Free Shipping on orders over 50$

British Pound Sterling - GBP Euro - EUR US Dollar - USD (EUR)

Welcom to Gentaur Biotech Products!


Be the first to review this product

Availability: In stock


Quick Overview




Product Tags

Use spaces to separate tags. Use single quotes (') for phrases.

(1) Enteric murine ganglionitis induced by autoimmune CD8 T cells mimics human gastrointestinal dysmotility.[TOP]

Pubmed ID :30593823
Publication Date : //
Inflammatory bowel diseases frequently cause gastrointestinal dysmotility suggesting that they may also affect the enteric nervous system. So far, the precise mechanisms that lead to gastrointestinal dysmotility in inflammatory bowel diseases have not been elucidated. To determine the impact of CD8 T cells on gastrointestinal motility, transgenic mice expressing ovalbumin on enteric neurons were generated. In these mice, adoptive transfer of ovalbumin-specific OT-I CD8 T cells induced severe enteric ganglionitis. CD8 T cells homed to submucosal and myenteric plexus neurons, 60% of which were lost, clinically resulting in severely impaired gastrointestinal transition. Anti-interferon-γ treatment rescued neurons by preventing their up-regulation of MHC class I antigen, thus, preserving gut motility. These preclinical murine data translated well into human gastrointestinal dysmotility. In a series of 30 colonic biopsies from patients with gastrointestinal dysmotility, CD8 T cell-mediated ganglionitis was detected that was followed by severe loss of enteric neurons (74.8%). Together, the preclinical and clinical data support the concept that autoimmune CD8 T cells play an important pathogenetic role in gastrointestinal dysmotility and may destroy enteric neurons.

Authors : Sanchez-Ruiz Monica, Brunn Anna, Montesinos-Rongen Manuel, Rudroff Claudia, Hartmann Melanie, Schlüter Dirk, Pfitzer Gabriele, Deckert Martina,

(2) Critical role of C5a in sickle cell disease.[TOP]

Pubmed ID :30569594
Publication Date : //
Innate immune complement activation may contribute to sickle cell disease (SCD) pathogenesis. Ischemia-reperfusion physiology is a key component of the inflammatory and vaso-occlusive milieu in SCD and is associated with complement activation. C5a is an anaphylatoxin, a potent pro-inflammatory mediator that can activate leukocytes, platelets, and endothelial cells, all of which play a role in vaso-occlusion. We hypothesize that hypoxia-reoxygenation (H/R) in SCD mice activates complement, promoting inflammation and vaso-occlusion. At baseline and after H/R, sickle Townes-SS mice had increased C3 activation fragments and C5b-9 deposition in kidneys, livers and lungs and alternative pathway Bb fragments in plasma compared to control AA-mice. Activated complement promoted vaso-occlusion (microvascular stasis) in SS-mice; infusion of zymosan-activated, but not heat-inactivated serum, induced substantial vaso-occlusion in the skin venules of SS-mice. Infusion of recombinant C5a induced stasis in SS, but not AA-mice that was blocked by anti-C5a receptor (C5aR) IgG. C5a-mediated stasis was accompanied by inflammatory responses in SS-mice including NF-κB activation and increased expression of TLR4 and adhesion molecules VCAM-1, ICAM-1, and E-selectin in the liver. Anti-C5aR IgG blocked these inflammatory responses. Also, C5a rapidly up-regulated Weibel-Palade body P-selectin and von Willebrand factor on the surface of human umbilical vein endothelial cells in vitro and on vascular endothelium in vivo. In SS-mice, a blocking antibody to P-selectin inhibited C5a-induced stasis. Similarly, an antibody to C5 that blocks murine C5 cleavage or an antibody that blocks C5aR inhibited H/R-induced stasis in SS-mice. These results suggest that inhibition of C5a may be beneficial in SCD.

Authors : Vercellotti Gregory M, Dalmasso Agustin P, Schaid Terry R, Nguyen Julia, Chen Chunsheng, Ericson Marna E, Abdulla Fuad, Killeen Trevor, Lindorfer Margaret A, Taylor Ronald P, Belcher John D,

(3) The antiviral activity of rodent and lagomorph SERINC3 and SERINC5 is counteracted by known viral antagonists.[TOP]

Pubmed ID :30566072
Publication Date : //
A first step towards the development of a human immunodeficiency virus (HIV) animal model has been the identification and surmounting of species-specific barriers encountered by HIV along its replication cycle in cells from small animals. Serine incorporator proteins 3 (SERINC3) and 5 (SERINC5) were recently identified as restriction factors that reduce HIV-1 infectivity. Here, we compared the antiviral activity of SERINC3 and SERINC5 among mice, rats and rabbits, and their susceptibility to viral counteraction to their human counterparts. In the absence of viral antagonists, rodent and lagomorph SERINC3 and SERINC5 displayed anti-HIV activity in a similar range to human controls. Vesicular stomatitis virus G protein (VSV-G) pseudotyped virions were considerably less sensitive to restriction by all SERINC3/5 orthologs. Interestingly, HIV-1 Nef, murine leukemia virus (MLV) GlycoGag and equine infectious anemia virus (EIAV) S2 counteracted the antiviral activity of all SERINC3/5 orthologs with similar efficiency. Our results demonstrate that the antiviral activity of SERINC3/5 proteins is conserved in rodents and rabbits, and can be overcome by all three previously reported viral antagonists.

Authors : de Sousa-Pereira Patrícia, Abrantes Joana, Bauernfried Stefan, Pierini Virginia, Esteves Pedro José, Keppler Oliver T, Pizzato Massimo, Hornung Veit, Fackler Oliver T, Baldauf Hanna-Mari,

(4) GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis.[TOP]

Pubmed ID :30523250
Publication Date : //
Autoantibodies have been associated with autoimmune diseases. However, studies have identified autoantibodies in healthy donors (HD) who do not develop autoimmune disorders. Here we provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in HD compared to patients with systemic sclerosis, Alzheimer's disease, and ovarian cancer. Sex, age and pathological conditions affect autoantibody correlation and hierarchical clustering signatures, yet many of the correlations are shared across all groups, indicating alterations to homeostasis. Furthermore, we identify relationships between autoantibodies targeting structurally and functionally related molecules, such as vascular, neuronal or chemokine receptors. Finally, autoantibodies targeting the endothelin receptor type A (EDNRA) exhibit chemotactic activity, as demonstrated by neutrophil migration toward HD-IgG in an EDNRA-dependent manner and in the direction of IgG from EDNRA-immunized mice. Our data characterizing the in vivo signatures of anti-GPCR autoantibodies thus suggest that they are a physiological part of the immune system.

Authors : Cabral-Marques Otavio, Marques Alexandre, Giil Lasse Melvær, De Vito Roberta, Rademacher Judith, Günther Jeannine, Lange Tanja, Humrich Jens Y, Klapa Sebastian, Schinke Susanne, Schimke Lena F, Marschner Gabriele, Pitann Silke, Adler Sabine, Dechend Ralf, Müller Dominik N, Braicu Ioana, Sehouli Jalid, Schulze-Forster Kai, Trippel Tobias, Scheibenbogen Carmen, Staff Annetine, Mertens Peter R, Löbel Madlen, Mastroianni Justin, Plattfaut Corinna, Gieseler Frank, Dragun Duska, Engelhardt Barbara Elizabeth, Fernandez-Cabezudo Maria J, Ochs Hans D, Al-Ramadi Basel K, Lamprecht Peter, Mueller Antje, Heidecke Harald, Riemekasten Gabriela,

(5) is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice.[TOP]

Pubmed ID :30519364
Publication Date : //
Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus.

Authors : Sergi Domenico, Campbell Fiona M, Grant Christine, Morris Amanda C, Bachmair Eva-Maria, Koch Christiane, McLean Fiona H, Muller Aifric, Hoggard Nigel, de Roos Baukje, Porteiro Begona, Boekschoten Mark V, McGillicuddy Fiona C, Kahn Darcy, Nicol Phyllis, Benzler Jonas, Mayer Claus-Dieter, Drew Janice E, Roche Helen M, Muller Michael, Nogueiras Ruben, Dieguez Carlos, Tups Alexander, Williams Lynda M,

(6) Protective role of c-Jun N-terminal kinase-2 (JNK2) in ibuprofen-induced acute liver injury.[TOP]

Pubmed ID :30264435
Publication Date : //
Ibuprofen is a worldwide used non-steroidal anti-inflammatory drug which may cause acute liver injury (ALI) requiring liver transplantation. We aimed to unveil the molecular pathways involved in triggering ibuprofen-induced ALI, which, at present, remain elusive. First, we investigated activation of essential pathways in human liver sections of ibuprofen-induced ALI. Next, we assessed the cytotoxicity of ibuprofen in vitro and developed a novel murine model of ibuprofen intoxication. To assess the role of JNK, we used animals carrying constitutive deletion of c-Jun N-terminal kinase 1 (Jnk1 ) or Jnk2 (Jnk2 ) expression and included investigations using animals with hepatocyte-specific Jnk deletion either genetically (Jnk1 ) or by siRNA (siJnk2 ). We found in human and murine samples of ibuprofen-induced acute liver failure that JNK phosphorylation was increased in the cytoplasm of hepatocytes and other non-liver parenchymal cells (non-LPCs) compared with healthy tissue. In mice, ibuprofen intoxication resulted in a significantly stronger degree of liver injury compared with vehicle-treated controls as evidenced by serum transaminases, and hepatic histopathology. Next, we investigated molecular pathways. PKCα, AKT, JNK and RIPK1 were significantly increased 8 h after ibuprofen intoxication. Constitutive Jnk1 and Jnk2 deficient mice exhibited increased liver dysfunction compared to wild-type (WT) animals. Furthermore, siJnk2 animals showed a dramatic increase in biochemical markers of liver function, which correlated with significantly higher serum liver enzymes and worsened liver histology, and MAPK activation compared to Jnk1 or WT animals. In our study, cytoplasmic JNK activation in hepatocytes and other non-LPCs is a hallmark of human and murine ibuprofen-induced ALI. Functional in vivo analysis demonstrated a protective role of hepatocyte-specific Jnk2 during ibuprofen ALI. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Authors : Zoubek Miguel E, Woitok Marius M, Sydor Svenja, Nelson Leonard J, Bechmann Lars P, Lucena Maria I, Andrade Raul J, Bast Aalt, Koek Ger H, Trautwein Christian, Cubero Francisco J,

(7) Novel amide derivatives of 1,3-dimethyl-2,6-dioxopurin-7-yl-alkylcarboxylic acids as multifunctional TRPA1 antagonists and PDE4/7 inhibitors: A new approach for the treatment of pain.[TOP]

Pubmed ID :30245393
Publication Date : //
A series of novel amide derivatives of 1,3-dimethyl-2,6-dioxopurin-7-yl-alkylcarboxylic acids designed using a structure-based computational approach was synthesized and assayed to evaluate their ability to block human TRPA1 channel and inhibit PDE4B/7A activity. We identified compounds 16 and 27 which showed higher potency against TRPA1 compared to HC-030031. In turn, compound 36 was the most promising multifunctional TRPA1 antagonist and PDE4B/7A dual inhibitor with IC values in the range of that of the reference rolipram and BRL-50481, respectively. Compound 36 as a combined TRPA1/PDE4B/PDE7A ligand was characterized by a distinct binding mode in comparison to 16 and 27, in the given protein targets. The inhibition of both cAMP-specific PDE isoenzymes resulted in a strong anti-TNF-α effect of 36in vivo. Moreover, the potent anti-inflammatory and analgesic efficacy of 36 was observed in animal models of pain and inflammation (formalin test in mice and carrageenan-induced paw edema in rats). This compound also displayed significant antiallodynic properties in the early phase of chemotherapy-induced peripheral neuropathy in mice. In turn, the pure TRPA1 antagonists 16 and 27 revealed a statistically significant antiallodynic effect in the formalin test and in the von Frey test performed in both phases of oxaliplatin-induced allodynia. Antiallodynic activity of the test compounds 16, 27 and 36 was observed at a dose range comparable to that of the reference drug - pregabalin. In conclusion, the proposed approach of pain treatment based on the concomitant blocking of TRPA1 channel and PDE4B/7A inhibitory activity appears to be interesting research direction for the future search for novel analgesics.

Authors : Chłoń-Rzepa Grażyna, Ślusarczyk Marietta, Jankowska Agnieszka, Gawalska Alicja, Bucki Adam, Kołaczkowski Marcin, Świerczek Artur, Pociecha Krzysztof, Wyska Elżbieta, Zygmunt Małgorzata, Kazek Grzegorz, Sałat Kinga, Pawłowski Maciej,

(8) Novel antibodies against GPIbα inhibit pulmonary metastasis by affecting vWF-GPIbα interaction.[TOP]

Pubmed ID :30223883
Publication Date : //
Platelet glycoprotein Ibα (GPIbα) extracellular domain, which is part of the receptor complex GPIb-IX-V, plays an important role in tumor metastasis. However, the mechanism through which GPIbα participates in the metastatic process remains unclear. In addition, potential bleeding complication remains an obstacle for the clinical use of anti-platelet agents in cancer therapy.

Authors : Qi Yingxue, Chen Wenchun, Liang Xinyu, Xu Ke, Gu Xiangyu, Wu Fengying, Fan Xuemei, Ren Shengxiang, Liu Junling, Zhang Jun, Li Renhao, Liu Jianwen, Liang Xin,

(9) Selective Inhibition of ADAM28 Suppresses Lung Carcinoma Cell Growth and Metastasis.[TOP]

Pubmed ID :30190423
Publication Date : //
ADAM28 (a disintegrin and metalloproteinase 28) is overexpressed by carcinoma cells in non-small cell lung carcinomas (NSCLC) and plays an important role in cancer cell proliferation and metastasis by reactivation of insulin-like growth factor-1 (IGF-1) and escaping from von Willebrand factor (VWF)-induced apoptosis through digestion of IGF-binding protein-3 and VWF, respectively. To aim for new target therapy of NSCLC patients, we developed human neutralizing antibodies 211-12 and 211-14 against ADAM28, which showed IC values of 62.4 and 37.5 nmol/L, respectively. Antibody 211-14 recognized the junctional region between cysteine-rich domain and secreted-specific domain and showed a K value of 94.7 pmol/L for the epitope-containing peptide. This antibody detected monkey and human secreted-form ADAM28s, although it was not reactive with mouse membrane-anchored ADAM28m. Antibody 211-14 effectively inhibited IGF-1-stimulated cell proliferation of lung adenocarcinoma cell lines with ADAM28 expression, including PC-9 cells, and promoted VWF-induced cell death in these cell lines. In lung metastasis models, antibody 211-14 significantly reduced tumor growth and metastases of PC-9 cells and prolonged survivals in the antibody-treated mice compared with the control IgG-treated ones. Combination therapy of the antibody and docetaxel was more effective than that of bevacizumab and docetaxel and showed further elongation of survival time compared with monotherapy. No adverse effects were observed even after administration of 10-fold more than effective dose of anti-ADAM28 antibody to normal mice. Our data demonstrate that antibody 211-14 is a neutralizing antibody specific to ADAM28s and suggest that this antibody may be a useful treatment remedy for NSCLC patients. .

Authors : Mochizuki Satsuki, Shimoda Masayuki, Abe Hitoshi, Miyamae Yuka, Kuramoto Junko, Aramaki-Hattori Noriko, Ishii Ken, Ueno Hideki, Miyakoshi Akira, Kojoh Kanehisa, Okada Yasunori,

(10) Influence of Phosphatidylinositol-3-Kinase/Protein Kinase B-Mammalian Target of Rapamycin Signaling Pathway on the Neuropathic Pain Complicated by Nucleoside Reverse Transcriptase Inhibitors for the Treatment of HIV Infection.[TOP]

Pubmed ID :30058583
Publication Date : //
Nucleoside reverse transcriptase inhibitors (NRTIs) are the earliest and most commonly used anti-human immunodeficiency virus drugs and play an important role in high active antiretroviral therapy. However, NRTI drug therapy can cause peripheral neuropathic pain. In this study, we aimed to investigate the mechanisms of rapamycin on the pain sensitization of model mice by in vivo experiments to explore the effect of mammalian target of rapamycin (mTOR) in the pathogenesis of neuropathic pain caused by NRTIs.

Authors : Cheng Hao, Wu Liang-Yu,