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https://www.readbyqxmd.com/read/28636088/multicompartment-drug-release-system-for-dynamic-modulation-of-tissue-responses
#1
Aaron H Morris, Rajwant S Mahal, Jillian Udell, Michelle Wu, Themis R Kyriakides
Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure...
June 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28631608/one-year-in-review-2017-pathogenesis-of-rheumatoid-arthritis
#2
REVIEW
Francesca Angelotti, Alice Parma, Giacomo Cafaro, Riccardo Capecchi, Alessia Alunno, Ilaria Puxeddu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e...
May 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28627972/immunomodulatory-effects-of-cigarette-smoke-condensate-in-mouse-macrophage-cell-line
#3
Junwei Zhao, Xiang Li, Fuwei Xie, Zhihua Yang, Xiujie Pan, Maoxiang Zhu, Pingping Shang, Cong Nie, Huimin Liu, Jianping Xie
Increasing evidence has demonstrated that the secretion of cytokines may be associated with cigarette smoke-induced immunomodulatory effects, but a comprehensive analysis of the cytokine profile for cigarette smoke condensate (CSC) exposure is lacking. The aims of this study were to (1) examine the release of 20 cytokines induced by CSC from 12 brands of cigarettes in macrophages cells (Ana-1) and (2) to investigate the general characteristics of the immunomodulatory effects of CSC. Luminex technology was used to simultaneously determine the levels of 20 cytokines (interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), keratinocyte-derived Chemokine (KC), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), induced protein 10 (IP-10), tumor necrosis factor α (TNF-α), vascular endothelial growth factor (VEGF), monkine inducible by γ interferon (MIG), and fibroblast growth factor (FGF)-basic) in the supernatants from Ana-1 cells treated with the CSC...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#4
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated hY3. The top ten upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response (e...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28624002/pathophysiology-of-venous-ulceration
#5
REVIEW
Joel M Crawford, Brajesh K Lal, Walter N Durán, Peter J Pappas
Our understanding of the pathophysiologic process of venous ulceration has dramatically increased during the past two decades because of dedicated, venous-specific basic science research. Currently, the mechanisms regulating venous ulceration are a combination of macroscopic and microscopic pathologic processes. Macroscopic alterations refer to pathologic processes related to varicose vein formation, vein wall architecture, and cellular abnormalities that impair venous function. These processes are primarily caused by genetic factors that lead to the destruction of normal vein wall architecture and venous hypertension...
July 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28623344/an-essential-role-of-pi3k-in-the-control-of-west-nile-virus-infection
#6
Leilei Wang, Long Yang, Erol Fikrig, Penghua Wang
The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3-16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620393/tweak-fn14-activation-participates-in-ro52-mediated-photosensitization-in-cutaneous-lupus-erythematosus
#7
Yale Liu, Meifeng Xu, Xiaoyun Min, Kunyi Wu, Ting Zhang, Ke Li, Shengxiang Xiao, Yumin Xia
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) binds to its sole receptor fibroblast growth factor-inducible 14 (Fn14), participating in various inflammatory responses. Recently, TWEAK/Fn14 activation was found prominent in the lesions of cutaneous lupus erythematosus (CLE). This study was designed to further reveal the potential role of this pathway in Ro52-mediated photosensitization. TWEAK, Fn14, and Ro52 were determined in the skin lesions of patients with CLE. Murine keratinocytes received ultraviolet B (UVB) irradiation or plus TWEAK stimulation and underwent detection for Ro52 and proinflammatory cytokines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620193/microrna-29a-counteracts-synovitis-in-knee-osteoarthritis-pathogenesis-by-targeting-vegf
#8
Jih-Yang Ko, Mel S Lee, Wei-Shiung Lian, Wen-Tsan Weng, Yi-Chih Sun, Yu-Shan Chen, Feng-Sheng Wang
Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616244/macrophages-and-fibroblasts-during-inflammation-and-tissue-repair-in-models-of-organ-regeneration
#9
REVIEW
Anthony L Mescher
This review provides a concise summary of the changing phenotypes of macrophages and fibroblastic cells during the local inflammatory response, the onset of tissue repair, and the resolution of inflammation which follow injury to an organ. Both cell populations respond directly to damage and present coordinated sequences of activation states which determine the reparative outcome, ranging from true regeneration of the organ to fibrosis and variable functional deficits. Recent work with mammalian models of organ regeneration, including regeneration of full-thickness skin, hair follicles, ear punch tissues, and digit tips, is summarized and the roles of local immune cells in these systems are discussed...
April 2017: Regeneration
https://www.readbyqxmd.com/read/28615126/unveiling-the-participation-of-avian-kinin-ornithokinin-and-its-receptors-in-the-chicken-inflammatory-response
#10
Rodrigo Guabiraba, Damien Garrido, Geoffrey Bailleul, Angélina Trotereau, Mélanie Pinaud, Anne-Christine Lalmanach, Nathalie K Chanteloup, Catherine Schouler
Vasoactive peptides are key early mediators of inflammation released through activation of different enzymatic systems. The mammalian kinin-kallikrein (K-KLK) system produces bradykinin (BK) through proteolytic cleavage of a kininogen precursor by enzymes named kallikreins. BK acts through specific ubiquitous G-protein coupled receptors (B1R and B2R) to participate in physiological processes and inflammatory responses, such as activation of mononuclear phagocytes. In chickens, the BK-like nonapeptide ornithokinin (OK) has been shown to promote intracellular calcium increase in embryonic fibroblasts and to be vasodilatory in vivo...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28611666/mineralocorticoid-receptor-signaling-as-a-therapeutic-target-for-renal-and-cardiac-fibrosis
#11
REVIEW
Greg H Tesch, Morag J Young
Activation of the mineralocorticoid receptor (MR) plays important roles in both physiological and pathological events. Blockade of MR signaling with MR antagonists (MRAs) has been used clinically to treat kidney and cardiac disease associated with hypertension and other chronic diseases, resulting in suppression of fibrosis in these organs. However, the current use of steroidal MRAs has been limited by off target effects on other hormone receptors or adverse effects on kidney tubular function. In this review, we summarize recent insights into the profibrotic roles of MR signaling in kidney and cardiovascular disease...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28607485/exosomes-facilitate-therapeutic-targeting-of-oncogenic-kras-in-pancreatic-cancer
#12
Sushrut Kamerkar, Valerie S LeBleu, Hikaru Sugimoto, Sujuan Yang, Carolina F Ruivo, Sonia A Melo, J Jack Lee, Raghu Kalluri
The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras(G12D), a common mutation in pancreatic cancer...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28602757/achillea-asiatica-extract-and-its-active-compounds-induce-cutaneous-wound-healing
#13
Banzragch Dorjsembe, Hee Ju Lee, Myungsuk Kim, Batsuren Dulamjav, Tunsag Jigjid, Chu Won Nho
ETHNOPHARMACOLOGICAL RELEVANCE: Achillea asiatica Serg. is a perennial herb belonging to the Asteraceae family that has long been traditionally used to treat acute intestinal and stomach inflammation, persistent fever, ulcers, wounds, and rheumatism. AIM OF THE STUDY: We investigated the effect of A. asiatica extract (AAE) on cutaneous wound healing. MATERIALS AND METHODS: To assess the effect of AAE on wounds, an incisional Sprague-Dawley (SD) rat model was topically treated with AAE for 2 weeks...
June 8, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28600230/cytokine-and-chemokine-profile-changes-in-patients-with-lower-segment-lumbar-degenerative-spondylolisthesis
#14
Juraj Sutovsky, Martin Benco, Martina Sutovska, Michaela Kocmalova, Lenka Pappova, Juraj Miklusica, Andrej Frano, Egon Kurca
BACKGROUND: Lumbar degenerative spondylolisthesis (DS) develops as a result of inflammatory and remodeling processes in facet joints (FJs). Several inflammatory cytokines are involved in the osteoarthritic and remodeling changes that occur and in low-back and/or radicular pain, the most prevalent clinical symptom of disease. This study improves knowledge related to the roles that 27 cytokines, chemokines and growth factors play in the pathophysiology of lumbar DS. MATERIAL AND METHODS: Cytokine levels were examined using capture sandwich immunoassay using the Bio-Plex(®) 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) separately in intervertebral discs (IVDs) and FJ bone tissue...
June 6, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28600163/involvement-of-tyrosine-specific-protein-kinase-and-protein-kinase-c-in-j774a-1-macrophage-functions-activated-by-tinospora-cordifoliain%C3%A2-vitro
#15
Priti More, Kalpana Pai
BACKGROUND: Macrophages are the first line of defense and constitute important participant in the bi-directional interaction between innate and specific immunity. Macrophages are in a quiescent form and get activated when given a stimulus. In our previous studies we have reported that guduchi or LPS treatment of macrophages enhanced production of nitric oxide (NO) and increased tumoricidal activity against L929 fibroblast cells. OBJECTIVE: In the present study effect of Tinospora cordifolia commonly known as guduchi on macrophage activation and the mechanism of action i...
June 6, 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/28594406/simvastatin-treatment-boosts-benefits-of-apoptotic-cell-infusion-in-murine-lung-fibrosis
#16
Ye-Ji Lee, Meung-Joo Kim, Young-So Yoon, Youn-Hee Choi, Hee-Sun Kim, Jihee Lee Kang
A single early-phase infusion of apoptotic cells can inhibit bleomycin-induced lung inflammation and fibrosis; however, it is unknown whether these effects can be enhanced with additional infusions and/or statin treatment. Here, we investigated whether an increased frequency of apoptotic cell injection, with or without efferocytosis enhancer simvastatin, facilitates therapeutic efficacy. An additional injection of apoptotic cells during the intermediate phase (7 days post-bleomycin treatment) or simvastatin administration alone on days 7-13 post-treatment did not promote anti-fibrotic responses beyond those induced by a single early apoptotic cell infusion alone...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28592892/noncanocial-cell-death-program-independent-of-caspase-activation-cascade-and-necroptotic-modules-is-elicited-by-loss-of-tgf%C3%AE-activated-kinase-1
#17
September R Mihaly, Yosuke Sakamachi, Jun Ninomiya-Tsuji, Sho Morioka
Programmed cell death (PCD) occurs in several forms including apoptosis and necroptosis. Apoptosis is executed by the activation of caspases, while necroptosis is dependent on the receptor interacting protein kinase 3 (RIPK3). Precise control of cell death is crucial for tissue homeostasis. Indeed, necroptosis is triggered by caspase inhibition to ensure cell death. Here we identified a previously uncharacterized cell death pathway regulated by TAK1, which is unexpectedly provoked by inhibition of caspase activity and necroptosis cascades...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588447/the-effects-of-epidermal-neural-crest-stem-cells-on-local-inflammation-microenvironment-in-the-defected-sciatic-nerve-of-rats
#18
Yue Li, Dongdong Yao, Jieyuan Zhang, Bin Liu, Lu Zhang, Hua Feng, Bingcang Li
Cell-based therapy is a promising strategy for the repair of peripheral nerve injuries (PNIs). epidermal neural crest stems cells (EPI-NCSCs) are thought to be important donor cells for repairing PNI in different animal models. Following PNI, inflammatory response is important to regulate the repair process. However, the effects of EPI-NCSCs on regulation of local inflammation microenviroment have not been investigated extensively. In the present study, these effects were studied by using 10 mm defected sciatic nerve, which was bridged with 15 mm artificial nerve composed of EPI-NCSCs, extracellular matrix (ECM) and poly (lactide-co-glycolide) (PLGA)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28588082/ire1%C3%AE-promotes-viral-infection-by-conferring-resistance-to-apoptosis
#19
Susan L Fink, Teshika R Jayewickreme, Ryan D Molony, Takao Iwawaki, Charles S Landis, Brett D Lindenbach, Akiko Iwasaki
The unfolded protein response (UPR) is an ancient cellular pathway that detects and alleviates protein-folding stresses. The UPR components X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1α (IRE1α) promote type I interferon (IFN) responses. We found that Xbp1-deficient mouse embryonic fibroblasts and macrophages had impaired antiviral resistance. However, this was not because of a defect in type I IFN responses but rather an inability of Xbp1-deficient cells to undergo viral-induced apoptosis...
June 6, 2017: Science Signaling
https://www.readbyqxmd.com/read/28587985/naturally-occurring-xanthone-and-benzophenone-derivatives-exert-significant-anti-proliferative-and-proapoptotic-effects-in-vitro-on-synovial-fibroblasts-and-macrophages-from-rheumatoid-arthritis-patients
#20
Izabella Henc, Adam Kokotkiewicz, Piotr Łuczkiewicz, Ewa Bryl, Maria Łuczkiewicz, Jacek M Witkowski
There is a need for novel, safer and cheaper drugs for the therapy of rheumatoid arthritis (RA), better targeted against the cellular processes involved in the disease pathogenesis. Using advanced analysis of microscopic images and flow cytometry, we demonstrate that naturally occurring xanthone and benzophenone derivatives exert strong, dose- and O2 concentration-dependent anti-proliferative and pro-apoptotic effects on RA patients' fibroblast-like synoviocytes (FLS) and macrophages. Suspensions containing fibroblasts, macrophages and other infiltrating cells were obtained from inflamed synovial tissue collected from female RA patients...
June 3, 2017: International Immunopharmacology
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