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Yoshitoshi Kasuya, Hiroki Umezawa, Masahiko Hatano
Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAPKs)-c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)-are activated in various types of cells in response to cellular stresses such as apoptotic stimuli and inflammatory waves...
March 15, 2018: International Journal of Molecular Sciences
Yawen Li, Fangming Xiu, Zezhong Mou, Zhiwei Xue, Huanhui Du, Chunxue Zhou, Yan Li, Yongyu Shi, Shenyi He, Huaiyu Zhou
AIM: Exosomes are nanoscale membranous vesicles secreted by most cell types able to transfer bioactive molecules among cells, which play crucial roles in intercellular communication. We characterized the exosomes derived from Toxoplasma gondii (T. gondii) and detected the immune response in macrophages. METHODS: We used transmission electron microscopy, nanotracking analysis and western blotting to identify T. gondii exosomes. Functional experiments were performed in RAW264...
March 15, 2018: Nanomedicine
Tao Liu, Yixiang Liao, Huangheng Tao, Jinmin Zeng, Gang Wang, Zhonghua Yang, Yongzhi Wang, Yu Xiao, Jiajie Zhou, Xinghuan Wang
Several studies have shown that transient receptor potential cation channel subfamily M member 8 (TRPM8), which has been regarded as a novel prostate-specific marker, serves a key role in processes such as the proliferation, viability and cell migration of prostate cancer cells. Efforts have been made to uncover the potential role of targeting TRPM8 in the management of prostate cancer; it has been verified that TRPM8-targeted blockade, either by RNA interference-mediated depletion or specific TRPM8 inhibitors, could reduce the rate of proliferation and proliferative fraction, and induce apoptosis in prostate cancer cells...
April 2018: Oncology Letters
Caroline Morel, Tessi Sherrin, Norman J Kennedy, Kelly H Forest, Seda Avcioglu Barutcu, Michael Robles, Ezekiel Carpenter-Hyland, Naghum Alfulaij, Claire L Standen, Robert A Nichols, Morris Benveniste, Roger J Davis, Cedomir Todorovic
The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Guohong Liu, Francois X Claret, Fuling Zhou, Yunbao Pan
C-Jun activation domain-binding protein-1 (Jab1) involves in controlling cellular proliferation, cell cycle, apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage response (DDR). Jab1/COPS5 dysregulation contributes to oncogenesis by deactivating several tumor suppressors and activating oncogenes. Jab1 overexpression was found in many tumor types, illuminating its important role in cancer initiation, progression, and prognosis. Jab1/COPS5 has spurred a strong research interest in developing inhibitors of oncogenes/oncoproteins for cancer therapy...
2018: Frontiers in Pharmacology
Liv Weichien Chen, Feng-Cheng Liu, Li-Feng Hung, Chuan-Yueh Huang, Shiu-Bii Lien, Leou-Chyr Lin, Jenn-Haung Lai, Ling-Jun Ho
Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study...
March 12, 2018: International Journal of Molecular Sciences
Haesol Lee, Dahae Lee, Ki Sung Kang, Ji Hoon Song, You-Kyoung Choi
Cisplatin is a well-known anticancer drug frequently used for treating solid tumors, including ovarian, testicular, bladder, and cervical tumors. However, usage of cisplatin has been limited because of its adverse effects, particularly nephrotoxicity. Therefore, the present study sought to investigate the protective effect of formononetin against cisplatin-induced cytotoxicity in LLC-PK1 pig kidney epithelial cells as well as the anticancer effect of cisplatin in three different human cervical cancer cell lines, including HeLa, SiHa, and CaSKi cells...
March 12, 2018: International Journal of Molecular Sciences
Takuya Uemura, Takuya Yashiro, Rei Oda, Naoki Shioya, Tadaaki Nakajima, Masakazu Hachisu, Shoko Kobayashi, Chiharu Nishiyama, Gen-Ichiro Arimura
Monoterpenoid perillaldehyde (PA) is the major component in Perilla frutescens leaf essential oil, but its function in the anti-inflammatory effect is unclear. We explored the anti-inflammatory activity of PA in a dextran sulfate sodium (DSS)-induced colitis mouse model using relief of bodyweight loss (avg. 49.2% recovery; P = 0.094) and colon damage (avg. 35.3% recovery; P < 0.05) by administration of PA at a 100 mg/kg dosage. The PA administration resulted in suppression of DSS-induced expression of pro-inflammatory cytokine genes and matrix metalloproteinase-9 in the colon (e...
March 13, 2018: Journal of Agricultural and Food Chemistry
Huan Liu, Tianjiao Xia, Fangxia Xu, Zhengliang Ma, Xiaoping Gu
Neuropathic pain is a chronic pain state associated with multiple etiologies that results in considerable social and economic burden. The identification of key genes associated with neuropathic pain is important for the development of novel therapies. Therefore, the present study downloaded the gene expression profile GSE15041 from the Gene Expression Omnibus database. The unverified gene chip was removed and the microarray data was normalized following quality control. The limma package in R was used to screen the differentially expressed genes (DEGs), followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis...
March 9, 2018: Molecular Medicine Reports
Shinwan Kany, Mathias Woschek, Niels Kneip, Ramona Sturm, Miriam Kalbitz, Marc Hanschen, Borna Relja
Osteosarcoma is the leading primary bone cancer in young adults and exhibits high chemoresistance rates. Therefore, characterization of both alternative treatment options and the underlying mechanisms is essential. Simvastatin, a cholesterol-lowering drug, has among its pleiotropic effects anticancer potential. Characterizing this potential and the underlying mechanisms in osteosarcoma is the subject of the present study. Human osteosarcoma cells (SaOS-2 and U2OS) were treated with simvastatin (4-66 µM) for 48 or 72 h...
April 2018: International Journal of Oncology
Asokan Devarajan, Feng Su, Victor Grijalva, Meghna Yalamanchi, Ashna Yalamanchi, Feng Gao, Hannah Trost, Josephine Nwokedi, Gina Farias-Eisner, Robin Farias-Eisner, Alan M Fogelman, Srinivasa T Reddy
Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue...
March 12, 2018: Cell Death & Disease
Xu Chen, Xuan Li, Wenyan Zhang, Jie He, Bo Xu, Bin Lei, Zhenhua Wang, Courtney Cates, Thomas Rousselle, Ji Li
BACKGROUND: AMP-activated Protein Kinase (AMPK) is a stress-activated kinase that protects against cardiomyocyte injury during ischemia and reperfusion. c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated by ischemia and reperfusion. NF-κB is an important transcription factor involved in ischemia and reperfusion injury. METHODS AND RESULTS: The intrinsic activation of AMPK attenuates the inflammation which occurred during ischemia/reperfusion through the modulation of the JNK mediated NF-κB signaling pathway...
March 8, 2018: Metabolism: Clinical and Experimental
Daeyeong Chung, Dae-Chul Cho, Seong-Hyun Park, Kyoung-Tae Kim, Joo-Kyung Sung, Younghoon Jeon
OBJECTIVE: The purpose of this study was to evaluate pain-related behaviors after bilateral C2 root resection and change in pain patterns in the suboccipital region in rats. METHODS: Male Sprague-Dawley rats were randomly assigned to three groups (n=25/group); näive, sham, and C2 resection. Three, 7, 10, and 14 days after surgery, cold allodynia was assessed using 20 μL of 99.7% acetone. c-Fos and c-Jun were immunohistochemically stained to evaluate activation of dorsal horn gray matter in C2 segments of the spinal cord 2 hours, 1 day, 7 days, and 14 days after surgery...
March 2018: Journal of Korean Neurosurgical Society
Lora J Kasselman, Nicholas A Vernice, Joshua DeLeon, Allison B Reiss
Cardiovascular disease associated with obesity and autoimmunity is the leading cause of death in these populations and significant residual risk remains despite current treatment approaches. Obesity, type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) are linked to chronic inflammation, and subjects with these disorders have characteristic shifts in their gut microbiome composition. Recent data suggest that alterations in gut microbial and metabolic composition may be responsible, in part, for induction of chronic inflammation, thus promoting cardiovascular disease...
March 2, 2018: Atherosclerosis
Chang Liu, Congcong Zhang, Lixin Jia, Boya Chen, Luxin Liu, Jie Sun, Wenmei Zhang, Bin You, Yulin Li, Ping Li, Jie Du
Thoracic aortic aneurysm and dissection (TAAD) is due to degeneration of the aorta and causes a high mortality rate, while molecular mechanisms for the development of TAAD are still not completely understood. In this study, 3-aminopropionitrile (BAPN) treatment was used to induce TAAD mouse model. Through transcriptome analysis, we found the expression levels of genes associated with interleukin-3 (IL-3) signaling pathway were upregulated during TAAD development in mouse, which were validated by real-time PCR...
March 9, 2018: Clinical Science (1979-)
Bo Xia, Lei Wang, Li Feng, Baofang Tian, Yuanjie Tan, Baoyin Du
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. This study aimed to explore the effects of long non-coding RNA CAT104 and microRNA-381 (miR-381) on osteosarcoma cell proliferation, migration, invasion and apoptosis, as well as the underlying potential mechanism. We found that CAT104 was highly expressed in osteosarcoma MG-63 and OS-732 cells. Knockdown of CAT104 significantly inhibited OS-732 cell proliferation, migration and invasion, but promoted cell apoptosis. CAT104 regulated the expression of miR-381 and miR-381 participated in the effects of CAT104 on OS-732 cells...
March 9, 2018: Oncology Research
Reut Hilu-Dadia, Ketty Hakim-Mishnaevski, Flonia Levy-Adam, Estee Kurant
Development of the central nervous system involves elimination of superfluous neurons through apoptosis and subsequent phagocytosis. In Drosophila, this occurs mainly during three developmental stages: embryogenesis, metamorphosis and emerging adult. Two transmembrane glial phagocytic receptors, SIMU (homolog of the mammalian Stabilin-2) and Draper (homolog of the mammalian MEGF10 and Jedi), mediate glial phagocytosis of apoptotic neurons during embryogenesis. However, less is known about the removal of apoptotic neurons during later stages of development...
March 9, 2018: Glia
Jinlan He, Lei Cai, Ye Chen, Yan He, Ming Wang, Jie Tang, Hui Guan, Jingjing Wang, Xingchen Peng
BACKGROUND AND PURPOSE: SKLB-163 is a novel benzothiazole-2-thiol derivative with antitumor activities. This study investigated the effects of SKLB-163 on nasopharyngeal carcinoma (NPC) and its mechanisms. MATERIALS AND METHODS: Rho GDP-dissociation inhibitor (RhoGDI) expression was examined in NPC cell lines by western blot. Effects of SKLB-163 on proliferation, migration and radiosensitivity were assessed by MTT, wound healing and colony formation assays in vitro...
March 5, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Peijun Zhao, Md Badrul Alam, Hongyan An, Hee-Jeong Choi, Yeong Ho Cha, Chi-Yeol Yoo, Hyo-Hyun Kim, Sang-Han Lee
In this study, the antimelanogenic effect of an ethyl acetate fraction of Oroxylum indicum Vent. seeds (OISEA) and its underlying mechanisms in melan-a cells were investigated. Antimelanogenesis activity was confirmed by assessing inhibition of tyrosinase activity and melanin content in the cells. Both transcriptional and translational expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase related protein-1 and 2 (TYRP-1 and TYRP-2), were also examined. The results depicted that pretreatment of OISEA significantly inhibits not only tyrosinase activity, but melanin production and intracellular tyrosinase activity...
March 7, 2018: International Journal of Molecular Sciences
Robert Carlsson, Ilknur Özen, Marco Barbariga, Abderahim Gaceb, Michaela Roth, Gesine Paul
Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation...
2018: PloS One
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