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https://www.readbyqxmd.com/read/29470488/intracellular-amyloid-beta-expression-leads-to-dysregulation-of-the-mitogen-activated-protein-kinase-and-bone-morphogenetic-protein-2-signaling-axis
#1
Eric Cruz, Sushil Kumar, Li Yuan, Jyothi Arikkath, Surinder K Batra
Alzheimer's disease (AD) is a neurodegenerative syndrome classically depicted by the parenchymal accumulation of extracellular amyloid beta plaques. However, recent findings suggest intraneuronal amyloid beta (iAβ1-42) accumulation precedes extracellular deposition. Furthermore, the pathologic increase in iAβ1-42 has been implicated in dysregulation of cellular mechanisms critically important in axonal transport. Owing to neuronal cell polarity, retrograde and anterograde axonal transport are essential trafficking mechanism necessary to convey membrane bound neurotransmitters, neurotrophins, and endosomes between soma and synaptic interfaces...
2018: PloS One
https://www.readbyqxmd.com/read/29470423/3-5-6-7-8-3-4-heptamethoxyflavone-a-citrus-flavonoid-inhibits-collagenase-activity-and-induces-type-i-procollagen-synthesis-in-hdfn-cells
#2
Hong-Il Kim, Yong-Un Jeong, Jong-Hyeon Kim, Young-Jin Park
Citrus fruits contain various types of flavonoids with powerful anti-aging and photoprotective effects on the skin, and have thus been attracting attention as potential, efficacious skincare agents. Here, we aimed to investigate the chemical composition of Citrus unshiu and its protective effects on photoaging. We isolated and identified a bioactive compound, 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), from C. unshiu peels using ethanol extraction and hexane fractionation. HMF inhibited collagenase activity and increased type I procollagen content in UV-induced human dermal fibroblast neonatal (HDFn) cells...
February 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29467321/development-of-mk-8353-an-orally-administered-erk1-2-inhibitor-in-patients-with-advanced-solid-tumors
#3
Stergios J Moschos, Ryan J Sullivan, Wen-Jen Hwu, Ramesh K Ramanathan, Alex A Adjei, Peter C Fong, Ronnie Shapira-Frommer, Hussein A Tawbi, Joseph Rubino, Thomas S Rush, Da Zhang, Nathan R Miselis, Ahmed A Samatar, Patrick Chun, Eric H Rubin, James Schiller, Brian J Long, Priya Dayananth, Donna Carr, Paul Kirschmeier, W Robert Bishop, Yongqi Deng, Alan Cooper, Gerald W Shipps, Blanca Homet Moreno, Lidia Robert, Antoni Ribas, Keith T Flaherty
BACKGROUND: Constitutive activation of ERK1/2 occurs in various cancers, and its reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual mechanism inhibitor SCH772984 has shown promising preclinical activity across various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts. METHODS: We have developed an orally bioavailable ERK inhibitor, MK-8353; conducted preclinical studies to demonstrate activity, pharmacodynamic endpoints, dosing, and schedule; completed a study in healthy volunteers (P07652); and subsequently performed a phase I clinical trial in patients with advanced solid tumors (MK-8353-001)...
February 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29466417/epinephrine-modulates-na-k-atpase-activity-in-caco-2-cells-via-src-p38mapk-erk-and-pge2
#4
Layla El Moussawi, Mohamed Chakkour, Sawsan I Kreydiyyeh
Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na+-gradient created by the Na+/K+-ATPase. Whether epinephrine acts via an effect on the Na+/K+-ATPase hasn't been studied before. The aim of this work was to investigate the effect of epinephrine on the Na+/K+-ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a model...
2018: PloS One
https://www.readbyqxmd.com/read/29463989/combined-delivery-of-sorafenib-and-a-mek-inhibitor-using-cxcr4-targeted-nanoparticles-reduces-hepatic-fibrosis-and-prevents-tumor-development
#5
Yun-Chieh Sung, Ya-Chi Liu, Po-Han Chao, Chih-Chun Chang, Pei-Ru Jin, Ts-Ting Lin, Ja-An Lin, Hui-Teng Cheng, Jane Wang, Charles P Lai, Ling-Hsuan Chen, Anthony Y Wu, Ting-Lun Ho, Tsaiyu Chiang, Dong-Yu Gao, Dan G Duda, Yunching Chen
Liver damage and fibrosis are precursors of hepatocellular carcinoma (HCC). In HCC patients, sorafenib-a multikinase inhibitor drug-has been reported to exert anti-fibrotic activity. However, incomplete inhibition of RAF activity by sorafenib may also induce paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in malignant cells. The consequence of this effect in non-malignant disease (hepatic fibrosis) remains unknown. This study aimed to examine the effects of sorafenib on activated hepatic stellate cells (HSCs), and develop effective therapeutic approaches to treat liver fibrosis and prevent cancer development...
2018: Theranostics
https://www.readbyqxmd.com/read/29463855/zearalenone-altered-the-cytoskeletal-structure-via-er-stress-autophagy-oxidative-stress-pathway-in-mouse-tm4-sertoli-cells
#6
Wanglong Zheng, Bingjie Wang, Mengxue Si, Hui Zou, Ruilong Song, Jianhong Gu, Yan Yuan, Xuezhong Liu, Guoqiang Zhu, Jianfa Bai, Jianchun Bian, ZongPing Liu
The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress...
February 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29459829/stimulation-of-jnk-phosphorylation-by-the-ptth-in-prothoracic-glands-of-the-silkworm-bombyx-mori
#7
Shi-Hong Gu, Gen Li, Hsiao-Yen Hsieh, Pei-Ling Lin, Sheng Li
In this study, phosphorylation of c-Jun N-terminal kinase (JNK) by the prothoracicotropic hormone (PTTH) was investigated in prothoracic glands (PGs) of the silkworm, Bombyx mori . Results showed that JNK phosphorylation was stimulated by the PTTH in time- and dose-dependent manners. In vitro activation of JNK phosphorylation in PGs by the PTTH was also confirmed in an in vivo experiment, in which a PTTH injection greatly increased JNK phosphorylation in PGs of day-6 last instar larvae. JNK phosphorylation caused by PTTH stimulation was greatly inhibited by U73122, a potent and specific inhibitor of phospholipase C (PLC) and an increase in JNK phosphorylation was also detected when PGs were treated with agents (either A23187 or thapsigargin) that directly elevated the intracellular Ca2+ concentration, thereby indicating involvement of PLC and Ca2+ ...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29456683/carbenoxolone-inhibits-mechanical-stress-induced-osteogenic-differentiation-of-mesenchymal-stem-cells-by-regulating-p38-mapk-phosphorylation
#8
Shenglong Li, Jing Wang, Yudi Han, Xiaoteng Li, Changjian Liu, Zhengshuai Lv, Xiuhui Wang, Xin Tang, Zhe Wang
The aim of the present study was to explore the effects of pannexin1 (Px1) protein channels on osteogenic differentiation of mesenchymal stem cells (MSCs) under mechanical stress stimulation. MSCs were isolated from Sprague Dawley rats (3 weeks old, weighing 100-120 g) and cultured in vitro . A safe concentration of carbenoxolone was determined (CBX, an inhibitor of Px1 channels; 100 µM) on MSCs using the Cell Counting Kit-8 (CCK8) method. MSCs were divided into 6 groups: Control, stress (4,000 µ strain), and stress following 3, 6, 12, and 24 h pretreatment with CBX...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29454790/increased-expression-of-the-long-non-coding-rna-linc01503-regulated-by-tp63-in-squamous-cell-carcinoma-and-effects-on-oncogenic-activities-of-cancer-cell-lines
#9
Jian-Jun Xie, Yan-Yi Jiang, Yuan Jiang, Chun-Quan Li, Lim-Mei Chee, Omer An, Anand Mayakonda, Ling-Wen Ding, Lin Long, Chun Sun, Le-Hang Lin, Li Chen, Jian-Yi Wu, Zhi-Yong Wu, Qi Cao, Wang-Kai Fang, Wei Yang, Stephen J Meltzer, Henry Yang, Melissa Fullwood, Li-Yan Xu, En-Min Li, De-Chen Lin, H Phillip Koeffler
BACKGROUND & AIMS: Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function. METHODS: We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription PCR assays to measure expression levels of LINC01503...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29451351/delphinidin-induces-apoptosis-and-inhibits-epithelial-to-mesenchymal-transition-via-the-erk-p38-mapk-signaling-pathway-in-human-osteosarcoma-cell-lines
#10
Hae-Mi Kang, Bong-Soo Park, Hyun-Kyung Kang, Hae-Ryoun Park, Su-Bin Yu, In-Ryoung Kim
Delphinidin is major anthocyanidin that is extracted from many pigmented fruits and vegetables. This substance has anti-oxidant, anti-inflammatory, anti-angiogenic, and anti-cancer properties. In addition, delphinidin strongly suppresses the migration and invasion of various cancer cells during tumorigenesis. Although delphinidin has anti-cancer effects, little is known about its functional roles in osteosarcoma (OS). For these reasons, we have demonstrated the effects of delphinidin on OS cell lines. The effects of delphinidin on cell viability and growth of OS cells were assessed using the MTT assay and colony formation assays...
February 16, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29450946/down-regulation-of-lrig1-by-microrna-20a-modulates-gastric-cancer-multidrug-resistance
#11
Lin Zhou, Xiaowei Li, Fan Zhou, Zhi'an Jin, Di Chen, Pin Wang, Shu Zhang, Yuzheng Zhuge, Yulong Shang, Xiaoping Zou
Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that up-regulation of LRIG1 enhanced chemo-sensitivity in GC cells...
February 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29449812/calycosin-orchestrates-osteogenesis-of-danggui-buxue-tang-in-cultured-osteoblasts-evaluating-the-mechanism-of-action-by-omics-and-chemical-knock-out-methodologies
#12
Amy G W Gong, Ran Duan, Huai Y Wang, Tina T X Dong, Karl W K Tsim
Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction commonly used to mitigate menopausal osteoporosis, contains two herbs: Astragali Radix (AR) and Angelicae Sinensis Radix (ASR). The exact efficacy of individual chemical(s) within DBT, or in any herbal mixture, is hard to be revealed. Calycosin and ferulic acid have been reported to be the predominant chemicals found within DBT, and its roles in regulating osteoblastic differentiation have been proposed here. To probe the roles of calycosin and ferulic acid, these chemicals were specifically depleted from the DBT extracts...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29449534/trim36-a-novel-androgen-responsive-gene-enhances-anti-androgen-efficacy-against-prostate-cancer-by-inhibiting-mapk-erk-signaling-pathways
#13
Chao Liang, Shangqian Wang, Chao Qin, Meilin Bao, Gong Cheng, Bianjiang Liu, Pengfei Shao, Qiang Lv, Ninghong Song, Lixin Hua, Min Gu, Jie Li, Zengjun Wang
Hormone therapy drugs, such as bicalutamide and enzalutamide, directed against prostate cancer focus on androgen receptor (AR) signaling and are initially effective, but the disease progresses to lethality as resistance to these drugs develops. A method to prolong the drug response time and improve the drug efficacy is still unavailable. TRIM36 was reported as a novel androgen signaling target gene and is upregulated in prostate cancer. In this study, we found that 63.4% (64/95) of PCa in TMA expressed the TRIM36 protein...
February 5, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449022/expression-patterns-of-claudin-5-and-its-related-signals-during-luteal-regression-in-pseudopregnant-rats-the-enhanced-effect-of-additional-pgf-treatment
#14
Lina Qi, Jingle Jiang, Pengjin Jin, Meiqian Kuang, Quanwei Wei, Fangxiong Shi, Dagan Mao
To study the expression patterns of claudin-5 and its related signals during luteal regression in rats, a sequential PMSG/hCG treatment paradigm was used to obtain a single, well-defined generation of corpus luteum (CL). A total of 35 rats were treated with one PGF or two PGF at an interval of 24 h from day 7 of pseudopregnancy to induce CL regression. Serum and ovaries were collected at 0, 2, 4, 8 or 24 h after one PGF injection (1 PGF), 2 or 24 h after two PGF injections (2 PGF). The serum progesterone level was detected by RIA; the ovarian expression of claudin-5, the phosphorylations of STAT3 (p-STAT3), Akt (p-Akt), ERK1/2 (p-ERK) and p38 MAPK (p-p38) were detected by western blot, real-time PCR and IHC...
February 12, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29445342/the-a-2b-adenosine-receptor-modulates-the-epithelial-mesenchymal-transition-through-the-balance-of-camp-pka-and-mapk-erk-pathway-activation-in-human-epithelial-lung-cells
#15
Chiara Giacomelli, Simona Daniele, Chiara Romei, Laura Tavanti, Tommaso Neri, Ilaria Piano, Alessandro Celi, Claudia Martini, Maria L Trincavelli
The epithelial-mesenchymal transition (EMT) is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A 2B adenosine receptor subtype activation, too...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29445192/spry2-is-a-novel-met-interactor-that-regulates-metastatic-potential-and-differentiation-in-rhabdomyosarcoma
#16
Masum Saini, Aakanksha Verma, Sam J Mathew
Rhabdomyosarcoma (RMS) is a predominantly pediatric soft-tissue cancer where the tumor cells exhibit characteristics of the developing skeletal muscle, and the two most common sub-types are embryonal and alveolar RMS. Elevated activation of the receptor tyrosine kinase (RTK) MET is frequent in RMS and is thought to cause increased tumor metastasis and lack of differentiation. However, the reasons underlying dysregulated MET expression and activation in RMS are not well understood. Therefore, we explored the role of Sprouty 2 (SPRY2), a modulator of RTK signaling, in regulating MET...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444893/dusp6-attenuates-ras-mapk-signaling-to-limit-zebrafish-heart-regeneration
#17
Maria A Missinato, Manush Saydmohammed, Daniel A Zuppo, Krithika S Rao, Graham W Opie, Bernhard Kühn, Michael Tsang
Zebrafish regenerate cardiac tissue through proliferation of pre-existing cardiomyocytes and neovascularization. Secreted growth factors such as FGFs, IGF, PDGFs, and Neuregulin (Nrg) play essential roles in stimulating cardiomyocyte proliferation. These factors activate the Ras/MAPK pathway, which is finely controlled by the feedback attenuator Dual Specificity Phosphatase 6 (Dusp6), an ERK phosphatase. Here we show that suppressing Dusp6 function enhanced cardiac regeneration. Inactivation of Dusp6 by small molecules or by gene inactivation increased cardiomyocyte proliferation, coronary angiogenesis, and reduced fibrosis after ventricular resection...
February 14, 2018: Development
https://www.readbyqxmd.com/read/29444261/selective-androgen-receptor-modulator-s42-suppresses-prostate-cancer-cell-proliferation
#18
Takako Kawanami, Tomoko Tanaka, Yuriko Hamaguchi, Takashi Nomiyama, Hajime Nawata, Tosihiko Yanase
We previously identified a novel selective androgen receptor modulator (SARM), S42, which does not stimulate prostate growth but has a beneficial effect on lipid metabolism. In the prostate cancer (PC) cell line LNCaP, S42 did not induce androgen receptor (AR) transactivation but antagonized 5α-dihydrotestosterone (DHT)-induced AR activation. Next, we investigated whether S42 suppresses the growth of PC cell lines. Basal growth of LNCaP cells was significantly suppressed by treatment with S42 compared with vehicle, as determined by cell counting and BrdU assays...
February 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29436689/microrna-655-attenuates-the-malignant-biological-behaviours-of-retinoblastoma-cells-by-directly-targeting-pax6-and-suppressing-the-erk-and-p38%C3%A2-mapk-signalling-pathways
#19
Min Zhang, Qiongxia Li, Yingzhe Pan, Hui Wang, Gang Liu, Hui Yin
Numerous studies have indicated that microRNAs (miRNAs) regulate signalling molecules by acting as oncogenes or tumour-suppressor genes in retinoblastoma (RB). Therefore, investigation of the expression pattern, biological roles and associated mechanisms of cancer-related miRNAs in RB may provide novel therapeutic targets for patients with this disease. miRNA-655 (miR-655) has been reported to be aberrantly expressed in many types of cancers. However, the expression pattern, detailed biological function and underlying molecular mechanisms of miR-655 in RB remain to be clarified...
February 13, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29436639/glycyrrhizin-affects-monocyte-migration-and-apoptosis-by-blocking-hmgb1-signaling
#20
Jia-Ying Tan, Feng Zhao, Shui-Xiang Deng, He-Chen Zhu, Ye Gong, Wei Wang
Monocytes serve an important role in systemic inflammation. High mobility group box‑1 protein (HMGB1) promotes recruitment and suppresses apoptosis in monocytes through the receptor for advanced glycation end products/ nuclear factor (NF)‑κB and toll‑like receptor 4/mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (ERK) signaling pathways. Glycyrrhizin (GL), an effective component of licorice, weakens the proinflammatory effect of HMGB1. The present study investigated the effect of GL on the migration and apoptosis of monocytes associated with HMGB1 signaling...
February 13, 2018: Molecular Medicine Reports
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