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Lisa Maria Mustachio, Yun Lu, Masanori Kawakami, Jason Roszik, Sarah J Freemantle, Xi Liu, Ethan Dmitrovsky
Ubiquitination and ubiquitin-like posttranslational modifications (PTM) regulate activity and stability of oncoproteins and tumor suppressors. This implicates PTMs as antineoplastic targets. One way to alter PTMs is to inhibit activity of deubiquitinases (DUB) that remove ubiquitin or ubiquitin-like proteins from substrate proteins. Roles of DUBs in carcinogenesis have been intensively studied, yet few inhibitors exist. Prior work provides a basis for the ubiquitin-specific protease 18 (USP18) as an antineoplastic target...
January 17, 2018: Cancer Research
L Han, Y Zhang, Q Wang, M Xin, K Yang, K Lei, M Sun
Epstein-Barr (EB) virus infection has long been speculated to evoke systemic lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN) system activation, we aimed to discover the relationship between the two in the progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with IFNα in patient sera were detected with enzyme-linked immunosorbent assays...
January 1, 2018: Lupus
Myung-Hwa Jung, Chamilani Nikapitiya, Sung-Ju Jung
Rock bream iridovirus (RBIV) causes severe mass mortalities in rock bream (Oplegnathus fasciatus) in Korea. In this study, we investigated the potential of viral membrane protein to induce antiviral status protecting rock bream against RBIV infection. We found that fish administered with ORF008L (myristoylated membrane protein, MMP) vaccine exhibited significantly higher levels of survival compared to ORF007L (major capsid protein, MCP). Moreover, ORF008L-based DNA vaccinated fish showed significant protection at 4 and 8 weeks post vaccination (wpv) than non-vaccinated fish after infected with RBIV (6...
January 8, 2018: Vaccine
Xiao-Quan Li, Xiao Ning Li, Jing-Jing Liang, Xin-Bin Cai, Qian Tao, Yu-Xiao Li, Qing Qin, Su-Ping Xu, Ting Rong Luo
Interferon (IFN)-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is heavily involved in immune response elicitation. As an important member of interferon regulatory factor (IRF) family, IRF1 can activate the expression of multiple genes, including the human optineurin gene (Sudhakar et al., 2013). In this study, a sequence in the promoter region of the optineurin gene was compared to the 5' flanking region of the porcine isg15 gene. Porcine IRF1 also possesses antiviral activity against several swine viruses (Li et al...
January 8, 2018: Molecular Immunology
Shyamal Desai, Meredith Juncker, Catherine Kim
Mitophagy is a cellular process by which dysfunctional mitochondria are degraded via autophagy. Increasing empirical evidence proposes that this mitochondrial quality-control mechanism is defective in neurons of patients with various neurodegenerative diseases such as Ataxia Telangiectasia, Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Accumulation of defective mitochondria and the production of reactive oxygen species due to defective mitophagy have been identified as causes underlying neurodegenerative disease pathogenesis...
January 1, 2018: Experimental Biology and Medicine
Paula Fernandes Dos Santos, Johan Van Weyenbergh, Murilo Delgobo, Daniel de Oliveira Patricio, Brian J Ferguson, Rodrigo Guabiraba, Tim Dierckx, Soraya Maria Menezes, André Báfica, Daniel Santos Mansur
IFN-stimulated gene 15 (ISG15) deficiency in humans leads to severe IFNopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. In this study, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. A balanced ISG15-induced monocyte/IL-10 versus lymphoid/IFN-γ expression, correlating with p38 MAPK and PI3K signaling, was found using targeted in vitro and ex vivo systems analysis of human transcriptomic datasets...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yi Huo, Zhaoyun Zong, Qingtao Wang, Zhenyu Zhang, Haiteng Deng
Tumor cells frequently evolved resistance to cisplatin that greatly compromises the efficacy of chemotherapy. Identification of the mechanisms underlying drug resistance is important for developing new therapeutic approaches. ISG15 is found to be elevated in many human carcinomas and cancer cell lines. Here, we identified that the expressions of ISG15 and ISG15-conjugating system were downregulated in drug resistant A549/DDP cells compared to drug sensitive A549 cells. Silencing of ISG15 robustly elevated the resistance to cisplatin, suggesting ISG15 plays an important role in cisplatin resistance...
December 8, 2017: Oncotarget
Yang Du, Tianhao Duan, Yanchun Feng, Qingxiang Liu, Meng Lin, Jun Cui, Rong-Fu Wang
The RIG-I-like receptors (RLRs) are critical for protection against RNA virus infection, and their activities must be stringently controlled to maintain immune homeostasis. Here, we report that leucine-rich repeat containing protein 25 (LRRC25) is a key negative regulator of RLR-mediated type I interferon (IFN) signaling. Upon RNA virus infection, LRRC25 specifically binds to ISG15-associated RIG-I to promote interaction between RIG-I and the autophagic cargo receptor p62 and to mediate RIG-I degradation via selective autophagy...
December 29, 2017: EMBO Journal
Wenzhen He, Duncan Wei, De Cai, Siqia Chen, Shunxian Li, Wenjie Chen
BACKGROUND: Our previous study described the important regulatory roles of microRNAs (miRNAs) in ischemic stroke. However, the functional significance of long non coding RNA (lncRNAs) in ischemic stroke was largely unknown. This study was aimed to identify the lncRNA profiling and elucidate the regulatory mechanisms in pathophysiology of stroke. MATERIALS AND METHODS: Herein, we used RNA sequencing to sequence the RNA from blood of three ischemic stroke patients and three normal controls...
December 28, 2017: Human Gene Therapy
Daniel Álvarez-Torres, Victoria Gómez-Abellán, Marta Arizcun, Esther García-Rosado, Julia Béjar, María P Sepulcre
Interferons (IFNs) play a key role in the innate immunity of vertebrates against viral infections by inducing hundreds of IFN-stimulated genes (ISGs), such as isg15. Isg15 is an ubiquitin-like protein, which can conjugate cellular and viral proteins in a process called ISGylation, although it can also act as a cytokine-like protein. Gilthead seabream (Sparus aurata L.) is an important asymptomatic carrier of viral haemorrhagic septicaemia virus (VHSV) and nodavirus, representing a threat to other co-cultivated susceptible species...
December 19, 2017: Fish & Shellfish Immunology
Xiaoqiang Xiao, Yingjie Cao, Haoyu Chen
Butyrate inhibits growth of lung cancer. However, the molecular mechanism is still unclear. Here we profiled miRNAs that responded to sodium butyrate(NaB) stimulation in A549 cells, a non-small cell lung cancer cell line, using microarray. We found 33 up-regulated microRNAs and 22 down-regulated microRNAs (log2≥1.5 folds, P-value<0.05). The expression of miR-3935, miR-574-3p and miR-494-3p was confirmed by realtime qPCR. Then,we explored their potential targets of miR-574-3p and miR-494-3p using long noncoding RNA(LncRNA) microarray...
December 12, 2017: Journal of Cellular Biochemistry
Aasif Ahmad Sheikh, O K Hooda, A K Dang
Interferon tau, a 23 KDa trophoblast derived protein diffuses out from the uterus into the circulation and leads to the expression of IFNτ stimulated genes viz. ISG15 and OAS1 in blood neutrophils. The IFNτ pathway is species as well as tissue specific. To unsnarl the IFNτ downstream signaling pathway, the blood neutrophils were incubated simultaneously with 10 ng/ml of Recombinant Bovine Interferon tau and the inhibitors of JAK2 (AG490), JAK3 (CP690550), p38 (SB202190), PI3K/Akt (LY294002) and MAPK/Erk (U0126) at specific doses for 4 hour duration...
November 30, 2017: Journal of Cellular Physiology
N Toji, S Shigeno, K Kizaki, K Koshi, H Matsuda, Y Hashiyada, K Imai, T Takahashi, T Ishiguro-Oonuma, K Hashizume
Early detection of gestation is important in the bovine industry. New methods have been developed to detect gene expression in leucocytes induced by interferon-tau (IFNT) as gestation biomarkers. However, it is debatable which blood cell is suitable for detecting gene expression. This study was aimed at confirming whether granulocytes respond to IFNT specifically. Granulocytes and mononuclear cells (MNCs) from cows, and several types of bovine cultured cells, were treated with recombinant (r) IFNT and gene expression was analysed by quantitative real-time reverse transcriptase (RT)-PCR and microarray analysis...
November 2017: Veterinary Journal
Gouri J Mahajan, Eric J Vallender, Michael R Garrett, Lavanya Challagundla, James C Overholser, George Jurjus, Lesa Dieter, Maryam Syed, Damian G Romero, Hamed Benghuzzi, Craig A Stockmeier
Major Depressive Disorder (MDD) is a common psychiatric disorder for which available medications are often not effective. The high prevalence of MDD and modest response to existing therapies compels efforts to better understand and treat the disorder. Decreased hippocampal volume with increasing duration of depression suggests altered gene expression or even a decrease in neurogenesis. Tissue punches from the dentate gyrus were collected postmortem from 23 subjects with MDD and 23 psychiatrically-normal control subjects...
November 22, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Hitomi Yoshino, Noriyuki Toji, Kouya Sasaki, Katsuo Koshi, Norio Yamagishi, Toru Takahashi, Toshina Ishiguro-Oonuma, Hideo Matsuda, Tadayuki Yamanouchi, Yutaka Hashiyada, Kei Imai, Yoshiaki Izaike, Keiichiro Kizaki, Kazuyoshi Hashizume
Interferon tau plays an important role in establishing bovine pregnancy. Interferon-stimulated genes (ISGs) have been examined to identify a suitable indicator for the diagnosis of early gestation in cows. Although ISGs can be specifically detected in peripheral white blood cells during early gestation, its reliability remains to be validated. In the current study, a predictive threshold level of ISGs to determine pregnancy in cows during Days 20-22 of gestation was verified by analyzing the expression of ISGs in granulocytes and peripheral blood leucocytes (a total of 57 cows were used, 28 of which were pregnant and 29 were non-pregnant)...
November 16, 2017: Theriogenology
Qishu Zhang, Lijun Qiao, Xiao Wang, Changkuan Ding, Jason J Chen
UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is an important epigenetic regulator that plays a part in DNA methylation, protein methylation and ubiquitination. It is also frequently overexpressed in many types of cancers, including cervical cancer, which is caused by human papillomavirus (HPV). In this study, we showed that UHRF1 was up-regulated in HPV oncogene E7 expressing cells and HPV-positive cervical cancer cells. We demonstrated that UHRF1 down-regulated the expression of UBE2L6 gene that encodes the ISG15-conjugating enzyme UbcH8...
November 20, 2017: Cell Cycle
Rong Wang, Jinbin Li, Yulan Zhao, Yapeng Li, Ling Yin
BACKGROUND: Breast cancer is a prevalent cancer in female. This study aims to investigate the therapeutic potential and mechanism of curcumin in breast cancer. METHODS: After cultivation, human breast cancer cells (MCF-7 cells) were treated with 0.1% (v/v) 15 µmol/ml curcumin-dimethylsulfoxide solution and 0.1% (v/v) dimethylsulfoxide, respectively, at 37 °C and 5% CO2 for 48 h. Total RNA was extracted, cDNA library was constructed, and cDNAs were amplified and sequenced...
November 14, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Jingxuan Chen, Hongqiang Du, Shuang Cui, Tong Liu, Guang Yang, Huaping Sun, Weiwei Tao, Baoping Jiang, Li Yu, Fuping You
E. fischeriana has long been used as a traditional Chinese medicine. Recent studies reported that some compounds of E. fischeriana exhibited antimicrobial and immune enhance activity. Innate immune system is essential for the immune surveillance of inner and outer threats, initial host defense responses and immune modulation. The role of natural drug compounds, including E. fischeriana, in innate immune regulation is largely unknown. Here we demonstrated that E. fischeriana compound Dpo is involved in antiviral signaling...
2017: Frontiers in Cellular and Infection Microbiology
Han-Kook Yang, Myung-Hwa Jung, Satheesha Avunje, Chamilani Nikapitiya, So Young Kang, Young Bae Ryu, Woo Song Lee, Sung-Ju Jung
The inhibition efficacy of an extract from Ecklonia cava (E. cava) was studied to determine whether the extract and compounds exhibited inhibitory activity against VHSV in the fathead minnow (FHM) cell line and following oral administration to the olive flounder. Based on its low toxicity and effective concentration, the E. cava extract (Ext) and compounds (eckol and phlorofucofuroeckol A) were selected for further analysis. In the plaque reduction assay, simultaneous co-exposure of VHSV to Ext, eckol and phlorofucofuroeckol A showed a higher level of inhibition than the pre- and post-exposure groups...
November 9, 2017: Fish & Shellfish Immunology
Harry L A Janssen, Maurizia R Brunetto, Yoon Jun Kim, Carlo Ferrari, Benedetta Massetto, Anh-Hoa Nguyen, Adarsh Joshi, Jacky Woo, Audrey H Lau, Anuj Gaggar, G Mani Subramanian, Eric M Yoshida, Sang Hoon Ahn, Naoky C S Tsai, Scott Fung, Edward J Gane
BACKGROUND & AIMS: Vesatolimod (GS-9620) is an oral agonist of toll-like receptor 7, an activator of innate and adaptive immune responses. Here the safety and efficacy of vesatolimod is assessed after once-weekly treatment in chronic hepatitis B (CHB) infected patients suppressed on oral antiviral treatment. METHODS: In a Phase 2, double-blind, randomized, placebo (PBO)-controlled study, 162 patients stratified by hepatitis B surface antigen (HBsAg) levels and serum HBeAg status were randomized 1:3:3:3 to once-weekly oral PBO or vesatolimod (1-, 2-, or 4-mg doses) for 4, 8 or 12 weeks per cohort and efficacy assessed by change in baseline HBsAg (log10 IU/mL) at the primary endpoint (Week 24)...
November 2, 2017: Journal of Hepatology
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