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https://www.readbyqxmd.com/read/28548934/ikbke-regulates-cell-proliferation-and-epithelial-mesenchymal-transition-of-human-malignant-glioma-via-the-hippo-pathway
#1
Jie Lu, Yi Yang, Gaochao Guo, Yang Liu, Zhimeng Zhang, Shicai Dong, Yang Nan, Zhenyi Zhao, Yue Zhong, Qiang Huang
IKBKE is increased in several types of cancers and is associated with tumour malignancy. In this study, we confirmed that IKBKE promoted glioma proliferation, migration and invasion in vitro. Then, we further discovered that IKBKE increased Yes-associated protein 1 (YAP1) and TEA domain family member 2 (TEAD2), two important Hippo pathway downstream factors, to induce an epithelial-mesenchymal transition (EMT), thus contributing to tumour invasion and metastasis. We also testified that YAP1 and TEAD2 promoted epithelial-mesenchymal transition (EMT) in malignant glioma...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546919/cell-viability-and-extracellular-matrix-synthesis-in-a-co-culture-system-of-corneal-stromal-cells-and-adipose-derived-mesenchymal-stem-cells
#2
Ting Shen, Jiang Shen, Qing-Qing Zheng, Qiu-Shi Li, Hai-Lan Zhao, Lei Cui, Chao-Yang Hong
AIM: To investigate the impact of adipose-derived mesenchymal stem cells (ADSCs) on cell viability and extracellular matrix (ECM) synthesis of corneal stromal cells (CSCs). METHODS: ADSCs and CSCs were obtained from the corneas of New Zealand white rabbits and indirectly co-cultured in vitro. The proliferative capacity of CSCs in the different groups was assessed by CCK-8 assays. Annexin V-fluorescein isothiocyanate (FITC)/proliferation indices (PI) assays were used to detect the apoptosis of CSCs...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28546033/long-term-follow-up-of-first-generation-versus-new-generation-drug-eluting-stents-in-three-vessel-coronary-artery-disease
#3
Toru Yoshizaki, Toru Naganuma, Tsuyoshi Kobayashi, Takeo Horikoshi, Hirokazu Onishi, Hiroyoshi Kawamoto, Shotaro Nakamura, Sunao Nakamura
BACKGROUNDS: Few reports have primarily focused on long-term clinical outcomes in three-vessel disease when patients were treated with either first- or new-generation drug-eluting stents (DES). The purpose of this study was to investigate different clinical outcomes after percutaneous coronary intervention (PCI) for three-vessel disease with first- or new-generation DES. METHODS: Between January 2007 and December 2013, a total of 200 patients who received complete revascularization of three-vessel disease with either first-generation DES (n=85) or new-generation DES (n=115) were analyzed in this retrospective study...
April 21, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28545672/enhancement-of-apoptotic-activities-on-brain-cancer-cells-via-the-combination-of-%C3%AE-tocotrienol-and-jerantinine-a
#4
Ibrahim Babangida Abubakar, Kuan-Hon Lim, Toh-Seok Kam, Hwei-San Loh
BACKGROUND: γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28545612/drug-repositioning-based-on-triangularly-balanced-structure-for-tissue-specific-diseases-in-incomplete-interactome
#5
Liang Yu, Jin Zhao, Lin Gao
Finding new uses for existing drugs has become a new strategy for decades to treat more patients. Few traditional approaches consider the tissue specificities of diseases. Moreover, disease genes, drug targets and protein interaction (PPI) networks remain largely incomplete and the relationships between drugs and diseases conform to the triangularly balanced structure. Therefore, based on tissue specificities of diseases, we apply the triangularly balanced theory and the module distance defined for incomplete interaction networks to build drug-disease associations...
March 2017: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/28545567/cancer-immunotherapy-by-targeting-immune-checkpoints-mechanism-of-t-cell-dysfunction-in-cancer-immunity-and-new-therapeutic-targets
#6
REVIEW
Hwei-Fang Tsai, Ping-Ning Hsu
Immune checkpoints or coinhibitory receptors, such as cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, play important roles in regulating T cell responses, and they were proven to be effective targets in treating cancer. In chronic viral infections and cancer, T cells are chronically exposed to persistent antigen stimulation. This is often associated with deterioration of T cell function with constitutive activation of immune checkpoints, a state called 'exhaustion', which is commonly associated with inefficient control of tumors and persistent viral infections...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28545522/brd4-inhibition-suppresses-cell-growth-migration-and-invasion-of-salivary-adenoid-cystic-carcinoma
#7
Limei Wang, Xiuyin Wu, Ruolin Wang, Chengzhe Yang, Zhi Li, Cunwei Wang, Fenghe Zhang, Pishan Yang
BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 μM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation...
May 25, 2017: Biological Research
https://www.readbyqxmd.com/read/28544767/a-poly-propyleneimine-dendrimer-based-polyplex-system-for-single-chain-antibody-mediated-targeted-delivery-and-cellular-uptake-of-sirna
#8
Stefanie Tietze, Isabell Schau, Susanne Michen, Franka Ennen, Andreas Janke, Gabriele Schackert, Achim Aigner, Dietmar Appelhans, Achim Temme
Therapeutics based on small interfering RNAs (siRNAs) offer a great potential to treat so far incurable diseases or metastatic cancer. However, the broad application of siRNAs using various nonviral carrier systems is hampered by unspecific toxic side effects, poor pharmacokinetics due to unwanted delivery of siRNA-loaded nanoparticles into nontarget organs, or rapid renal excretion. In order to overcome these obstacles, several targeting strategies using chemically linked antibodies and ligands have emerged...
May 22, 2017: Small
https://www.readbyqxmd.com/read/28543623/regulatory-effect-of-microrna-34a-on-osteogenesis-and-angiogenesis-in-glucocorticoid-induced-osteonecrosis-of-the-femoral-head
#9
Xiaolong Zha, Bolin Sun, Rufan Zhang, Chen Li, Zuoqin Yan, Jifei Chen
BACKGROUND AND AIMS: Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is a common and devastating orthopedic disease, and its underlying mechanism remains unclear. The aim of this study was to determine the role of microRNA-34a (mir-34a) in GIOFH. METHODS: C57 mouse mesenchymal stem cells (mMSCs) and human umbilical vein endothelial cells (HUVECs) were cultured with dexamethasone (Dex). A total of 48 adult rats were treated with glucocorticoids, and after the onset of GIOFH, each femoral head was removed...
May 20, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28542706/modulatory-features-of-the-novel-spider-toxin-%C3%AE-trtx-df1a-isolated-from-the-venom-of-the-spider-davus-fasciatus
#10
Fernanda C Cardoso, Zoltan Dekan, Jennifer J Smith, Jennifer R Deuis, Irina Vetter, Volker Herzig, Paul F Alewood, Glenn F King, Richard J Lewis
BACKGROUND AND PURPOSE: Naturally occurring dysfunction in NaV channels results in complex disorders such as chronic pain, making these channels an attractive target for new therapies. In the pursuit of novel NaV modulators, we investigated spider venoms for new inhibitors of NaV channels. EXPERIMENTAL APPROACH: We used high-throughput screens to identify a NaV modulator in venom of the spider Davus fasciatus. Further characterization of this venom peptide was undertaken using fluorescent and electrophysiological assays, molecular modeling and a rodent pain model...
May 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28542436/stress-induced-release-of-oct-1-from-the-nuclear-envelope-is-mediated-by-jnk-phosphorylation-of-lamin-b1
#11
Ivan I Boubriak, Ashraf N Malhas, Marek M Drozdz, Lior Pytowski, David J Vaux
The nuclear lamina can bind and sequester transcription factors (TFs), a function lost if the lamina is abnormal, with missing or mutant lamin proteins. We now show that TF sequestration is not all-or-nothing, but a dynamic physiological response to external signals. We show that the binding of the ubiquitous TF, Oct-1, to lamin B1 was reversed under conditions of cellular stress caused, inter alia, by the chemical methylating agent methylmethanesulfonate (MMS). A search for lamin B1 post-translational modifications that might mediate changes in Oct-1 binding using kinase inhibitors uncovered a role for c-Jun N-terminal kinase (JNK)...
2017: PloS One
https://www.readbyqxmd.com/read/28542246/a-drastic-superoxide-dependent-oxidative-stress-is-prerequisite-for-the-down-regulation-of-irp1-insights-from-studies-on-sod1-deficient-mice-and-macrophages-treated-with-paraquat
#12
Anna Milczarek, Rafał R Starzyński, Agnieszka Styś, Aneta Jończy, Robert Staroń, Agnieszka Grzelak, Paweł Lipiński
Iron regulatory protein 1 (IRP1) is a cytosolic bifunctional [4Fe-4S] protein which exhibits aconitase activity or binds iron responsive elements (IREs) in untranslated regions of specific mRNA encoding proteins involved in cellular iron metabolism. Superoxide radical (O2.-) converts IRP1 from a [4Fe-4S] aconitase to a [3Fe-4S] "null" form possessing neither aconitase nor trans-regulatory activity. Genetic ablation of superoxide dismutase 1 (SOD1), an antioxidant enzyme that acts to reduce O2.- concentration, revealed a new O2...
2017: PloS One
https://www.readbyqxmd.com/read/28541665/identification-of-small-molecule-translesion-synthesis-inhibitors-that-target-the-rev1-ct-rir-protein-protein-interaction
#13
Vibhavari Sail, Alessandro A Rizzo, Nimrat Chatterjee, Radha Charan Dash, Zuleyha Ozen, Graham C Walker, Dmitry M Korzhnev, M Kyle Hadden
Translesion synthesis (TLS) is an important mechanism through which proliferating cells tolerate DNA damage during replication. The mutagenic Rev1/Polζ-dependent branch of TLS helps cancer cells survive first-line genotoxic chemotherapy and introduces mutations that can contribute to the acquired resistance so often observed with standard anti-cancer regimens. As such, inhibition of Rev1/Polζ-dependent TLS has recently emerged as a strategy to enhance the efficacy of first-line chemotherapy and reduce the acquisition of chemoresistance by decreasing tumor mutation rate...
May 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28539470/the-src-c-abl-pathway-is-a-potential-therapeutic-target-in-amyotrophic-lateral-sclerosis
#14
Keiko Imamura, Yuishin Izumi, Akira Watanabe, Kayoko Tsukita, Knut Woltjen, Takuya Yamamoto, Akitsu Hotta, Takayuki Kondo, Shiho Kitaoka, Akira Ohta, Akito Tanaka, Dai Watanabe, Mitsuya Morita, Hiroshi Takuma, Akira Tamaoka, Tilo Kunath, Selina Wray, Hirokazu Furuya, Takumi Era, Kouki Makioka, Koichi Okamoto, Takao Fujisawa, Hideki Nishitoh, Kengo Homma, Hidenori Ichijo, Jean-Pierre Julien, Nanako Obata, Masato Hosokawa, Haruhiko Akiyama, Satoshi Kaneko, Takashi Ayaki, Hidefumi Ito, Ryuji Kaji, Ryosuke Takahashi, Shinya Yamanaka, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28538730/blocking-fsh-induces-thermogenic-adipose-tissue-and-reduces-body-fat
#15
Peng Liu, Yaoting Ji, Tony Yuen, Elizabeth Rendina-Ruedy, Victoria E DeMambro, Samarth Dhawan, Wahid Abu-Amer, Sudeh Izadmehr, Bin Zhou, Andrew C Shin, Rauf Latif, Priyanthan Thangeswaran, Animesh Gupta, Jianhua Li, Valeria Shnayder, Samuel T Robinson, Yue Eric Yu, Xingjian Zhang, Feiran Yang, Ping Lu, Yu Zhou, Ling-Ling Zhu, Douglas J Oberlin, Terry F Davies, Michaela R Reagan, Aaron Brown, T Rajendra Kumar, Solomon Epstein, Jameel Iqbal, Narayan G Avadhani, Maria I New, Henrik Molina, Jan B van Klinken, Edward X Guo, Christoph Buettner, Shozeb Haider, Zhuan Bian, Li Sun, Clifford J Rosen, Mone Zaidi
Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the β-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the β-subunit of Fsh to block its action...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28537004/mek-inhibitors-in-the-treatment-of-metastatic-melanoma-and-solid-tumors
#16
REVIEW
Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella, Martina Strudel, Paolo A Ascierto
The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines...
May 23, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28536503/epigenetic-activation-of-asct2-in-the-hippocampus-contributes-to-depression-like-behavior-by-regulating-d-serine-in-mice
#17
Jiesi Wang, Ke Zhang, Xiaojuan Chen, Xiaoqian Liu, Huajing Teng, Mei Zhao, Zhongsheng Sun
The roles of D-serine in depression are raised concerned recently as an intrinsic co-agonist for the NMDA receptor. However, the mechanisms underlying its regulation are not fully elucidated. ASCT2 is a Na(+)-dependent D-serine transporter. We found that decreased D-serine and increased hippocampal ASCT2 levels correlated with chronic social defeat stress (CSDS) in mice. Lentivirus-mediated shRNA-mediated knockdown of ASCT2 and the administration of exogenous D-serine in the hippocampus alleviated CSDS-induced social avoidance and immobility...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28535565/ephrinb-ephb-signaling-induces-hyperalgesia-through-erk5-creb-pathway-in-rats
#18
Li-Na Yu, Li-Hong Sun, Min Wang, Lie-Ju Wang, Ying Wu, Jing Yu, Wen-Na Wang, Feng-Jiang Zhang, Xue Li, Min Yan
BACKGROUND: There are numerous studies implicating that EphB receptors and ephrinB ligands play important roles in modulating the transduction of spinal nociceptive information. EphrinB-EphB signaling may contribute to hyperalgesia via various kinds of downstream molecules, the mechanisms of which have not been completely understood. OBJECTIVE: The aim of the present study was to identify whether ephrinB-EphB signaling could contribute to hyperalgesia through ERK5/CREB pathway...
May 2017: Pain Physician
https://www.readbyqxmd.com/read/28535426/new-role-of-pcsk9-in-atherosclerotic-inflammation-promotion-involving-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#19
Zhi-Han Tang, Juan Peng, Zhong Ren, Jing Yang, Ting-Ting Li, Tao-Hua Li, Zuo Wang, Dang-Heng Wei, Lu-Shan Liu, Xi-Long Zheng, Zhi-Sheng Jiang
BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin 9 (PCSK9) has emerged as a popular target in the development of new cholesterol-lowering drugs and therapeutic interventions for atherosclerosis. PCSK9 could accelerate atherosclerosis through mechanisms beyond the degradation of the hepatic low-density lipoprotein receptor. Several clinical studies suggested that PCSK9 is involved in atherosclerotic inflammation. Accordingly, this study aimed to explore the role of PCSK9 in vascular inflammation that promotes atherosclerotic progression...
April 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28534939/mir%C3%A2-181b%C3%A2-5p-mediates-tgf%C3%A2-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-non-small-cell-lung-cancer-stem-like-cells-derived-from-lung-adenocarcinoma-a549-cells
#20
Xuetao Li, Jing Han, Haizhen Zhu, Lina Peng, Zhengtang Chen
The ability of non-small cell lung cancer (NSCLC) cells to invade and metastasize is associated with epithelial-to-mesenchymal transition (EMT). The process of EMT is, at least in part, regulated by microRNAs. However, it is unknown whether microRNAs regulate EMT in cancer stem-like cells (CSLCs), or which microRNAs are involved. In the present study, we compared microRNA expression in A549 cells, TGF‑β1-treated A549 cells, CSLCs characterized by the CD133+/CD326+ phenotype, and TGF‑β1-treated CSLCs. We found that miR‑181b‑5p expression was upregulated by TGF‑β1...
May 17, 2017: International Journal of Oncology
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