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https://www.readbyqxmd.com/read/28918124/polyphenols-reported-to-shift-apap-induced-changes-in-mapk-signaling-and-toxicity-outcomes
#1
REVIEW
Ngoc Uy Nguyen, Brendan David Stamper
Due to its widespread availability, acetaminophen (APAP) is the leading cause for drug-induced liver injury in many countries including United States and United Kingdom. When used as recommended, APAP is relatively safe. However, in overdose cases, increased metabolism of APAP to N-acetyl-para-benzoquinoneimine (NAPQI), a reactive metabolite, leads to glutathione (GSH) depletion, oxidative stress, and cellular injury. Throughout this process, a variety of factors play important roles in propagating toxicity, including c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family...
September 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28916723/fibroblast-growth-factor-2-fgf2-regulates-cytoglobin-expression-and-activation-of-human-hepatic-stellate-cells-via-jnk-signaling
#2
Misako Sato-Matsubara, Tsutomu Matsubara, Atsuko Daikoku, Yoshinori Okina, Lisa Longato, Krista Rombouts, Le Thi Thanh Thuy, Jun Adachi, Takeshi Tomonaga, Kazuo Ikeda, Katsutoshi Yoshizato, Massimo Pinzani, Norifumi Kawada
Cytoglobin (CYGB) belongs to the mammalian globin family and is exclusively expressed in hepatic stellate cells (HSCs) in the liver. In addition to its gas-binding ability, CYGB is relevant to hepatic inflammation, fibrosis, and cancer because of its antioxidative properties; however, the regulation of CYGB gene expression remains unknown. Here, we sought to identify factors that induce CYGB expression in HSCs and to clarify the molecular mechanism involved. We used the human HSC cell line HHSteC and primary human HSCs isolated from intact human liver tissues...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#3
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916299/non-canonical-wnt-mediated-neurogenic-differentiation-of-human-bone-marrow-derived-mesenchymal-stem-cells
#4
Sujeong Jang, Hyong-Ho Cho, Jong-Seong Park, Han-Seong Jeong
Bone marrow-derived mesenchymal stem cells (BM-MSCs), which are characterized by multipotency and self-renewal, are responsible for tissue regeneration and repair. We have previously reported in adipose tissue-derived MSCs that only Wnt5a is enhanced at neurogenic differentiation, and the mechanism of differentiation is dependent on the Wnt5a/JNK pathway; however, the role of Wnt/MAPK pathway is yet to be investigated in neurogenic differentiation in BM-MSCs. We compared the transcriptional expression of Wnt in neurogenic induced-hBM-MSCs (NI-hBM-MSCs) with that in primary hBM-MSCs, using RT-PCR, qPCR, and western blotting...
September 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28915644/phytoagent-deoxyelephantopin-derivative-inhibits-triple-negative-breast-cancer-cell-activity-by-inducing-oxidative-stress-mediated-paraptosis-like-cell-death
#5
Jeng-Yuan Shiau, Kyoko Nakagawa-Goto, Kuo-Hsiung Lee, Lie-Fen Shyur
Triple negative breast cancer (TNBC) is a highly metastatic cancer among the breast cancer subgroups. A thorny issue for clinical therapy of TNBC is lack of an efficient targeted therapeutic strategy. We previously created a novel sesquiterpene lactone analog (named DETD-35) derived from plant deoxyelephantopin (DET) which exhibits potent effects against human TNBC MDA-MB-231 tumor growth in a xenograft mouse model. Here we studied the mechanisms of both DET and DETD-35 against MDA-MB-231 cells. DETD-35 (3-fold decreased in IC50) exhibited better anti-TNBC cell activity than DET as observed through induction of reactive oxygen species production (within 2 h treatment) and damage to the ER structures, resulting in ER-derived cytoplasmic vacuolation and ubiquitinated protein accumulation in the treated cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915597/il-8-promotes-inflammatory-mediators-and-stimulates-activation-of-p38-mapk-erk-nf-%C3%AE%C2%BAb-pathway-and-reduction-of-jnk-in-hnscc
#6
Leong-Perng Chan, Cheng Liu, Feng-Yu Chiang, Ling-Feng Wang, Ka-Wo Lee, Wan-Ting Chen, Po-Lin Kuo, Chia-Hua Liang
This investigation identifies interleukin 8 (IL-8) as the main inflammatory mediator in head and neck squamous cell carcinoma (HNSCC). The expressions of chemokines of IL-8, IL-1β and IL-6 and the cytokines of tumor necrosis factor-α (TNF-α) were higher in HNSCC patient tissues than in non-cancerous matched tissues (NCMT) whereas the expression of IL-10 was lower. IL-8 is most highly expressed in the tissues of patients with HNSCC. Treatment of HNSCC cells with IL-8 increased the secretion of IL-1β, IL-6 and TNF-α and reduced IL-10 expression; the increase in the expression of IL-1β was particularly considerable...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915576/hepatic-b-cell-leukemia-3-suppresses-chemically-induced-hepatocarcinogenesis-in-mice-through-altered-mapk-and-nf-%C3%AE%C2%BAb-activation
#7
Nadine Gehrke, Marcus A Wörns, Amrit Mann, Yvonne Huber, Nadine Hoevelmeyer, Thomas Longerich, Ari Waisman, Peter R Galle, Jörn M Schattenberg
The transcriptional nuclear factor kappa B (NF-κB)-coactivator B cell leukemia-3 (Bcl-3) is a molecular regulator of cell death and proliferation. Bcl-3 has been shown to be widely expressed in different cancer types including hepatocellular carcinoma (HCC). Its influence on hepatocarcinogenesis is still undetermined. To examine the role of Bcl-3 in hepatocarcinogenesis mice with hepatocyte-specific overexpression of Bcl-3 (Bcl-3(Hep)) were exposed to diethylnitrosamine (DEN) and phenobarbital (PB). Hepatic Bcl-3 overexpression attenuated DEN/PB-induced hepatocarcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913568/piperlongumine-induces-g2-m-phase-arrest-and-apoptosis-in-cholangiocarcinoma-cells-through-the-ros-jnk-erk-signaling-pathway
#8
Sunisa Thongsom, Wipa Suginta, Kyung Jin Lee, Han Choe, Chutima Talabnin
Cholangiocarcinoma (CCA) is an aggressive, metastatic bile duct cancer. CCA is difficult to diagnose, and responds poorly to current radio- and chemo-therapy. Piperlongumine (PL) is a naturally-occurring small molecule selectively toxic to cancer cells by targeting reactive oxygen species (ROS). In this study, we demonstrated the potential anticancer activity of PL in CCA. PL markedly induced death in CCA cell lines in a dose- and time-dependent manner through the activation of caspase-3 and PARP. PL also stimulated ROS accumulation in CCA...
September 14, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#9
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28912272/the-transcription-factor-hoxb7-regulates-erk-kinase-activity-and-thereby-stimulates-the-motility-and-invasiveness-of-pancreatic-cancer-cells
#10
Makiko Tsuboi, Keisuke Taniuchi, Takahiro Shimizu, Motoaki Saito, Toshiji Saibara
HOX genes encode transcription factors that function as sequence-specific transcription factors that are involved in cellular proliferation, differentiation, and death. The aim of this study was to investigate the role of a HOX family protein, HOXB7, in the motility and invasiveness of pancreatic cancer cells. We previously identified a HOXB7 transcript that is one of a number of transcripts that are preferentially translated in membrane protrusions in pancreatic cancer cells. Immunocytochemistry showed that HOXB7 was localized to the cell protrusions of migrating pancreatic cancer cells...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912082/mapk-signalling-pathway-in-cancers-olive-products-as-cancer-preventive-and-therapeutic-agents
#11
REVIEW
Ilaria Peluso, Nagendra Sastry Yarla, Roberto Ambra, Gianni Pastore, George Perry
The mitogen-activated protein kinases (MAPKs) are fundamental in inflammation and cancer control, through the crosstalk between the redox regulated nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-kB (NFκB) gene expression. MAPKs regulate various cellular activities involved in cancer progression, including proliferation, apoptosis and immune escape and blockade of upstream kinases is a current therapeutic strategy. However, these therapies are associated with some adverse effects and with the paradoxical activation of the MAPKs pathway...
September 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28910144/ask1-inhibition-halts-disease-progression-in-preclinical-models-of-pulmonary-arterial-hypertension
#12
Grant R Budas, Mario Boehm, Baktybek Kojonazarov, Gayathri Viswanathan, Xia Tian, Swathi Veeroju, Tatyana Novoyatleva, Friedrich Grimminger, Ford Hinojosa-Kirschenbaum, Hossein A Ghofrani, Norbert Weissmann, Werner Seeger, John T Liles, Ralph T Schermuly
RATIONALE Progression of pulmonary arterial hypertension (PAH) is associated with pathologic remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of mitogenactivated protein kinases (MAPKs) which stimulate apoptosis, inflammation and fibrosis. OBJECTIVES We investigated whether pharmacological inhibition of the redoxsensitive apical MAPK Apoptosis Signal-Regulating Kinase 1 (ASK1) can halt the progression of pulmonary vascular and RV remodeling...
September 14, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28906110/anti-in%C3%AF-ammatory-effect-of-essential-oil-from-citrus-aurantium-l-var-amara-engl
#13
Chun-Yan Shen, Jian-Guo Jiang, Qin Ou-Yang, Wei Zhu
Essential oil has been popularly used as an alternative for the treatment of inflammation. The bioactivities of essential oil from blossoms of Citrus aurantium L. var. amara Engl (CAVAO) showed greater anti-inflammation potential than that of antioxidant, anticancer, and 3T3-L1 proliferation inhibition. CAVAO (250 μg/mL) significantly inhibited production of nitric oxide (NO) (99.54%±2.81), interleukin-6 (IL-6) (98.11%±1.62), tumor necrosis factor-alpha (TNF-α) (41.84%±1.52) and interleukin-1beta (IL-1β) (56...
September 14, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28905993/overexpression-of-f-box-only-protein-31-predicts-poor-prognosis-and-deregulates-p38%C3%AE-and-jnk-mediated-apoptosis-in-esophageal-squamous-cell-carcinoma
#14
Jia Liu, Liang Lv, Jian Gong, Yuyong Tan, Yun Zhu, Yinghuan Dai, Xin Pan, Michael S Y Huen, Bin Li, Sai Wah Tsao, Jirong Huo, Annie L M Cheung
F-box only protein 31 (FBXO31), a subunit of the Skp1-Cul1-F box ubiquitin ligase, plays a crucial role in DNA damage response and tumorigenesis. Yet its expression and function vary in different types of human cancer. The expression of FBXO31 in esophageal squamous cell carcinoma (ESCC) and its association with clinicopathological features is not well studied. The underlying mechanism by which deregulated FBXO31 contributes to ESCC tumorigenesis is largely unknown. By immunohistochemical analysis of a tissue microarray containing 85 cases of ESCC and matched adjacent non-cancerous tissue and an additional 10 cases of ESCC tissue samples, we found that FBXO31 was overexpressed in ESCC, and that its expression was significantly correlated with histological grade (P = 0...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28905938/triptolide-induces-sertoli-cell-apoptosis-in-mice-via-ros-jnk-dependent-activation-of-the-mitochondrial-pathway-and-inhibition-of-nrf2-mediated-antioxidant-response
#15
Yu Wang, Su-Han Guo, Xue-Jun Shang, Li-Sha Yu, Jian-Wei Zhu, Ang Zhao, Yan-Fen Zhou, Guo-Hua An, Qi Zhang, Bo Ma
Triptolide (TP), an oxygenated diterpene, has a variety of beneficial pharmacodynamic activities but its clinical applications are restricted due to severe testicular injury. This study aimed to delineate the molecular mechanisms of TP-induced testicular injury in vitro and in vivo. TP (5-50000 nmol/L) dose-dependently decreased the viability of TM4 Sertoli cells with an IC50 value of 669.5-269.45 nmol/L at 24 h. TP (125, 250, and 500 nmol/L) dose-dependently increased the accumulation of ROS, the phosphorylation of JNK, mitochondrial dysfunction and activation of the intrinsic apoptosis pathway in TM4 cells...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28904993/abnormalities-of-signal-transduction-networks-in-chronic-schizophrenia
#16
Jennifer L McGuire, Erica A Depasquale, Adam J Funk, Sinead M O'Donnovan, Kathryn Hasselfeld, Shruti Marwaha, John H Hammond, Vahram Hartounian, James H Meador-Woodruff, Jarek Meller, Robert E McCullumsmith
Schizophrenia is a serious neuropsychiatric disorder characterized by disruptions of brain cell metabolism, microstructure, and neurotransmission. All of these processes require coordination of multiple kinase-mediated signaling events. We hypothesize that imbalances in kinase activity propagate through an interconnected network of intracellular signaling with potential to simultaneously contribute to many or all of the observed deficits in schizophrenia. We established a workflow distinguishing schizophrenia-altered kinases in anterior cingulate cortex using a previously published kinome array data set...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28904363/calcitriol-reduces-kidney-development-disorders-in-rats-provoked-by-losartan-administration-during-lactation
#17
Lucas Ferreira de Almeida, Heloísa Della Coletta Francescato, Cleonice Giovanini Alves da Silva, Roberto Silva Costa, Terezila Machado Coimbra
Calcitriol has important effects on cellular differentiation and proliferation, as well as on the regulation of the renin gene. Disturbances in renal development can be observed in rats exposed to angiotensin II (AngII) antagonists during lactation period. The lack of tubular differentiation in losartan-treated rats can affect calcitriol uptake. This study evaluated the effect of calcitriol administration in renal development disturbances in rats provoked by losartan (AngII type 1 receptor antagonist) administration during lactation...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28902366/heat-shock-protein-27-hspb1-suppresses-the-pdgf-bb-induced-migration-of-osteoblasts
#18
Shingo Kainuma, Haruhiko Tokuda, Naohiro Yamamoto, Gen Kuroyanagi, Kazuhiko Fujita, Tetsu Kawabata, Go Sakai, Rie Matsushima-Nishiwaki, Osamu Kozawa, Takanobu Otsuka
Heat shock protein 27 (HSP27/HSPB1), one of the small heat shock proteins, is constitutively expressed in various tissues. HSP27 and its phosphorylation state participate in the regulation of multiple physiological and pathophysiological cell functions. However, the exact roles of HSP27 in osteoblasts remain unclear. In the present study, we investigated the role of HSP27 in the platelet-derived growth factor‑BB (PDGF‑BB)‑stimulated migration of osteoblast-like MC3T3-E1 cells. PDGF-BB by itself barely upregulated the expression of HSP27 protein, but stimulated the phosphorylation of HSP27 in these cells...
September 1, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28902357/expression-of-wnt3a-in-hepatocellular-carcinoma-and-its-effects-on-cell-cycle-and-metastasis
#19
Caijie Lu, Yifeng He, Juan Duan, Yongguang Yang, Chunqiang Zhong, Jian Zhang, Weiguo Liao, Xiaojie Huang, Runzhi Zhu, Mingyi Li
Invasion and metastasis are the primary causes of mortality from hepatocellular carcinoma (HCC). Effective inhibition against participants in the tumourigenesis and metastasis process is critical for treatment of HCC. Wnt3a is involved in the development and metastasis of many malignant tumours. However, the specific mechanisms of Wnt3a-mediated cell proliferation, invasion and metastasis in HCC remain unclear. In this study, we found that Wnt3a and its target gene c‑Myc showed higher expression in tumour tissues than normal liver tissues in HCC patients; 71...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28901513/antitumor-activity-of-2%C3%A2-2e-%C3%A2-3-7%C3%A2-dimethyl%C3%A2-2-6%C3%A2-octadienyl-%C3%A2-6%C3%A2-methyl%C3%A2-2-5%C3%A2-cyclohexadiene%C3%A2-1-4%C3%A2-dione-isolated-from-the-aerial-part-of-atractylodes%C3%A2-macrocephala-in-hepatocellular-carcinoma
#20
Lei Li, Rui Zhao, Ying Li, Wen-Hui Wang
2‑[(2E)‑3,7‑dimethyl‑2,6‑octadienyl]‑6‑methy l‑2,5‑cyclohexadiene‑1,4‑dione (DMD) is a compound isolated from Atractylodes macrocephala; however, its antitumor activity has not yet been investigated. Therefore, the present study aimed to investigate the antitumor activity of DMD in the H22 mouse hepatocellular carcinoma (HCC) cell line in vitro and in vivo. In the present study, the antiproliferative effects of DMD against H22 cells were evaluated using the MTT assay in vitro. Furthermore, xenograft nude mice were established to evaluate the antitumor effects of DMD on H22 cells in vivo...
August 29, 2017: Molecular Medicine Reports
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