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https://www.readbyqxmd.com/read/28655070/inhibitory-effect-of-carnosol-on-phthalic-anhydride-induced-atopic-dermatitis-via-inhibition-of-stat3
#1
Do Yeon Lee, Chul Ju Hwang, Ji Yeon Choi, Mi Hee Park, Min Ji Song, Ki Wan Oh, Dong Ju Son, Seung Hwa Lee, Sang Bae Han, Jin Tae Hong
Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264...
June 27, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28654706/differential-effects-of-heat-shock-protein-90-and-serine-1179-phosphorylation-on-endothelial-nitric-oxide-synthase-activity-and-on-its-cofactors
#2
Yuanzhuo Chen, Bojie Jiang, Yugang Zhuang, Hu Peng, Weiguo Chen
Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. Previous studies showed that bovine eNOS serine 1179 (Serine 1177 for human eNOS) phosphorylation enhanced NO synthesis. Meanwhile, heat shock protein 90 (Hsp90) plays a critical role in maintenance of eNOS structure and function. However, the regulatory difference and importance between Serine 1179 phosphorylation and Hsp90 on eNOS activity have not been evaluated. In current studies, S1179D eNOS was employed to mimic phospho-eNOS and exhibited markedly increased enzyme activity than wild type eNOS (WT eNOS)...
2017: PloS One
https://www.readbyqxmd.com/read/28654306/gene-expression-profile-of-peripheral-blood-mononuclear-cells-in-response-to-intracerebral-hemorrhage
#3
Ming Sang, Xuanbin Wang, Hanyao Zhang, Xiaodong Sun, Xudong Ding, Puqing Wang, Rong Jiao, Huaxian Cheng, Sijun Yang, Guibin Zhang
RNA-sequencing, a powerful tool, yields a comprehensive view of whole transcriptome. Intracerebral hemorrhage (ICH) is a devastating form of stroke. To date, RNA-sequencing analysis of ICH has not been reported. Peripheral blood mononuclear cells (PBMCs) were used as a source of mRNA for gene expression profile analysis in stroke. In this study, we performed transcriptome analyses for PBMCs from four ICH patients and four healthy volunteers on Illumina platform. We identified 4040 significantly differentially expressed genes (DEGs)...
June 27, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28654261/astragalin-reduces-hexokinase-2-through-increasing-mir-125b-to-inhibit-the-proliferation-of-hepatocellular-carcinoma-cells-in-vitro-and-in-vivo
#4
Wei Li, Ji Hao, Lang Zhang, Zhuo Cheng, Xukun Deng, Guangwen Shu
Astragalin (ASG) can be found in a variety of food components. ASG exhibits cytotoxic effects on several different types of malignant cells. However, its effects on hepatocellular carcinoma (HCC) cells and the underlying molecular mechanisms have remained to be fully elucidated. Here, we revealed that ASG remarkably suppressed the proliferation of HCC cells. In HCC cells, ASG inhibited glucose glycolysis and promoted oxidative phosphorylation, resulting in a surge of reactive oxygen species (ROS). Mechanistically, ASG suppressed the expression of hexokinase 2 (HK2)...
June 27, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28653133/dysregulation-of-cerebellar-adrenomedullin-signaling-during-hypertension
#5
Leticia Figueira, Anita Israel
Adrenomedullin (AM) is a peptide involved in blood pressure regulation. AM activates three different receptors, the AM type 1 (AM1), type 2 (AM2), and calcitonin gene-related peptide 1 (CGRP1) receptors. AM triggers several signaling pathways such as adenylyl cyclase (AC), guanylyl cyclase (GC), and extracellular signal-regulated kinases (ERK) and modulates reactive oxygen species (ROS) metabolism. Cerebellar AM, AM-binding sites, and its receptor components are altered during hypertension, although it is unknown if these alterations are associated with changes in AM signaling...
June 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28652704/rhein-attenuates-inflammation-through-inhibition-of-nf-%C3%AE%C2%BAb-and-nalp3-inflammasome-in-vivo-and-in-vitro
#6
Hui Ge, Hao Tang, Yanbing Liang, Jingguo Wu, Qing Yang, Lijin Zeng, Zhongfu Ma
Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28652406/deciphering-the-role-of-the-signal-and-sty1-kinase-dependent-phosphorylation-of-the-stress-responsive-transcription-factor-atf1-on-gene-activation
#7
Clàudia Salat-Canela, Esther Paulo, Laura Sánchez-Mir, Mercè Carmona, José Ayté, Baldo Oliva, Elena Hidalgo
Adaptation to stress triggers the most dramatic shift in gene expression in fission yeast (Schizosaccharomyces pombe), and this response is driven by signaling via the MAPK Sty1. Upon activation, Sty1 accumulates in the nucleus, and stimulates expression of hundreds of genes via the nuclear transcription factor Atf1, including expression of atf1 itself. However, the role of stress-induced, Sty1-mediated Atf1 phosphorylation in transcriptional activation is unclear. To this end, we expressed Atf1 phosphorylation mutants from a constitutive promoter, to uncouple Atf1 activity from endogenous, stress-activated Atf1 expression...
June 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28652330/exploiting-the-synthetic-lethality-between-terminal-respiratory-oxidases-to-kill-mycobacterium-tuberculosis-and-clear-host-infection
#8
Nitin P Kalia, Erik J Hasenoehrl, Nurlilah B Ab Rahman, Vanessa H Koh, Michelle L T Ang, Dannah R Sajorda, Kiel Hards, Gerhard Grüber, Sylvie Alonso, Gregory M Cook, Michael Berney, Kevin Pethe
The recent discovery of small molecules targeting the cytochrome bc1 :aa3 in Mycobacterium tuberculosis triggered interest in the terminal respiratory oxidases for antituberculosis drug development. The mycobacterial cytochrome bc1 :aa3 consists of a menaquinone:cytochrome c reductase (bc1 ) and a cytochrome aa3 -type oxidase. The clinical-stage drug candidate Q203 interferes with the function of the subunit b of the menaquinone:cytochrome c reductase. Despite the affinity of Q203 for the bc1 :aa3 complex, the drug is only bacteriostatic and does not kill drug-tolerant persisters...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28652193/triglyceride-metabolism-in-exercising-muscle
#9
REVIEW
Matthew J Watt, Yunsheng Cheng
Triglycerides are stored within lipid droplets in skeletal muscle and can be hydrolyzed to produce fatty acids for energy production through β-oxidation and oxidative phosphorylation. While there was some controversy regarding the quantitative importance of intramyocellular triglyceride (IMTG) as a metabolic substrate, recent advances in proton magnetic resonance spectroscopy and confocal microscopy support earlier tracer and biopsy studies demonstrating a substantial contribution of IMTG to energy production, particularly during moderate-intensity endurance exercise...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28650663/overexpression-and-lowexpression-of-selenoprotein-s-impact-ochratoxin-a-induced-porcine-cytotoxicity-and-apoptosis-in-vitro
#10
Fang Gan, Zhihua Hu, Yajiao Zhou, Kehe Huang
Our previous study demonstrated that selenium could alleviate ochratoxin A (OTA)-induced nephrotoxicity in PK15 cells. Selenoprotein S (SelS) has antioxidant activities, but it is unclear whether SelS plays a role in the alleviating effects of selenium on OTA-induced nephrotoxicity. We previously have stably transfected pig pCDNA3.1-SelS to PK15 cells to over-express SelS. Here, we demonstrated that SelS overexpression alleviated OTA-induced cytotoxicity and apoptosis as demonstrated by cell viabilities, LDH activities, Annexin V-bing, caspase 3 activities and apoptotic nuclei...
June 26, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28650095/sex-differences-in-brain-mitochondrial-metabolism-influence-of-endogenous-steroids-and-stroke
#11
REVIEW
P Gaignard, M Fréchou, P Liere, P Thérond, M Schumacher, A Slama, R Guennoun
Steroids are neuroprotective and growing body of evidence indicates that mitochondria are a potential target of their effects. The mitochondria are the site of cellular energy synthesis, regulate oxidative stress and play a key role in cell death after brain injury and neurodegenerative diseases. After a summary of the literature on the general functions of mitochondria and the effects of sex steroid administrations on mitochondrial metabolism, we will summarize and discuss our recent findings concerning sex differences in brain mitochondrial function in physiological and pathological conditions...
June 26, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28649430/predicting-growth-of-the-healthy-infant-using-a-genome-scale-metabolic-model
#12
Avlant Nilsson, Adil Mardinoglu, Jens Nielsen
An estimated 165 million children globally have stunted growth, and extensive growth data are available. Genome scale metabolic models allow the simulation of molecular flux over each metabolic enzyme, and are well adapted to analyze biological systems. We used a human genome scale metabolic model to simulate the mechanisms of growth and integrate data about breast-milk intake and composition with the infant's biomass and energy expenditure of major organs. The model predicted daily metabolic fluxes from birth to age 6 months, and accurately reproduced standard growth curves and changes in body composition...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28649426/conserved-and-species-specific-molecular-denominators-in-mammalian-skeletal-muscle-aging
#13
Evi M Mercken, Miriam Capri, Bethany A Carboneau, Maria Conte, Juliana Heidler, Aurelia Santoro, Alejandro Martin-Montalvo, Marta Gonzalez-Freire, Husam Khraiwesh, José A González-Reyes, Ruin Moaddel, Yongqing Zhang, Kevin G Becker, José M Villalba, Julie A Mattison, Ilka Wittig, Claudio Franceschi, Rafael de Cabo
Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28649367/nitric-oxide-signalling-and-neuronal-nitric-oxide-synthase-in-the-heart-under-stress
#14
REVIEW
Yin Hua Zhang
Nitric oxide (NO) is an imperative regulator of the cardiovascular system and is a critical mechanism in preventing the pathogenesis and progression of the diseased heart. The scenario of bioavailable NO in the myocardium is complex: 1) NO is derived from both endogenous NO synthases (endothelial, neuronal, and/or inducible NOSs [eNOS, nNOS, and/or iNOS]) and exogenous sources (entero-salivary NO pathway) and the amount of NO from exogenous sources varies significantly; 2) NOSs are located at discrete compartments of cardiac myocytes and are regulated by distinctive mechanisms under stress; 3) NO regulates diverse target proteins through different modes of post-transcriptional modification (soluble guanylate cyclase [sGC]/cyclic guanosine monophosphate [cGMP]/protein kinase G [PKG]-dependent phosphorylation, S-nitrosylation, and transnitrosylation); 4) the downstream effectors of NO are multidimensional and vary from ion channels in the plasma membrane to signalling proteins and enzymes in the mitochondria, cytosol, nucleus, and myofilament; 5) NOS produces several radicals in addition to NO (e...
2017: F1000Research
https://www.readbyqxmd.com/read/28649127/the-novel-%C3%AE-glucan-ycp-improves-the-survival-rates-and-symptoms-in-septic-mice-by-regulating-myeloid-derived-suppressor-cells
#15
Dan Liu, Ming You, Guang-Feng Zhao, Xiu-Jun Li, Yu-Xian Song, Huan Dou, Wen-Bing Yao, Xiang-Dong Gao, Ya-Yi Hou
Sepsis is a life-threatening health condition that is initially characterized by uncontrolled inflammation, followed by the development of persistent immunosuppression. YCP is a novel α-glucan purified from the mycelium of the marine fungus Phoma herbarum YS4108, which has displayed strong antitumor activity via enhancing host immune responses. In this study, we investigated whether YCP could influence the development of sepsis in a mouse model. Caecal ligation and puncture (CLP)-induced sepsis was established in mice that were treated with YCP (20 mg/kg, ip or iv) 2 h before, 4 and 24 h after the CLP procedure, and then every other day...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28649033/danazol-alters-mitochondria-metabolism-of-fibrocystic-breast-mcf10a-cells
#16
Zhazira Irgebay, Banu Yeszhan, Bhaswati Sen, Sultan Tuleukhanov, Ari D Brooks, Richard Sensenig, Zulfiya Orynbayeva
Fibrocystic Breast Disease (FBD) or Fibrocystic change (FC) affects about 60% of women at some time during their life. Although usually benign, it is often associated with pain and tenderness (mastalgia). The synthetic steroid danazol has been shown to be effective in reducing the pain associated with FBD, but the cellular and molecular mechanisms for its action have not been elucidated. We investigated the hypothesis that danazol acts by affecting energy metabolism. Effects of danazol on Mcf10A cells homeostasis, including mechanisms of oxidative phosphorylation, cytosolic calcium signaling and oxidative stress, were assessed by high-resolution respirometry and flow cytometry...
June 22, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28648907/sulfated-dehydropolymer-of-caffeic-acid-in-vitro-anti-lung-cell-death-activity-and-in-vivo-intervention-in-emphysema-induced-by-vegf-receptor-blockade
#17
Tien M Truong, Hua Li, Sneha Dhapare, Umesh R Desai, Nobert F Voelkel, Masahiro Sakagami
Induced lung cell death and impaired hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) signaling are proposed as a pathobiologic mechanism for alveolar structural destruction and loss in emphysema. We hypothesized that our sulfated dehydropolymer of caffeic acid, CDSO3, exerts anti-cell death activities and therapeutic interventions in emphysema by virtue of Fe(2+) chelation-based HIF-1α/VEGF stabilization and elevation. The Fe(2+) chelating activity was determined in the chromogenic ferrozine-Fe(2+) chelation inhibitory assay...
June 22, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28648749/transcriptome-profiling-of-3d-co-cultured-cardiomyocytes-and-endothelial-cells-under-oxidative-stress-using-a-photocrosslinkable-hydrogel-system
#18
Xiaoshan Yue, Aylin Acun, Pinar Zorlutuna
Myocardial infarction (MI) is one of the most common among cardiovascular diseases. Endothelial cells (ECs) are considered to have protective effects on cardiomyocytes (CMs) under stress conditions such as MI; however, the paracrine CM-EC crosstalk and the resulting endogenous cellular responses that could contribute to this protective effect are not thoroughly investigated. Here we created biomimetic synthetic tissues containing CMs and human induced pluripotent stem cell (hiPSC)-derived ECs (iECs), which showed improved cell survival compared to single cultures under conditions mimicking the aftermath of MI, and performed high-throughput RNA-sequencing to identify target pathways that could govern CM-iEC crosstalk and the resulting improvement in cell viability...
June 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28648093/s-nitrosylation-of-ras-mediates-nitric-oxide-dependent-post-injury-neurogenesis-in-a-seizure-model
#19
Ana Isabel Santos, Bruno Pereira Carreira, Alicia Izquierdo-Álvarez, Elena Ramos, Ana Sofia Lourenço, Daniela Santos, Maria Inês Morte, Luís Filipe Ribeiro, Ana Marreiros, Nuria Sánchez-López, Anabel Marina, Caetana Monteiro Carvalho, Antonio Martínez-Ruiz, Inês M Araújo
AIMS: Nitric oxide (NO) is involved in the upregulation of endogenous neurogenesis in the subventricular zone and in the hippocampus after injury. One of the main neurogenic pathways activated by NO is the ERK/MAPK pathway, downstream of the EGF receptor. However, the mechanism by which NO stimulates cell proliferation through activation of the ERK/MAPK pathway remains unknown, although p21Ras seems to be one of the earliest targets of NO. Here, we aimed to study the possible neurogenic action of NO by post-translational modification of p21Ras as a relevant target for early neurogenic events promoted by NO in neural stem cells (NSC)...
June 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28647871/cytoskeleton-as-a-target-of-quinolinic-acid-neurotoxicity-insight-from-animal-models
#20
REVIEW
Paula Pierozan, Regina Pessoa-Pureur
Cytoskeletal proteins are increasingly recognized as having important roles as a target of the action of different neurotoxins. In the last years, several works of our group have shown that quinolinic acid (QUIN) was able to disrupt the homeostasis of the cytoskeleton of neural cells and this was associated with cell dysfunction and neurodegeneration. QUIN is an excitotoxic metabolite of tryptophan metabolism and its accumulation is associated with several neurodegenerative diseases. In the present review, we provide a comprehensive view of the actions of QUIN upstream of glutamate receptors, eliciting kinase/phosphatase signaling cascades that disrupt the homeostasis of the phosphorylation system associated with intermediate filament proteins of astrocytes and neurons...
June 24, 2017: Molecular Neurobiology
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