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https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#1
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27911401/an-optimized-protocol-to-analyze-glycolysis-and-mitochondrial-respiration-in-lymphocytes
#2
Javier Traba, Pietro Miozzo, Billur Akkaya, Susan K Pierce, Munir Akkaya
Lymphocytes respond to a variety of stimuli by activating intracellular signaling pathways, which in turn leads to rapid cellular proliferation, migration and differentiation, and cytokine production. All of these events are tightly linked to the energy status of the cell, and therefore studying the energy-producing pathways may give clues about the overall functionality of these cells. The extracellular flux analyzer is a commonly used device for evaluating the performance of glycolysis and mitochondrial respiration in many cell types...
November 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911343/pink1-parkin-and-mitochondrial-quality-control-what-can-we-learn-about-parkinson-s-disease-pathobiology
#3
Dominika Truban, Xu Hou, Thomas R Caulfield, Fabienne C Fiesel, Wolfdieter Springer
The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27911090/antitumor-activity-of-portulaca-oleracea-l-polysaccharide-on-hela-cells-through-inducing-tlr4-nf-%C3%AE%C2%BAb-signaling
#4
Rui Zhao, Tao Zhang, Baoling Ma, Xing Li
Abstarct We have previously shown that Portulaca oleracea L. polysaccharide (POL-P3b) possesses the ability to inhibit cervical cancer cell growth in vitro and in vivo. In this study, we explored how toll-like receptor 4 (TLR4) signaling correlated with the antitumor mechanism of POL-P3b. Western blotting was utilized to detect the expression of TLR4 and the downstream signaling pathway. The level of inflammatory mediator was quantified using enzyme-linked immunosorbent assay (ELISA) kits. The effects of POL-P3b on the proliferation and apoptosis in HeLa cells were determined by WST-8 assay and Hoechst 33342/propidium iodide (PI) assay...
December 2, 2016: Nutrition and Cancer
https://www.readbyqxmd.com/read/27910952/protective-effects-of-ginsenoside-rg1-on-intestinal-ischemia-reperfusion-injury-induced-oxidative-stress-and-apoptosis-via-activation-of-the-wnt-%C3%AE-catenin-pathway
#5
Guo Zu, Jing Guo, Ningwei Che, Tingting Zhou, Xiangwen Zhang
Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910951/molecular-imaging-with-engineered-physiology
#6
Mitul Desai, Adrian L Slusarczyk, Ashley Chapin, Mariya Barch, Alan Jasanoff
In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27910925/thrombomodulin-regulates-monocye-differentiation-via-pkc%C3%AE-and-erk1-2-pathway-in-vitro-and-in-atherosclerotic-artery
#7
Chien-Sung Tsai, Yi-Wen Lin, Chun-Yao Huang, Chun-Min Shih, Yi-Ting Tsai, Nai-Wen Tsao, Chin-Sheng Lin, Chun-Che Shih, Hellen Jeng, Feng-Yen Lin
Thrombomodulin (TM) modulates the activation of protein C and coagulation. Additionally, TM regulates monocyte migration and inflammation. However, its role on monocyte differentiation is still unknown. We investigated the effects of TM on monocyte differentiation. First, we found that TM was increased when THP-1 cells were treated with phorbol-12-myristate-13-acetate (PMA). Overexpression of TM enhanced the macrophage markers, CD14 and CD68 expression in PMA-induced THP-1. TM siRNA depressed the PMA-induced increase of p21(Cip1/WAF1) via ERK1/2-NF-kB p65 signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910913/loss-of-egfr-asap1-signaling-in-metastatic-and-unresectable-hepatoblastoma
#8
Sarangarajan Ranganathan, Mylarappa Ningappa, Chethan Ashokkumar, Brandon W Higgs, Jun Min, Qing Sun, Lori Schmitt, Shankar Subramaniam, Hakon Hakonarson, Rakesh Sindhi
Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-β-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-β-catenin signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910912/bhx-inhibits-the-wnt-signaling-pathway-by-suppressing-%C3%AE-catenin-transcription-in-the-nucleus
#9
Fengxia Ding, Meisa Wang, Yibo Du, Shuangshuang Du, Zhongling Zhu, Zhao Yan
BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell lines. In our study, MTT(3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) and xenograft model assay indicated that cell growth was inhibited by BHX at a range of concentrations in vitro and in vivo...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910893/interference-with-protease-activated-receptor-1-alleviates-neuronal-cell-death-induced-by-lipopolysaccharide-stimulated-microglial-cells-through-the-pi3k-akt-pathway
#10
Yuxin Li, Wuyang Yang, Alfredo Quinones-Hinojosa, Baocheng Wang, Shujun Xu, Weijie Zhu, Feng Yu, Shaoji Yuan, Peigang Lu
Excessive microglial cells activation in response to inflammatory stimuli leads to synaptic loss, dysfunction, and neuronal cell death. Activated microglia are involved in the pathogenesis of neurological conditions and frequently contribute to several complications. Accumulating evidence suggests that signaling through PAR-1 is involved in inflammation, however, its function has yet to be fully elucidated. Here, we have demonstrated that the suppression of PAR-1 leads to down-regulation of inflammatory factors including IL-1β, IL-6, TNF-α, NO, as well as the prevention of activation of NF-κB in BV2 cells...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910862/methylphenidate-enhances-early-stage-sensory-processing-and-rodent-performance-of-a-visual-signal-detection-task
#11
Rachel L Navarra, Brian D Clark, Andrew T Gargiulo, Barry D Waterhouse
Methylphenidate (MPH) is used clinically to treat attention-deficit/hyperactivity disorder (ADHD) and off-label as a performance enhancing agent in healthy individuals. MPH enhances catecholamine transmission via blockade of norepinephrine (NE) and dopamine (DA) reuptake transporters. However, it is not clear how this action impacts neural circuits performing cognitive and sensorimotor functions driving performance enhancement. The dorsal lateral geniculate nucleus (dLGN) is the primary thalamic relay for visual information from the retina to the cortex and is densely innervated by NE-containing fibers from the locus coeruleus (LC), a pathway known to modulate state-dependent sensory processing...
December 2, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27910855/l-type-calcium-channels-regulate-filopodia-stability-and-cancer-cell-invasion-downstream-of-integrin-signalling
#12
Guillaume Jacquemet, Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu, Johanna Ivaska
Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27910749/role-of-toll-like-receptors-in-hepatitis-c-virus-pathogenesis-and-treatment
#13
Usman Ali Ashfaq, Muhammad Sarfaraz Iqbal, Saba Khaliq
Viral infections are rising every day, and viruses appear to be the most dangerous pathogens in the world. Hepatitis C virus (HCV) is accepted as one of the major destructive factors of promoting severe hepatic disorders by infecting more than 180 million individuals throughout the world. Chronic infection caused by HCV poses a serious global health emergency and appears to be a powerful threat to humanity. Almost 20 years have passed since the disclosure of HCV, but even now, treatment preferences remain limited...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27910746/nutrition-and-diabetes-mellitus-how-are-they-interlinked
#14
Kanwal Rehman, Muhammad Sajid Hamid Akash
The prevalence of type 2 diabetes mellitus (T2DM) has risen exponentially, and the number of incidences increases every day. The purpose of this article is to summarize the experimental evidence supporting the important association between nutrition and diet-based therapy for the control and management of T2DM. Evidence from several in vitro, in vivo, and human studies broadly found that nutrition-based therapy enriched with several important phytochemical constituents modulates lipid and carbohydrate metabolism, and it ameliorates glucolipotoxicity and insulin resistance...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27910206/balance-between-il-3-and-type-iinterferons-and-their-interrelationship-with-fasl-dictates-lifespan-and-effector-functions-of-human-basophils
#15
B R Hagmann, A Odermatt, T Kaufmann, C A Dahinden, M Fux
BACKGROUND: In contrast to eosinophils and neutrophils, the regulation of the lifespan of human basophils is poorly defined, with the exception of the potent anti-apoptotic effect of IL-3 that also promotes pro-inflammatory effector functions and phenotypic changes. Type I IFNs (IFN-α, IFN-β), which are well known for their anti-viral activities, have the capacity to inhibit allergic inflammation. OBJECTIVE: To elucidate whether type I IFNs have the potential to abrogate the lifespan and/or effector functions of human basophils...
November 5, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27910163/serum-amyloid-a-an-acute-phase-protein-stimulates-proliferative-and-proinflammatory-responses-of-keratinocytes
#16
Ning Yu, Shujie Zhang, Jiajing Lu, Ying Li, Xuemei Yi, Li Tang, Lina Su, Yangfeng Ding
OBJECTIVES: Serum amyloid A (SAA), an acute phase protein, is highly expressed in psoriatic lesions but its function is not fully understood. The aim of this study was to explore its role in activation of keratinocytes. MATERIALS AND METHODS: Real-time PCR and immunofluorescence were performed to examine SAA expression in imiquimod (IMQ)-induced psoriasis-like mice. In vivo function of SAA was examined by treating psoriasis-like mice with SAA neutralising antibody...
December 2, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27910071/pi3k-pten-akt-genetic-mouse-models-of-endometrial-carcinoma
#17
Ayesha Joshi, Lora Hedrick Ellenson
The PI3K/PTEN/AKT pathway is the most frequently mutated pathway in endometrial carcinoma. Mouse models are invaluable tools to understand, at the molecular level, the contributions of components of this pathway towards initiation and progression of endometrial carcinoma. This chapter summarizes results of germline and tissue specific knockout mouse models generated to understand how mutations in components of this pathway lead to development of carcinoma and its interactions with other frequently altered pathways like mismatch repair and estrogen signaling...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27910068/endometrial-carcinoma-specific-targeted-pathways
#18
Nuria Eritja, Andree Yeramian, Bo-Juen Chen, David Llobet-Navas, Eugenia Ortega, Eva Colas, Miguel Abal, Xavier Dolcet, Jaume Reventos, Xavier Matias-Guiu
Endometrial cancer (EC) is the most common gynecologic malignancy in the western world with more than 280,000 cases per year worldwide. Prognosis for EC at early stages, when primary surgical resection is the most common initial treatment, is excellent. Five-year survival rate is around 70 %.Several molecular alterations have been described in the different types of EC. They occur in genes involved in important signaling pathways. In this chapter, we will review the most relevant altered pathways in EC, including PI3K/AKT/mTOR, RAS-RAF-MEK-ERK, Tyrosine kinase, WNT/β-Catenin, cell cycle, and TGF-β signaling pathways...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27910056/cardiac-gene-delivery-using-recirculating-devices
#19
Melissa J Byrne, David M Kaye
Cardiac gene delivery has become an important issue following the emergence of gene therapy for the possible treatment of heart failure. Despite many advances in the management of heart failure (HF), treatment options for many patients with advanced HF remain limited. At a cellular and molecular level, many of the fundamental alterations that contribute to the pathogenesis of HF are becoming better understood and this has resulted in the discovery of new therapeutic targets in animal models of HF, in particular in the area of gene therapy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909990/orexin-hypocretin-signaling
#20
Jyrki P Kukkonen
Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX1 and OX2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling...
December 2, 2016: Current Topics in Behavioral Neurosciences
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