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Akira Inoue, Tsunekazu Mizushima, Xin Wu, Daisuke Okuzaki, Nanami Kambara, Sho Ishikawa, Jiaqi Wang, Yamin Qian, Haruka Hirose, Yuhki Yokoyama, Ryo Ikeshima, Masayuki Hiraki, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto
We previously demonstrated that miR-29b-3p is a hopeful microRNA (miRNA)-based therapies against colorectal cancer (CRC). In this study, we aimed to clarify a value of miR-29b-1-5p as a next generation treatment, especially for KRAS mutant CRC. RT-PCR assay showed that expression of miR-29b-3p was high and its partner strand, miR-29b-1-5p level was only negligible in clinical CRC samples. Mimic-miR-29b-1-5p significantly inhibited proliferation of KRAS mutant CRC cell lines DLD1 and SW480 and KRAS wild type HT29 cells...
March 15, 2018: Molecular Cancer Therapeutics
Pierre Paradis, Ernesto L Schiffrin
No abstract text is available yet for this article.
March 8, 2018: European Heart Journal
Kendra C Foley, Michael I Nishimura, Tamson V Moore
Immunotherapy is a promising method of treatment for a number of cancers. Many of the curative results have been seen specifically in advanced-stage melanoma. Despite this, single-agent therapies are only successful in a small percentage of patients, and relapse is very common. As chemotherapy is becoming a thing of the past for treatment of melanoma, the combination of cellular therapies with immunotherapies appears to be on the rise in in-vivo models and in clinical trials. These forms of therapies include tumor-infiltrating lymphocytes, T-cell receptor, or chimeric antigen receptor-modified T cells, cytokines [interleukin (IL-2), IL-15, IL-12, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-α, interferon-α, interferon-γ], antibodies (αPD-1, αPD-L1, αTIM-3, αOX40, αCTLA-4, αLAG-3), dendritic cell-based vaccines, and chemokines (CXCR2)...
March 8, 2018: Melanoma Research
Wenying Zhang, Qiongwei Wu, Chao Wang, Longtao Yang, Ping Liu, Chengbin Ma
Upregulation of A-kinase-interacting protein 1 (AKIP1) has been observed in breast and esophageal cancers, indicating that AKIP1 may be a potent oncogenic protein. However, the role of AKIP1 in cervical cancer still remains unknown. This study aimed to explore the role of AKIP1 in cervical cancer and to investigate the underlying mechanism of AKIP1 in tumor growth. Expression of AKIP1 in cervical cancer cells was determined by qRT-PCR and western blotting. Cell-Light EdU and colony formation assays were used to determine cell proliferation...
March 8, 2018: Molecular and Cellular Biochemistry
Ciarán S Ó Léime, Alan E Hoban, Cara M Hueston, Roman Stilling, Gerard Moloney, John F Cryan, Yvonne M Nolan
TLX is an orphan nuclear receptor highly expressed within neural progenitor cells (NPCs) in the hippocampus where is regulates proliferation. Inflammation has been shown to have negative effects on hippocampal function as well as on NPC proliferation. Specifically, the pro-inflammatory cytokine IL-1β has been shown to suppress NPC proliferation as well as TLX expression in the hippocampus. However, it is unknown whether TLX itself is involved in regulating the inflammatory response in the hippocampus. To explore the role of TLX in inflammation, we assessed changes in the transcriptional landscape of the hippocampus of TLX knockout mice (TLX-/- ) compared to wildtype (WT) littermate controls with and without intrahippocampal injection of IL-1β using a whole transcriptome RNA sequencing approach...
March 5, 2018: Brain, Behavior, and Immunity
Lin Zhou, Yahui Hu, Chengyuan Li, Yunyi Yan, Luyao Ao, Boyang Yu, Weirong Fang, Jihua Liu, Yunman Li
Vincristine is a commonly used chemotherapeutic drug that can produce painful peripheral neuropathy. The chemokine (C-X-C motif) ligand 1 (CXCL1) and its receptor chemokine (C-X-C motif) receptor 2 (CXCR2) may mediate the resolution of this inflammation. In this study, we investigated whether and how CXCL1 contributes to vincristine-induced pain and the underlying mechanisms of levo-corydalmine (l-CDL, a tetrahydroprotoberberine). Oxycodone hydrochloride (a semisynthetic opioid analgesic) was used as positive control in vivo experiments...
March 5, 2018: Neuropharmacology
Rosa Mistica C Ignacio, Yuan-Lin Dong, Syeda M Kabir, Hyeongjwa Choi, Eun-Sook Lee, Andrew J Wilson, Alicia Beeghly-Fadiel, Margaret M Whalen, Deok-Soo Son
Ovarian cancer (OC) has the highest rate of mortality among gynecological malignancy. Chemokine receptor CXCR2 in OC is associated with poor outcomes. However, the mechanisms by which CXCR2 regulates OC proliferation remain poorly understood. We generated CXCR2-positive cells from parental p53 wild-type (WT), mutant and null OC cells, and assessed the roles of CXCR2 on proliferation of OC cells in p53-dependent and independent manner. CXCR2 promoted cell growth rate: p53WT > mutant = null cells. Nutlin-3, a p53 stabilizer, inhibited cell proliferation in p53WT cells, but had little effect in p53-mutant or null cells, indicating p53-dependence of CXCR2-mediated proliferation...
February 9, 2018: Oncotarget
Lei Wang, Yun-Long Zhang, Qiu-Yue Lin, Yu Liu, Xu-Min Guan, Xiao-Lei Ma, Hua-Jun Cao, Ying Liu, Jie Bai, Yun-Long Xia, Jie Du, Hui-Hua Li
Aims: Chemokine-mediated monocyte infiltration into the damaged heart represents an initial step in inflammation during cardiac remodelling. Our recent study demonstrates a central role for chemokine receptor CXCR2 in monocyte recruitment and hypertension; however, the role of chemokine CXCL1 and its receptor CXCR2 in angiotensin II (Ang II)-induced cardiac remodelling remain unknown. Methods and results: Angiotensin II (1000 ng kg-1 min-1) was administrated to wild-type (WT) mice treated with CXCL1 neutralizing antibody or CXCR2 inhibitor SB265610, knockout (CXCR2 KO) or bone marrow (BM) reconstituted chimeric mice for 14 days...
March 5, 2018: European Heart Journal
Okan W Bastian, Mikolaj H Mrozek, Marco Raaben, Luke P H Leenen, Leo Koenderman, Taco J Blokhuis
A controlled local inflammatory response is essential for adequate fracture healing. However, the current literature suggests that local and systemic hyper-inflammatory conditions after major trauma induce increased influx of neutrophils into the fracture hematoma (FH) and impair bone regeneration. Inhibiting neutrophil chemotaxis towards the FH without compromising the hosts' defense may therefore be a target of future therapies that prevent impairment of fracture healing after major trauma. We investigated whether chemotaxis of neutrophils towards the FH could be studied in vitro...
March 6, 2018: Inflammation
Shinji Okano, Kareem Abu-Elmagd, Danielle D Kish, Karen Keslar, William M Baldwin, Robert L Fairchild, Masato Fujiki, Ajai Khanna, Mohammed Osman, Guilherme Costa, John Fung, Charles Miller, Hiroto Kayashima, Koji Hashimoto
Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33+ CD11b+ lineage(CD3/CD56/CD19)- HLA-DR-/low cells with 3 subsets, CD14- CD15- (e-MDSC), CD14+ CD15- (M-MDSC), and CD14- CD15+ (PMN-MDSC), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs following ITx; among MDSC subsets, M-MDSC numbers were maintained at high level after 2 months following ITx...
March 6, 2018: American Journal of Transplantation
Mingo Ming-Ho Yung, Hermit Wai-Man Tang, Patty Chun-Hui Cai, Thomas Ho-Yin Leung, Siew-Fei Ngu, Karen Kar-Loen Chan, Dakang Xu, Huijuan Yang, Hextan Yuen-Sheung Ngan, David Wai Chan
Intraperitoneal metastasis is a common occurrence and is usually involved in the poor prognosis of ovarian cancer. Its specific metastatic pattern implies that certain indispensable microenvironmental factors secreted in the peritoneal cavity can direct metastatic ovarian cancer cells to permissive niches for secondary lesion formation. However, the underlying molecular mechanisms are ill defined. Herein, we report that GRO-α and IL-8 are predominately upregulated in culture media derived from either normal or cancerous omenta and are associated with increased ovarian cancer aggressiveness...
2018: Theranostics
Yang Zhao, Xiao-Fei Shen, Ke Cao, Jie Ding, Xing Kang, Wen-Xian Guan, Yi-Tao Ding, Bao-Rui Liu, Jun-Feng Du
How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro . However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance...
2018: Frontiers in Immunology
Weiyang Dai, Wenmin Chen, Bikash Debnath, Wu Yong, Nouri Neamati
Herein, we describe the synthesis and structure-activity relationship of 3-aminocyclohex-2-en-1-one derivatives as novel CXCR2 antagonists. Thirteen out of 44 derivatives inhibit CXCR2 down-stream signaling in a Tango assay specific for CXCR2 with IC50 values less than 10 µM. In silico ADMET prediction suggests that all active compounds possess drug-like properties. None of these compounds show cytotoxicity, suggesting their potential application in inflammatory mediated diseases. A structure-activity relationship (SAR) map has been generated to gain better understanding of their binding mechanism to guide further optimization of these new CXCR2 antagonists...
February 28, 2018: ChemMedChem
Dong Cui, Yongfu Zhao, Jingchao Xu
Initiation of epithelial-to-mesenchymal transition (EMT) is common in papillary thyroid carcinoma (PTC) and may contribute to its metastasis. Aims of the present study are to investigate whether and how the C-X-C motif chemokine ligand (CXCL)-5/C-X-C motif receptor 2 (CXCR2) axis affects PTC metastasis, with a focus on the EMT process. Herein, two PTC cell lines, KTC-1 and B-CPAP cells, identified as CXCR2-positive cells were used as the cell model. We found that a 24-h stimulation of 1 or 10 nM recombinant human CXCL5 (rhCXCL5) enhanced the migration and invasion of both KTC-1 and B-CPAP cells without affecting their proliferation...
February 19, 2018: Biochimie
Tao Zhang, Juhua Zhou, Gene Chi Wai Man, Kam Tong Leung, Bo Liang, Bo Xiao, Xinting Ma, Shaoyan Huang, Huaxiang Huang, Venkatesh L Hegde, Yin Zhong, Yanmin Li, Grace Wing Shan Kong, Alice KaWah Yiu, Joseph Kwong, Pak Cheung Ng, Prakash S Nagarkatti, Mitzi Nagarkatti, Chi Chiu Wang
Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically-induced endometriosis. Majority of MDSCs were granulocytic, produced ROS and arginase, and suppressed T cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice...
February 20, 2018: European Journal of Immunology
Zongshan Shen, Jiancheng Wang, Qiting Huang, Yue Shi, Zhewei Wei, Xiaoran Zhang, Yuan Qiu, Min Zhang, Yi Wang, Wei Qin, Shuheng Huang, Yinong Huang, Xin Liu, Kai Xia, Xinchun Zhang, Zhengmei Lin
Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting...
February 14, 2018: Cell Death & Disease
Zheng Liu, Fei Yang, Hao Zheng, Zhan Fan, Sha Qiao, Lei Liu, Juan Tao, Qingming Luo, Zhihong Zhang
It remains unclear how monocytes are mobilized to amplify inflammatory reactions in T cell-mediated adaptive immunity. Here, we investigate dynamic cellular events in the cascade of inflammatory responses through intravital imaging of a multicolor-labeled murine contact hypersensitivity (CHS) model. We found that monocytes formed clusters around hair follicles in the CHS model. In this process, effector T cells encountered dendritic cells under regions of monocyte clusters and secreted IFN-γ, which mobilizes CCR2-dependent monocyte interstitial migration and CXCR2-dependent monocyte cluster formation...
January 31, 2018: Journal of Investigative Dermatology
Hongfu Lu, Ting Yang, Zhongmiao Xu, Xichen Lin, Qian Ding, Yueting Zhang, Xin Cai, Kelly Dong, Sophie Gong, Wei Zhang, Metul Patel, Royston C B Copley, Jianing Xiang, Xiaoming Guan, Paul Wren, Feng Ren
CXCR2 has emerged as a therapeutic target for not only peripheral inflammatory diseases but also neurological abnormalities in the central nervous system (CNS). Herein, we describe the discovery of a novel 1-cyclopentenyl-3-phenylurea series as potent and CNS penetrant CXCR2 antagonists. Extensive SAR studies, wherein molecules' property forecast index (PFI) was carefully optimized for overall balanced developability profiles, led to the discovery of the advanced lead compound 68 with a desirable PFI. Compound 68 demonstrated good in vitro pharmacology with excellent selectivity over CXCR1 and other chemokine receptors...
February 6, 2018: Journal of Medicinal Chemistry
Liam Chung, Erik Thiele Orberg, Abby L Geis, June L Chan, Kai Fu, Christina E DeStefano Shields, Christine M Dejea, Payam Fathi, Jie Chen, Benjamin B Finard, Ada J Tam, Florencia M McAllister, Hongni Fan, Xinqun Wu, Sudipto Ganguly, Andriana Lebid, Paul Metz, Sara W Van Meerbeke, David L Huso, Elizabeth C Wick, Drew M Pardoll, Fengyi Wan, Shaoguang Wu, Cynthia L Sears, Franck Housseau
Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using ApcMin mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis...
February 1, 2018: Cell Host & Microbe
Yuh-Feng Lin, Tsung-Ta Liu, Chou-Hui Hu, Chun-Chi Chen, Jia-Yi Wang
Despite growing evidence that cytokines and chemokines are expressed in humans and rats after heat stress, the cellular mechanisms underlying the effects on the brain after heatstroke (HS) are not fully understood. In this study, we observed time course changes of chemokines in rat brain tissues and elucidated what kinds of cortical cells were affected after HS. Male SD rats were anesthetized and randomly separated into two groups as follows: (a) normothermic sham and (b) HS rats. Rats were sacrificed at different time points (0, 1, 3, 6, and 12h after heat exposure, n=5 in each group) to the end of the experiment in order to extract the mRNA/proteins of cortical tissues...
January 29, 2018: Journal of Neuroimmunology
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