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Jun Pan, Rilong Jin, Miaoda Shen, Ronghuan Wu, Sanzhong Xu
Osteoarthritis is a type of joint disease that results from the breakdown of joint cartilage and underlying bone and is believed to be caused by mechanical stress on the joint and low-grade inflammatory processes. Acamprosate significantly ameliorates the pathological features of experimental autoimmune encephalomyelitis due to its anti-inflammatory effect. The aims of the present study were to investigate the anti-arthritis activities of acamprosate and elucidate the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced by intradermal injection of complete Freund's adjuvant...
April 14, 2018: Inflammation
Panagiotis Drakopoulos, Jérôme Rosetti, Nicola Pluchino, Christophe Blockeel, Samuel Santos-Ribeiro, Michael de Brucker, Petros Drakakis, Michel Camus, Herman Tournaye, Nikolaos P Polyzos
Since the introduction of gonadotropin-releasing hormone (GnRH) antagonists, an extensive amount of literature investigating the role of the downregulation protocols on pregnancy outcomes has been published. However, these studies were mainly performed in the general infertile population where patients with endometriosis were often excluded or underrepresented. This study is a large retrospective cohort study including 386 endometriosis patients undergoing IVF/ICSI, who had been previously classified according to the rAFS system...
April 12, 2018: Gynecological Endocrinology
Garry Ceccon, Jan-Michael Werner, Veronika Dunkl, Caroline Tscherpel, Gabriele Stoffels, Anna Brunn, Martina Deckert, Gereon R Fink, Norbert Galldiks
Novel therapeutic targets in malignant glioma patients are urgently needed. Point mutations of the v-Raf murine sarcoma viral oncogene homolog B ( BRAF ) gene occur predominantly in melanoma patients, but may also occur in gliomas. Thus, this is a target of great interest for this group of patients. In a nine-year-old male patient, an anaplastic astrocytoma in the left temporoparietal region was diagnosed histologically. After first- and second-line treatment, a malignant progression to a secondary glioblastoma was observed ten years after the initial diagnosis...
April 5, 2018: International Journal of Molecular Sciences
Zhaomeng Wu, Qingyi Zhu, Yu Zhang, Yingying Yin, Dan Kang, Runyi Cao, Qian Tian, Shan Lu, Ping Liu
Traditional Chinese medicine (TCM) has the synergistic effect of the combination of a single ingredient and a monomer, and systemic and local therapeutic effects in cancer treatment, through which TCM is able to enhance the curative effect and reduce the side effects. The present study analyzed the effect of TCM‑1 (an anti‑cancer TCM) on prostate cancer (PCa) cell lines, and studied in detail the mechanism of cell death induced by TCM‑1 in vitro and in vivo. From the present results, it was identified for the first time, to the best of our knowledge, that TCM‑1 arrested the cell cycle at the G1 phase, decreased cell viability and increased nuclear rupture in a dose‑dependent manner; these effects finally resulted in apoptosis in PCa cells...
March 28, 2018: Molecular Medicine Reports
Yu-Ru Zhao, Hong-Mei Li, Meilin Zhu, Jing Li, Tao Ma, Qiang Huo, Young-Soo Hong, Cheng-Zhu Wu
Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from the genetically engineered Streptomyces hygroscopicus , was found to haveanticancer activity against two human breast cancer cell lines.WK-88-1 produced concentration-dependent inhibition in cell proliferation, cell cycle arrest, and apoptosis inestrogen receptor (ER)-positive MCF-7 andER-negativeMDA-MB-231 cell lines...
April 6, 2018: Journal of Microbiology and Biotechnology
Brantley Coleman, Irini Topalidou, Michael Ailion
The heterotrimeric G protein Gq regulates neuronal activity through distinct downstream effector pathways. In addition to the canonical Gq effector phospholipase Cb, the small GTPase Rho was recently identified as a conserved effector of Gq. To identify additional molecules important for Gq signaling in neurons, we performed a forward genetic screen in the nematode Caenorhabditis elegans for suppressors of the hyperactivity and exaggerated waveform of an activated Gq mutant. We isolated two mutations affecting the MAP kinase scaffold protein KSR-1 and found that KSR-1 modulates locomotion downstream of or in parallel to the Gq-Rho pathway...
April 3, 2018: Genetics
Damián Balfagón, Sara I Zandalinas, Pablo Baliño, María Muriach, Aurelio Gómez-Cadenas
Usually several environmental stresses occur in nature simultaneously causing a unique plant response. However, most of the studies until now have focused in individually-applied abiotic stress conditions. Carrizo citrange (Poncirus trifoliata L. Raf. X Citrus sinensis L. Osb.) and Cleopatra mandarin (Citrus reshni Hort. ex Tan.) are two citrus rootstocks with contrasting tolerance to drought and heat stress and have been used in this work as a model for the study of plant tolerance to the combination of drought and high temperatures...
March 27, 2018: Plant Physiology and Biochemistry: PPB
Ali Dehghanifard, Saeid Kaviani, Saeid Abroun, Mahshad Mehdizadeh, Sajedeh Saiedi, Amirhosein Maali, Sasan Ghaffari, Mehdi Azad
Multiple myeloma (MM) results from malignancy in plasma cells and occurs at ages > 50 years. MM is the second most common hematologic malignancy after non-Hodgkin lymphoma, which constitutes 1% of all malignancies. Despite the great advances in the discovery of useful drugs for this disease such as dexamethasone and bortezomib, it is still an incurable malignancy owing to the development of drug resistance. The tumor cells develop resistance to apoptosis, resulting in greater cell survival, and, ultimately, develop drug resistance by changing the various signaling pathways involved in cell proliferation, survival, differentiation, and apoptosis...
March 17, 2018: Clinical Lymphoma, Myeloma & Leukemia
Meng-Hsun Yu, Tsung-Yuan Yang, Hsieh-Hsun Ho, Hui-Pei Huang, Kuei-Chuan Chan, Chau-Jong Wang
Atherosclerosis is characterized by the buildup of plaque inside arteries. Our recent studies demonstrated that polyphenolic natural products can reduce oxidative stress, inflammation, angiogenesis, hyperlipidemia, and hyperglycemia. A previous study also showed that mulberry water extract (MWE) can inhibit atherosclerosis and contains considerable amounts of polyphenols. Therefore, in the present study, we investigated whether mulberry polyphenol extract (MPE) containing high levels of polyphenolic compounds could affect vascular smooth muscle cell (VSMC; A7r5 cell) motility...
April 2, 2018: Journal of Agricultural and Food Chemistry
Luca Mologni, Mariantonia Costanza, Geeta Geeta Sharma, Michela Viltadi, Luca Massimino, Stefania Citterio, Stefania Purgante, Hima Raman, Alessandra Pirola, Massimo Zucchetti, Rocco Piazza, Carlo Gambacorti-Passerini
BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFV600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactivation of MAPK signaling by several mechanisms has been shown to cause drug resistance and disease recurrence. In this work, we describe the co-occurrence of an in-frame deletion within an amplified BRAFV600E locus and a missense point mutation of the transcriptional repressor BCORL1 in vemurafenib-resistant A375 melanoma cells...
March 28, 2018: Neoplasia: An International Journal for Oncology Research
Peng-Fei Wang, Yong-Jiao Zhang, Dong Wang, Hui-Min Hu, Zhong-Chang Wang, Chen Xu, Han-Yue Qiu, Hai-Liang Zhu
The association of deregulated signal pathways with various diseases has long been a research hotspot. One of the most important signal pathways, the MAPK (mitogen-activated protein kinase) signal pathway, plays a vital role in transducing extracellular signals into vital intracellular mechanisms. While mutations on its key component Raf kinase lead to sever diseases, targeted inhibition has thereby become an attractive therapeutic strategy. Several drugs have been approved for the treatment of Raf relevant diseases, yet more candidates are ever needed as the known drugs have confronted resistance and side effects...
March 26, 2018: Bioorganic & Medicinal Chemistry
Hsiang-Ruei Liao, Ih-Sheng Chen, Fu-Chao Liu, Shinn-Zhi Lin, Ching-Ping Tseng
This study investigates the effect and the underlying mechanism of 2',3-dihydroxy-5-methoxybiphenyl (RIR-2), a lignan extracted from the roots of Rhaphiolepis indica (L.) Lindl. ex Ker var. tashiroi Hayata ex Matsum. & Hayata (Rosaceae), on N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced respiratory burst and cathepsin G in human neutrophils. Signaling pathways regulated by RIR-2 which modulated fMLP-induced respiratory burst were evaluated by an interaction between β subunit of G-protein (Gβ) with downstream signaling induced by fMLP and by immunoblotting analysis of the downstream targets of Gβ-protein...
March 27, 2018: European Journal of Pharmacology
Mengnan Zhao, Cheng Zhan, Ming Li, Xiaodong Yang, Xinyu Yang, Yong Zhang, Miao Lin, Yifeng Xia, Mingxiang Feng, Qun Wang
Background: The aberrant status of target genes and their associations with clinicopathologic characteristics are still unclear in primary lung adenocarcinoma. Methods: The common mutations and translocations of nine target genes were evaluated in 1,247 specimens of surgically-resected primary lung adenocarcinoma. Immunohistochemistry was used to analyze the expressions of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in 731 specimens. The frequency of the aberrations and their associations with clinicopathologic characteristics were analyzed...
January 2018: Journal of Thoracic Disease
Ming Liu, Yongqing Wang, Huifen Lu, Hao Wang, Xiaoming Shi, Xuan Shao, Yu-Xia Li, Yangyu Zhao, Yan-Ling Wang
Preeclampsia is a pregnancy-specific complication defined as newly onset gestational hypertension and proteinuria. Deficiency in placental development is considered as the predominant cause of preeclampsia. Our previous study found that the expression of miR-518b increased significantly in the preeclamptic placentas, indicating the potential participation of this small RNA in the occurrence of preeclampsia. In this study, data analysis using multiple databases predicted Rap1b as a candidate target of miR-518b...
2018: Frontiers in Endocrinology
Elisabeth I Heath, Filipa Lynce, Joanne Xiu, Angela Ellerbrock, Sandeep K Reddy, Elias Obeid, Stephen V Liu, Aliccia Bollig-Fischer, Duska Separovic, Ari Vanderwalde
BACKGROUND/AIM: African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. MATERIALS AND METHODS: DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing...
April 2018: Anticancer Research
Elizabeth A Germino, Joseph P Miller, Lauri Diehl, Carter J Swanson, Steffen Durinck, Zora Modrusan, Jeffrey H Miner, Andrey S Shaw
Given the frequency with which MAP kinase signaling is dysregulated in cancer, much effort has been focused on inhibiting RAS signaling for therapeutic benefit. KSR1, a pseudokinase that interacts with RAF, is a potential target; it was originally cloned in screens for suppressors of constitutively active RAS, and its deletion prevents RAS-mediated transformation of mouse embryonic fibroblasts. In this work, we used a genetically engineered mouse model of pancreatic cancer to assess whether KSR1 deletion would influence tumor development in the setting of oncogenic RAS...
2018: PloS One
Zhen Liu, Menik Hettihewa, Yang Shu, Chunqiong Zhou, Qian Wan, Lihong Liu
A study is presented on the binding kinetics and mechanism of the adsorption of dsDNA on citrate-capped gold nanoparticles (AuNPs). Methods include fluorescence titration, isothermal calorimetry (ITC) titration, dynamic light scattering and gel electrophoresis. It is found that the fluorescence of probe DNA (labeled with Rhodamine Green and measured at excitation/emission peaks of 498/531 nm) is quenched by addition of AuNPs. The Stern-Volmer quenching constant (Ksv) is 1.67 × 10^ 9 L·mol-1 at 308 K and drops with increasing temperature...
March 27, 2018: Mikrochimica Acta
Verena Pfeiffer, Rudolf Götz, Guadelupe Camarero, Helmut Heinsen, Robert Blum, Ulf Rüdiger Rapp
RAF kinases are major constituents of the mitogen activated signaling pathway, regulating cell proliferation, differentiation and cell survival of many cell types, including neurons. In mammals, the family of RAF proteins consists of three members, ARAF, BRAF, and CRAF. Ablation of CRAF kinase in inbred mouse strains causes major developmental defects during fetal growth and embryonic or perinatal lethality. Heterozygous germline mutations in CRAF result in Noonan syndrome, which is characterized by neurocognitive impairment that may involve hippocampal physiology...
2018: PloS One
Yen-Hsiu Yeh, Ho-Fu Hsiao, Yen-Cheng Yeh, Tien-Wen Chen, Tsai-Kun Li
BACKGROUND: Tumor microenvironments (TMEs) activate various axes/pathways, predominantly inflammatory and hypoxic responses, impact tumorigenesis, metastasis and therapeutic resistance significantly. Although molecular pathways of individual TME are extensively studied, evidence showing interaction and crosstalk between hypoxia and inflammation remain unclear. Thus, we examined whether interferon (IFN) could modulate both inflammatory and hypoxic responses under normoxia and its relation with cancer development...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
Xican Li, Hong Xie, Ruicai Zhan, Dongfeng Chen
Two 2-phenyl-benzofurans, moracin C {2-[3',5'-dihydroxy-4'-(3-methlbut-2-enyl)phenyl]-6-hydroxybenzofuran} and its isomer iso- moracin C{2-[3',5'-dihydroxy-4'-(3-methlbut-1-enyl)phenyl]-6-hydroxybenzofuran}, were comparatively studied using redox-related antioxidant assays and non-redox antioxidant assays. Moracin C always resulted in higher IC50 values than iso -moracin C in the redox-related antioxidant assays, including •O₂- -inhibition, Cu2+ -reducing power, DPPH•-inhibition, and ABTS⁺•-inhibition assays...
March 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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