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https://www.readbyqxmd.com/read/28544630/synthesis-admet-properties-and-biological-evaluation-of-benzothiazole-compounds-targeting-cxcr2
#1
Wesam E Mehanna, Tiangong Lu, Bikash Debnath, Deena S Lasheen, Rabah A T Serya, Khaled A Abouzid, Nouri Neamati
Herein, we describe the synthesis and biological evaluation of a series of novel benzothiazoles based on a diaryl urea scaffold previously reported in some allosteric CXCR2 inhibitors. From a library of 41 new compounds, 17 showed significant inhibition of CXCR2 with IC50 less than 10 M and selectivity over CXCR4. Our ADMET simulations suggest favorable drug-like properties for the active compounds. Importantly, we developed a predictive model that can distinguish active from inactive compounds and will serve as a valuable tool to guide the design of optimized compounds to be evaluated in preclinical models...
May 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28539339/mif-2-d-dt-enhances-proximal-tubular-cell-regeneration-through-slpi-and-atf4-dependent-mechanisms
#2
Akinobu Ochi, Dong Chen, Wibke Schulte, Lin Leng, Nickolas Gilbert Moeckel, Marta Piecychna, Luisa Averdunk, Christian Stoppe, Richard Bucala, Gilbert W Moeckel
Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions that is produced by several organs and cell types. Depending on the target cell and the inflammatory context, MIF can engage its two component receptor complex CD74 and CD44, and the chemokine receptors CXCR2/4. MIF is constitutively expressed in renal proximal tubular cells, stored in intracellular preformed pools and is released at a low rate. Recently a second MIF-like protein (i.e. MIF-2/D-DT) has been characterized in mammals...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28538177/chemokine-signaling-and-the-regulation-of-bidirectional-leukocyte-migration-in-interstitial-tissues
#3
Davalyn Powell, Sebastien Tauzin, Laurel E Hind, Qing Deng, David J Beebe, Anna Huttenlocher
Motile cells navigate through complex tissue environments that include both attractive and repulsive cues. In response to tissue wounding, neutrophils, primary cells of the innate immune response, exhibit bidirectional migration that is orchestrated by chemokines and their receptors. Although progress has been made in identifying signals that mediate the recruitment phase, the mechanisms that regulate neutrophil reverse migration remain largely unknown. Here, we visualize bidirectional neutrophil migration to sterile wounds in zebrafish larvae and identify specific roles for the chemokine receptors Cxcr1 and Cxcr2 in neutrophil recruitment to sterile injury and infection...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28533661/macrophage-inflammatory-protein-2-as-mediator-of-inflammation-in-acute-liver-injury
#4
REVIEW
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen
Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28529998/complement-c5a-receptor-is-the-key-initiator-of-neutrophil-adhesion-igniting-immune-complex-induced-arthritis
#5
Yoshishige Miyabe, Chie Miyabe, Thomas T Murooka, Edward Y Kim, Gail A Newton, Nancy D Kim, Bodduluri Haribabu, Francis W Luscinskas, Thorsten R Mempel, Andrew D Luster
The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC initiate and propagate neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28514506/human-adipose-derived-mesenchymal-stem-cell-secreted-cxcl1-and-cxcl8-facilitate-breast-tumor-growth-by-promoting-angiogenesis
#6
Yuan Wang, Junli Liu, Qingyuan Jiang, Jie Deng, Fen Xu, Xiaolei Chen, Fuyi Cheng, Yujing Zhang, Yunqi Yao, Zhemin Xia, Xia Xu, Xiaolan Su, Meijuan Huang, Lei Dai, Yang Yang, Shuang Zhang, Dechao Yu, Robert Chunhua Zhao, Yuquan Wei, Hongxin Deng
Autologous adipose tissue or adipose tissue with additive adipose-derived mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast cancer patients who undergo mastectomy. ADSCs play an important role in the angiogenesis and adipogenesis, which make it much better than other materials. However, ADSCs may promote residual tumor cells to proliferate or metastasize, and the mechanism is still not fully understood. In our present study, we demonstrated that hADSCs could facilitate tumor cells growth after co-injection with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but hADSCs showed limited effect on the growth of MDA-MB-231 BCCs...
May 17, 2017: Stem Cells
https://www.readbyqxmd.com/read/28484461/blockade-of-neutrophil-s-chemokine-receptors-cxcr1-2-abrogate-liver-damage-in-acute-on-chronic-liver-failure
#7
Arshi Khanam, Nirupma Trehanpati, Peggy Riese, Archana Rastogi, Carlos Alberto Guzman, Shiv Kumar Sarin
BACKGROUND: Neutrophils serve as critical players in the pathogenesis of liver diseases. Chemokine receptors CXCR1 and CXCR2 are required for neutrophil chemotaxis to the site of inflammation/injury and are crucial in hepatic inflammatory response. However, key mechanism of neutrophil-mediated liver injury in acute-on-chronic liver failure (ACLF) remains highly elusive; which could be targeted for the development of new therapeutic interventions. METHODS: To demonstrate the role of CXCR1/CXCR2-expressing neutrophils in hepatic injury, we investigated CXCR1/CXCR2 receptor expression in 17 hepatitis B virus-related ACLF patients in comparison to 42 chronic hepatitis B and 18 healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28481874/a-positive-crosstalk-between-cxcr4-and-cxcr2-promotes-gastric-cancer-metastasis
#8
Z Xiang, Z-J Zhou, G-K Xia, X-H Zhang, Z-W Wei, J-T Zhu, J Yu, W Chen, Y He, R E Schwarz, R A Brekken, N Awasthi, C-H Zhang
The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28458362/elucidation-of-distinct-roles-of-guinea-pig-cxcr1-and-cxcr2-in-neutrophil-migration-toward-il-8-and-gro%C3%AE-by-specific-antibodies
#9
Kento Tanaka, Tomomi Yoshitomi, Kazuki Hirahara
Chemokine receptors CXCR1 and CXCR2 are conserved between guinea pigs and humans, but the distinct role of each receptor in chemotactic responses of neutrophils against chemokine ligands has not been elucidated due in part to the lack of specific inhibitors against these receptors in guinea pigs. In this study, we investigated the roles of guinea pig CXCR1 and CXCR2 on neutrophils in chemotactic responses to guinea pig interleukin (IL)-8 and growth-regulated oncogene (GRO)α by using specific inhibitory antibodies against these receptors...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28455419/cxcl1-is-critical-for-pre-metastatic-niche-formation-and-metastasis-in-colorectal-cancer
#10
Dingzhi Wang, Haiyan Sun, Jie Wei, Bo Cen, Raymond N DuBois
Emerging evidence suggests that the primary tumor influences the development of supportive metastatic microenvironments, referred to as pre-metastatic niches, in certain distant organs before arrival of metastatic cells.  However, the mechanisms underlying the contributions of the primary tumor to pre-metastatic niche formation are not fully understood.  Here we demonstrate that colorectal carcinoma cells secrete VEGF-A, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor.  Elevation of CXCL1 in pre-metastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a pre-metastatic niche that ultimately promoted liver metastases...
April 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28450382/an-adaptive-signaling-network-in-melanoma-inflammatory-niches-confers-tolerance-to-mapk-signaling-inhibition
#11
Helen L Young, Emily J Rowling, Mattia Bugatti, Emanuele Giurisato, Nadia Luheshi, Imanol Arozarena, Juan-Carlos Acosta, Jivko Kamarashev, Dennie T Frederick, Zachary A Cooper, Alexandre Reuben, Jesus Gil, Keith T Flaherty, Jennifer A Wargo, William Vermi, Michael P Smith, Claudia Wellbrock, Adam Hurlstone
Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound clinical responses in advanced cutaneous melanoma, but complete remissions are frustrated by the development of acquired resistance. Before resistance emerges, adaptive responses establish a mutation-independent drug tolerance. Antagonizing these adaptive responses could improve drug effects, thereby thwarting the emergence of acquired resistance. In this study, we reveal that inflammatory niches consisting of tumor-associated macrophages and fibroblasts contribute to treatment tolerance through a cytokine-signaling network that involves macrophage-derived IL-1β and fibroblast-derived CXCR2 ligands...
April 27, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28446981/role-of-cxc-group-chemokines-in-lung-cancer-development-and-progression
#12
Artjoms Spaks
BACKGROUND: Clinical and translational research on lung cancer patients undergoing surgical treatment can provide valuable scientific data and unique opportunity to study tumor microenvironment. CXC chemokines, which are members of a big family of cytokines, are undoubtedly involved in tumor growth regulation and metastasizing pathways. For better understanding of CXC chemokine involvement in the process of carcinogenesis we have studied the cohort of early stage non-small cell lung cancer patients undergoing surgery with curative intent...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28430080/generation-and-characterization-of-inhibitory-antibodies-specific-to-guinea-pig-cxcr1-and-cxcr2
#13
Kento Tanaka, Chigusa Yoshimura, Tetsuo Shiina, Tomoko Terauchi, Tomomi Yoshitomi, Kazuki Hirahara
CXCR1 and CXCR2 are chemokine receptors that have different selectivity of chemokine ligands, but the distinct role of each receptor is not clearly understood. This is due to the absence of specific inhibitors in guinea pigs, which are the appropriate species for investigation of CXCR1 and CXCR2 because of their functional similarity to humans. In this study, we generated and evaluated monoclonal antibodies that specifically bound to guinea pig CXCR1 (gpCXCR1) and guinea pig CXCR2 (gpCXCR2) for acquisition of specific inhibitors...
April 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28430079/monoclonal-antibody-abcr1-against-guinea-pig-cxcr1-and-monoclonal-antibody-abcr2-against-guinea-pig-cxcr2
#14
(no author information available yet)
No abstract text is available yet for this article.
April 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28429504/induced-pluripotent-stem-cells-reduce-neutrophil-chemotaxis-via-activating-grk2-in-endotoxin-induced-acute-lung-injury
#15
Vincent Yi-Fong Su, Shih-Hwa Chiou, Chi-Shiuan Lin, Wei-Chih Chen, Wen-Kuang Yu, Yen-Wen Chen, Cheng-Yu Chen, Kuang-Yao Yang
BACKGROUND AND OBJECTIVE: We investigated the effect of induced pluripotent stem cells (iPSCs) in moderating neutrophil chemotaxis in endotoxin-induced acute lung injury (ALI). METHODS: Male C57BL/6 mice at 8-12 weeks of age were studied. Murine iPSCs were delivered through the tail veins of mice 4 h after intratracheal instillation of endotoxin. Lung histopathological findings, neutrophil counts in peripheral blood and bronchoalveolar lavage fluid (BALF), bone marrow (BM) cell distribution, expression of chemokine receptors and regulatory signalling pathways were analysed after 24 h...
April 21, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28423567/cxcr1-2-pathways-in-paclitaxel-induced-neuropathic-pain
#16
Laura Brandolini, Elisabetta Benedetti, Pier Adelchi Ruffini, Roberto Russo, Loredana Cristiano, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Antonio Giordano, Marcello Allegretti, Annamaria Cimini
Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain that represents a frequent and serious consequence of chemotherapy agents. Over the last years, significant progress has been achieved in elucidating the underlying pathogenesis of CIPN. The interference of taxanes with microtubule has been proposed as a mechanism that leads to altered axonal transport and to permanent neurological damages. The inflammatory process activated by chemotherapeutic agents has been considered as a potential trigger of nociceptive process in CIPN...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423359/epithelial-mesenchymal-transition-induced-by-gro-%C3%AE-cxcr2-promotes-bladder-cancer-recurrence-after-intravesical-chemotherapy
#17
Lu Chen, Xiu-Wu Pan, Hai Huang, Yi Gao, Qi-Wei Yang, Lin-Hui Wang, Xin-Gang Cui, Dan-Feng Xu
Non-muscle invasive bladder cancers (NMIBC) are typically treated by transurethral resection with intravesical chemotherapy. However, the post-therapeutic incidence of tumor recurrence and progression to muscle invasive disease is high, and the underlying mechanism(s) remains unknown. In this study, we observed that recurrent bladder cancer cells exhibit a mesenchymal phenotype, which is initiated by the autocrine GRO-α signaling. Mechanically, the chemotherapeutic drug epidoxorubicin induces GRO-α expression in primary bladder cancer cells at G1/S phase via p38-dependent activation of NF-κB...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420714/pancreatic-islet-inflammation-an-emerging-role-for-chemokines
#18
J Jason Collier, Tim E Sparer, Michael D Karlstad, Susan J Burke
Both Type 1 and Type 2 diabetes exhibit features of inflammation associated with alterations in pancreatic islet function and mass. These immunological disruptions, if unresolved, contribute to the overall pathogenesis of disease onset. This review presents the emerging role of pancreatic islet chemokine production as a critical factor regulating immune cell entry into pancreatic tissue as well as an important facilitator of changes in tissue resident leukocyte activity. Signaling through two specific chemokine receptors (i...
April 18, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28418782/knockdown-of-il-8-provoked-premature-senescence-of-placenta-derived-mesenchymal-stem-cells
#19
Juan-Juan Li, Feng-Xia Ma, You-Wei Wang, Fang Chen, Shi-Hong Lu, Ying Chi, Wen-Jing Du, Bao-Quan Song, Liang-Ding Hu, Hu Chen, Zhong-Chao Han
Mesenchymal stem cells (MSCs) have shown promise for use in cell therapy, and due to their tumor tropism can serve as vehicles for delivering therapeutic agents to tumor sites. Because interleukin-8 (IL-8) is known to mediate the protumor effect of MSCs, elimination of IL-8 secretion by MSCs may enhance their safety for use in cancer gene therapy. However, little is known concerning the effect of endogenously secreted IL-8 on MSCs. We performed studies using placenta-derived MSCs (PMSCs) to determine whether knockdown of IL-8 would influence their biological activity...
April 18, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28416308/implantation-of-endothelial-cells-with-mesenchymal-stem-cells-accelerates-dental-pulp-tissue-regeneration-healing-in-pulpotomized-rat-molars
#20
Yukiko Sueyama, Tomoatsu Kaneko, Takafumi Ito, Reika Kaneko, Takashi Okiji
INTRODUCTION: This study aimed to examine whether the implantation of mesenchymal stem cells (MSCs) with endothelial cells (ECs) accelerates pulp tissue regeneration/healing and induces dentin bridge formation in a rat model of molar coronal pulp regeneration. METHODS: The maxillary first molars of Wistar rats were subjected to pulpotomy. Then, pulp chambers were implanted with biodegradable hydrogel-made scaffolds carrying MSCs together or without dermal microvascular ECs, and the cavities were sealed with mineral trioxide aggregate...
April 14, 2017: Journal of Endodontics
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