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https://www.readbyqxmd.com/read/28339906/interstitial-fibrosis-scored-on-whole-slide-digital-imaging-of-kidney-biopsies-is-a-predictor-of-outcome-in-proteinuric-glomerulopathies
#1
Laura H Mariani, Sebastian Martini, Laura Barisoni, Pietro A Canetta, Jonathan P Troost, Jeffrey B Hodgin, Matthew Palmer, Avi Z Rosenberg, Kevin V Lemley, Hui-Ping Chien, Jarcy Zee, Abigail Smith, Gerald B Appel, Howard Trachtman, Stephen M Hewitt, Matthias Kretzler, Serena M Bagnasco
Background.: Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. Methods.: We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37)...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28334726/preparation-characterization-and-anti-ulcer-efficacy-of-sanguinarine-loaded-solid-lipid-nanoparticles
#2
Qing Sun, Weifeng Li, Huani Li, Xiumei Wang, Yu Wang, Xiaofeng Niu
AIM: This study was designed to develop sanguinarine-loaded solid lipid nanoparticles (SG-SLNs) and investigate its gastroprotective effect on ethanol-induced gastric mucosal lesions in mice. METHODS: SG-SLNs were prepared by high temperature melt-cool solidification method using glycerol monostearate as the lipid and a combination of lecithin with poloxamer 188 as the surfactants. Solid lipid nanoparticles (SLNs) were designed at varying lipid concentrations (5, 10, 15, and 20 mg/mL), surfactant mixture concentrations (6, 12, and 18 mg/mL), and drug contents (5, 10, 15, and 20 mg/mL) in "one factor at a time" fashion...
March 24, 2017: Pharmacology
https://www.readbyqxmd.com/read/28333279/inhibition-of-pim1-kinase-attenuates-inflammation-induced-pro-labour-mediators-in-human-fetal-membranes-in-vitro
#3
Ratana Lim, Gillian Barker, Martha Lappas
STUDY QUESTION: Does proviral integration site for Moloney murine leukemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? SUMMARY ANSWER: PIM1 kinase plays a critical role in fetal membranes in regulating pro-inflammatory and pro-labour mediators. WHAT IS KNOWN ALREADY: Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes...
March 9, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333124/bap31-is-involved-in-t-cell-activation-through-tcr-signal-pathways
#4
Kunwei Niu, Jialin Xu, Yuhua Cao, Yue Hou, Mu Shan, Yanqing Wang, Yang Xu, Mingyi Sun, Bing Wang
BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331294/spotlight-on-blisibimod-and-its-potential-in-the-treatment-of-systemic-lupus-erythematosus-evidence-to-date
#5
REVIEW
Aleksander Lenert, Timothy B Niewold, Petar Lenert
B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28330786/investigating-acetaminophen-hepatotoxicity-in-multi-cellular-organotypic-liver-models
#6
Sophia M Orbach, Margaret E Cassin, Marion F Ehrich, Padmavathy Rajagopalan
In vivo studies clearly demonstrate the participation and subsequent death of non-parenchymal liver cells (NPCs) with corresponding hepatocyte effects. This results in a critical need to investigate how major liver cell types function cohesively during hepatotoxicity. However, virtually no studies replicate these phenomena in vitro. We report the design of multi-cellular three-dimensional (3D) organotypic liver models of primary rat hepatocytes, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs)...
March 19, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28326325/a-potential-of-sfasl-in-preventing-gland-injury-in-sjogren-s-syndrome
#7
Jiao Luo, Ying Wang, Bing Yu, Hongyan Qian, Yan He, Guixiu Shi
Fas and its ligand FasL, members of tumor necrosis factor receptor superfamily, have been implicated in the process of cell apoptosis. FasL consists of two forms, membrane FasL (mFasL) and soluble FasL (sFasL). sFasL can be produced by mFasL cleaved by matrix metalloproteinases (MMP) and also reveals a role for binding to Fas which is expressed on cell surface. Although Fas/FasL axis has been implicated in a variety of diseases, its role in Sjogren's syndrome still remains ill defined. In this study, we investigated the potential of sFasL in the pathogenesis of Sjogren's syndrome (SS)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28326166/trail-delivery-by-msc-derived-extracellular-vesicles-is-an-effective-anticancer-therapy
#8
ZhengQiang Yuan, Krishna K Kolluri, Kate H C Gowers, Sam M Janes
Extracellular vesicles (EVs) are lipid membrane-enclosed nanoparticles released by cells. They mediate intercellular communication by transferring biological molecules and therefore have potential as innovative drug delivery vehicles. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of cancer cells. Unfortunately, the clinical application of recombinant rTRAIL has been hampered by its low bioavailability and resistance of cancer cells. EV-mediated TRAIL delivery may circumvent these problems...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28323882/mir-181-interacts-with-signaling-adaptor-molecule-denn-madd-and-enhances-tnf-induced-cell-death
#9
Samira Ghorbani, Farideh Talebi, Sedigheh Ghasemi, Ali Jahanbazi Jahan Abad, Mohammed Vojgani, Farshid Noorbakhsh
MicroRNAs are small noncoding RNAs, which regulate the expression of protein coding transcripts through mRNA degradation or translational inhibition. Numerous reports have highlighted the role of miRNAs in regulating cell death pathways including the expression of genes involved in the induction of apoptosis. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine which can send pro-death signals through its receptor TNFR1. Diverse adaptor molecules including DENN/MADD adaptor protein have been shown to modulate TNF-α pro-death signaling via recruitment of MAP kinases to TNFR1 and activation of pro-survival NFκB signaling...
2017: PloS One
https://www.readbyqxmd.com/read/28323513/transmembrane-tnf-dependent-uptake-of-anti-tnf-antibodies
#10
Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee, Mark Michalak, Medha Tomlinson, Qingfeng Tao, Nidhi Gaur, Bohdan Harvey, Shaun McLoughlin, Boris Labkovsky, Tariq Ghayur
TNF-alpha (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-alpha converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with two distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biological effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases...
March 21, 2017: MAbs
https://www.readbyqxmd.com/read/28323130/monocyte-activation-drives-preservation-of-membrane-thiols-by-promoting-release-of-oxidised-membrane-moieties-via-extracellular-vesicles
#11
K É Szabó-Taylor, E Á Tóth, A M Balogh, B W Sódar, L Kádár, K Pálóczi, N Fekete, A Németh, X Osteikoetxea, K V Vukman, M Holub, É Pállinger, Gy Nagy, P G Winyard, E I Buzás
The redox state of cellular exofacial molecules is reflected by the amount of available thiols. Furthermore, surface thiols can be considered as indicators of immune cell activation. One group of thiol containing proteins, peroxiredoxins, in particular, have been associated with inflammation. In this study, we assessed surface thiols of the U937 and Thp1 monocyte cell lines and primary monocytes in vitro upon inflammatory stimulation by irreversibly labelling the cells with a fluorescent derivative of maleimide...
March 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28318628/b-and-t-cell-subpopulations-in-patients-with-severe-idiopathic-membranous-nephropathy-may-predict-an-early-response-to-rituximab
#12
Michelle Rosenzwajg, Eva Languille, Hanna Debiec, Joana Hygino, Karine Dahan, Tabassome Simon, David Klatzmann, Pierre Ronco
Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56(bright)CD16(-/lo) NK subset...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28315997/trans-fatty-acids-suppress-tnf-%C3%AE-induced-inflammatory-gene-expression-in-endothelial-huvec-and-hepatocellular-carcinoma-hepg2-cells
#13
Marine S Da Silva, Pierre Julien, Jean-François Bilodeau, Olivier Barbier, Iwona Rudkowska
Trans fatty acids (TFA) intake has been linked to cardiovascular diseases and liver diseases; yet the effect of TFA on inflammation remains controversial. Accordingly, the objective of this paper was to determine the in vitro effects of TFA on inflammatory gene expression. Human umbilical vein endothelial cells (HUVEC) and human hepatocellular carcinoma (HepG2) cells were treated for 24 h with either trans-vaccenic acid (tVA), trans-palmitoleic acid (tPA) or elaidic acid (EA) at concentrations of 5-150 µM, or with a mixture of tVA and tPA (150/50 µM)...
March 18, 2017: Lipids
https://www.readbyqxmd.com/read/28315956/axonal-transport-deficits-in-multiple-sclerosis-spiraling-into-the-abyss
#14
REVIEW
Robert van den Berg, Casper C Hoogenraad, Rogier Q Hintzen
The transport of mitochondria and other cellular components along the axonal microtubule cytoskeleton plays an essential role in neuronal survival. Defects in this system have been linked to a large number of neurological disorders. In multiple sclerosis (MS) and associated models such as experimental autoimmune encephalomyelitis (EAE), alterations in axonal transport have been shown to exist before neurodegeneration occurs. Genome-wide association (GWA) studies have linked several motor proteins to MS susceptibility, while neuropathological studies have shown accumulations of proteins and organelles suggestive for transport deficits...
March 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28315353/crystal-structure-of-the-extracellular-domain-of-the-human-dendritic-cell-surface-marker-cd83
#15
Christiane S Heilingloh, Stefan Klingl, Claudia Egerer-Sieber, Benedikt Schmid, Sigrid Weiler, Petra Mühl-Zürbes, Jörg Hofmann, Joachim D Stump, Heinrich Sticht, Mirko Kummer, Alexander Steinkasserer, Yves A Muller
CD83 is a type-I membrane protein and an efficient marker for identifying mature dendritic cells. Whereas membrane-bound full-length CD83 co-stimulates the immune system, a soluble variant (sCD83), consisting of the extracellular domain, only, displays strong immune-suppressive activities. Besides a prediction that sCD83 adopts a V-set Ig-like fold, however, little is known about the molecular architecture of CD83 and the mechanism by which CD83 exerts is function on dendritic cells and additional immune cells...
March 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28315342/ethanol-induced-erectile-dysfunction-and-increased-expression-of-pro-inflammatory-proteins-in-the-rat-cavernosal-smooth-muscle-are-mediated-by-nadph-oxidase-derived-reactive-oxygen-species
#16
Letícia N Leite, Gabriel T do Vale, Janaina A Simplicio, Bruno S De Martinis, Fernando S Carneiro, Carlos R Tirapelli
Ethanol consumption is associated with an increased risk of erectile dysfunction (ED), but the molecular mechanisms through which ethanol causes ED remain elusive. Reactive oxygen species are described as mediators of ethanol-induced cell toxicity/damage in distinctive tissues. The enzyme NADPH oxidase is the main source of reactive oxygen species in the endothelium and vascular smooth muscle cells and ethanol is described to increase NADPH oxidase activation and reactive oxygen species generation. This study evaluated the contribution of NADPH oxidase-derived reactive oxygen species to ethanol-induced ED, endothelial dysfunction and production of pro-inflammatory and redox-sensitive proteins in the rat cavernosal smooth muscle (CSM)...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28302163/matrix-metalloproteinase-activity-stimulates-n-cadherin-shedding-and-the-soluble-n-cadherin-ectodomain-promotes-classical-microglial-activation
#17
Katherine Conant, Stefano Daniele, P Lorenzo Bozzelli, Tsion Abdi, Amanda Edwards, Arek Szklarczyk, India Olchefske, David Ottenheimer, Kathleen Maguire-Zeiss
BACKGROUND: Matrix metalloproteinases (MMPs) are a family of enzymes that are typically released from intracellular stores to act on specific extracellular substrates. MMP expression and activity can be increased in a neuronal activity-dependent manner, and further increased in response to tissue injury. MMP substrates include cell adhesion molecules (CAMs) that are abundantly expressed in the brain and well positioned for membrane proximal cleavage. Importantly, CAM integrity is important to synaptic structure and axon-myelin interactions, and shed ectodomains may themselves influence cellular function...
March 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28296282/sildenafil-reduces-neuroinflammation-in-cerebellum-restores-gabaergic-tone-and-improves-motor-in-coordination-in-rats-with-hepatic-encephalopathy
#18
Ana Agusti, Vicente Hernández-Rabaza, Tiziano Balzano, Lucas Taoro-Gonzalez, Andrea Ibañez-Grau, Andrea Cabrera-Pastor, Santos Fustero, Marta Llansola, Carmina Montoliu, Vicente Felipo
AIMS: Patients with liver disease may develop hepatic encephalopathy (HE), with cognitive impairment and motor in-coordination. Rats with HE due to portacaval shunts (PCS) show motor in-coordination. We hypothesized that in PCS rats: (i) Motor in-coordination would be due to enhanced GABAergic tone in cerebellum; (ii) increased GABAergic tone would be due to neuroinflammation; (iii) increasing cGMP would reduce neuroinflammation and GABAergic tone and restore motor coordination. To assess these hypotheses, we assessed if (i) treatment with sildenafil reduces neuroinflammation; (ii) reduced neuroinflammation is associated with reduced GABAergic tone and restored motor coordination...
March 11, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28287172/killing-of-staphylococcus-aureus-and-salmonella-enteritidis-and-neutralization-of-lipopolysaccharide-by-17-residue-bovine-lactoferricins-improved-activity-of-trp-ala-containing-molecules
#19
Ya Hao, Na Yang, Xiumin Wang, Da Teng, Ruoyu Mao, Xiao Wang, Zhanzhan Li, Jianhua Wang
Bovine lactoferricin (LfcinB) has potent antibacterial, antifungal and antiparasitic activities but is also hemolytic. Our objective was to identify LfcinB17-31 derivatives with reduced hemolysis and improved antimicrobial activity via substituting Cys3, Arg4, Gln7, Met10, and Gly14 with more hydrophobic residues. Two peptides, Lfcin4 and Lfcin5, showed higher activity against Staphylococcus aureus and Salmonella enteritidis and lower hemolytic activity than the parent peptide LfcinB17-31. These peptides permeabilized the outer and inner membranes of S...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286482/restoration-of-epithelial-sodium-channel-function-by-synthetic-peptides-in-pseudohypoaldosteronism-type-1b-mutants
#20
Anita Willam, Mohammed Aufy, Susan Tzotzos, Heinrich Evanzin, Sabine Chytracek, Sabrina Geppert, Bernhard Fischer, Hendrik Fischer, Helmut Pietschmann, Istvan Czikora, Rudolf Lucas, Rosa Lemmens-Gruber, Waheed Shabbir
The synthetically produced cyclic peptides solnatide (a.k.a. TIP or AP301) and its congener AP318, whose molecular structures mimic the lectin-like domain of human tumor necrosis factor (TNF), have been shown to activate the epithelial sodium channel (ENaC) in various cell- and animal-based studies. Loss-of-ENaC-function leads to a rare, life-threatening, salt-wasting syndrome, pseudohypoaldosteronism type 1B (PHA1B), which presents with failure to thrive, dehydration, low blood pressure, anorexia and vomiting; hyperkalemia, hyponatremia and metabolic acidosis suggest hypoaldosteronism, but plasma aldosterone and renin activity are high...
2017: Frontiers in Pharmacology
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