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https://www.readbyqxmd.com/read/28646512/wmj-8-b-a-novel-hydroxamate-derivative-induces-mda-mb-231-breast-cancer-cell-death-via-shp-1-stat3-survivin-cascade
#1
Yu-Fan Chuang, Shiu-Wen Huang, Ya-Fen Hsu, Meng-Chieh Yu, George Ou, Wei-Jan Huang, Ming-Jen Hsu
BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors with broad-spectrum anti-tumor properties has been described and attracted lots of attention in the field of drug discovery. However, the underlying anti-tumor mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms of a novel hydroxamate-based HDAC inhibitor, WMJ-8-B, in inducing MDA-MB-231 breast cancer cell death. EXPERIMENTAL APPROACH: WMJ-8-B's effects on cell viability, cell cycle distribution, apoptosis, as well as signaling molecules modification and activation were analyzed by MTT assay, flowcytometric analysis, immunoblotting, reporter assay, ChIP analysis and siRNA strategy...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28645914/bile-salt-homeostasis-in-normal-and-bsep-gene-knock-out-rats-with-single-and-repeated-doses-of-troglitazone
#2
Yaofeng Cheng, Shenjue Chen, Chris Freeden, Weiqi Chen, Yueping Zhang, Pamela Abraham, David Nelson, William G Humphreys, Jinpin Gan, Yurong Lai
The interference of bile acid secretion through bile salt export pump (BSEP) inhibition was one of the mechanisms for troglitazone (TGZ) induced hepatotoxicity. Here we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep KO rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on Day-1 and Day-7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7...
June 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28641719/surfactant-protein-d-inhibits-interleukin-12p40-production-by-macrophages-through-the-sirp%C3%AE-rock-erk-signaling-pathway
#3
Rui Yamaguchi, Arisa Sakamoto, Takatoshi Yamamoto, Yasuji Ishimaru, Shinji Narahara, Hiroyuki Sugiuchi, Yasuo Yamaguchi
OBJECTIVE: Interleukin (IL)-12 has a pivotal profibrotic role in the development of idiopathic pulmonary fibrosis (IPF). Medical research trials based on IPF registry databases have actively recruited patients. Surfactant protein D (SP-D) is a useful biomarker in patients with IPF. SP-D binds to signal regulatory protein α (SIRPα), which acts as an inhibitory receptor, and this SP-D/SIRPα interaction may have an anti-inflammatory effect. Accordingly, the inhibitory effect of SP-D on IL-12p40 production by lipopolysaccharide (LPS)-stimulated macrophages was investigated...
June 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28637315/attenuated-effects-of-bile-acids-on-glucose-metabolism-and-insulin-sensitivity-in-a-male-mouse-model-of-prenatal-undernutrition
#4
Huijuan Ma, Vicencia M Sales, Ashley R Wolf, Sathish Subramanian, Tucker J Matthews, Michael Chen, Aparna Sharma, Walt Gall, Wim Kulik, David E Cohen, Yusuke Adachi, Nicholas W Griffin, Jeffrey I Gordon, Mary-Elizabeth Patti, Elvira Isganaitis
Prenatal undernutrition and low birth weight are associated with risk of type 2 diabetes and obesity. Prenatal caloric restriction results in low birth weight, glucose intolerance, obesity, and reduced plasma bile acids (BA) in offspring mice. Since BAs can regulate systemic metabolism and glucose homeostasis, we hypothesized that BA supplementation could prevent diet-induced obesity and glucose intolerance in this model of developmental programming. Pregnant dams were food restricted by 50% from gestational days 12...
June 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#5
Weixi Shen, Chunhong Chen, Yuanyuan Guan, Xiaowei Song, Yinghua Jin, Jingfang Wang, Yu Hu, Tao Xin, Qiuying Jiang, Li Zhong
The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28629696/new-criteria-to-determine-the-destabilization-of-the-acidogenic-anaerobic-co-digestion-of-organic-fraction-of-municipal-solid-waste-ofmsw-with-mixed-sludge-ms
#6
R Angeriz-Campoy, L A Fdez-Güelfo, Vinay Kumar Tyagi, C J Álvarez-Gallego, L I Romero-García
Effect of hydraulic retention time (HRT) on bio-hydrogen production from co-digestion of organic fraction of municipal solid waste (OFMSW) and mixed sludge (MS) in dry thermophilic conditions (55°C and 20% total solids) was investigated. A decreasing sequence of six HRTs, from 2.9 to 0.8-days, was performed to evaluate the stability of the system and the influence of HRT on the organic matter solubilization, the daily hydrogen production (HP) and the specific hydrogen production (SHP). Best results were obtained operating at 1...
June 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28629595/a-novel-intestinal-restricted-fxr-agonist
#7
Hong Wang, Zhou Zhao, Jiyu Zhou, Yitong Guo, Guangji Wang, Haiping Hao, Xiaowei Xu
In this study, a new intestinal-restricted FXR agonist named fexaramine-3 (Fex-3) was developed and investigated both in vitro and in vivo. Fex-3 could selectively activate intestinal FXR and promote the expression of BSEP and SHP while suppressing CYP7A1 which is involved in bile acids syntheses better than the reported intestinal-restricted FXR agonist fexaramine (Fex). We demonstrated that Fex-3 targeted on FXR in ileum and has better selectivity than Fex. And the study of utilizing Fex-3 to reduce obesity was undergoing...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28626233/themis-releases-the-brakes-on-tcr-signaling-during-thymocyte-selection-by-disabling-shp-1
#8
Laura Patrussi, Cosima T Baldari
No abstract text is available yet for this article.
June 19, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28620155/shp-2-activating-mutation-promotes-malignant-biological-behaviors-of-glioma-cells
#9
Yong Zhao, Lin Lin, Yonghui Zhang, Dangmurenjiafu Geng
BACKGROUND This study investigated the mechanism underlying the activating mutation of SHP-2 in promoting malignant biological behaviors of glioma cells. MATERIAL AND METHODS The SHP-2 empty plasmid pcDNA3.1 and SHP-2 activating mutation plasmid pcDNA3.1 SHP-2 D61G mutant eukaryotic expression vectors were designed; stable SHP-2-expressing cells transfected with pcDNA3.1 SHP-2 D61G mutant were set as the mutation group; cells transfected with pcDNA3.1 were set as the empty vector group; and cells without transfection were set as the control group...
June 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28619847/targeted-activation-of-the-shp-1-pp2a-signalling-axis-elicits-apoptosis-of-chronic-lymphocytic-leukemia-cells
#10
Elena Tibaldi, Mario Angelo Pagano, Federica Frezzato, Valentina Trimarco, Monica Facco, Giuseppe Zagotto, Giovanni Ribaudo, Valeria Pavan, Luciana Bordin, Andrea Visentin, Francesca Zonta, Gianpietro Semenzato, Anna Maria Brunati, Livio Trentin
The Src Family Kinase (SFK) Lyn is a key factor in the dysregulation of survival and apoptotic pathways of malignant B cells in chronic lymphocytic leukemia. One of the effects of Lyn's action is the spatial and functional segregation of the tyrosine phosphatase SHP-1 into two pools, one beneath the plasma membrane in an active state promoting pro-survival signals, the other in the cytosol in an inhibited conformation and unable to counter the elevated level of cytosolic tyrosine phosphorylation. We herein show that SHP-1 activity can be elicited directly by nintedanib, an agent also known as a triple angiokinase inhibitor, circumventing the phospho-S591-dependent inhibition of the phosphatase, leading to the dephosphorylation of pro-apoptotic players such as procaspase-8 and the serine/threonine phosphatase 2A, eventually triggering apoptosis...
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28594363/alteration-of-shp-1-p-stat3-signaling-a-potential-target-for-anticancer-therapy
#11
REVIEW
Tzu-Ting Huang, Jung-Chen Su, Chun-Yu Liu, Chung-Wai Shiau, Kuen-Feng Chen
The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1), a non-receptor protein tyrosine phosphatase, has been reported as a negative regulator of phosphorylated signal transducer and activator of transcription 3 (STAT3) and linked to tumor development. In this present review, we will discuss the importance and function of SHP-1/p-STAT3 signaling in nonmalignant conditions as well as malignancies, its cross-talk with other pathways, the current clinical development and the potential role of inhibitors of this pathway in anticancer therapy and clinical relevance of SHP-1/p-STAT3 in cancers...
June 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28586124/shp-deletion-prevents-hepatic-steatosis-and-when-combined-with-fxr-loss-protects-against-type-2-diabetes
#12
Oludemilade Akinrotimi, Ryan Riessen, Philip VanDuyne, Jung Eun Park, Yoon Kwang Lee, Lee-Jun Wong, Ann M Zavacki, Kristina Schoonjans, Sayeepriyadarshini Anakk
Nuclear receptors Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP) are important regulators of bile acid, lipid and glucose homeostasis. Here we show that global Fxr (-/-) Shp(-/-) double knockout (DKO) mice are refractory to weight gain, glucose intolerance and hepatic steatosis when challenged with high-fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice are also very active and that correlates well with the observed increase in Pepck expression, type IA fibers and mitochondrial function in the skeletal muscle...
June 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28582435/school-and-household-tuberculosis-contact-investigations-in-swaziland-active-tb-case-finding-in-a-high-hiv-tb-burden-setting
#13
Piluca Alonzo Ustero, Alexander W Kay, Katherine Ngo, Rachel Golin, Bhekisisa Tsabedze, Bulisile Mzileni, Jessica Glickman, Mildred Wisile Xaba, Gcinile Mavimbela, Anna Maria Mandalakas
BACKGROUND: Investigation of household contacts exposed to infectious tuberculosis (TB) is widely recommended by international guidelines to identify secondary cases of TB and limit spread. There is little data to guide the use of contact investigations outside of the household, despite strong evidence that most TB infections occur outside of the home in TB high burden settings. In older adolescents, the majority of infections are estimated to occur in school. Therefore, as part of a project to increase active case finding in Swaziland, we performed school contact investigations following the identification of a student with infectious TB...
2017: PloS One
https://www.readbyqxmd.com/read/28578456/sequential-combination-of-docetaxel-with-a-shp-1-agonist-enhanced-suppression-of-p-stat3-signaling-and-apoptosis-in-triple-negative-breast-cancer-cells
#14
Chun-Yu Liu, Kuen-Feng Chen, Tzu-I Chao, Pei-Yi Chu, Chun-Teng Huang, Tzu-Ting Huang, Hsiu-Ping Yang, Wan-Lun Wang, Chia-Han Lee, Ka-Yi Lau, Wen-Chun Tsai, Jung-Chen Su, Chia-Yun Wu, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng
Triple negative breast cancer (TNBC) is an aggressive cancer for which prognosis remains poor. Combination therapy is a promising strategy for enhancing treatment efficacy. Blockade of STAT3 signaling may enhance the response of cancer cells to conventional chemotherapeutic agents. Here we used a SHP-1 agonist SC-43 to dephosphorylate STAT3 thereby suppressing oncogenic STAT3 signaling and tested it in combination with docetaxel in TNBC cells. We first analyzed messenger RNA (mRNA) expression of SHP-1 gene (PTPN6) in a public TNBC dataset (TCGA) and found that higher SHP-1 mRNA expression is associated with better overall survival in TNBC patients...
June 4, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28570941/diet-dependent-retinoid-effects-on-liver-gene-expression-include-stellate-and-inflammation-markers-and-parallel-effects-of-the-nuclear-repressor-shp
#15
Meghan Maguire, Justin R Bushkofsky, Michele Campaigne Larsen, Yee Hoon Foong, Sherry A Tanumihardjo, Colin R Jefcoate
For mice, a maternal vitamin A (VA)-deficient diet initiated from midgestation (GVAD) produces serum retinol deficiency in mature offspring. We hypothesize that the effects of GVAD arise from preweaning developmental changes. We compare the effect of this GVAD protocol in combination with a postweaning high-fat diet (HFD) or high-carbohydrate diet (LF12). Each is compared to an equivalent VA-sufficient combination. GVAD extensively decreased serum retinol and liver retinol, retinyl esters, and retinoid homeostasis genes (Lrat, Cyp26b1 and Cyp26a1)...
April 19, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28565861/global-methylation-and-promoter-specific-methylation-of-the-p16-socs-1-e-cadherin-p73-and-shp-1-genes-and-their-expression-in-patients-with-multiple-myeloma-during-active-disease-and-remission
#16
Déborah Martínez-Baños, Beatríz Sánchez-Hernández, Guadalupe Jiménez, Georgina Barrera-Lumbreras, Olga Barrales-Benítez
Tumor suppressor gene promoter CpG island methylation is a well-recognized mechanism in cancer pathogenesis, but its role in multiple myeloma (MM) is controversial. The present study investigated the methylation status and expression of P16, suppressor of cytokine signaling 1 (SOCS-1), P73, E-cadherin and Src homology region 2 domain-containing phosphatase 1 (SHP-1), as well as global methylation in patients with MM during active disease and remission. Bone marrow samples were obtained from 43 patients at the Multiple Myeloma Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (Mexico City, Mexico) during active disease and remission...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28557053/a-novel-streptococcal-cell-cell-communication-peptide-promotes-pneumococcal-virulence-and-biofilm-formation
#17
Rolando A Cuevas, Rory Eutsey, Anagha Kadam, Jacob A West-Roberts, Carol A Woolford, Aaron P Mitchell, Kevin M Mason, N Luisa Hiller
Streptococcus pneumoniae (pneumococcus) is a major human pathogen. It is a common colonizer of the human respiratory track, where it utilizes cell-cell communication systems to coordinate population-level behaviors. We reasoned that secreted peptides that are highly expressed during infection are pivotal for virulence. Thus, we used in silico pattern searches to define a pneumococcal secretome, and analyzed the transcriptome of the clinically important PMEN1 lineage to identify which peptide-encoding genes are highly expressed in vivo...
May 29, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28556679/molecular-characterization-and-risk-assessment-of-bacillus-cereus-sensu-lato-isolated-from-ultrahigh-temperature-and-pasteurized-milk-marketed-in-rio-de-janeiro-brazil
#18
Jeane Q Chaves, Eislaine P de Paiva, Leon Rabinovitch, Adriana M Vivoni
The presence of Bacillus cereus in milk is a major concern in the dairy industry. In this study 27 Bacillus cereus sensu lato isolates from pasteurized and ultrahigh-temperature (UHT) milk (24 whole UHT and 4 pasteurized samples) collected at supermarket chains in Rio de Janeiro, Brazil, were evaluated to assess the potential risk for food poisoning. Toxigenic and virulence profiles were defined by gene-specific PCR. Affiliation to phylogenetic groups was assigned by panC sequencing. Microbiological analysis revealed the presence of B...
May 30, 2017: Journal of Food Protection
https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#19
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28550200/t-cells-deficient-in-the-tyrosine-phosphatase-shp-1-resist-suppression-by-regulatory-t-cells
#20
Emily R Mercadante, Ulrike M Lorenz
The balance between activation of T cells and their suppression by regulatory T cells (Tregs) is dysregulated in autoimmune diseases and cancer. Autoimmune diseases feature T cells that are resistant to suppression by Tregs, whereas in cancer, T cells are unable to mount antitumor responses due to the Treg-enriched suppressive microenvironment. In this study, we observed that loss of the tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, renders naive CD4(+) and CD8(+) T cells resistant to Treg-mediated suppression in a T cell-intrinsic manner...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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