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https://www.readbyqxmd.com/read/28088386/trypsin-induces-biphasic-muscle-contraction-and-relaxation-via-transient-receptor-potential-vanilloid-1-and-neurokinin-receptors-1-2-in-porcine-esophageal-body
#1
Bai Xiaopeng, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Kayoko Nakano, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura
Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28065449/a-specific-immune-tolerance-toward-offspring-cells-is-to-exist-after-the-mother-lymphocyte-infusion
#2
Haizhou Xing, Shiqin Liu, Xue Chen, Fang Fang, Xueqiang Wu, Ping Zhu
PURPOSE: To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion. METHODS: Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10(7) of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected...
December 26, 2016: Immunobiology
https://www.readbyqxmd.com/read/28056922/herbal-formula-xian-fang-huo-ming-yin-regulates-differentiation-of-lymphocytes-and-production-of-pro-inflammatory-cytokines-in-collagen-induced-arthritis-mice
#3
Jinyu Li, Yi Wei, Xue Li, Dashuai Zhu, Bo Nie, Jingwei Zhou, Lixia Lou, Bin Dong, Aiming Wu, Yongzhe Che, Meng Chen, Lingqun Zhu, Mingwei Mu, Limin Chai
BACKGROUND: Xian-Fang-Huo-Ming-Yin (XFHM), a traditional herbal formula, has been used to treat sores and carbuncles for hundreds of years in Asia. Nowadays, its clinical effects in treatment of rheumatoid arthritis (RA) have been validated. In this study, we want to study its possible molecular mechanisms of regulating the differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis (CIA) mice for RA treatment. METHODS: A high performance liquid chromatography-electrospray ionization/mass spectrometer (HPLC-ESI/MS(n)) system was used to analyze the constituents of XFHM granules...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28035212/interleukin-17-expressing-innate-synovial-cells-drive-k-bxn-serum-induced-arthritis
#4
Wang Shik Cho, Eunkyeong Jang, Ho-Youn Kim, Jeehee Youn
K/BxN serum can induce arthritis in normal mice because of abundant autoantibodies that trigger an innate inflammatory response in joints. To determine whether IL-17 is involved in the pathogenesis of serum-induced arthritis, we injected wild-type and IL-17(-/-) mice with K/BxN serum and evaluated them for signs of arthritis. Unlike wild-type mice, IL-17(-/-) mice did not show any signs of arthritis. IL-17 was produced predominantly by CD3(-) CD4(-) γδTCR(-) NK1.1(-) Sca1(int) Thy1(hi) cells residing in the inflamed synovial tissue...
December 2016: Immune Network
https://www.readbyqxmd.com/read/28032216/effectiveness-of-aprepitant-in-addition-to-ondansetron-in-the-prevention-of-nausea-and-vomiting-caused-by-fractionated-radiotherapy-to-the-upper-abdomen-avert
#5
Steven Ades, M Halyard, K Wilson, T Ashikaga, R Heimann, S Kumar, W Blackstock
PURPOSE: Despite a lower risk of nausea and vomiting in patients receiving radiotherapy to the upper abdomen (UA-RINV) with prophylactic 5-HT3 antagonist therapy, patients can still experience UA-RINV. The aim of this multicenter phase II study was to assess effectiveness, safety, and tolerability of protracted dual NK1-receptor and 5-HT3 antagonist prophylaxis against UA-RINV. METHODS: Patients receiving fractionated radiotherapy with radiosensitizing chemotherapy received oral ondansetron 8 mg po q12 h and aprepitant 125/80/80 mg on a Monday, Wednesday, Friday schedules throughout radiotherapy...
December 28, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28028361/characterization-of-smooth-muscle-enteric-nerve-interstitial-cells-of-cajal-and-fibroblast-like-cells-in-the-gastric-musculature-of-patients-with-diabetes-mellitus
#6
Kyung Sik Park, Kwang Bum Cho, Il Seon Hwang, Jae Hyung Park, Byung Ik Jang, Kyeong Ok Kim, Sung Woo Jeon, Eun Soo Kim, Chang Sik Park, Joong Goo Kwon
AIM: To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus (DM). METHODS: Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson's Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), neurokinin-1 (NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha, (PDGFRα)]...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27993375/role-of-hemokinin-1-in-health-and-disease
#7
REVIEW
Éva Borbély, Zsuzsanna Helyes
Hemokinin-1 (HK-1), the newest tachykinin encoded by the Tac4 gene was discovered in 2000. Its name differs from that of the other members of this peptide family due to its first demonstration in B lymphocytes. Since tachykinins are classically found in the nervous system, the significant expression of HK-1 in blood cells is a unique feature of this peptide. Due to its widespread distribution in the whole body, HK-1 is involved in different physiological and pathophysiological functions involving pain inflammation modulation, immune regulation, respiratory and endocrine functions, as well as tumor genesis...
December 13, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27982126/interleukin-12-bypasses-common-gamma-chain-signalling-in-emergency-natural-killer-cell-lymphopoiesis
#8
Isabel Ohs, Maries van den Broek, Kathrin Nussbaum, Christian Münz, Sebastian J Arnold, Sergio A Quezada, Sonia Tugues, Burkhard Becher
Differentiation and homeostasis of natural killer (NK) cells relies on common gamma-chain (γc)-dependent cytokines, in particular IL-15. Consequently, NK cells do not develop in mice with targeted γc deletion. Herein we identify an alternative pathway of NK-cell development driven by the proinflammatory cytokine IL-12, which can occur independently of γc-signalling. In response to viral infection or upon exogenous administration, IL-12 is sufficient to elicit the emergence of a population of CD122(+)CD49b(+) cells by targeting NK-cell precursors (NKPs) in the bone marrow (BM)...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27982034/a-tlr9-agonist-promotes-il-22-dependent-pancreatic-islet-allograft-survival-in-type-1-diabetic-mice
#9
Deepak Tripathi, Sambasivan Venkatasubramanian, Satyanarayana S Cheekatla, Padmaja Paidipally, Elwyn Welch, Amy R Tvinnereim, Ramakrishna Vankayalapati
Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1(+) cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1(+) cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1(+) cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27925267/genetic-variation-and-gene-conversions-within-the-bovine-nk-lysin-gene-family
#10
J Chen, M O Lee, J E Womack
In contrast to a single copy of the NK-lysin gene in humans and many other mammals, we previously identified a family of four expressed NK-lysin genes arising by tandem duplications on cattle chromosome 11. Here, we report two genetic variants in the bovine NK-lysin complex with potential importance in the bovine innate immune system. The first one is a 9-bp deletion causing a three-amino-acid deletion in the pro-region of the NK1 gene product. The second is a deletion of NK2B in some Holstein cattle, resulting in copy number variation that is in disequilibrium with a SNP from the bovine 770K HD SNP array...
December 7, 2016: Animal Genetics
https://www.readbyqxmd.com/read/27904941/trpa1-substance-p-histamine-and-5-hydroxytryptamine-interact-in-an-interdependent-way-to-induce-nociception
#11
Luana Fischer, Maria Isabel Lavoranti, Mariana de Oliveira Borges, Alana Farias Miksza, Natalia Fantin Sardi, Bruno Jacson Martynhak, Claudia H Tambeli, Carlos Amílcar Parada
BACKGROUND: Although TRPA1, SP, histamine and 5-hydroxytryptamine (5-HT) have recognized contribution to nociceptive mechanisms, little is known about how they interact with each other to mediate inflammatory pain in vivo. In this study we evaluated whether TRPA1, SP, histamine and 5-HT interact, in an interdependent way, to induce nociception in vivo. METHODS AND RESULTS: The subcutaneous injection of the TRPA1 agonist allyl isothiocyanate (AITC) into the rat's hind paw induced a dose-dependent and short lasting behavioral nociceptive response that was blocked by the co-administration of the TRPA1 antagonist, HC030031, or by the pretreatment with antisense ODN against TRPA1...
November 30, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27895167/pgi2-controls-pulmonary-nk-cells-that-prevent-airway-sensitization-to-house-dust-mite-allergen
#12
Bryan Simons, Maria E Ferrini, Sophia Carvalho, David J P Bassett, Zeina Jaffar, Kevan Roberts
In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2 IP receptor-deficient [IP(-/-)]) were compared with wild type (WT) mice. Surprisingly, IP(-/-) mice had increased numbers of pulmonary CD3(-)NK1.1(+)Ly49b(+) NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared with WT animals...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27889278/safety-and-efficacy-of-nepa-an-oral-fixed-combination-of-netupitant-and-palonosetron-in-older-patients
#13
Matti Aapro, Karin Jordan, Richard J Gralla, Giada Rizzi, Giorgia Rossi, Marco Palmas, Anna V Alyasova, Alla S Lisyanskaya, Snežana M Bošnjak, Paul J Hesketh
OBJECTIVES: Prevention of chemotherapy-induced nausea and vomiting is critical in older cancer patients. NEPA is an oral fixed combination of netupitant 300mg, a new NK1 receptor antagonist (RA), and palonosetron 0.5mg, a pharmacologically distinct 5-HT3 RA. This retrospective analysis evaluated the efficacy and safety of NEPA in older patients. METHODS: Patients aged ≥65 and ≥70years from one phase II and two phase III trials were considered. Chemotherapy-naive patients with malignant tumors were treated with anthracycline-cyclophosphamide (AC), non-AC-based moderately emetogenic chemotherapy (non-AC MEC), or highly emetogenic chemotherapy (HEC)...
November 23, 2016: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/27885469/nepa-a-fixed-oral-combination-of-netupitant-and-palonosetron-improves-control-of-chemotherapy-induced-nausea-and-vomiting-cinv-over-multiple-cycles-of-chemotherapy-results-of-a-randomized-double-blind-phase-3-trial-versus-oral-palonosetron
#14
Matti Aapro, Meinolf Karthaus, Lee Schwartzberg, Igor Bondarenko, Tomasz Sarosiek, Cristina Oprean, Servando Cardona-Huerta, Vincent Hansen, Giorgia Rossi, Giada Rizzi, Maria Elisa Borroni, Hope Rugo
PURPOSE: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study...
November 24, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27810232/potential-role-of-il-17-producing-cd4-cd8-double-negative-%C3%AE-%C3%AE-t-cells-in-psoriatic-skin-inflammation-in-a-tpa-induced-stat3c-transgenic-mouse-model
#15
Azumi Ueyama, Chihiro Imura, Yasuyuki Fusamae, Kenichiro Tsujii, Yoko Furue, Miwa Aoki, Minoru Suzuki, Tomohiko Okuda, Itsuki Oshima, Kiyoshi Yasui, Michitaka Shichijo, Mina Yamamoto
BACKGROUND: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders and is accompanied by erythematous scaly plaques. There is growing evidence that the IL-23/Th17 axis plays a critical role in development of the disease. It was recently shown that in addition to CD4(+) Th17 cells, various IL-17-producing cell subsets such as CD8(+) Tc17 cells, dermal γδ T cells, and innate lymphoid cells are also involved in the development of psoriatic inflammation in humans...
January 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27784644/mcrt-a-chimeric-peptide-based-on-morphiceptin-and-pfrtic-nh2-regulates-the-depressor-effects-induced-by-endokinin-a-b
#16
Jing Zhang, Chunbo He, Xiong Pi, Yan Wang, Lanxia Zhou, Shouliang Dong
The interactions of the chimeric peptide MCRT (YPFPFRTic-NH2), based on morphiceptin and neuropeptide FF derivative PFRTic-NH2, on the effects of endokinin A/B (EKA/B) on mean arterial blood pressure of the urethane-anaesthetized rat have been investigated in the absence and presence of tachykinin receptor antagonists, naloxone and NO synthase inhibitors. While MCRT produced dose dependent decreases in mean arterial pressure, in its presence only a small but statistically insignificant decreases in the magnitude and the time course of the depressor effect of EKA/B (10nmol/kg) were observed...
December 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27783671/nk-cd11c-cell-crosstalk-in-diabetes-enhances-il-6-mediated-inflammation-during-mycobacterium-tuberculosis-infection
#17
Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan Kumar Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27774091/microrna-7-deficiency-ameliorates-the-pathologies-of-acute-lung-injury-through-elevating-klf4
#18
Juanjuan Zhao, Chao Chen, Mengmeng Guo, Yijin Tao, PanPan Cui, Ya Zhou, Nalin Qin, Jing Zheng, Jidong Zhang, Lin Xu
Recent evidence showed that microRNA-7 (miR-7) played an important role in the pathologies of lung-related diseases. However, the potential role of miR-7 in acute lung injury (ALI) still remains poorly understood. Here, we assessed the effect of miR-7 deficiency on the pathology of ALI. We, first, found that the expression of miR-7 was upregulated in lung tissue in murine LPS-induced ALI model. Notably, we generated miR-7 knock down mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathologies of lung as evidenced by accelerated body weight recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and decreased number of BAL cells in ALI mice...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27757308/chemo-immunotherapy-mediates-durable-cure-of-orthotopic-kras-g12d-p53-pancreatic-ductal-adenocarcinoma
#19
Vanaja Konduri, Dali Li, Matthew M Halpert, Dan Liang, Zhengdong Liang, Yunyu Chen, William E Fisher, Silke Paust, Jonathan M Levitt, Qizhi Cathy Yao, William K Decker
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, exhibiting a five-year overall survival (OS) of only 7% despite aggressive standard of care. Recent advances in immunotherapy suggest potential application of immune-based treatment approaches to PDAC. To explore this concept further, we treated orthotopically established K-ras(G12D)/p53(-/-) PDAC tumors with gemcitabine and a cell-based vaccine previously shown to generate durable cell-mediated (TH1) immunity...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27744678/discovery-of-indazoles-as-potent-orally-active-dual-neurokinin-1-receptor-antagonists-and-serotonin-transporter-inhibitors-for-the-treatment-of-depression
#20
Andrew P Degnan, George O Tora, Hong Huang, David A Conlon, Carl D Davis, Umesh M Hanumegowda, Xiaoping Hou, Yi Hsiao, Joanna Hu, Rudolph Krause, Yu-Wen Li, Amy E Newton, Rick L Pieschl, Joseph Raybon, Thorsten Rosner, Jung-Hui Sun, Matthew T Taber, Sarah J Taylor, Michael K Wong, Huiping Zhang, Nicholas J Lodge, Joanne J Bronson, John E Macor, Kevin W Gillman
Combination studies of neurokinin 1 (NK1) receptor antagonists and serotonin-selective reuptake inhibitors (SSRIs) have shown promise in preclinical models of depression. Such a combination may offer important advantages over the current standard of care. Herein we describe the discovery and optimization of an indazole-based chemotype to provide a series of potent dual NK1 receptor antagonists/serotonin transporter (SERT) inhibitors to overcome issues of ion channel blockade. This effort culminated in the identification of compound 9, an analogue that demonstrated favorable oral bioavailability, excellent brain uptake, and robust in vivo efficacy in a validated depression model...
December 21, 2016: ACS Chemical Neuroscience
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