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https://www.readbyqxmd.com/read/29353218/sulforaphane-prevents-angiotensin-ii-induced-cardiomyopathy-by-activation-of-nrf2-via-stimulating-the-akt-gsk-3%C3%A3-fyn-pathway
#1
Ying Xin, Yang Bai, Xin Jiang, Shanshan Zhou, Yuehui Wang, Kupper A Wintergerst, Taixing Cui, Honglei Ji, Yi Tan, Lu Cai
AIMS: Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by sulforaphane (SFN) protects from, and deletion of the Nrf2 gene exaggerates, diabetic cardiomyopathy. Angiotensin II (Ang II) plays a critical role in the development of diabetic cardiomyopathy. Therefore, whether SFN prevents Ang II-induced cardiomyopathy through activation of Nrf2 was examined using wild-type, global deletion of Nrf2 gene (Nrf2-KO) and cardiomyocyte-specific overexpression of Nrf2 gene (Nrf2-TG) mice...
January 2, 2018: Redox Biology
https://www.readbyqxmd.com/read/29353209/mir-182-promotes-prostate-cancer-progression-through-activating-wnt-%C3%AE-catenin-signal-pathway
#2
Dawei Wang, Guoliang Lu, Yuan Shao, Da Xu
Although prostate cancer can be surgical excised and effectively treated by androgen-deprivation therapy, radiotherapy, or chemotherapy, management of patients with advanced or drug-resistance prostate cancer stills remains a big trouble. Accumulated evidence indicated that miR-182 and Wnt/β-catenin function as tumor oncogene in the progression of a variety of tumors. However, little is known about how miR-182 regulates β-catenin signal molecular and impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of qRT-PCR, we found that prostate cancer tissues expressed much more miR-182 than non-cancer tissues did...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#3
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352207/ethanol-sensitizes-hepatocytes-for-tgf-%C3%AE-triggered-apoptosis
#4
Haristi Gaitantzi, Christoph Meyer, Pia Rakoczy, Maria Thomas, Kristin Wahl, Franziska Wandrer, Heike Bantel, Hamed Alborzinia, Stefan Wölfl, Sabrina Ehnert, Andreas Nüssler, Ina Bergheim, Loredana Ciuclan, Matthias Ebert, Katja Breitkopf-Heinlein, Steven Dooley
Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29346712/synergetic-effects-of-prenatal-and-postnatal-high-sucrose-intake-on-glucose-tolerance-and-hepatic-insulin-resistance-in-rat-offspring
#5
Pengjie Zhang, Di Zhu, Yueming Zhang, Lingjun Li, Xionghui Chen, Wenna Zhang, Ruixiu Shi, Jianying Tao, Bing Han, Zhice Xu
SCOPE: High sucrose intake during pregnancy is linked to type 2 diabetes mellitus and altered insulin resistance. METHODS AND RESULTS: This study attempted to ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the detrimental effects of high postnatal sugar consumption in the offspring, and the molecular mechanisms were investigated using a rat model. High prenatal sucrose exposure increased the body weight of the offspring at 1 to 3 weeks of age...
January 18, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29346514/optimal-water-networks-in-protein-cavities-with-gasol-and-3d-rism
#6
Lucia Fusani, Ian Wall, David Palmer, Alvaro Cortes
Motivation: Water molecules in protein binding sites play essential roles in biological processes. The popular 3D-RISM prediction method can calculate the solvent density distribution within minutes, but is difficult to convert it into explicit water molecules. Results: We present GAsol, a tool that is capable of finding the network of water molecules that best fits a particular 3D-RISM density distribution in a fast and accurate manner and that outperforms other available tools by finding the globally optimal solution thanks to its genetic algorithm...
January 15, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29346315/dietary-total-prenylflavonoids-from-the-fruits-of-psoralea-corylifolia-l-prevents-age-related-cognitive-deficits-and-down-regulates-alzheimer-s-markers-in-samp8-mice
#7
Zhi-Jing Chen, Yan-Fang Yang, Ying-Tao Zhang, Dong-Hui Yang
Alzheimer's disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29345351/k313-a-novel-benzoxazole-derivative-exhibits-anti-inflammatory-properties-via-inhibiting-gsk3%C3%AE-activity-in-lps-induced-raw264-7-macrophages
#8
Bo-Bo Zhao, Hui-Jie Guo, Yang Liu, Xing-Yan Luo, Shu-Xia Yang, Yan-Tang Wang, Xiao Leng, Chun-Fen Mo, Qiang Zou
Benzoxazole and its derivatives have been widely studied in recent years due to their various biological properties. A previous study has demonstrated that K313 (1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)), a novel benzoxazole derivative, inhibits T cell proliferation to yield immunosuppressive effects. However, there are no related reports about its anti-inflammatory effects. In the present study, we investigated the anti-inflammatory properties and the underlying molecular mechanism of K313 in lipopolysaccharide (LPS)-induced RAW264...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345253/3-acetyl-oleanolic-acid-ameliorates-non-alcoholic-fatty-liver-disease-in-high-fat-diet-treated-rats-by-activating-ampk-related-pathways
#9
Qiong Ou-Yang, Chun-Xiao Xuan, Xue Wang, Han-Qiong Luo, Jin-E Liu, Lan-Lan Wang, Ting-Ting Li, Yu-Peng Chen, Jun Liu
3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In this study we investigated whether 3Ac-OA exerted beneficial effect on non-alcoholic fatty liver disease (NAFLD) in rats and its potential underlying mechanisms. Treatment with 3Ac-OA (1-100 μmol/L) dose-dependently decreased the intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA-treated primary rat hepatocytes and human HepG2 cell lines in vitro...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29344668/blocking-of-autocrine-igf-1-reduces-viability-of-human-umbilical-cord-mesenchymal-stem-cells-via-inhibition-of-the-akt-gsk-3%C3%AE-signaling-pathway
#10
Qi Wang, Fenxi Zhang, Yan Hong
Human umbilical cord mesenchymal stem cells (hUCMSCs) are able to secrete growth factors, such as hepatocyte growth factor, vascular endothelial growth factor and insulin‑like growth factor‑1 (IGF‑1). The secretion of these growth factors by transplanted hUCMSCs have been identified to stimulate the growth of the host cells in the target organs or tissues. The aim of the present study was to investigate the effect of autocrine IGF‑1 on cell viability of hUCMSCs. The expression levels of IGF‑1 and the IGF‑1 receptor (IGF‑1R) in hUCMSCs were identified using immunocytochemistry staining...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344218/atra-increases-iodine-uptake-and-inhibits-the-proliferation-and-invasiveness-of-human-anaplastic-thyroid-carcinoma-sw1736-cells-involvement-of-%C3%AE-catenin-phosphorylation-inhibition
#11
Ling Lan, Spyros Basourakos, Dai Cui, Xuemei Zuo, Wei Deng, Lili Huo, Hailing Chen, Guoying Zhang, Lili Deng, Bingyin Shi, Yong Luo
All-trans-retinoic acid (ATRA) can enhance iodine uptake capability of thyroid tumors, but the mechanisms remain poorly understood. The aim of the present study was to investigate the effects of ATRA on isotope susceptibility, proliferation and invasion of anaplastic thyroid carcinoma (ATC) and potential mechanisms. SW1736 cells were treated with 1 µmol/l ATRA or 1% ethanol for 5 days. A cell line stably expressing β-catenin-shRNA was established. An iodine uptake assay was performed using 125I. Proliferation and invasiveness were tested using MTT and Transwell assays, respectively...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343851/ndrg2-facilitates-colorectal-cancer-differentiation-through-the-regulation-of-skp2-p21-p27-axis
#12
Liangliang Shen, Xuan Qu, Huichen Li, Chunsheng Xu, Mengying Wei, Qinhao Wang, Yi Ru, Bei Liu, Yuqiao Xu, Kai Li, Junbi Hu, Lifeng Wang, Yongzheng Ma, Mengyang Li, Xiaofeng Lai, Lei Gao, Kaichun Wu, Libo Yao, Jianyong Zheng, Jian Zhang
Poorly differentiated colorectal cancers (CRCs) are more aggressive and lack targeted therapies. We and others previously reported the predominant role of tumor-suppressor NDRG2 in promoting CRC differentiation, but the underlying mechanism is largely unknown. Herein, we demonstrate that NDRG2 induction of CRC cell differentiation is dependent on the repression of E3 ligase Skp2 activity. In patients and Ndrg2 knockout mice, NDRG2 and Skp2 are negatively correlated and associated with cell differentiation stage...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29337646/stability-of-an-aluminum-salt-adjuvanted-protein-d-conjugated-pneumococcal-vaccine-after-exposure-to-subzero-temperatures
#13
Juliette Fortpied, Florence Wauters, Christelle Rochart, Philippe Hermand, Bernard Hoet, Nicolas Moniotte, Ivo Vojtek
Accidental exposure of a vaccine containing an aluminum-salt adjuvant to temperatures below 0°C in the cold chain can lead to freeze damage. Our study evaluated the potential for freeze damage in a licensed aluminum-salt-containing protein-D-conjugated pneumococcal vaccine (PHiD-CV; Synflorix, GSK) in conditions that included static storage, single subzero-temperature excursions, and simulated air-freight transportation. Several parameters were assessed including freezing at subzero temperatures, aluminum-salt-particle size, antigen integrity and immunogenicity in the mouse...
January 16, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29336924/immunization-of-preterm-infants-with-gsk-s-hexavalent-combined-diphtheria-tetanus-acellular-pertussis-hepatitis-b-inactivated-poliovirus-haemophilus-influenzae-type-b-conjugate-vaccine-a-review-of-safety-and-immunogenicity
#14
Felix Omeñaca, Liliana Vázquez, Pilar Garcia-Corbeira, Narcisa Mesaros, Linda Hanssens, Jan Dolhain, Ivonne Puente Gómez, Johannes Liese, Markus Knuf
BACKGROUND: Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed. METHODS: Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials...
January 11, 2018: Vaccine
https://www.readbyqxmd.com/read/29335245/cdk9-mediated-phosphorylation-controls-the-interaction-of-tip60-with-the-transcriptional-machinery
#15
Prisca Brauns-Schubert, Florian Schubert, Manuela Wissler, Martina Weiss, Lisa Schlicher, Simon Bessler, Mariam Safavi, Cornelius Miething, Christoph Borner, Tilman Brummer, Ulrich Maurer
The acetyltransferase TIP60 is regulated by phosphorylation, and we have previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53-mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3 requires a priming phosphorylation on S90, and here, we identify CDK9 as a TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant, TIP60S90A, exhibits reduced interaction with chromatin, histone 3 and RNA Pol II, while its association with the TIP60 complex subunit EPC1 is not affected...
January 15, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29334667/lithium-a-classic-drug-in-psychiatry-improves-nilotinib-mediated-antileukemic-effects
#16
Janaína Peixoto-da-Silva, Andrana K Calgarotto, Katiucha R Rocha, Caroline Palmeira-Dos-Santos, Soraya S Smaili, Gustavo J S Pereira, Fernando V Pericole, Adriana da Silva S Duarte, Sara T O Saad, Claudia Bincoletto
Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3β phosphorylation and Bcr-Abl oncoprotein levels reduction...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29332582/dual-bace-1-gsk-3%C3%AE-inhibitors-to-combat-alzheimer-s-disease-a-focus-review
#17
Angela Rampa, Silvia Gobbi, Rita Maria Concetta Di Martino, Federica Belluti, Alessandra Bisi
In industrialized countries, Alzheimer's disease represents the most devastating neurodegenerative disorder in elderly people and the search for a disease modifying agent is still justified by this unmet need. Several possible targets have been explored to find an appropriate drug therapy, and in this review dual inhibitors of beta secretase and glycogen synthase kinase 3, recently reported in literature, will be appraised. Applying a ligand-based approach, the triazinone core emerged as a suitable scaffold to simultaneously bind the aspartic dyad of BACE-1 and the ATP site of GSK-3β, leading to a series of small molecules endowed with a balanced micromolar affinity and a promising pharmacokinetic profile...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29331585/cathepsin-l-promotes-ionizing-radiation-induced-u251-glioma-cell-migration-and-invasion-through-regulating-the-gsk-3%C3%AE-cux1-pathway
#18
Yao Fei, Yajie Xiong, Xiao Shen, Yifan Zhao, Ying Zhu, Long Wang, Zhongqin Liang
Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by tumor cells. Our previous study found that CTSL was involved in ionizing radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase of glioma invasion and migration. However, the mechanisms by which CTSL promoted this IR-induced glioma migration and invasion remained unclear. In this study, we demonstrated that IR reduced glycogen synthase kinase-3β (GSK-3β) activity, via the CTSL-mediated phosphorylation of its serine-9 residue, in U251 cells...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29331511/maresin-1-regulates-autophagy-and-inflammation-in-human-periodontal-ligament-cells-through-glycogen-synthase-kinase-3%C3%AE-%C3%AE-catenin-pathway-under-inflammatory-conditions
#19
Li Du, Yucheng Li, Weifeng Liu
OBJECTIVE: Accumulating lines of evidence suggest that maresin 1 (MaR-1) exerts anti-inflammatory effects in many cell types and plays beneficial roles in inflammatory disease, such as peritonitis and colitis. Moreover, it has been demonstrated that MaR-1 play protective roles against localized aggressive periodontitis. However, the function and mechanism of MaR-1 in human periodontal ligament cells (PDL) cells from periodontitis are poorly understood. The present study aimed to clarify the effects and molecular mechanism of MaR-1 in PDL cell survival and inflammation...
December 23, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29331082/mechanistic-target-of-rapamycin-complex-1-and-2-in-human-temporal-lobe-epilepsy
#20
Delia M Talos, Leah M Jacobs, Sarah Gourmaud, Carlos A Coto, Hongyu Sun, Kuei-Cheng Lim, Timothy H Lucas, Kathryn A Davis, Maria Martinez-Lage, Frances E Jensen
OBJECTIVE: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) Complex 1 (mTORC1) and Complex 2 (mTORC2) activities in the brain, as both pathways may represent unique targets for treatment. METHODS: Surgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by Western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes...
January 13, 2018: Annals of Neurology
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