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Thi Thinh Nguyen, Trong Thuan Ung, Shinan Li, Sen Lian, Yong Xia, Sun Young Park, Young Do Jung
Metformin, an inexpensive, well-tolerated oral agent that is a commonly used first-line treatment for type 2 diabetes, has become the focus of intense research as a potential anticancer agent. In this study, we describe the inhibitory effect of metformin in interleukin 8 (IL-8) upregulation by lithocholic acid (LCA) in HCT116 colorectal cancer (CRC) cells. Pharmacological inhibition studies indicated that reactive oxygen species (ROS) were involved in LCA-induced IL-8 upregulation through activation of the transcription factor NF-κB...
February 14, 2019: Scientific Reports
Shan Su, Xueqin Sun, Qinghua Zhang, Zhe Zhang, Ju Chen
Ovarian cancer (OC) is one of prevalent tumors and this study aimed to explore CCL20's effects on doxorubicin resistance of OC and related mechanisms. Doxorubicin-resistant SKOV3 DR cells were established from SKOV3 cells via 6-month continuous exposure to gradient concentrations of doxorubicin. Quantitative PCR and Western blot assay showed that SKOV3 DR cells had higher level of CCL20 than SKOV3 cells, and doxorubicin upregulated CCL20 expression in SKOV3 cells. MTT and cell count assay found that CCL20 overexpression plasmid enhanced doxorubicin resistance of SKOV3 and OVCA433 cells compared to empty vector, as shown by the increase in cell viability...
2019: Cell Structure and Function
Yuejun Wang, Yunsong Liu, Min Zhang, Longwei Lv, Xiao Zhang, Ping Zhang, Yongsheng Zhou
BACKGROUND: Tissue inflammation is an important problem in the field of human adipose-derived stem cell (ASC)-based therapeutic bone regeneration. Many studies indicate that inflammatory cytokines are disadvantageous for osteogenic differentiation and bone formation. Therefore, overcoming inflammation would be greatly beneficial in promoting ASC-mediated bone regeneration. The present study aims to investigate the potential anti-inflammatory role of Prostaglandin G/H synthase 1 (PTGS1) during the osteogenic differentiation of ASCs...
February 13, 2019: Stem Cell Research & Therapy
G Kanigur Sultuybek, T Soydas, G Yenmis
Aging can be defined as the progressive failure of repair and maintenance systems with a consequent accumulation of cellular damage in nucleic acids, proteins, and lipids. These various types of damage promote aging by driving cellular senescence and apoptosis. NF-kB (nuclear factor-kappa B) pathway is one of the key mediators of aging and this pathway is activated by genotoxic, oxidative and inflammatory stress, and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell cycle progression, and inflammation...
February 12, 2019: Clinical and Experimental Pharmacology & Physiology
Anny-Claude Luissint, Holly C Williams, Wooki Kim, Sven Flemming, Veronica Azcutia, Roland S Hilgarth, Monique N O' Leary, Timothy L Denning, Asma Nusrat, Charles A Parkos
Junctional adhesion molecule-A (JAM-A) is a transmembrane glycoprotein expressed on leukocytes, endothelia, and epithelia that regulates biological processes including barrier function and immune responses. While JAM-A has been reported to facilitate tissue infiltration of leukocytes under inflammatory conditions, the contributions of leukocyte-expressed JAM-A in vivo remain unresolved. We investigated the role of leukocyte-expressed JAM-A in acute peritonitis induced by zymosan, lipopolysaccharide (LPS), or TNFα using mice with selective loss of JAM-A in myelomonocytic cells (LysM-Cre;Jam-afl/fl )...
February 11, 2019: Mucosal Immunology
Jian Yang, Yuqi Guo, Cuijie Lu, Ruohan Zhang, Yaoyu Wang, Liang Luo, Yanli Zhang, Catherine H Chu, Katherine J Wang, Sabrine Obbad, Wenbo Yan, Xin Li
Prostate cancer (PCa) initiation and progression requires activation of numerous oncogenic signaling pathways. Nuclear-cytoplasmic transport of oncogenic factors is mediated by Karyopherin proteins during cell transformation. However, the role of nuclear transporter proteins in PCa progression has not been well defined. Here, we report that the KPNB1, a key member of Karyopherin beta subunits, is highly expressed in advanced prostate cancers. Further study showed that targeting KPNB1 suppressed the proliferation of prostate cancer cells...
February 11, 2019: Oncogene
Jonathan J Cho, Zhiwei Xu, Upasana Parthasarathy, Theodore T Drashansky, Eric Y Helm, Ashley N Zuniga, Kyle J Lorentsen, Samira Mansouri, Joshua Y Cho, Mariola J Edelmann, Duc M Duong, Torben Gehring, Thomas Seeholzer, Daniel Krappmann, Mohammad N Uddin, Danielle Califano, Rejean L Wang, Lei Jin, Hongmin Li, Dongwen Lv, Daohong Zhou, Liang Zhou, Dorina Avram
Polyubiquitination promotes proteasomal degradation, or signaling and localization, of targeted proteins. Here we show that the E3 ubiquitin ligase Hectd3 is necessary for pathogenic Th17 cell generation in experimental autoimmune encephalomyelitis (EAE), a mouse model for human multiple sclerosis. Hectd3-deficient mice have lower EAE severity, reduced Th17 program and inefficient Th17 cell differentiation. However, Stat3, but not RORγt, has decreased polyubiquitination, as well as diminished tyrosine-705 activating phosphorylation...
February 11, 2019: Nature Communications
Wei Wang, Nicole M Chapman, Bo Zhang, Mingqi Li, Meiyun Fan, R Nicholas Laribee, M Raza Zaidi, Lawrence M Pfeffer, Hongbo Chi, Zhao-Hui Wu
Solar ultraviolet radiation (UVR) suppresses skin immunity, which facilitates initiation of skin lesions and establishment of tumors by promoting immune evasion. It is unclear whether immune checkpoints are involved in the modulation of skin immunity by UVR. Here we report that UVR exposure significantly increased expression of immune checkpoint molecule PD-L1 in melanoma cells. The damage-associated molecular patterns molecule HMGB1 was secreted by melanocytes and keratinocytes upon UVR, which subsequently activated the receptor for advanced glycation endproducts (RAGE) receptor to promote NF-kB- and IRF3-dependent transcription of PD-L1 in melanocytes...
February 8, 2019: Cancer Research
Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Kyu Chang Won
Altered metabolism is implicated in the pathogenesis of beta-cell failure in type 2 diabetes (T2D). Plasma and tissue levels of ceramide species play positive roles in inflammatory and oxidative stress responses in T2D. However, oxidative targets and mechanisms underlying ceramide signaling are unclear. We investigated the role of CD36-dependent redoxosome (redox-active endosome), a membrane-based signaling agent, in ceramide-induced beta-cell dysfunction and failure. Exposure of beta cells to C2-ceramide (N-acetyl-sphingosine) induced a CD36-dependent non-receptor tyrosine kinase Src-mediated redoxosome (Vav2-Rac1-NOX) formation...
February 5, 2019: Free Radical Biology & Medicine
Islamy Rahma Hutami, Eiji Tanaka, Takashi Izawa
Rheumatoid arthritis (RA) mainly affects various joints of the body, including the temporomandibular joint (TMJ), and it involves an infiltration of autoantibodies and inflammatory leukocytes into articular tissues and the synovium. Initially, the synovial lining tissue becomes engaged with several kinds of infiltrating cells, including osteoclasts, macrophages, lymphocytes, and plasma cells. Eventually, bone degradation occurs. In order to elucidate the best therapy for RA, a comprehensive study of RA pathogenesis needs to be completed...
November 2019: Japanese Dental Science Review
Huqun Li, Shiyong Peng, Shihong Li, Shouqing Liu, Yifan Lv, Ni Yang, Liangyu Yu, Ya-Hui Deng, Zhongjian Zhang, Maosheng Fang, Yunxiang Huo, Ying Chen, Taohua Sun, Weiyong Li
Olanzapine is a second-generation anti-psychotic drug used to prevent neuroinflammation in patients with schizophrenia. However, the long-term administration of olanzapine leads to insulin resistance (IR); the mechanisms of this effect remains poorly understood. Using cellular and rodent models of IR induced by olanzapine, we found that chronic olanzapine treatment induces differential inflammatory cytokine reactions in peripheral adipose and the central nervous system. Long-term treatment of olanzapine caused metabolic symptoms, including IR, by markedly elevating the plasma levels of pro-inflammatory cytokines, including IL-1ß, IL-6, IL-8 and TNFα; these findings are consistent with observations from schizophrenia patients chronically treated with olanzapine...
February 7, 2019: Scientific Reports
Xiaotong Zhang, Xi Liu, Zhifei Jing, Jianbin Bi, Zeliang Li, Xiankui Liu, Jun Li, Zhenhua Li, Zhe Zhang, Chuize Kong
Accumulating evidence shows that circular RNAs (circRNAs) function as microRNA sponges that regulate gene expression in the progression of human cancers. However, the roles of circRNAs and functional miRNA sponges in bladder cancer (BC) remain largely unknown. In the present study, we applied bioinformatics methods and hypothesised that miR-146b may target the 3'-untranslated region (UTR) of CARMA3 mRNA and circINTS4 may serve as a sponge for miR-146b in BC tumorigenesis. Expression of circINTS4 was significantly increased in miR-146b-downregulated BC tissues and cell lines compared to adjacent normal tissues...
February 6, 2019: Cancer Gene Therapy
Majid Ahmad Ganaie, Abdulaziz Al Saeedan, Hassan Madhkali, Basit Lateef Jan, Tanvir Khatlani, Ishfaq Ahmad Sheikh, Muneeb U Rehman, Khalida Wani
Colorectal cancer is one of the most common cancers worldwide. Development of naturally occurring inexpensive and safe alternatives can be effective in suppressing colon related proliferations. Zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one), a polyphenolic alkanone of ginger, has massive pharmacological properties and thus can be used as promising candidate against various ailments. In the current study, we aimed at demonstrating the protective effect of zingerone against experimental colon carcinogenesis and elucidating its possible mechanism by studying inflammatory and Nrf-2 signaling cascade...
February 5, 2019: Environmental Toxicology
Minghui Zhu, Yan Xu, Wenbin Zhang, Tianyi Gu, Daming Wang
Acute pancreatitis is a life-threatening disease accompanied by systemic inflammatory response. NF-kB and p38 signal pathway are activated in acute pancreatitis induced by cerulein. And PAKs are multifunctional effectors of Rho GTPases with kinase activity. In this study, the function of PAK1 in acute pancreatitis was investigated, and found that PAK1 was up-regulated in pancreas of acute pancreatitis mice model, and led to NF-kB and p38 pathway activation. PAK1 inhibition by shRNA or small molecule inhibitor FRAX597 decreased NF-kB and p38 activity, also alleviated the pathological damage in the pancreas of acute pancreatitis mice model, including decreasing the amylase and lipase level in serum, decreasing the levels of tumor necrosis factor-α, interleukin -6 and interleukin-1β in acute pancreatitis...
February 4, 2019: Bioscience Reports
Yamei Shen, Chunling Xue, Xuechun Li, Li Ba, Junjie Gu, Zhao Sun, Qin Han, Robert Chunhua Zhao
Mesenchymal stem cells (MSCs) are an important component of the tumor microenvironment, which play an important role in tumor development. Exosomes derived from tumor cells can affect the biological characteristics of MSCs. Our study examined the effects of exosomes derived from gastric cancer cells on MSC immunomodulatory functions. Exosomes were extracted from gastric cancer cell line AGS (AGS-Exos) and cultured with MSCs. MSCs were then co-cultured with both human peripheral blood mononuclear cells (PBMC) and macrophages...
February 4, 2019: Stem Cells and Development
Michael Bobardt, Joseph Kuo, Udayan Chatterji, Sumit Chanda, Susan J Little, Norbert Wiedemann, Gregoire Vuagniaux, Philippe A Gallay
Antiretroviral therapy (ART) suppresses HIV replication, but does not cure the infection because replication-competent virus persists within latently infected CD4+ T cells throughout years of therapy. These reservoirs contain integrated HIV-1 genomes and can resupply active virus. Thus, the development of strategies to eliminate the reservoir of latently infected cells is a research priority of global significance. In this study, we tested efficacy of a new inhibitor of apoptosis protein antagonist (IAPa) called Debio 1143 at reversing HIV latency and investigated its mechanisms of action...
2019: PloS One
M V Igotti, S B Svetlikova, V A Pospelov
The adenoviral E1A protein induces cell proliferation, transformation, and tumor formation in rodents, on the one hand. On the other hand, E1A expression increases cell sensitivity to a number of cytotoxic agents. Therefore, E1A is a candidate for use as a component of combination therapy for malignant tumors. The highest augmentation in the cytotoxic effect was achieved by a combined use of E1A expression and histone deacetylases (HDAC) inhibitors. However, HDAC inhibitors do not induce apoptosis in cells transformed with E1A and cHa-ras oncogenes...
October 2018: Acta Naturae
Deborah J Robinson, Ankit Patel, Karin J Purdie, Jun Wang, Hasan Rizvi, Martin Hufbauer, Paola Ostano, Baki Akgül, Giovanna Chiorino, Catherine Harwood, Daniele Bergamaschi
Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the UK. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kB signalling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical in epidermal homeostasis. We hypothesised a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies...
January 30, 2019: Journal of Investigative Dermatology
Bin Liu, Yumei Rong, Dan Sun, Wuwei Li, Hong Chen, Bo Cao, Taoyuan Wang
Specific study about the inhibitory effect of costunolide (CN) and relevant mechanism is of great significance for the treatment of pulmonary fibrosis. Here, the pharmacological activity of costunolide on the treatment of pulmonary fibrosis was investigated in vivo and in vitro. The in vivo mice study, mice were received intratracheal injection of bleomycin (BLM, 5 mg/kg) on 0 day to obtain BLM-induced pulmonary fibrosis firstly. From 2 day to 21 day, mice were orally administered with different dose of CN (low dose(CNL): 10 mg/kg, high dose(CNH): 20 mg/kg) and pirfenidone (PFD)(positive control, 50 mg/kg)...
March 5, 2019: Biochemical and Biophysical Research Communications
Barbara Frossi, Giulia Antoniali, Kefei Yu, Nahid Akhtar, Mark H Kaplan, Mark R Kelley, Gianluca Tell, Carlo E M Pucillo
The base excision repair (BER) pathway is an important DNA repair pathway and is essential for immune responses. In fact, it regulates both the antigen-stimulated somatic hypermutation (SHM) process and plays a central function in the process of class switch recombination (CSR). For both processes, a central role for apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated. APE1 acts also as a master regulator of gene expression through its redox activity. APE1's redox activity stimulates the DNA-binding activity of several transcription factors, including NF-kB and a few others involved in inflammation and in immune responses...
January 31, 2019: Journal of Biological Chemistry
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