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https://www.readbyqxmd.com/read/29161771/tetramethylpyrazine-nitrone-activates-akt-creb-through-increasing-bdnf-expression-to-promote-post-ischemic-neuroregeneration-and-recovery-of-neurological-functions-in-rats
#1
Gaoxiao Zhang, Tao Zhang, Ning Li, Liangmiao Wu, Jianbo Gu, Cuimei Li, Chen Zhao, Wei Liu, Luchen Shan, Pei Yu, Xifei Yang, Yaohui Tang, Guo-Yuan Yang, Yuqiang Wang, Yewei Sun, Zaijun Zhang
BACKGROUND AND PURPOSE: Neuronal regeneration from endogenous precursors is an attractive strategy for the treatment of ischemic stroke; however, most stroke-generated new born neurons die over time. Therefore, a drug that is both neuroprotective and pro-neurogenic may be promising. In this study, we assessed the neurogenic and oligodendrogenic effects of tetramethylpyrazine nitrone (TBN), a neuroprotective drug candidate for stroke, in a rat model of ischemic stroke. EXPERIMENTAL APPROACH: Sprague Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO)...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29161765/mir-335-inhibited-cell-proliferation-of-lung-cancer-cells-by-target-tra2%C3%AE
#2
Jian Liu, Tingting Bian, Jia Feng, Li Qian, Jianguo Zhang, Daishan Jiang, Qing Zhang, Xiaoli Li, Yifei Liu, Jiahai Shi
Accumulating evidence has suggested that the dysregulation of miRNAs is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR-335 expression is reduced in non-small cell lung cancer (NSCLC) tumors relative to non-cancerous adjacent tissues, whilst the expression of Tra2β is increased. In addition, clinical data revealed that the increased Tra2β and decreased miR-335 expression observed in NSCLC cells was associated with poor patient survival rates. In-vitro experimentation showed that the overexpression of miR-335 inhibited the growth, invasion and migration capabilities of A459 lung cancer cells, by targeting Tra2β...
November 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/29161463/the-il-21-mtor-axis-blocks-treg-differentiation-and-function-by-suppression-of-autophagy-in-patients-with-systemic-lupus-erythematosus
#3
Hiroshi Kato, Andras Perl
OBJECTIVES: The mechanistic target of rapamycin (mTOR) has become a therapeutic target in systemic lupus erythematosus (SLE). mTOR regulates normal T-cell lineage specification, including development of regulatory cells (Tregs). Therefore, we investigated whether mTOR is activated within Tregs and causes their depletion and dysfunction in patients with SLE. METHODS: Activities of mTOR complexes 1 (mTORC1) and 2 (mTORC2) were examined by phosphorylation of 4E-BP1, S6K, and Akt, respectively, in SLE patients relative to healthy control females age-matched for each experiment...
November 21, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29161347/pharmacological-blockage-of-the-cxcr4-cxcl12-axis-in-endometriosis-leads-to-contrasting-effects-in-proliferation-migration-and-invasion
#4
Abigail Ruiz, Lynnette Ruiz, Mariano Colón-Caraballo, Bryan J Torres-Collazo, Janice B Monteiro, Manuel Bayona, Asgerally T Fazleabas, Idhaliz Flores
High levels of inflammatory factors including chemokines have been reported in peritoneal fluid and blood of women with endometriosis. CXCL12 mediates its action by interaction with its specific receptor, CXCR4, which has been reported to be elevated in human endometriosis lesions and in the rat model of endometriosis. Activation of the CXCR4-CXCL12 axis increases cell proliferation, migration and invasion of cancer cells. To obtain insights into the CXCR4 expression profile in lesions and endometrium, as well as functionality of the CXCR4-CXCL12 axis in endometriosis we analysed the expression of CXCR4 in tissues on a human tissue array and studied CXCL12-mediated activation of proliferation, invasion, and migration in vitro...
November 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29160922/igf1r-signalling-in-testicular-germ-cell-tumour-cells-impacts-on-cell-survival-and-acquired-cisplatin-resistance
#5
Joanna Selfe, Neil C Goddard, Alan McIntyre, Kathryn R Taylor, Jane Renshaw, Sergey D Popov, Khin Thway, Brenda Summersgill, Robert A Huddart, Duncan C Gilbert, Janet M Shipley
Testicular germ cell tumours (TGCT) are the most frequent malignancy and cause of death from solid tumours in the 20-40 year age group. Although most cases show sensitivity to cis-platinum-based chemotherapy, this is associated with long-term toxicities and chemo-resistance. Roles for receptor tyrosine kinases other than KIT are largely unknown in TGCT. We therefore conducted a phosphoproteomic screen and identified the insulin growth factor receptor-1 (IGF1R) as both highly expressed and activated in TGCT cell lines representing the non-seminomatous subtype...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29160911/simultaneous-use-of-erythropoietin-and-lfm-a13-as-a-new-therapeutic-approach-for-colorectal-cancer
#6
Anna Tankiewicz-Kwedlo, Justyna Magdalena Hermanowicz, Tomasz Domaniewski, Krystyna Pawlak, Małgorzata Rusak, Anna Pryczynicz, Arkadiusz Surazynski, Tomasz Kaminski, Adam Kazberuk, Dariusz Pawlak
BACKGROUND AND PURPOSE: Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase involved in the activation of signaling pathways responsible for cell maturation and viability. BTK has previously been reported to be overexpressed in colon cancers. This kind of cancer is often accompanied by anemia, which is treated with an erythropoietin supplement. The goal of the present study was to assess the effects of combination therapy with erythropoietin beta (Epo) and LFM-A13 (BTK inhibitor) on colon cancer in in vitro and in vivo models...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29160747/lipopolysaccharide-mediates-hepatic-stellate-cell-activation-by-regulating-autophagy-and-retinoic-acid-signaling
#7
Ming Chen, Jiaxing Liu, Wenqi Yang, Wenhua Ling
Bacterial translocation and lipopolysaccharide (LPS) leakage occur at a very early stage of liver fibrosis in animal models. We studied the role of LPS in hepatic stellate cell (HSC) activation and the underlying mechanisms in vitro and in vivo. Herein, we demonstrated that LPS treatment led to a dramatic increase in autophagosome formation and autophagic flux in LX-2 cells and HSCs, which was mediated through the AKT-MTOR and AMPK-ULK1 pathway. LPS significantly decreased the lipid content, including the lipid droplet (LD) number and lipid staining area in HSCs; pretreatment with macroautophagy/autophagy inhibitors or silencing ATG5 attenuated this decrease...
November 21, 2017: Autophagy
https://www.readbyqxmd.com/read/29160412/exosomes-promote-cetuximab-resistance-via-the-pten-akt-pathway-in-colon-cancer-cells
#8
S Zhang, Y Zhang, J Qu, X Che, Y Fan, K Hou, T Guo, G Deng, N Song, C Li, X Wan, X Qu, Y Liu
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29160373/the-role-of-histone-deacetylase-inhibitors-in-regulation-of-akt-gsk-3%C3%AE-signaling-pathway-in-mice-following-transient-focal-cerebral-ischemia
#9
Bo Zhao, Lian Liu, Yan Leng, Quan Yuan, Jiabao Hou, Yang Wu, Wenwei Gao
PURPOSE: To investigate whether the neuroprotective effect of TSA on cerebral ischemia reperfusion injury is mediated by the activation of Akt/GSK-3β signaling pathway. METHODS: Mice were randomly divided into four groups (n=15): sham group (S); ischemia reperfusion group (IR); ischemia reperfusion and pretreated with TSA group (IR+T); ischemia reperfusion and pretreated with TSA and LY294002 group (IR+T+L). The model of cerebral ischemia reperfusion was established by 1h of MCAO following 24h of reperfusion...
October 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29160133/inhibition-of-metastasis-and-angiogenesis-in-hep-2-cells-by-wheatgrass-extract-an-in-vitro-and-in-silico-approach
#10
Garima Shakya, Sangeetha Balasubramanian, Muddasarul Hoda, Rukkumani Rajagopalan
Metastasis is the major hindrance in the treatment of all cancers, including laryngeal squamous cell carcinoma. Intensive researches are under way to identify the effective natural polyphenols with anti-metastatic ability for cancer treatment. Wheatgrass, an herbal plant has been reported to show anticancer effects. Hence, in this study, we aimed to analyze the anti-metastatic effect of methanol extract of wheatgrass (MEWG). The levels of metastatic marker proteins were determined by western blot. PI3K and AKT levels were determined by real time (RT)-PCR analysis...
November 21, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29160061/a-dual-macrophage-targeting-nanovector-for-delivery-of-oligodeoxynucleotides-to-overcome-cancer-associated-immunosuppression
#11
Xiao-Yan He, Bo-Ya Liu, Jin-Long Wu, Shu-Lun Ai, Ren-Xi Zhuo, Si-Xue Cheng
To overcome cancer-associated immunosuppression, we prepared a dual-targeting vector to deliver CpG oligodeoxynucleotides (ODN) to macrophages. The dual-targeting system composed of mannosylated carboxymethyl chitosan (MCMC)/hyaluronan (HA) for macrophage targeting and protamine sulfate (PS) for ODN complexation was prepared by self-assembly. The effects of ODN delivery on immune cells was studied in J774A.1 cells. Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibits a higher immune stimulatory activity compared with the mono-targeting delivery system containing either MCMC or HA, resulting in dramatically enhanced secretion of pro-inflammatory cytokines and a successful shift to activated macrophages (M1)...
November 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29159980/role-of-pi3k-in-myocardial-ischaemic-preconditioning-mapping-pro-survival-cascades-at-the-trigger-phase-and-at-reperfusion
#12
Xavier Rossello, Jaime A Riquelme, Sean M Davidson, Derek M Yellon
The Reperfusion Injury Salvage Kinase (RISK) pathway is considered the main pro-survival kinase cascade mediating the ischaemic preconditioning (IPC) cardioprotective effect. To assess the role of PI3K-Akt, its negative regulator PTEN and other pro-survival proteins such as ERK and STAT3 in the context of IPC, C57BL/6 mouse hearts were retrogradely perfused in a Langendorff system and subjected to 4 cycles of 5 min. ischaemia and 5 min. reperfusion prior to 35 min. of global ischaemia and 120 min. of reperfusion...
November 20, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29159601/activating-fgfr1-mutations-in-sporadic-pheochromocytomas
#13
Jenny Welander, Małgorzata Łysiak, Michael Brauckhoff, Laurent Brunaud, Peter Söderkvist, Oliver Gimm
INTRODUCTION: Pheochromocytomas are neuroendocrine tumors of the adrenal glands. Up to 40% of the cases are caused by germline mutations in one of at least 15 susceptibility genes, making them the human neoplasms with the highest degree of heritability. Recurrent somatic alterations are found in about 50% of the more common sporadic tumors with NF1 being the most common mutated gene (20-25%). In many sporadic tumors, however, a genetic explanation is still lacking. MATERIALS AND METHODS: We investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples and extended confirmation analysis in 2 additional cohorts comprising a total of 80 sporadic pheochromocytomas...
November 20, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29158991/ndufa4l2-is-associated-with-clear-cell-renal-cell-carcinoma-malignancy-and-is-regulated-by-elk1
#14
Lei Wang, Zhiqiang Peng, Kaizhen Wang, Yijun Qi, Ying Yang, Yue Zhang, Xinyuan An, Shudong Luo, Junfang Zheng
Background: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated...
2017: PeerJ
https://www.readbyqxmd.com/read/29158883/the-role-of-protein-kinase-b-signaling-pathway-in-anti-cancer-effect-of-rolipram-on-glioblastoma-multiforme-an-in-vitro-study
#15
Sara Ramezani, Mahmoudreza Hadjighassem, Nasim Vousooghi, Mansour Parvaresh, Farshid Arbabi, Naser Amini, Mohammad Taghi Joghataei
Introduction: The mechanism of putative cytotoxicity of 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone (rolipram), a specific phosphodiesterase-4 (PDE4) inhibitor, on glioblastoma multiforme (GBM) is almost unknown. This study aimed to investigate the role of protein kinase B (Akt) pathway in the cytotoxic effect of rolipram on human GBM U87 MG cell line and Tumor-Initiating Cells (TICs) isolated from patient's GBM specimen. Methods: TICs were characterized by using flow cytometry and quantitative real-time PCR...
July 2017: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/29158820/ph-sensitive-nano-complexes-overcome-drug-resistance-and-inhibit-metastasis-of-breast-cancer-by-silencing-akt-expression
#16
Jieying Yin, Tianqun Lang, Dongmei Cun, Zhong Zheng, Yan Huang, Qi Yin, Haijun Yu, Yaping Li
The therapy of breast cancer is encumbered by drug resistance and metastasis, which can be due to a defective PI3K/AKT/mTOR signaling pathway. This study was aimed at improving the anti-cancer effect of the chemotherapeutic agent paclitaxel (PTX) on the drug resistant and metastatic breast cancer by co-delivering PTX and a siRNA, siAkt, directed at silencing the Akt expression. Methods: The pH-sensitive amphiphilic polymer, poly [(1,4-butanediol)-diacrylate-β-N, N-diisopropylethylenediamine]-polyethyleneimine (BDP) was synthesized...
2017: Theranostics
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#17
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29158773/construction-of-an-mirna-regulated-pathway-network-reveals-candidate-biomarkers-for-postmenopausal-osteoporosis
#18
Min Shao
We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP) via establishing an microRNAs- (miRNA-) regulated pathway network (MRPN). Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS). Significant pathways based on differentially expressed genes (DEGs) using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods...
2017: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/29158682/unbs5162-inhibits-proliferation-of-human-retinoblastoma-cells-by-promoting-cell-apoptosis
#19
Bing Wang, Jiaquan Shen, Jue Wang
Human retinoblastomas are malignant intraocular tumors and have a high incidence in children. Chemotherapy combined with local therapy is the principal means of retinoblastoma treatment, the application of which has saved the eye of many children and avoided external irradiation. UNBS5162, a naphthalimide, has broad prospects as a tumor treatment, with fewer toxic side effects and higher cancer-suppression efficiency. However, the efficacy of UNBS5162 in human retinoblastomas is still not clear. In the present study, we investigated the specific mechanism of UNBS5162 in the human retinoblastoma cell lines WERIRb1 and Y79...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29158583/patient-derived-ipscs-show-premature-neural-differentiation-and-neuron-type-specific-phenotypes-relevant-to-neurodevelopment
#20
E Yeh, D Q Dao, Z Y Wu, S M Kandalam, F M Camacho, C Tom, W Zhang, R Krencik, K A Rauen, E M Ullian, L A Weiss
Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAF(Q257R), the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation...
November 21, 2017: Molecular Psychiatry
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