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Zhao Liu, Yan Yan, Sizhe Cao, Yi Chen
This study aimed to elucidate the roles of long non-coding RNA SNHG14 in gastric cancer development. LncRNA SNHG14 was markedly up-regulated in gastric cancer tissues and cells. Knockdown of SNHG14 significantly inhibited SGC-7901 cell viability, migration, invasion, and promoted cell apoptosis. In addition, miR-145 was negatively regulated by SNHG14 and the effects of SNHG14 knockdown on cell viability, apoptosis, migration, invasion, and the expression of apoptosis-related proteins and EMT-markers were reversed by inhibition of miR-145 at the same time...
April 18, 2018: Journal of Cellular Biochemistry
Marion T Kasaian, Julie Lee, Agnes Brennan, Spencer I Danto, Kendall E Black, Lori Fitz, Anne E Dixon
BACKGROUND: A major goal of asthma therapy is to achieve disease control, with maintenance of lung function, reduced need for rescue medication, and prevention of exacerbation. Despite current standard of care, up to 70% of patients with asthma remain poorly controlled. Analysis of serum and sputum biomarkers could offer insights into parameters associated with poor asthma control. OBJECTIVE: To identify signatures as determinants of asthma disease control, we performed proteomics using Olink proximity extension analysis...
April 17, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Fabrizio Martino, Mohinder Pal, Hugo Muñoz-Hernández, Carlos F Rodríguez, Rafael Núñez-Ramírez, David Gil-Carton, Gianluca Degliesposti, J Mark Skehel, S Mark Roe, Chrisostomos Prodromou, Laurence H Pearl, Oscar Llorca
The R2TP/Prefoldin-like co-chaperone, in concert with HSP90, facilitates assembly and cellular stability of RNA polymerase II, and complexes of PI3-kinase-like kinases such as mTOR. However, the mechanism by which this occurs is poorly understood. Here we use cryo-EM and biochemical studies on the human R2TP core (RUVBL1-RUVBL2-RPAP3-PIH1D1) which reveal the distinctive role of RPAP3, distinguishing metazoan R2TP from the smaller yeast equivalent. RPAP3 spans both faces of a single RUVBL ring, providing an extended scaffold that recruits clients and provides a flexible tether for HSP90...
April 16, 2018: Nature Communications
Mohamed A Fouda, Hanan M El-Gowelli, Sahar M El-Gowilly, Mahmoud M El-Mas
BACKGROUND: Chronic nicotine administration impairs reflex chronotropic responses that follow arterial baroreceptor unloading in female rats with repleted, but not depleted (ovariectomized, OVX), estrogen (E2 ). This study investigated whether products of nitric oxide synthase (NOS) and/or heme oxygenase (HO) and related soluble guanylate cyclase (sGC)/phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinases (MAPKs) signaling mediate the E2 -sensitive depressant effect of nicotine on reflex tachycardia...
October 3, 2017: Pharmacological Reports: PR
Shun Chen, Xinchen Li, Wenjie Zhang, Mengting Zi, Yuekang Xu
As professional antigen-presenting cells, dendritic cells (DCs) initiate and regulate immune responses against inflammation. The invasion of pathogens into the body, however, can in turn cause the change of DCs in both activity and viability, which ultimately affect immune homeostasis. The exact mechanisms that the bacteria utilize to alter the lifespan of DCs, however, are far from clear. In this study, we found that the bacterial wall compound lipopolysaccharide(LPS)can promote the survival of GM-CSF-differentiated DCs (GM-DCs)...
April 6, 2018: Immunology and Cell Biology
Takahito Sugase, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Tomoharu Ohkawara, Kosuke Hiramatsu, Toshirou Nishida, Seiichi Hirota, Yurina Saito, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Kazuhiro Hanasaki, Tadamitsu Kishimoto, Masaki Mori, Yuichiro Doki, Tetsuji Naka
BACKGROUND: Most of the gastrointestinal stromal tumors (GIST) have mutations in the KIT gene, encoding a receptor tyrosine kinase. Imatinib, a receptor tyrosine kinase inhibitor, is the first-line therapy for unresectable and metastatic GISTs. Despite the revolutionary effects of imatinib, some patients are primarily resistant to imatinib and many become resistant because of acquisition of secondary mutations in KIT. This study investigated the antitumor effects of SOCS1 gene therapy, which targets several signaling pathways...
April 5, 2018: Gastric Cancer
Haiying Wang, Danping Wang, Chunsun Li, Xingsong Zhang, Xiaolin Zhou, Jianan Huang
Karyopherin β1 (Kpnβ1), also known as importin-β, is part of the karyopherin superfamily of nuclear transport proteins. Kpnβ1 is an oncogene that is overexpressed in various human cancers. Recent studies have showed that Kpnβ1 is one of the leading causes of cancer-related deaths in the world. However, the role of Kpnβ1 in non-small cell lung cancer (NSCLC) remains uncertain. In this study, we used western blotting to show that Kpnβ1 expression is higher in lung-cancer tissues and cells, and immunohistochemistry analysis revealed that Kpnβ1 was significantly associated with the clinicopathological features of NSCLC...
April 2018: Tissue & Cell
Darren W Gray, Michael D Welsh, Fawad Mansoor, Simon Doherty, Olivier P Chevallier, Christopher T Elliott, Mark H Mooney
Bovine Respiratory Disease (BRD) is a major source of economic loss within the agricultural industry. Vaccination against BRD-associated viruses does not offer complete immune protection and vaccine failure animals present potential routes for disease spread. Serological differentiation of infected from vaccinated animals (DIVA) is possible using antigen-deleted vaccines, but during virus outbreaks DIVA responses are masked by wild-type virus preventing accurate serodiagnosis. Previous work by the authors has established the potential for metabolomic profiling to reveal metabolites associated with systemic immune responses to vaccination...
2018: PloS One
Kirti S Prabhu, Iman W Achkar, Shilpa Kuttikrishnan, Sabah Akhtar, Abdul Q Khan, Kodapully S Siveen, Shahab Uddin
Natural products have been gaining recognition and are becoming a significant part of research in the area of drug development and discovery. Phytochemicals derived from these sources have been comprehensively studied and have displayed a wide range of activities against many fatal diseases including cancer. One such product that has gained recognition from its pharmacological properties and nontoxic nature is embelin, obtained from Embelia ribes. Amid all the vivid pharmacological activities, embelin has gained its prominence in the area of cancer research...
April 5, 2018: Future Medicinal Chemistry
Hongjuan You, Fanyun Kong, Kai Zhou, Xiao Wei, Lei Hu, Wei Hu, Wenya Luo, Yanbo Kou, Xiaomei Liu, Xi Chen, Kuiyang Zheng, Renxian Tang
LIM and SH3 domain protein 1 (LASP-1) is known to participate in the progression of hepatocellular carcinoma (HCC). We previously showed that ectopic expression of hepatitis B virus (HBV) X protein (HBX) enhanced the expression of LASP-1, which promoted proliferation and migration of HCC cells. Here, we further demonstrated the molecular mechanism underlying upregulation of LASP-1, mediated by HBX, in HBV-infected HCC cells. Through a luciferase activity assay, we discovered that the LASP-1 promoter region regulated by HBX contained an AP-1 binding element in human hepatoma cells...
March 30, 2018: Journal of Cellular Physiology
Sally L Elshaer, Tahira Lemtalsi, Azza B El-Remessy
Diabetes and hyperglycemia are associated with increased retinal oxidative and nitrative stress and vascular cell death. Paradoxically, high glucose stimulates expression of survival and angiogenic growth factors. Therefore, we examined the hypothesis that high glucose-mediated tyrosine nitration causes inhibition of the survival protein PI3-kinase, and in particular, its regulatory p85 subunit in retinal endothelial cell (EC) cultures. Retinal EC were cultured in high glucose (HG, 25 mM) for 3 days or peroxynitrite (PN, 100 µM) overnight in the presence or absence of a peroxynitrite decomposition catalyst (FeTPPs, 2...
March 25, 2018: Antioxidants (Basel, Switzerland)
Xinzhong Li, Xiang He, He Wang, Mengsha Li, Senlin Huang, Guojun Chen, Yuanwen Jing, Shifei Wang, Yanmei Chen, Wangjun Liao, Yulin Liao, Jianping Bin
Aims: Long noncoding RNAs (lncRNAs) are critical regulators of cardiovascular lineage commitment and heart wall development, but their roles in regulating endogenous cardiac regeneration are unclear. The present study investigated the role of human-derived lncRNA in regulating endogenous cardiac regeneration as well as the underlying mechanisms. Methods and Results: We compared RNA sequencing data from human fetal and adult hearts and identified a novel lncRNA that was upregulated in adult hearts (Genesymbol NONHSAG000971), which we named regulator of cardiac regeneration (ROCR)...
March 23, 2018: Cardiovascular Research
Helison Do Carmo, Sapna Arjun, Orlando Petrucci, Derek M Yellon, Sean M Davidson
PURPOSE: Protecting the heart from ischaemia-reperfusion (IR) injury is a major goal in patients presenting with an acute myocardial infarction. Pyroptosis is a novel form of cell death in which caspase 1 is activated and cleaves interleukin 1β. VX-785 is a highly selective, prodrug caspase 1 inhibitor that is also clinically available. It has been shown to be protective against acute IR in vivo rat model, and therefore might be a promising possibility for future cardioprotective therapy...
March 26, 2018: Cardiovascular Drugs and Therapy
Liyan Du, Xiaomei Li, Linhong Zhen, Weiling Chen, Lingguang Mu, Yang Zhang, Ailin Song
Breast cancer is one of the most prevalent malignancies and the leading cause of cancer‑associated mortality in women worldwide and in China. Everolimus (C53H83NO14) is an efficient anti-cancer drug for breast cancer which targets mammalian target of rapamycin (mTOR). The present study investigated the inhibitory effects of everolimus on breast cancer cells and an MCF‑7‑bearing mouse model. The potential mechanism of the everolimus‑mediated decrease in growth and aggressiveness of breast cancer cells was reported...
March 16, 2018: Molecular Medicine Reports
Zhao-Jia Gao, Wei-Dong Yuan, Jun-Qiang Yuan, Kai Yuan, Yong Wang
PURPOSE: Lung cancer, the leading cause of cancer-related death worldwide, shows a poor 5-year overall survival rate. In our previous study, we demonstrated that miR-486-5p can be a potential blood-based biomarker for early diagnosis and recurrence prediction of non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the possible roles and related target genes of miR-486-5p in NSCLC progression. METHODS: pcDNA3.1(+)/Pri-miR486 recombinant plasmid and miR-486-5p inhibitor were transfected into NSCLC cells and theirs effects were evaluated by qRT-PCR...
March 15, 2018: Pathology, Research and Practice
Seungwoo Kim, Hyosoon Cheon, Sam-Moon Kim, Young-Youl Kim
Background: Previous studies indicated that cadmium (Cd) increases PI3-kinase/Akt phosphorylation, resulting in an alteration in GSK-3β activity. However, the mechanism of Cd-induced endoplasmic reticulum (ER) stress in neuronal cells has yet to be studied in needs further elucidation. We examined the role of GSK-3β in Cd-induced neuronal cell death and the related downstream signaling pathways. Methods: SH-SY5Y human neuroblastoma cells were treated with 10 or 20 μM BAPTA-AM and 1 μM wortmannin for 30 min and then incubated with 25 μM Cd for 12 h...
2018: Cellular & Molecular Biology Letters
David Michalovich, Sergey Nejentsev
Activated PI3 kinase delta syndrome (APDS) is a primary immunodeficiency caused by dominant mutations that increase activity of phosphoinositide-3-kinase δ (PI3Kδ). APDS can be caused by mutations in the PIK3CD gene that encodes PI3Kδ catalytic subunit p110δ (APDS1) or mutations in the PIK3R1 gene that encodes regulatory subunit p85α (APDS2). APDS research advanced rapidly after the initial discovery in 2013. More than 200 APDS patients have been identified around the world. Multiple novel APDS mutations were reported and molecular mechanisms leading to PI3Kδ activation have been elucidated...
2018: Frontiers in Immunology
Ting Deng, Yu Zhang, Yang Wu, Ping Ma, Jiufei Duan, Wei Qin, Xu Yang, Mingqing Chen
Epidemiological studies suggest a positive relationship between phthalate exposure and diabetes. However, little is known about the impact of dibutyl phthalate (DBP) exposure on the development of diabetes. To determine the role of DBP exposure on the development of type 2 diabetes, mice were orally exposed to DBP dosages of 0.5, 5, 50 mg/kg/day for 7 weeks, combined with a high fat diet and injections of a low dose of streptozotocin (STZ). The results showed that exposure to 50 mg/kg/day DBP alone induced a marked decrease in insulin secretion and glucose intolerance, but had no influence on insulin resistance...
March 8, 2018: Toxicology Letters
Katerina Kapodistria, Effie-Photini Tsilibary, Eleni Kotsopoulou, Petros Moustardas, Paraskevi Kitsiou
Liraglutide, a human long-lasting GLP-1 analogue, is currently regarded as a powerful treatment option for type 2 diabetes. Apart from glucoregulatory and insulinotropic actions, liraglutide increases β-cell mass through stimulation of β-cell proliferation and islet neogenesis, as well as inhibition of β-cell apoptosis. However, the underline molecular mechanisms have not been fully characterized. In this study, we investigated the mechanism by which liraglutide preserves islet β-cells in an animal model of overt diabetes, the obese db/db mice, and protects a mouse pancreatic β-cell line (βTC-6 cells) against apoptosis...
March 10, 2018: Journal of Cellular and Molecular Medicine
Razieh Rabani, Allen Volchuk, Mirjana Jerkic, Lindsay Ormesher, Linda Garces-Ramirez, Johnathan Canton, Claire Masterson, Stephane Gagnon, Kate C Tatham, John Marshall, Sergio Grinstein, John G Laffey, Katalin Szaszi, Gerard F Curley
Human Mesenchymal Stem/Stromal Cells (MSCs) have been reported to produce an M2-like, alternatively activated phenotype in macrophages. In addition, MSCs mediate effective bacterial clearance in pre-clinical sepsis models. Thus, MSCs have a paradoxical anti-microbial and anti-inflammatory response that is not understood. Here we studied the phenotypic and functional response of monocyte-derived human macrophages to MSC exposure in vitro MSCs induced two distinct, co-existent phenotypes: M2-like macrophages (generally elongated morphology, CD163 positive, acute phagosomal acidification, low NADPH oxidase expression and low phagosomal superoxide production) and M1-like macrophages, characterised by high levels of phagosomal superoxide production...
March 8, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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