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https://www.readbyqxmd.com/read/28170447/comparison-of-mkp-and-bsk-h-media-for-the-cultivation-and-isolation-of-borrelia-burgdorferi-sensu-lato
#1
Eva Ružić-Sabljić, Vera Maraspin, Daša Stupica, Tereza Rojko, Petra Bogovič, Franc Strle, Tjaša Cerar
The isolation of B. burgdorferi sensu lato requires the use of complex cultivation media. The aim of the study was to compare the usefulness of BSK-H (a commercial medium produced by HiMedia, India) and MKP medium. MKP and BSK-H media were prepared in accordance with the relevant protocols. Borrelia strains and skin culture biopsies were simultaneously inoculated into both media, incubated and checked for growth. Borrelial growth characteristics, isolation rates and characteristics of the isolated borreliae were analysed and compared...
2017: PloS One
https://www.readbyqxmd.com/read/28161489/antiproliferative-effects-of-bortezomib-in-endothelial-cells-transformed-by-viral-g-protein-coupled-receptor-associated-to-kaposi-s-sarcoma
#2
A Suares, M Mori Sequeiros Garcia, C Paz, V González-Pardo
The Kaposi's Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. We have previously demonstrated that the proteasome inhibitor Bortezomib inhibits NF-κB pathway, which is required for tumor maintenance in endothelial cells that express vGPCR (vGPCR cells). In this work, we further investigated Bortezomib anti-proliferative mechanism of action. We demonstrated that Bortezomib decreases vGPCR cell number in a dose-dependent manner and induces cell morphology changes...
February 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28158298/administration-of-bovine-casein-derived-peptide-prevents-cognitive-decline-in-alzheimer-disease-model-mice
#3
Li-Juan Min, Yodai Kobayashi, Masaki Mogi, Kana Tsukuda, Akio Yamada, Koji Yamauchi, Fumiaki Abe, Jun Iwanami, Jin-Zhong Xiao, Masatsugu Horiuchi
There is a growing interest in identifying natural food ingredients that may serve to prevent dementia such as that due to Alzheimer disease (AD). Peptides derived from food proteins have been demonstrated to have various physiological activities such as a hypotensive action. Recent findings have indicated possible associations of hypertension with AD progression, and suggest that angiotensin converting enzyme (ACE) inhibitors with potential to pass through the blood brain barrier (BBB) may reduce the risk of AD...
2017: PloS One
https://www.readbyqxmd.com/read/28154014/a-tumor-cell-selective-inhibitor-of-mitogen-activated-protein-kinase-phosphatases-sensitizes-breast-cancer-cells-to-lymphokine-activated-killer-cell-activity
#4
Christof T Kaltenmeier, Laura L Vollmer, Lawrence A Vernetti, Lindsay Caprio, Keanu Davis, Vasiliy N Korotchenko, Billy W Day, Michael Tsang, Keren I Hulkower, Michael T Lotze, Andreas Vogt
Dual specificity mitogen activated protein kinase (MAPK) phosphatases (DUSP-MKPs) have been hypothesized to maintain cancer cell survival by buffering excessive MAPK signaling caused by upstream activating oncogenic products. A large and diverse body of literature suggests that genetic depletion of DUSP-MKPs can reduce tumorigenicity, suggesting that hyperactivating MAPK signaling by DUSP-MKP inhibitors could be a novel strategy to selectively affect the transformed phenotype. Through in vivo structure activity relationship studies in transgenic zebrafish we recently identified a hyperactivator of Fibroblast Growth Factor signaling (BCI-215) that is devoid of developmental toxicity and restores defective MAPK activity caused by overexpression of DUSP1 and DUSP6 in mammalian cells...
February 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28130620/extranodal-spread-is-associated-with-recurrence-and-poor-survival-in-stage-iii-cutaneous-melanoma-patients
#5
Thomas R Crookes, Richard A Scolyer, Serigne Lo, Martin Drummond, Andrew J Spillane
BACKGROUND: Inconsistent data suggests extranodal spread (ENS) is an adverse prognostic factor in Stage III melanoma patients but it remains contentious. By rigorously matching cohorts, this study sought to clarify associations with recurrence and survival. METHODS: Melanoma patients with lymph node metastases (AJCC Stage III), with or without ENS, sub-classified on the basis of known (MKP) or unknown primary (MUP), were identified from a single institution prospective database...
January 27, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28111292/disruption-of-brain-mek-erk-sequential-phosphorylation-and-activation-during-midazolam-induced-hypnosis-in-mice-roles-of-gabaa-receptor-mek1-inactivation-and-phosphatase-mkp-3
#6
María Álvaro-Bartolomé, Glòria Salort, Jesús A García-Sevilla
Midazolam is a positive allosteric modulator at GABAA receptor that induces a short hypnosis and neuroplasticity, in which the sequential phosphorylation of MEK1/2 and ERK1/2 was shown to play a role. This study investigated the parallel activation of p-MEK and p-ERK and regulatory mechanisms induced by midazolam through the stimulation of GABAA receptors in the mouse brain. During the time course of midazolam (60mg/kg)-induced sleep in mice (lasting for about 2h) p-Ser217/221 MEK1/2 was increased (+146% to +258%) whereas, unexpectedly, p-Tyr204/Thr202 ERK1/2 was found decreased (-16% to -38%), revealing uncoupling of MEK to ERK signals in various brain regions...
January 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28110053/development-and-optimization-of-an-in-vitro-cultivation-protocol-allows-for-isolation-of-borrelia-miyamotoi-from-patients-with-hard-tick-borne-relapsing-fever
#7
Joris Koetsveld, Nadezhda M Kolyasnikova, Alex Wagemakers, Marina G Toporkova, Denis S Sarksyan, Anneke Oei, Alexander E Platonov, Joppe W Hovius
OBJECTIVES: Borrelia miyamotoi has been shown to infect humans in Eurasia and North America causing hard tick-borne relapsing fever (HTBRF). In vitro cultivation of B. miyamotoi was described recently; however, clinical isolation of relapsing fever Borrelia is cumbersome. Our aim was to develop a straightforward protocol enabling B. miyamotoi isolation directly from blood of patients. METHODS: MKP-F media, with or without anticoagulants, or blood from healthy human volunteers, was spiked with B...
January 18, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28096466/a-phosphoproteomic-screen-identifies-a-guanine-nucleotide-exchange-factor-for-rab3a-as-a-map-kinase-phosphatase-5-regulated-map-kinase-target-in-il-6-secretion-and-myogenesis
#8
Hojin Lee, Kisuk Min, Jae-Sung Yi, Hao Shi, Woochul Chang, Leandra Jackson, Anton M Bennett
The mitogen-activated protein kinases (MAPKs) have been shown to regulate skeletal muscle function. Previously, we showed that MAPK phosphatase-5 (MKP-5) negatively regulates myogenesis and regeneration of skeletal muscle through inhibition of p38 MAPK and c-Jun N-terminal kinase (JNK). However, the identity and contribution of MKP-5-dependent MAPK targets in the regulation of skeletal muscle function and regenerative myogenesis has not been established. In order to identify MKP-5-dependent MAPK substrates in skeletal muscle, we performed a global differential phospho-MAPK substrate screen in regenerating skeletal muscles of wild type and MKP-5-deficient mice...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28053233/dual-specificity-phosphatase-5-controls-the-localized-inhibition-propagation-and-transforming-potential-of-erk-signaling
#9
Andrew M Kidger, Linda K Rushworth, Julia Stellzig, Jane Davidson, Christopher J Bryant, Cassidy Bayley, Edward Caddye, Tim Rogers, Stephen M Keyse, Christopher J Caunt
Deregulated extracellular signal-regulated kinase (ERK) signaling drives cancer growth. Normally, ERK activity is self-limiting by the rapid inactivation of upstream kinases and delayed induction of dual-specificity MAP kinase phosphatases (MKPs/DUSPs). However, interactions between these feedback mechanisms are unclear. Here we show that, although the MKP DUSP5 both inactivates and anchors ERK in the nucleus, it paradoxically increases and prolongs cytoplasmic ERK activity. The latter effect is caused, at least in part, by the relief of ERK-mediated RAF inhibition...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27997807/roflumilast-n-oxide-in-combination-with-formoterol-enhances-the-anti-inflammatory-effect-of-dexamethasone-in-asm-cells
#10
Brijeshkumar S Patel, Md Mostafizur Rahman, Gina Baehring, Dikaia Xenaki, Francesca Su-May Tang, Brian G Oliver, Alaina J Ammit
Roflumilast is an orally active phosphodiesterase 4 (PDE4) inhibitor approved for use in chronic obstructive pulmonary disease. Roflumilast N-oxide (RNO) is the active metabolite of roflumilast and has demonstrated anti-inflammatory impact in vivo and in vitro. To date, the effect of RNO on the synthetic function of airway smooth muscle (ASM) cells is unknown. We address this herein and investigate the effect of RNO on β2-adrenoceptor-mediated, cAMP-dependent responses in ASM cells in vitro, and whether RNO enhances steroid-induced repression of inflammation...
December 20, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27958388/map-kinase-phosphatase-2-deficient-mice-develop-attenuated-experimental-autoimmune-encephalomyelitis-through-regulating-dendritic-cells-and-t-cells
#11
Mark Barbour, Robin Plevin, Hui-Rong Jiang
Mitogen-activated protein kinase phosphatases (MKPs) play key roles in inflammation and immune mediated diseases. Here we investigated the mechanisms by which MKP-2 modulates central nervous system (CNS) inflammation in experimental autoimmune encephalomyelitis (EAE). Our results show that MKP-2 mRNA levels in the spinal cord and lymphoid organs of EAE mice were increased compared with naive controls, indicating an important role for MKP-2 in EAE development. Indeed, MKP-2(-/-) mice developed reduced EAE severity, associated with diminished CNS immune cell infiltration, decreased proinflammatory cytokine production and reduced frequency of CD4(+) and CD8(+) T cells in spleens and lymph nodes...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913746/anti-trachea-inflammatory-effects-of-diosgenin-from-dioscorea-nipponica-through-interactions-with-glucocorticoid-receptor-%C3%AE
#12
Yang Junchao, Wang Zhen, Wang Yuan, Xu Liying, Jiang Libin, Zhu Yuanhong, Zhao Wei, Chen Ruilin, Zhai Lu
Asthma is a heterogeneous disease characterized by symptoms of chronic inflammation and airway structural and functional changes. It affects about 300 million people worldwide and causes 250 000 deaths annually, but its symptoms can be greatly relieved by regular use of inhaled glucocorticoids (GCs). GCs exert their function through interacting with glucocorticoid receptors (GRs). Diosgenin is a naturally occurring steroidal saponin abundantly present in many medicinal plants, including Dioscorea nipponica, which shares a similar steroidal structure with GC...
December 2, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27852250/impaired-anti-inflammatory-action-of-glucocorticoid-in-neutrophil-from-patients-with-steroid-resistant-asthma
#13
Meijia Wang, Pengfei Gao, Xiaojie Wu, Yuetao Chen, Yikuan Feng, Qun Yang, Yongjian Xu, Jianping Zhao, Jungang Xie
BACKGROUND: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics. METHODS: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment...
November 16, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27783995/mkp-1-attenuates-lps-induced-blood-testis-barrier-dysfunction-and-inflammatory-response-through-p38-and-i%C3%AE%C2%BAb%C3%AE-pathways
#14
Yiqing Pan, Yue Liu, Li Wang, Feng Xue, Yanqin Hu, Ran Hu, Chen Xu
Sertoli cells create a local tolerogenic microenvironment to maintain testicular immune privilege especially through the formation of a blood-testis barrier (BTB). However, the molecular mechanisms underlying the immune modulation function and BTB dynamics of Sertoli cells remained elusive. MAP phosphatase (MKP)-1 acts as a crucial negative regulator of the inflammatory response. Nevertheless, the role of MKP-1 in regulating Sertoli cells has not been elucidated. In this study, we have for the first time uncovered distinct cellular localization of MKP-1 in the cells at different stages of mouse testis, and the level of MKP-1 expression was significantly up-regulated by LPS-induced acute testis inflammation...
October 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#15
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27771463/upregulation-of-mkp-7-in-response-to-rosiglitazone-treatment-ameliorates-lipopolysaccharide-induced-destabilization-of-sirt1-by-inactivating-jnk
#16
Jung Seok Hwang, Sun Ah Ham, Taesik Yoo, Won Jin Lee, Kyung Shin Paek, Jae-Hwan Kim, Chi-Ho Lee, Han Geuk Seo
Silent mating type information regulation 2 homolog 1 (SIRT1), a NAD-dependent deacetylase, mediates cellular processes involved in gene silencing and aging. The regulation of lifespan by SIRT1 has been extensively investigated, but less is known about the mechanisms associated with its cellular turnover during inflammatory responses. In this study, we found that peroxisome proliferator-activated receptor (PPAR) γ is associated with SIRT1 stability in murine macrophage RAW 264.7 cells exposed to lipopolysaccharide (LPS)...
December 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27677845/resveratrol-suppresses-nthi-induced-inflammation-via-up-regulation-of-the-negative-regulator-myd88-short
#17
Carla S Andrews, Shingo Matsuyama, Byung-Cheol Lee, Jian-Dong Li
Upper respiratory tract inflammatory diseases such as asthma and chronic obstructive pulmonary diseases (COPD) affect more than one-half billion people globally and are characterized by chronic inflammation that is often exacerbated by respiratory pathogens such as nontypeable Haemophilus influenzae (NTHi). The increasing numbers of antibiotic-resistant bacterial strains and the limited success of currently available pharmaceuticals used to manage the symptoms of these diseases present an urgent need for the development of novel anti-inflammatory therapeutic agents...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27670844/monocytic-mkp-1-is-a-sensor-of-the-metabolic-environment-and-regulates-function-and-phenotypic-fate-of-monocyte-derived-macrophages-in-atherosclerosis
#18
Hong Seok Kim, Sina Tavakoli, Leigh Ann Piefer, Huynh Nga Nguyen, Reto Asmis
Diabetes promotes the S-glutathionylation, inactivation and subsequent degradation of mitogen-activated protein kinase phosphatase 1 (MKP-1) in blood monocytes, and hematopoietic MKP-1-deficiency in atherosclerosis-prone mice accelerates atherosclerotic lesion formation, but the underlying mechanisms were not known. Our aim was to determine the mechanisms through which MKP-1 deficiency in monocytes and macrophages promotes atherogenesis. Transplantation of MKP-1-deficient bone marrow into LDL-R(-/-) (MKP-1LeuKO) mice accelerated high-fat diet (HFD)-induced atherosclerotic lesion formation...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27620528/4-hydroxy-2-nonenal-induces-apoptosis-by-activating-erk1-2-signaling-and-depleting-intracellular-glutathione-in-intestinal-epithelial-cells
#19
Yun Ji, Zhaolai Dai, Guoyao Wu, Zhenlong Wu
Excessive reactive oxygen species (ROS) induces oxidative damage to cellular constituents, ultimately leading to induction of apoptotic cell death and the pathogenesis of various diseases. The molecular mechanisms for the action of ROS in intestinal diseases remain poorly defined. Here, we reported that 4-hydroxy-2-nonenal (4-HNE) treatment led to capses-3-dependent apoptosis accompanied by increased intracellular ROS level and reduced glutathione concentration in intestinal epithelial cells. These effects of 4-HNE were markedly abolished by the antioxidant L-cysteine derivative N-acetylcysteine (NAC)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27599524/c-jun-n-terminal-kinase-inactivation-by-mitogen-activated-protein-kinase-phosphatase-1-determines-resistance-to-taxanes-and-anthracyclines-in-breast-cancer
#20
Raul Rincon, Sandra Zazo, Cristina Chamizo, Rebeca Manso, Paula González-Alonso, Ester Martin-Aparicio, Ion Cristobal, Carmen Cañadas, Rosario Perona, Ana Lluch, Pilar Eroles, Jesus Garcia-Foncillas, Joan Albanell, Ana Rovira, Juan Madoz-Gurpide, Federico Rojo
Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is overexpressed during malignant transformation of the breast in many patients, and it is usually associated with chemoresistance through interference with JNK-driven apoptotic pathways. Although the molecular settings of the mechanism have been documented, details about the contribution of MKP-1 to the failure of chemotherapeutic interventions are unclear. Transient overexpression of MKP-1 and treatment with JNK-modulating agents in breast carcinoma cells confirmed the mediation of MKP-1 in the resistance to taxanes and anthracyclines in breast cancer, through the inactivation of JNK½...
September 6, 2016: Molecular Cancer Therapeutics
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