisms of disease progression. Here we report that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2) which mediates histone H3 lysine 27 trimethylation (H3K27me3), is over-expressed in CD30+ anaplastic cells in PCALCL and large-cell transformed CTCL...
December 14, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29245343/altered-expression-of-txnip-in-the-peripheral-leukocytes-of-patients-with-coronary-atherosclerotic-heart-disease
#20
Yujing Zhang, Jian Huang, Xinglin Yang, Xiaofei Sun, Qincheng Xu, Baokui Wang, Peng Zhong, Zixiu Wei
BACKGROUND: Coronary atherosclerotic heart disease (CAD) is mainly caused by atherosclerosis, an inflammatory disease characterized by plaque formation in arteries. Reactive oxygen species caused structural damage and dysfunction of arterial endothelial cells. Thioredoxin-interacting protein (TXNIP) is the endogenous inhibitor and regulator of thioredoxin, a major cellular antioxidant and antiapoptotic system. In order to explore the role of TXNIP in the occurrence and development of CAD, we detected the TXNIP expression and discussed its molecular mechanisms in CAD...
December 2017: Medicine (Baltimore)
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