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https://www.readbyqxmd.com/read/28537941/pathophysiology-of-anca-associated-vasculitis
#1
Turki Al-Hussain, Maged H Hussein, Walter Conca, Hadeel Al Mana, Mohammed Akhtar
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized as inflammation of small-sized to medium-sized blood vessels and encompasses several clinicopathologic entities including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited ANCA-associated vasculitis. Over the past several decades, significant progress has been made in understanding the pathophysiology of ANCA-associated vasculitis. Although neutrophils contain a multitude of granular proteins, clinically significant autoantibodies are only recognized against myeloperoxidase and proteinase 3, both of which are present in the azurophilic granules...
May 22, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28537730/discovery-of-small-molecules-as-multi-toll-like-receptor-agonists-with-proinflammatory-and-anticancer-activities
#2
Lei Zhang, Varun Dewan, Hang Hubert Yin
Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput screening of a small-molecule library based on TLR3-mediated NF-κB activation. Subsequent structural optimization and counter screening of other TLRs produced the first small molecule (CU-CPT24e) capable of simultaneously activating TLRs 3, 8, and 9. Biochemical studies demonstrated that CU-CPT24e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28534191/tgf-%C3%AE-in-inflammatory-bowel-disease-a-key-regulator-of-immune-cells-epithelium-and-the-intestinal-microbiota
#3
REVIEW
Sozaburo Ihara, Yoshihiro Hirata, Kazuhiko Koike
Inflammatory bowel disease (IBD) is defined as chronic intestinal inflammation, and includes ulcerative colitis and Crohn's disease. Multiple factors are involved in the pathogenesis of IBD, and the condition is characterized by aberrant mucosal immune reactions to intestinal microbes in genetically susceptible hosts. Transforming growth factor-β (TGF-β) is an immune-suppressive cytokine produced by many cell types and activated by integrins. Active TGF-β binds to its receptor and regulates mucosal immune reactions through the TGF-β signaling pathway...
May 22, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28534138/a-chemically-modified-curcumin-cmc-2-24-inhibits-nuclear-factor-%C3%AE%C2%BAb-activation-and-inflammatory-bone-loss-in-murine-models-of-lps-induced-experimental-periodontitis-and-diabetes-associated-natural-periodontitis
#4
Muna S Elburki, Carlos Rossa, Morgana R Guimarães-Stabili, Hsi-Ming Lee, Fabiana A Curylofo-Zotti, Francis Johnson, Lorne M Golub
The purpose of this study was to assess the effect of a novel chemically modified curcumin (CMC 2.24) on NF-κB and MAPK signaling and inflammatory cytokine production in two experimental models of periodontal disease in rats. Experimental model I: Periodontitis was induced by repeated injections of LPS into the gingiva (3×/week, 3 weeks); control rats received vehicle injections. CMC 2.24, or the vehicle, was administered by daily oral gavage for 4 weeks. Experimental model II: Diabetes was induced in adult male rats by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia...
May 22, 2017: Inflammation
https://www.readbyqxmd.com/read/28533444/t-follicular-helper-cell-derived-il-4-is-required-for-ige-production-during-intestinal-helminth-infection
#5
Alexandre P Meli, Ghislaine Fontés, Cindy Leung Soo, Irah L King
IgE production plays a crucial role in protective as well as pathogenic type 2 immune responses. Although the cytokine IL-4 is required for the development of IgE-producing plasma cells, the source of IL-4 and cellular requirements for optimal IgE responses remain unclear. Recent evidence suggests that T follicular helper (Tfh) cells are the primary producer of IL-4 in the reactive lymph node during type 2 immune responses. As Tfh cells are also required for the development of plasmablasts derived from germinal center and extrafollicular sources, we hypothesized that this cell subset is essential for the IgE plasmablast response...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28531919/bupleurum-chinense-extract-ameliorates-an-ova-induced-murine-allergic-asthma-through-the-reduction-of-the-th2-and-th17-cytokines-production-by-inactivation-of-nf%C3%AE%C2%BAb-pathway
#6
Thi Tho Bui, Chun Hua Piao, Chang Ho Song, Hee Soon Shin, Ok Hee Chai
Bupleurum chinense belongs to the Bupleurum spp. family that has been used in traditional herbal medicine for over thousand years. It has been reported to have anti-inflammatory, anti-oxidant, hepato-protective, antipyretic, analgesic, anti-fibrotic and immunomodulatory effect. However, the effect of B. Chinense on allergic asthma remains unclear. This study investigated the immunomodulatory effects of B. Chinense extracts (BCE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we evaluated the number of total cells, differential inflammatory cells and the production of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung homogenate as well as histological structure...
May 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28530657/normal-and-cancerous-mammary-stem-cells-evade-interferon-induced-constraint-through-the-mir-199a-lcor-axis
#7
Toni Celià-Terrassa, Daniel D Liu, Abrar Choudhury, Xiang Hang, Yong Wei, Jose Zamalloa, Raymundo Alfaro-Aco, Rumela Chakrabarti, Yi-Zhou Jiang, Bong Ihn Koh, Heath A Smith, Christina DeCoste, Jun-Jing Li, Zhi-Ming Shao, Yibin Kang
Tumour-initiating cells, or cancer stem cells (CSCs), possess stem-cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses...
May 22, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28528966/nampt-inhibitor-protects-ischemic-neuronal-injury-in-rat-brain-via-anti-neuroinflammation
#8
Chen-Xiang Chen, Jing Huang, Ga-Qi Tu, Jia-Tong Lu, Xian Xie, Bing Zhao, Ming Wu, Qiao-Juan Shi, San-Hua Fang, Er-Qing Wei, Wei-Ping Zhang, Yun-Bi Lu
Nicotinamide phosphoribosyltransferase (NAMPT) is an important neuroprotective factor in cerebral ischemia, and it has been reported that NAMPT inhibitors can aggravate neuronal injury in the acute phase. However, because it is a cytokine, NAMPT participates in many inflammatory diseases in the peripheral system, and its inhibitors have therapeutic effects. Following cerebral ischemia, the peripheral and resident inflammatory and immune cells produce many pro-inflammatory mediators in the ischemic area, which induce neuroinflammation and impair the brain...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28528914/systemic-sclerosis-dermal-fibroblasts-suppress-th1-cytokine-production-via-galectin-9-overproduction-due-to-fli1-deficiency
#9
Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Megumi Hirabayashi, Shunsuke Miura, Takashi Yamashita, Takashi Taniguchi, Yohei Ichimura, Takehiro Takahashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato
Dermal fibroblasts promote skin-localized transdifferentiation of Tregs to Th2-like cells in systemic sclerosis (SSc). However, the entire effect of SSc dermal fibroblasts on immune cells still remains unknown. Since galectin-9 induces Th2 cytokine-predominant immune imbalance by negatively regulating Th1/Th17 cells in inflammatory diseases, we investigated the contribution of galectin-9 to Th immune balance in SSc lesional skin. We utilized human clinical samples and Fli1(+/-) mice because Fli1 deficiency induces SSc-like phenotypes in various cell types...
May 18, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#10
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28528700/directed-differentiation-of-human-pluripotent-stem-cells-to-microglia
#11
Panagiotis Douvaras, Bruce Sun, Minghui Wang, Ilya Kruglikov, Gregory Lallos, Matthew Zimmer, Cecile Terrenoire, Bin Zhang, Sam Gandy, Eric Schadt, Donald O Freytes, Scott Noggle, Valentina Fossati
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28527302/aortic-adventitial-fibroblast-sensitivity-to-mitogen-activated-protein-kinase-inhibitors-depends-on-substrate-stiffness
#12
Rebecca A Scott, Prathamesh M Kharkar, Kristi L Kiick, Robert E Akins
Adventitial fibroblasts (AFs) are key determinants of arterial function and critical mediators of arterial disease progression. The effects of altered stiffness, particularly those observed across individuals during normal vascular function, and the mechanisms by which AFs respond to altered stiffness, are not well understood. To study the effects of matrix stiffness on AF phenotype, cytokine production, and the regulatory pathways utilized to interpret basic cell-matrix interactions, human aortic AFs were grown in 5%, 7...
May 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28526636/rebamipide-ameliorates-radiation-induced-intestinal-injury-in-a-mouse-model
#13
Sehwan Shim, Hyo-Sun Jang, Hyun-Wook Myung, Jae Kyung Myung, Jin-Kyu Kang, Min-Jung Kim, Seung Bum Lee, Won-Suk Jang, Sun-Joo Lee, Young-Woo Jin, Seung-Sook Lee, Sunhoo Park
Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased...
May 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28526535/tnf-%C3%AE-is-superior-to-conventional-inflammatory-mediators-in-forecasting-ivig-nonresponse-and-coronary-arteritis-in-chinese-children-with-kawasaki-disease
#14
Peng Hu, Guang Mei Jiang, Yue Wu, Bao Yu Huang, Si Yan Liu, Dong Dong Zhang, Yao Xu, Yang Fang Wu, Xun Xia, Wei Wei, Bo Hu
BACKGROUND: Tumor necrosis factor (TNF) -α is of inflammatory cytokines produced chiefly by activated monocyte/macrophages, and has been implicated in the pathogenesis of Kawasaki disease (KD). We elucidated the relationship of plasma TNF-α with conventional inflammatory mediators, clinical classification, intravenous immunoglobulin (IVIG) response and coronary arteritis in the course of KD. METHODS: Seventy Chinese children with KD were enrolled and divided into 6 subgroups, including complete KD, incomplete KD, IVIG-responsive KD, IVIG-nonresponsive KD, coronary artery (CA) -noninvolvement KD and CA-involvement KD...
May 16, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28523372/dietary-eicosapentaenoic-acid-normalizes-hippocampal-omega-3-and-6-polyunsaturated-fatty-acid-profile-attenuates-glial-activation-and-regulates-bdnf-function-in-a-rodent-model-of-neuroinflammation-induced-by-central-interleukin-1%C3%AE-administration
#15
Yilong Dong, Min Xu, Allan V Kalueff, Cai Song
PURPOSE: Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer's disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear...
May 18, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28522598/immunotherapeutic-approaches-of-il-1-neutralization-in-the-tumor-microenvironment
#16
REVIEW
Ron N Apte, Elena Voronov
IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type I (IL-1R1) and induce similar biologic functions. The IL-1R antagonist (IL-1Ra) is a physiologic inhibitor of IL-1R1 signaling. In the tumor microenvironment, IL-1 is expressed by malignant, stromal, and infiltrating cells and supports tumor invasiveness and progression. We have shown that in the tumor microenvironment, the IL-1 agonistic molecules act different as a result of their local amounts and their compartmentalization within the producing cells...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522569/brain-derived-neurotrophic-factor-and-airway-fibrosis-in-asthma
#17
Michelle R Freeman, Venkatachalem Sathish, Logan J Manlove, Shengyu Wang, Rodney D Britt, Michael A Thompson, Christina M Pabelick, Y S Prakash
Airway remodeling in asthma driven by inflammation involves proliferation of epithelial cells and airway smooth muscle (ASM), as well as enhanced extracellular matrix (ECM) generation and deposition, i.e. fibrosis. Accordingly, understanding pro-fibrotic mechanisms is important for developing novel therapeutic strategies in asthma. Recent studies, including our own, have suggested a role for locally-produced growth factors such as brain-derived neurotrophic factor (BDNF) in mediating and modulating inflammation effects...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-and-checkpoint-blockade
#18
Jun Zhou, Kathleen M Mahoney, Anita Giobbie-Hurder, Fengmin Zhao, Sandra Lee, Xiaoyun Liao, Scott Rodig, Jingjing Li, Xinqi Wu, Lisa H Butterfield, Matthias Piesche, Michael P Manos, Lauren M Eastman, Glenn Dranoff, Gordon J Freeman, F Stephen Hodi
Blockade of the pathway including Programmed death-ligand 1 (PD-L1) and its receptor Programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers.  Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma.  However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood.  We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted...
May 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28520696/an-ovine-model-of-hyperdynamic-endotoxemia-and-vital-organ-metabolism
#19
Liam Byrne, Nchafatso G Obonyo, Sara Diab, Kimble Dunster, Margaret Passmore, Ai Ching Boon, Louise See Hoe, Karen Hay, Frank Van Haren, John-Paul Tung, Louise Cullen, Kiran Shekar, Kathryn Maitland, John F Fraser
BACKGROUND: Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs...
May 17, 2017: Shock
https://www.readbyqxmd.com/read/28520463/a-preclinical-assessment-of-early-continuous-passive-motion-and-treadmill-therapeutic-exercises-for-generating-chondroprotective-effects-after-anterior-cruciate-ligament-rupture
#20
Nai-Jen Chang, Kuan-Wei Lee, Chih-Jou Chu, Ming-You Shie, Pei-Hsi Chou, Chih-Chan Lin, Peir-In Liang
BACKGROUND: Anterior cruciate ligament (ACL) injury is a well-known risk factor for the development of posttraumatic osteoarthritis (PTOA). However, whether using continuous passive motion (CPM) with or without additional treadmill exercise (TRE) in early ACL injury might provide chondroprotective effects and further decrease the risk of PTOA has yet to be determined. HYPOTHESIS: CPM may offer an enhanced chondroprotective effect, but TRE may attenuate that effect due to the mechanical stress on the joint and inflammatory cytokines in the joint...
May 1, 2017: American Journal of Sports Medicine
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