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https://www.readbyqxmd.com/read/28109197/everolimus-is-better-than-rapamycin-in-attenuating-neuroinflammation-in-kainic-acid-induced-seizures
#1
Ming-Tao Yang, Yi-Chin Lin, Whae-Hong Ho, Chao-Lin Liu, Wang-Tso Lee
BACKGROUND: Microglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation. METHODS: In vitro, we treated BV2 cells with KA and LPS...
January 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28109186/interleukin-1-as-a-mediator-of-fatigue-in-disease-a-narrative-review
#2
REVIEW
Megan E Roerink, Marieke E van der Schaaf, Charles A Dinarello, Hans Knoop, Jos W M van der Meer
Fatigue is commonly reported in a variety of illnesses, and it has major impact on quality of life. Previously, it was thought that fatigue originates in the skeletal muscles, leading to cessation of activity. However, more recently, it has become clear that the brain is the central regulator of fatigue perception. It has been suggested that pro-inflammatory cytokines, especially interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β), play a prominent role in the development of central fatigue, and several studies have been performed to elucidate the connection between inflammation and these central processes...
January 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28109179/quantitative-and-integrative-analysis-of-paracrine-hepatocyte-activation-by-non-parenchymal-cells-upon-lipopolysaccharide-induction
#3
Katharina Beuke, Frank A Schildberg, Federico Pinna, Ute Albrecht, Roman Liebe, Michaela Bissinger, Peter Schirmacher, Steven Dooley, Johannes G Bode, Percy A Knolle, Ursula Kummer, Kai Breuhahn, Sven Sahle
Gut-derived bacterial lipopolysaccharides (LPS) stimulate the secretion of tumor necrosis factor (TNF) from liver macrophages (MCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs), which control the acute phase response in hepatocytes through activation of the NF-κB pathway. The individual and cooperative impact of non-parenchymal cells on this clinically relevant response has not been analysed in detail due to technical limitations. To gain an integrative view on this complex inter- and intracellular communication, we combined a multi-scale mathematical model with quantitative, time-resolved experimental data of different primary murine liver cell types...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109174/%C3%AE-%C3%AE-nac-cooperates-with-sam37-to-mediate-early-stages-of-mitochondrial-protein-import
#4
J Carlos Ponce-Rojas, M Clara Avendaño-Monsalve, A Roberto Yañez-Falcón, Fabiola Jaimes-Miranda, Erika Garay, Francisco Torres-Quiroz, Alexander DeLuna, Soledad Funes
The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial sub-compartments until they reach their functional destination. It has been suggested that NAC - a cytosolic chaperone which recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated co-translational import are still not clear...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109167/cell-cycle-tailored-targeting-of-metastatic-melanoma-challenges-opportunities
#5
Nikolas K Haass, Brian Gabrielli
The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the 'bad guy' to the 'poster child' in oncology. Current targeted therapies are effective; although here is a clear need to develop combination therapies to delay the onset of resistance. Many anti-melanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors...
January 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28109147/-co-culture-with-umbilical-cord-mesenchymal-stem-cells-promotes-the-synthesis-and-mechnism-of-milk-protein-in-bovine-mammary-epithelial-cells
#6
Yankun Zhao, Wei Shao, Chenglong Luo, Kaile Wu, Xiong Yu
Objective To explore the possible mechanism of umbilical cord mesenchymal stem cells (UCMSCs) regulating milk protein synthesis in bovine mammary gland epithelial cells (BMECs). Methods UCMSCs and BMECs were co-cultured by double-chamber Transwell(TM), and other BMECs were cultured alone as a control group. Insulin like growth factor 1 receptor (IGF-1R) inhibitor AG1024 was used to treat cells. IGF-1, β casein (CSN2) and κ casein (CSN3) content in the supernatants were determined by ELISA; the relative expression abundance of Janus kinase and signal transducer and activator of transcription factor (JAK/STAT) signaling pathway-related genes were detected by quantitative real-time PCR (qRT-PCR); and after the cells were treated with JAK2 signal blocker AG490, qRT-PCR was performed to test the relative expression abundance of CSN2 and CSN3 mRNAs...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109142/-changes-and-role-evaluation-of-tnf-%C3%AE-and-il-1%C3%AE-in-lung-tissues-of-ards-mice
#7
Jianing Liang, Qianqian Zhou, Tianxiang Zhang, Xiaosu Wang, Liqiang Song
Objective To study the expression levels of TNF-α and IL-1β in the lung tissues of acute respiratory distress syndrome (ARDS) mice and their relationships with the severity of lung injury in the mice. Methods A mouse model of ARDS was induced by lipopolysaccharide (LPS). The morphological changes of lung tissue was observed by HE staining, and the lung injury score was calculated. Quantitative real-time PCR was employed to detect the mRNA expression levels of TNF-α and IL-1β in lung tissues and ELISA was performed to test the protein levels of TNF-α and IL-1β in bronchoalveolar lavage fluid (BALF)...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109112/-targeted-imaging-ability-of-a-biotinylated-imaging-probe-biotin-s-s-rhodol-for-breast-cancer-cells-in-vitro
#8
Bi-Juan Wu, Xing-Zi Zhou, Jing-Wen Sun, Cui-Wen Tan, Xin-Rong Wu
OBJECTIVE: To investigate performance of a biotinylated imaging probe 3a for targeted imaging of breast cancer cells. METHODS: Ultraviolet absorption spectrum and fluorescence spectrum were employed to analyze the spectral characteristics of 3a. The fluorescence spectrums of 3a treated with different concentrations of glutathione (GSH) were obtained to determine the sensibility of 3a to GSH. Flow cytometry was used to determine the cellular uptake of 3a by MCF-7 cells, MDA-MB-231 cells and Hs 578Bst cells in the presence or absence of biotin, and the imaging performance of 3a in the 3 cell lines was assessed under an inverted fluorescent microscope...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28109051/shear-induced-platelet-aggregation-and-distribution-of-thrombogenesis-at-stenotic-vessels
#9
Hiroki Kamada, Yohsuke Imai, Masanori Nakamura, Takuji Ishikawa, Takami Yamaguchi
OBJECTIVE: Shear-induced platelet aggregation (SIPA), which is mediated by von Willebrand factor (vWF), is a key mechanism in arterial thrombosis under an abnormally high shear rate of blood flow. We investigated the influence of SIPA on thrombogenesis, focusing on alterations in blood flow at stenotic vessels. METHODS: We carried out a computer simulation of thrombogenesis in stenotic vessels at three different injury positions (i.e., upstream, apex, and downstream of the stenosis) to evaluate the effect of SIPA...
January 21, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28109039/nkx2-5-regulates-endothelin-converting-enzyme-1-during-pharyngeal-arch-patterning
#10
Jennifer M Iklé, Andre L P Tavares, Marisol King, Hailei Ding, Sophie Colombo, Beth A Firulli, Anthony B Fiulli, Kimara L Targoff, Deborah Yelon, David E Clouthier
In gnathostomes, dorsoventral (D-V) patterning of neural crest cells (NCC) within the pharyngeal arches is crucial for the development of hinged jaws. One of the key signals that mediates this process is Endothelin-1 (EDN1). Loss of EDN1 binding to the Endothelin-A receptor (EDNRA) results in loss of EDNRA signaling and subsequent facial birth defects in humans, mice and zebrafish. A rate-limiting step in this crucial signaling pathway is the conversion of immature EDN1 into a mature active form by Endothelin converting enzyme-1 (ECE1)...
January 20, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28109037/a-new-strategy-for-development-of-anti-thrombotic-agents-inhibition-of-the-c-terminal-active-site-of-pdi
#11
L Wang, D W Essex
Protein disulfide isomerase (PDI) was discovered over fifty years ago as an enzyme that forms disulfide bonds in newly synthesized proteins in the endoplasmic reticulum [1]. Twenty five years ago PDI was shown to be released from activated platelets [2] opening up a new field of research on extracellular functions of this enzyme. PDI was subsequently localized to the platelet surface [3] and shown to mediate platelet aggregation [4, 5]. This article is protected by copyright. All rights reserved.
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28109026/refinement-of-the-criteria-for-ultrastructural-peritubular-capillary-basement-membrane-multilayering-in-the-diagnosis-of-chronic-active-acute-antibody-mediated-rejection
#12
Heounjeong Go, Sung Shin, Young Hoon Kim, Duck Jong Han, Yong Mee Cho
Chronic active/acute antibody-mediated rejection (cABMR) is the main cause of late renal allograft loss. Severe peritubular capillary basement membrane multilayering (PTCML) assessed on electron microscopy is one diagnostic feature of cABMR according to the Banff2013 classification. We aimed to refine the PTCML criteria for an earlier diagnosis of cABMR. We retrospectively investigated ultrastructural features of 159 consecutive renal allografts and 44 non-allografts. The presence of serum donor-specific antibodies at the time of biopsy of allografts was also examined...
January 21, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28109023/intraportal-islet-transplantation-the-impact-of-the-liver-micro-environment
#13
REVIEW
Vaihere Delaune, Thierry Berney, Stéphanie Lacotte, Christian Toso
The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver micro-environment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver micro-environment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood mediated inflammatory reaction (IBMIR), the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets...
January 21, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28109007/retinoic-acid-inducible-gene-i-rig-i-like-receptors-rlrs-in-fish-current-knowledge-and-future-perspectives
#14
REVIEW
Shan Nan Chen, Peng Fei Zou, Pin Nie
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2 together with the downstream molecules such as MITA, TRAF3 and TBK1 have been identified in a range of fish species. However, it is a bit unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic double-stranded RNA (dsRNA), poly(I:C), leading to the production of type I IFNs and the expression of IFN stimulated genes (ISGs)...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28108988/blood-brain-barrier-closure-time-after-controlled-ultrasound-induced-opening-is-independent-of-opening-volume
#15
Meaghan A O'Reilly, Olivia Hough, Kullervo Hynynen
OBJECTIVES: Microbubble-mediated focused ultrasound (US) opening of the blood-brain barrier (BBB) has shown promising results for the treatment of brain tumors and conditions such as Alzheimer disease. Practical clinical implementation of focused US treatments would aim to treat a substantial portion of the brain; thus, the safety of opening large volumes must be investigated. This study investigated whether the opened volume affects the time for the BBB to be restored after treatment...
January 21, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/28108952/transcriptional-regulators-dictate-innate-lymphoid-cell-fates
#16
REVIEW
Chao Zhong, Jinfang Zhu
Research on innate lymphoid cells (ILC) has recently been a fast paced topic of immunological research. As ILCs are able to produce signature Th cytokine, ILCs have garnered considerable attention and have been described to represent the innate counterpart of the CD4(+) T helper (Th) cells. The development and function of ILCs are precisely regulated by a network of crucial transcription factors, which are also involved in the development or differentiation of conventional natural killer (cNK) cells and T cells...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108950/t-cell-receptor-engineered-t-cells-for-cancer-treatment-current-status-and-future-directions
#17
REVIEW
Yu Ping, Chaojun Liu, Yi Zhang
T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1)...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108937/glycyrrhizin-ameliorates-experimental-colitis-through-attenuating-interleukin-17-producing-t-cell-responses-via-regulating-antigen-presenting-cells
#18
Xiangyu Chen, Dai Fang, Lingyun Li, Liyong Chen, Qirui Li, Feili Gong, Min Fang
Glycyrrhizin, a component of Chinese medicine licorice root, has the ability to inhibit the functions of high-mobility group box 1 (HMGB1). While glycyrrhizin is known to have anti-inflammatory activities, the underlying mechanisms by which glycyrrhizin inhibits inflammation during the development of trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis are not well understood. This study systemically examined the regulatory effects of glycyrrhizin on inflammatory response in TNBS-induced murine colitis and explored the potential mechanisms involved in this process...
January 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28108936/a-group-mediated-physical-activity-intervention-in-older-knee-osteoarthritis-patients-effects-on-social-cognitive-outcomes
#19
Brian C Focht, Matthew J Garver, Alexander R Lucas, Steven T Devor, Charles F Emery, Kevin V Hackshaw, Ciaran M Fairman, Jessica Bowman, W Jack Rejeski
The objective of the present study was to compare a group-mediated cognitive behavioral (GMCB) physical activity intervention with traditional exercise therapy (TRAD) upon select social cognitive outcomes in sedentary knee osteoarthritis (knee OA) patients. A total of 80 patients (mean age = 63.5 years; 84% women) were recruited using clinic and community-based strategies to a 12-month, single-blind, two-arm, randomized controlled trial. Mobility-related self-efficacy, self-regulatory self-efficacy (SRSE), and satisfaction with physical function (SPF) were assessed at baseline, 3, and 12 months...
January 20, 2017: Journal of Behavioral Medicine
https://www.readbyqxmd.com/read/28108877/a-moderated-mediation-model-of-hiv-related-stigma-depression-and-social-support-on-health-related-quality-of-life-among-incarcerated-malaysian-men-with-hiv-and-opioid-dependence
#20
Roman Shrestha, Michael Copenhaver, Alexander R Bazazi, Tania B Huedo-Medina, Archana Krishnan, Frederick L Altice
Although it is well established that HIV-related stigma, depression, and lack of social support are negatively associated with health-related quality of life (HRQoL) among people living with HIV (PLH), no studies to date have examined how these psychosocial factors interact with each other and affect HRQoL among incarcerated PLH. We, therefore, incorporated a moderated mediation model (MMM) to explore whether depression mediates the effect of HIV-related stigma on HRQoL as a function of the underlying level of social support...
January 20, 2017: AIDS and Behavior
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