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https://www.readbyqxmd.com/read/28433935/distinct-on-off-fluorescence-signals-from-dual-responsive-activatable-nanoprobes-allows-detection-of-inflammation-with-improved-contrast
#1
Mathieu L Viger, Guillaume Collet, Jacques Lux, Viet Anh Nguyen Huu, Monica Guma, Alexandra Foucault-Collet, Jason Olejniczak, Shivanjali Joshi-Barr, Gary S Firestein, Adah Almutairi
Visualization of biochemical changes associated with disease is of great clinical significance, as it should allow earlier, more accurate diagnosis than structural imaging, facilitating timely clinical intervention. Herein, we report combining stimuli-responsive polymers and near-infrared fluorescent dyes (emission max: 790 nm) to create robust activatable fluorescent nanoprobes capable of simultaneously detecting acidosis and oxidative stress associated with inflammatory microenvironments. The spectrally-resolved mechanism of fluorescence activation allows removal of unwanted background signal (up to 20-fold reduction) and isolation of a pure activated signal, which enables sensitive and unambiguous localization of inflamed areas; target-to-background ratios reach 22 as early as 3 h post-injection...
March 28, 2017: Biomaterials
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#2
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432476/immunological-mechanisms-of-adsorptive-cytapheresis-in-inflammatory-bowel-disease
#3
REVIEW
Esteban Sáez-González, Inés Moret, Diego Alvarez-Sotomayor, Francia Carolina Díaz-Jaime, Elena Cerrillo, Marisa Iborra, Pilar Nos, Belén Beltrán
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). The study of immunological pathways involved in the onset of IBD is of fundamental importance to identify potential biological markers of disease activity and specific targets for therapy. Removing excess and activated circulating leukocytes with adsorptive cytapheresis has been shown to be a potentially effective treatment for patients with an inflamed bowel. Adsorptive cytapheresis is a non-pharmacological approach for active IBD, in which known sources of inflammatory cytokines such as activated myeloid lineage leucocytes are selectively depleted from the circulatory system...
April 21, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28429342/assessment-of-serum-endothelin-1-levels-in-rat-appendicitis-model-and-the-effects-of-bosentan
#4
S B Sarsu, K Sahin, H Kilincaslan, S L Mirapoglu, N Buyukpınarbasili, M E Duz, I Aydogdu
OBJECTIVE: In this study, the diagnostic value of serum endothelin-1 (ET-1) levels and the therapeutic effects of bosentan have been investigated in an experimental appendicitis rat model. MATERIALS AND METHODS: Twenty-one male Sprague-Dawley rats were chosen for the study. The rats were allocated into three groups as follows: Group 1 (control, n = 7), Group 2 (appendicitis, n = 7), and Group 3 (bosentan treatment, n = 7). At the 6th hour of the experiment, Groups 1 and 2 received 2 ml saline, and group 3 received 30 mg/kg bosentan intraperitoneally...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428556/treatment-of-donor-corneal-tissue-with-immunomodulatory-cytokines-a-novel-strategy-to-promote-graft-survival-in-high-risk-corneal-transplantation
#5
Maryam Tahvildari, Parisa Emami-Naeini, Masahiro Omoto, Alireza Mashaghi, Sunil K Chauhan, Reza Dana
Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428344/vascular-adhesion-protein-1-is-elevated-in-primary-sclerosing-cholangitis-is-predictive-of-clinical-outcome-and-facilitates-recruitment-of-gut-tropic-lymphocytes-to-liver-in-a-substrate-dependent-manner
#6
Palak J Trivedi, Joseph Tickle, Mette Nåmdal Vesterhus, Peter J Eddowes, Tony Bruns, Jani Vainio, Richard Parker, David Smith, Evaggelia Liaskou, Liv Wenche Thorbjørnsen, Gideon M Hirschfield, Kaisa Auvinen, Stefan G Hubscher, Marko Salmi, David H Adams, Chris J Weston
OBJECTIVE: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of IBD. This clinical association is linked pathologically to the recruitment of mucosal T cells to the liver, via vascular adhesion protein (VAP)-1-dependent enzyme activity. Our aim was to examine the expression, function and enzymatic activation of the ectoenzyme VAP-1 in patients with PSC. DESIGN: We examined VAP-1 expression in patients with PSC, correlated levels with clinical characteristics and determined the functional consequences of enzyme activation by specific enzyme substrates on hepatic endothelium...
April 20, 2017: Gut
https://www.readbyqxmd.com/read/28428091/characterization-of-the-effects-of-l-4-chlorokynurenine-on-nociception-in-rodents
#7
Tony L Yaksh, Robert Schwarcz, H Ralph Snodgrass
Upon systemic administration in rats, the prodrug L-4-chlorokynurenine (4-Cl-KYN) (AV-101) is rapidly absorbed, actively transported across the blood-brain barrier, and converted in astrocytes to 7-chlorokynurenic acid (7-Cl-KYNA), a potent and specific antagonist of the GlyB co-agonist site of the NMDA receptor. We examined the effects of 4-Cl-KYN in several rat models of hyperalgesia and allodynia and determined the concentrations of 4-Cl-KYN and newly produced 7-Cl-KYNA in serum, brain and spinal cord. Adult male rats were given 4-Cl-KYN (56, 167, 500 mg/kg), the NMDA receptor antagonist MK-801 (0...
April 17, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28428089/enhanced-anti-rheumatic-activity-of-methotrexate-entrapped-ultradeformable-liposomal-gel-in-adjuvant-induced-arthritis-rat-model
#8
Alam Zeb, Omer Salman Qureshi, Chan-Hee Yu, Muhammad Akram, Hyung-Seo Kim, Myung-Sic Kim, Jong-Ho Kang, Arshad Majid, Sun-Young Chang, Ok-Nam Bae, Jin-Ki Kim
The aim of this study is to investigate in vivo anti-rheumatic activity of methotrexate-entrapped ultradeformable liposomal gel (MTX-UDLs-gel) in adjuvant-induced arthritis rat model. Methotrexate-entrapped ultradeformable liposomes (MTX-UDLs) with the optimal phosphatidylcholine to Tween 80 ratio (7:3, w/w) were incorporated into 1% Carbopol gel. MTX-UDLs-gel was characterized in terms of appearance, clarity, homogeneity, pH and drug content. The permeation of MTX-UDLs-gel across rat skin was investigated using Franz diffusion cell...
April 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28428053/discrimination-between-ulcerative-colitis-and-crohn-s-disease-using-phage-display-identified-peptides-and-virus-mimicking-synthetic-nanoparticles
#9
Sonia Facchin, Liboria Digiglio, Renata D'Incà, Elisabetta Casarin, Elisa Dassie, Monica Dettin, Annj Zamuner, Andrea Buda, Michele De Boni, Duilio Della Libera, Alessandra D'Urso, Giacomo Carlo Sturniolo, Margherita Morpurgo
Discrimination between Crohn Disease (CD) and Ulcerative Colitis (UC) is an unsolved clinical issue in up to 10-15% of inflammatory bowel disease (IBD) patients. We developed a method capable to discriminate between the two clinical conditions by combining random peptide phage display screenings and nanoparticle (NP) based assays. We identified two peptides able to recognize selectively biopsies of inflamed mucosa of either CD or UC patients. The peptides were integrated into synthetic virus-mimicking nanoassemblies using a poly-avidin NP platform...
April 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28424241/microbiota-induced-antibodies-are-essential-for-host-inflammatory-responsiveness-to-sterile-and-infectious-stimuli
#10
Daniel Cisalpino, Caio T Fagundes, Camila B Brito, Fernando R Ascenção, Celso M Queiroz-Junior, Angélica T Vieira, Lirlândia P Sousa, Flávio A Amaral, Leda Q Vieira, Jacques R Nicoli, Mauro M Teixeira, Danielle G Souza
The indigenous intestinal microbiota is frequently considered an additional major organ of the human body and exerts profound immunomodulating activities. Germ-free (GF) mice display a significantly different inflammatory responsiveness pattern compared with conventional (CV) mice, and this was dubbed a "hyporesponsive phenotype." Taking into account that the deposition of immune complexes is a major event in acute inflammation and that GF mice have a distinct Ig repertoire and B cell activity, we aimed to evaluate whether this altered Ig repertoire interferes with the inflammatory responsiveness of GF mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28422750/differential-expression-of-gpr15-on-t-cells-during-ulcerative-colitis
#11
Alexandra Adamczyk, Daniel Gageik, Annika Frede, Eva Pastille, Wiebke Hansen, Andreas Rueffer, Jan Buer, Jürgen Büning, Jost Langhorst, Astrid M Westendorf
G protein-coupled receptor 15 (GPR15) was recently highlighted as a colon-homing receptor for murine and human CD4+ T cells. The aim of this study was to explore the functional phenotype of human GPR15+CD4+ T cells, focusing on Tregs and effector T cells (Teffs), and to determine whether GPR15 is the driver for the migration of T cells to the colon during ulcerative colitis (UC). In the peripheral blood, GPR15 was expressed on Tregs and Teffs; both GPR15+ T cell subsets produced less IFN-γ and IL-4 but more IL-17 after stimulation and showed a higher migration activity compared with GPR15-CD4+ T cells...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422073/chemopreventive-strategies-for-inflammation-related-carcinogenesis-current-status-and-future-direction
#12
REVIEW
Yusuke Kanda, Mitsuhiko Osaki, Futoshi Okada
A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421818/cell-origin-dictates-programming-of-resident-versus-recruited-macrophages-during-acute-lung-injury
#13
Kara J Mould, Lea Barthel, Michael P Mohning, Stacey M Thomas, Alexandra L McCubbrey, Thomas Danhorn, Sonia M Leach, Tasha E Fingerlin, Brian P O'Connor, Julie A Reisz, Angelo D'Alessandro, Donna L Bratton, Claudia V Jakubzick, William J Janssen
Two populations of alveolar macrophages (AMs) co-exist in the inflamed lung: resident AMs that arise during embryogenesis, and recruited AMs that originate postnatally from circulating monocytes. The objective of this study was to determine whether origin or environment dictates the transcriptional, metabolic, and functional programming of these two ontologically distinct populations over the time course of acute inflammation. RNA sequencing demonstrated marked transcriptional differences between resident and recruited AMs affecting three main areas: proliferation, inflammatory signaling, and metabolism...
April 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28421155/an-appendiceal-carcinoid-tumor-within-an-amyand-s-hernia-mimicking-an-incarcerated-inguinal-hernia
#14
Gregorios Christodoulidis, Konstantinos Perivoliotis, Alexandros Diamantis, Dionysios Dimas, Michael Spyridakis, Konstantinos Tepetes
Introduction. We report the case of an appendiceal carcinoid tumor within an Amyand's hernia, presenting as an incarcerated right inguinal hernia. Presentation of Case. A 52-year-old male presented in the emergency department due to a persistent right inguinal pain. Clinical examination revealed a tender right groin mass. Laboratory tests revealed leukocytosis and an increased serum CRP. Under the diagnosis of an incarcerated right inguinal hernia, an emergency operation was taken. Intraoperatively, an inflamed appendix and a part of the cecum were found in the hernia sac...
2017: Case Reports in Surgery
https://www.readbyqxmd.com/read/28421005/autoimmune-aspects-of-neurodegenerative-and-psychiatric-diseases-a-template-for-innovative-therapy
#15
REVIEW
Peter de Haan, Hans C Klein, Bert A 't Hart
Neurodegenerative and psychiatric diseases (NPDs) are today's most important group of diseases, surpassing both atherosclerotic cardiovascular disease and cancer in morbidity incidence. Although NPDs have a dramatic impact on our society because of their high incidence, mortality, and severe debilitating character, remarkably few effective interventions have become available. The current treatments, if available, comprise the lifelong intake of general immunosuppressants to delay disease progression or neurotransmitter antagonists/agonists to dampen undesired behaviors...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28420668/hypercholesterolemia-induces-differentiation-of-regulatory-t-cells-in-the-liver
#16
Reiner K Mailer, Anton Gisterå, Konstantinos A Polyzos, Daniel F Ketelhuth, Göran K Hansson
Rationale: The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T cell differentiation remains unknown. Objective: To investigate hepatic T cell subsets upon hypercholesterolemia. Methods and Results: We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor beta 1 in the liver...
April 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28420308/nanodispersion-loaded-mucoadhesive-polymeric-inserts-for-prolonged-treatment-of-postoperative-ocular-inflammation
#17
Nadia Morsi, Dalia Ghorab, Hanan Refai, Hoda Teba
Mucoadhesive polymeric films incorporated with ketorolac tromethamine loaded nanodispersion aiming the sustained delivery of the drug to the cornea have been developed and characterized for the treatment of postoperative ocular inflammation. Nanodispersions were prepared by ionic gelation method with various concentrations of chitosan and sodium tripolyphosphate. The developed nanodispersions were analyzed for morphology, particle size, dispersion homogeneity, zeta potential, entrapment efficiency and drug release...
April 19, 2017: Journal of Microencapsulation
https://www.readbyqxmd.com/read/28419613/peg-poly-l-lysine-based-polymeric-micelle-mri-contrast-agent-feasibility-study-of-a-gd-micelle-contrast-agent-for-mr-lymphography
#18
Hiroyuki Akai, Kouichi Shiraishi, Masayuki Yokoyama, Koichiro Yasaka, Masanori Nojima, Yusuke Inoue, Osamu Abe, Kuni Ohtomo, Shigeru Kiryu
PURPOSE: To investigate the feasibility of polymeric micelle of poly(ethyleneglycol) (PEG)-b-poly(L-lysine-DOTA) (Gd-micelle) as a contrast agent for magnetic resonance lymphography (MRL). MATERIALS AND METHODS: Twenty-four female BALB/c mice were randomly divided into four groups of six mice each. Among them, mice of two groups were injected of complete Freund's adjuvant to obtain inflamed lymph nodes. We subcutaneously injected 0.5 μmol Gd per mouse of Gd-micelle or gadofluorine P in the right rear footpad...
April 17, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28419540/deep-granuloma-annulare-mimicking-inflamed-cysts-in-a-teenager
#19
Emily L Guo, Catherine A Degesys, Richard Jahan-Tigh, Audrey Chan
We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed cysts. Reactive inflammation and sterile purulent drainage may be an underrecognized feature of DGA.
April 17, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28419144/stepwise-inhibition-of-t-cell-recruitment-at-post-capillary-venules-by-orally-active-desulfated-heparins-in-inflammatory-arthritis
#20
Hasan Al Faruque, Jin Hee Kang, Seung Rim Hwang, Shijin Sung, Md Mahmudul Alam, Keum Hee Sa, Eon Jeong Nam, Young Ro Byun, Young Mo Kang
Identification of the structure-function relationship of heparin, particularly between 2-O-, 6-O-, and N-sulfation and its anticoagulant or anti-inflammatory activities, is critical in order to evaluate the biological effects of heparin, especially in conjunction with modifications for oral formulation. In this study, we demonstrated that removal of 2-O, 6-O, or N-desulfation and their hydrophobic modifications have differential effects on the blocking of interactions between sLeX and P-and L-selectins, with highest inhibition by 6-O desulfation, which was consistent with their in vivo therapeutic efficacies on CIA mice...
2017: PloS One
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