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https://www.readbyqxmd.com/read/28822855/tetrandrine-cardioprotection-in-ischemia-reperfusion-i-r-injury-via-jak3-stat3-hexokinase-ii
#1
Tie-Jun Zhang, Rui-Xia Guo, Xia Li, Yan-Wei Wang, Yong-Jun Li
Tetrandrine(TET), a bisbenzylisoquinoline alkaloid has been used for the treatment of cardiovascular diseases and hypertension. This study was to investigate whether tetrandrine exerts cardioprotection in ischemia-reperfusion (I/R) injury and the mechanisms involved. The cardioprotection effect and mechanisms of tetrandrine was evaluated by I/R injury cardiac cell model. Hexokinase II (HKII) is the critical regulators of mitochondrial dysfunction in cardiac I/R injury and it participate in the regulation of glycolysis and energy metabolism...
August 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28819023/therapeutic-effects-of-xpo1-inhibition-in-thymic-epithelial-tumors
#2
Fabio Conforti, Xu Zhang, Guanhua Rao, Tommaso De Pas, Yoko Yonemori, Jose A Rodriguez, Justine N McCutcheon, Raneen Rahhal, Anna T Alberobello, Yisong Wang, Yu-Wen Zhang, Udayan Guha, Giuseppe Giaccone
Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export (SINE) compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins (TSP) including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells and induces p53-dependent and -independent antitumor activity in vitro...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28776225/forced-expression-of-vascular-endothelial-growth-factor-a-in-podocytes-decreases-mesangial-cell-numbers-and-attenuates-endothelial-cell-differentiation-in-the-mouse-glomerulus
#3
Masahiro Suyama, Yoichi Miyazaki, Taiji Matsusaka, Naoki Sugano, Hiroyuki Ueda, Tetsuya Kawamura, Makoto Ogura, Takashi Yokoo
BACKGROUND: Glomerular podocyte-derived vascular endothelial growth factor (VEGF) is indispensable for the migration and proliferation of glomerular endothelial cells. In contrast, podocyte-specific Vegf overexpression leads to the collapse of glomerular tufts; however, the mechanisms underlying this outcome have not yet been reported. METHODS: To further clarify the effects of elevated levels of Vegf expression on glomerular cells, we established a dual transgenic mouse line in which Vegf was exclusively and inducibly expressed in podocytes under the control of the "Tet-on system" (Podocin-rtTA/TetO-Vegf164 mice)...
August 3, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28740169/analysis-of-newly-detected-tetracycline-resistance-genes-and-their-flanking-sequences-in-human-intestinal-bifidobacteria
#4
Na Wang, Xiaomin Hang, Min Zhang, Xianglong Liu, Hong Yang
Due to tetracycline abuse, the safe bifidobacteria in the human gastrointestinal intestinal tract (GIT) may serve as a reservoir of tetracycline resistance genes. In the present investigation of 92 bifidobacterial strains originating from the human GIT, tetracycline resistance in 29 strains was mediated by the tet(W), tet(O) or tet(S) gene, and this is the first report of tet(O)- and tet(S)-mediated tetracycline resistance in bifidobacteria. Antibiotic resistance genes harbored by bifidobacteria are transferred from other bacteria...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738272/evolution-of-corresponding-resistance-genes-in-the-water-of-fish-tanks-with-multiple-stresses-of-antibiotics-and-heavy-metals
#5
Xiaolin He, Yanbin Xu, Jinliang Chen, Jiayin Ling, Yafei Li, Lu Huang, Xiao Zhou, Li Zheng, Guangyan Xie
Abuse of antibiotics and heavy metals in aquaculture has been widely concerned and might aggravate the spread of resistance genes in environment. To investigate the occurrence and proliferation of antibiotic resistance genes (ARGs) and heavy metal resistance genes (HMRGs), three commonly used antibiotics (tetracycline, sulfanilamide, cefotaxime) and two heavy metals (Zn and Cu) were designed to add individually or jointly in nine fish tanks including five individual exposure tanks of tetracycline (tet), sulfanilamide (sul), cefotaxime (cef), Cu, Zn and four combination exposure tanks of tetracycline + sulfanilamide (tet + sul), tetracycline + sulfanilamide + cefotaxime (tet + sul + cef), tetracycline + sulfanilamide + Cu (tet + sul + Cu), tetracycline + sulfanilamide + Zn (tet + sul + Zn) as well as the control during the experiment period of 180 days...
July 19, 2017: Water Research
https://www.readbyqxmd.com/read/28731140/integrated-analysis-of-genome%C3%A2-wide-gene-expression-and-dna-methylation-microarray-of-diffuse-large-b%C3%A2-cell-lymphoma-with-tet-mutations
#6
Pengfei Liu, Wenhua Jiang, Jinkun Zhao, Huilai Zhang
Diffuse large B-cell lymphoma (DLBCL), the most frequently occurring type of lymphoid malignancy, has been demonstrated to be associated with mutations of Ten‑Eleven Translocation (TET). In order to explore the association between DLBCL and TET mutations, the present study analyzed the gene expression and methylation profiles in human DLBCL biopsy tissues with wildtype and mutated TET2. The microarray dataset GSE37365, containing two subseries: the genome‑wide gene expression dataset GSE37362 and the DNA methylation microarray dataset GSE37363, was downloaded from the Gene Expression Omnibus database...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28727740/genetically-engineered-suicide-gene-in-mesenchymal-stem-cells-using-a-tet-on-system-for-anaplastic-thyroid-cancer
#7
Senthilkumar Kalimuthu, Ji Min Oh, Prakash Gangadaran, Liya Zhu, Ho Won Lee, Yong Hyun Jeon, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Anaplastic thyroid cancer (ATC) is the most aggressive malignancy of the thyroid, during which undifferentiated tumors arise from the thyroid follicular epithelium. ATC has a very poor prognosis due to its aggressive behavior and poor response to conventional therapies. Gene-directed enzyme/prodrug therapy using genetically engineered mesenchymal stromal cells (MSC) is a promising therapeutic strategy. The doxycycline (DOX)-controlled Tet inducible system is the most widely utilized regulatory system and could be a useful tool for therapeutic gene-based therapies...
2017: PloS One
https://www.readbyqxmd.com/read/28716722/dynamics-of-proliferative-and-quiescent-stem-cells-in-liver-homeostasis-and-injury
#8
Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M A Verstegen, Marcel J C Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk Ten Berge, Dave Sprengers, Herold J Metselaar, Luc J W van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P Peppelenbosch, Qiuwei Pan
BACKGROUND & AIMS: Adult liver stem cells are usually maintained in a quiescent/slow cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. METHODS: We studied LGR5-positive stem cells using diphtheria toxin receptor (DTR) and green fluorescent protein (GFP) knock-in mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28680748/mycn-is-an-immunosuppressive-oncogene-dampening-the-expression-of-ligands-for-nk-cell-activating-receptors-in-human-high-risk-neuroblastoma
#9
Elisa Brandetti, Irene Veneziani, Ombretta Melaiu, Annalisa Pezzolo, Aurora Castellano, Renata Boldrini, Elisa Ferretti, Doriana Fruci, Lorenzo Moretta, Vito Pistoia, Franco Locatelli, Loredana Cifaldi
Neuroblastoma (NB) is the most common extracranial solid tumor occurring in childhood. Amplification of the MYCN oncogene is associated with poor prognosis. Downregulation on NB cells of ligands recognized by Natural Killer (NK) cell-activating receptors, involved in tumor cell recognition and lysis, may contribute to tumor progression and relapse. Here, we demonstrate that in human NB cell lines MYCN expression inversely correlates with that of ligands recognized by NKG2D and DNAM1 activating receptors in human NB cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28678681/profiling-of-oxbs-450k-5-hydroxymethylcytosine-in-human-placenta-and-brain-reveals-enrichment-at-imprinted-loci
#10
Jose Ramon Hernandez Mora, Marta Sanchez-Delgado, Paolo Petazzi, Sebastian Moran, Manel Esteller, Isabel Iglesias-Platas, David Monk
DNA methylation (5-methylcytosine, 5mC) is involved in many cellular processes and is an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that 5mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the "sixth base" of DNA and provides additional complexity to what was originally thought to be a stable repressive mark. However, our knowledge of the genome-wide distribution of 5hmC in different tissues is currently limited. Here, we sought to define loci enriched for 5hmC in the placenta genome by combining oxidative bisulphite (oxBS) treatment with high-density Illumina Infinium HumanMethylation450 methylation arrays and to compare our results with those obtained in brain...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28668389/inducible-liver-specific-overexpression-of-gankyrin-in-zebrafish-results-in-spontaneous-intrahepatic-cholangiocarcinoma-and-hepatocellular-carcinoma-formation
#11
Shin-Jie Huang, Chih-Lun Cheng, Jim-Ray Chen, Hong-Yi Gong, Wangta Liu, Jen-Leih Wu
Liver cancer is the second leading cause of death worldwide. As such, establishing animal models of the disease is important for both basic and translational studies that move toward developing new therapies. Gankyrin is a critical oncoprotein in the genetic control of liver pathology. In order to evaluate the oncogenic role of gankyrin without cancer cell inoculation and drug treatment, we overexpressed gankyrin under the control of the fabp10a promoter. A Tet-Off system was used to drive expression in hepatocytes...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28660881/ten-eleven-translocation-2-interacts-with-forkhead-box-o3-and-regulates-adult-neurogenesis
#12
Xuekun Li, Bing Yao, Li Chen, Yunhee Kang, Yujing Li, Ying Cheng, Liping Li, Li Lin, Zhiqin Wang, Mengli Wang, Feng Pan, Qing Dai, Wei Zhang, Hao Wu, Qiang Shu, Zhaohui Qin, Chuan He, Mingjiang Xu, Peng Jin
Emerging evidence suggests that active DNA demethylation machinery plays important epigenetic roles in mammalian adult neurogenesis; however, the precise molecular mechanisms and critical functional players of DNA demethylation in this process remain largely unexplored. Ten-eleven translocation (Tet) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and its downstream derivatives. Here we show that 5hmC is elevated during the differentiation of adult neural stem cells (aNSCs), and Tet2 is primarily responsible for modulating 5hmC dynamics...
June 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28652359/triplet-triplet-energy-transfer-in-artificial-and-natural-photosynthetic-antennas
#13
Junming Ho, Elizabeth Kish, Dalvin D Méndez-Hernández, Katherine WongCarter, Smitha Pillai, Gerdenis Kodis, Jens Niklas, Oleg G Poluektov, Devens Gust, Thomas A Moore, Ana L Moore, Victor S Batista, Bruno Robert
In photosynthetic organisms, protection against photooxidative stress due to singlet oxygen is provided by carotenoid molecules, which quench chlorophyll triplet species before they can sensitize singlet oxygen formation. In anoxygenic photosynthetic organisms, in which exposure to oxygen is low, chlorophyll-to-carotenoid triplet-triplet energy transfer (T-TET) is slow, in the tens of nanoseconds range, whereas it is ultrafast in the oxygen-rich chloroplasts of oxygen-evolving photosynthetic organisms. To better understand the structural features and resulting electronic coupling that leads to T-TET dynamics adapted to ambient oxygen activity, we have carried out experimental and theoretical studies of two isomeric carotenoporphyrin molecular dyads having different conformations and therefore different interchromophore electronic interactions...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28651214/dna-methylation-and-the-preservation-of-cell-identity
#14
REVIEW
Ozren Bogdanović, Ryan Lister
DNA methylation is a major epigenetic modification of vertebrate genomes that is mostly associated with transcriptional repression. During embryogenesis, DNA methylation together with other epigenetic factors plays an essential role in selecting and maintaining cell identity. Recent technological advances are now allowing for the exploration of this mark at unprecedented resolution. This has resulted in a wealth of studies describing the developmental roles of DNA methylation in various vertebrate model systems...
June 23, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#15
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642344/a-role-for-tet2-in-parathyroid-carcinoma
#16
Elham Barazeghi, Anthony J Gill, Stan Sidhu, Olov Norlén, Roberto Dina, F Fausto Palazzo, Per Hellman, Peter Stålberg, Gunnar Westin
Primary hyperparathyroidism (pHPT) is rarely caused by parathyroid carcinoma (PC, <1-5% of pHPT cases). The TET proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and inactivation by mutation or epigenetic deregulation of TET1 and TET2 play important roles in various cancers. Recently, we found that 5hmC was severely reduced in all of the analyzed PCs and with deranged expression of TET1 for the majority of PCs. Here, we have examined the expression of the TET2 protein in 15 5hmC-negative PCs from patients who had local invasion or metastases...
July 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28629934/recent-advances-in-leishmania-reverse-genetics-manipulating-a-manipulative-parasite
#17
REVIEW
Samuel M Duncan, Nathaniel G Jones, Jeremy C Mottram
In this review we describe the expanding repertoire of molecular tools with which to study gene function in Leishmania. Specifically we review the tools available for studying functions of essential genes, such as plasmid shuffle and DiCre, as well as the rapidly expanding portfolio of available CRISPR/Cas9 approaches for large scale gene knockout and endogenous tagging. We include detail on approaches that allow the direct manipulation of RNA using RNAi and protein levels via Tet or DiCre induced overexpression and destabilization domain mediated degradation...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28623268/ascorbate-induces-apoptosis-in-melanoma-cells-by-suppressing-clusterin-expression
#18
Sushmita Mustafi, David W Sant, Zhao-Jun Liu, Gaofeng Wang
Pharmacological levels of ascorbate have long been suggested as a potential treatment of cancer. However, we observed that EC50 of ascorbate was at a similar level for cultured healthy melanocytes and melanoma cells, suggesting a limit of pharmacological ascorbate in treating cancer. Loss of 5-hydroxymethylcytosine (5 hmC) is an epigenetic hallmark of cancer and ascorbate promotes 5 hmC generation by serving as a cofactor for TET methylcytosine dioxygenases. Our previous work demonstrated that ascorbate treatment at physiological level (100 μM) increased 5 hmC content in melanoma cells toward the level of healthy melanocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613399/immunosuppressive-efficacy-of-tetrandrine-combined-with-methylprednisolone-against-mitogen-activated-peripheral-blood-mononuclear-cells-of-haemodialysis-patients
#19
Wencheng Xu, Kehan Meng, Junichi Kusano, Hiroto Matsuda, Yoshikazu Hara, Yoshiaki Fujii, Shinya Suzuki, Eiki Ando, Xiaoqin Wang, Yuanchao Tu, Sachiko Tanaka, Kentaro Sugiyama, Haruki Yamada, Toshihiko Hirano
Immunosuppressive therapy for prevention of acute rejection episode occasionally causes serious adverse effects, and thus it is important to develop new therapeutic approach for renal transplant recipients. This study evaluated the immunosuppressive pharmacodynamics of tetrandrine (TET) and/or methylprednisolone (MP) in haemodialysis patients in vitro by using the peripheral blood mononuclear cells (PBMCs) isolated from whole blood of haemodialysis patients. The median (range) of MP IC50 values against the proliferation of patients PBMCs was 7...
September 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28609472/no-evidence-for-genome-editing-in-mouse-zygotes-and-hek293t-human-cell-line-using-the-dna-guided-natronobacterium-gregoryi-argonaute-ngago
#20
Nay Chi Khin, Jenna L Lowe, Lora M Jensen, Gaetan Burgio
A recently published research article reported that the extreme halophile archaebacterium Natronobacterium gregoryi Argonaute enzyme (NgAgo) could cleave the cellular DNA under physiological temperature conditions in cell line and be implemented as an alternative to CRISPR/Cas9 genome editing technology. We assessed this claim in mouse zygotes for four loci (Sptb, Tet-1, Tet-2 and Tet-3) and in the human HEK293T cell line for the EMX1 locus. Over 100 zygotes were microinjected with nls-NgAgo-GK plasmid provided from Addgene and various concentrations of 5'-phosphorylated guide DNA (gDNA) from 2...
2017: PloS One
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