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https://www.readbyqxmd.com/read/28230287/therapeutic-potential-of-targeting-pi3k-akt-pathway-in-treatment-of-colorectal-cancer-rational-and-progress
#1
Afsane Bahrami, Majid Khazaei, Malihe Hasanzadeh, Soodabeh ShahidSales, Mona Joudi Mashhad, Marjaneh Farazestanian, Hamid Reza Sadeghnia, Majid Rezayi, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
PI3K/AKT/mTOR signaling pathway is one of the key dysregulated pathways in different tumor types, including colorectal cancer (CRC). Activation of this pathway is shown to be related with cellular transformation, tumor progression, cell survival and drug resistance. There is growing body of data evaluating the value of PI3K/AKT/mTOR inhibitors in CRC (e.g., BEZ235, NVP-BEZ235, OSI-027, everolimus, MK-2206, KRX-0401, BYL719 and BKM120). This report summarizes the current knowledge about PI3K/AKT pathway and its cross talk with ERK/MAPK and mTOR pathways with particular emphasis on the value of targeting this pathway as a potential therapeutic target in treatment of colorectal cancer...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28225870/pdk2-promotes-chondrogenic-differentiation-of-mesenchymal-stem-cells-by-upregulation-of-sox6-and-activation-of-jnk-mapk-erk-pathway
#2
H Wang, X B Shan, Y J Qiao
This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males). Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6), type ΙΙ procollagen gene (COL2A1), cartilage oligomeric matrix protein (COMP), aggrecan (AGC1), type ΙX procollagen gene (COL9A2) and collagen type 1 alpha 1 (COL1A1) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR)...
February 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28224114/ha-triggers-the-switch-from-mek1-sumoylation-to-phosphorylation-of-the-erk-pathway-in-influenza-a-virus-infected-cells-and-facilitates-its-infection
#3
Chengmin Wang, Huimin Liu, Jing Luo, Lin Chen, Meng Li, Wen Su, Na Zhao, Shelan Liu, Li Xie, Yaxiong Jia, Hua Ding, Xiufeng Wan, Hongxuan He
Several post-translational modifications in host cells are hijacked by pathogens to facilitate their propagation. A number of components of the influenza virus have been reported to be modified by small ubiquitin-like modifier (SUMO) proteins during infection. We hypothesized that the MAPK/ERK pathway could be modified by SUMO1 because the SUMOylation of MEK1 was quickly eliminated after influenza A virus infection. We identified host cell MEK1 as a target of SUMO1 through LC/MS/MS, and enhanced MEK1 SUMOylation inhibited the infection of the virus, while inhibition of host cell MEK1 SUMOylation facilitated virus propagation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#4
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28222438/microrna-29b-inhibits-angiogenesis-by-targeting-vegfa-through-the-mapk-erk-and-pi3k-akt-signaling-pathways-in-endometrial-carcinoma
#5
Hong-Xia Chen, Xiao-Xia Xu, Bu-Zhen Tan, Zhi Zhang, Xiao-Dong Zhou
OBJECTIVE: The purpose of this study is to explore the effects of microRNA-29b (miR-29b) regulating MAPK/ERK and PI3K/Akt signaling pathways on angiogenesis in endometrial carcinoma (EC) by targeting VEGFA. METHODS: Between February 2013 and April 2015, 126 EC patients admitted to the Second Affiliated Hospital of Nanchang University were randomly selected, with 126 EC tissues and the corresponding adjacent normal tissues collected after surgery. The human EC cell lines RL-95-2 and HEC-1-B and human endometrial cells were assigned to the normal group (human endometrial cells), the blank group (untransfected RL-95-2 or HEC-1-B cells), the pMIR-control group (RL-95-2 or HEC-1-B cells transfected with an empty vector), the pMIR-miR-29b group (RL-95-2 or HEC-1-B cells transfected with the miR-29b plasmid), LNA-control group (RL-95-2 or HEC-1-B cells transfected with an oligonucleotide inhibitors control), the LNA-miR-29b inhibitors group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors), the LNA-miR-29b inhibitors + PD98059 group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and PD98059, an inhibitor of the MAPK/ERK signaling pathway) and the LNA-miR-29b inhibitors + wortmannin group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and wortmannin, an inhibitor of the PI3K/Akt signaling pathway)...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28219951/generation-of-thalamic-neurons-from-mouse-embryonic-stem-cells
#6
Atsushi Shiraishi, Keiko Muguruma, Yoshiki Sasai
Thalamus is a diencephalic structure that plays crucial roles in relaying and modulating sensory and motor information to the neocortex. The thalamus develops in the dorsal part of the neural tube at the level of the caudal forebrain. However, the molecular mechanisms that are essential for thalamic differentiation are still unknown. Here we have succeeded in the generation of thalamic neurons from mouse ES cells (mESCs) by modifying the default method that induces the most-anterior neural type in self-organizing culture...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28219807/setd2-is-associated-with-strontium-induced-bone-regeneration
#7
Jia Xiaoshi, Long Qiaoyun, Richard J Miron, Yin Chengcheng, Wei Yan, Zhang Yufeng, Wu Min
: Strontium Ranelate has been utilized as a preventative treatment option for osteoporosis with the release of Sr ions having a direct effect on preventing osteoclast activation and promoting osteoblast differentiation. Previously our group has prepared and characterized a porous Sr-mesoporous bioactive glass (Sr-MBG) scaffold demonstrating its ability to enhance new bone formation when compared to MBG alone. The goal of the present study was to elucidate the bone-inducing properties of Sr by utilizing RNA-seq on in vivo tissue samples to investigate potential target genes responsible for Sr-induced new bone formation...
February 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28216890/evaluate-the-antigenotoxicity-and-anticancer-role-of-%C3%AE-sitosterol-by-determining-oxidative-dna-damage-and-the-expression-of-phosphorylated-mitogen-activated-protein-kinases-c-fos-c-jun-and-endothelial-growth-factor-receptor
#8
Ramalingam Sharmila, Ganapathy Sindhu
BACKGROUND: Plant sterols are the major source of micronutrients and have not shown any obvious side effects in human. β-sitosterol is one of the most prevalent phytosterols which have been recorded in ancient medicinal history for its use in the treatment of many chronic diseases, especially cancer. The modulations of mitogen-activated protein kinases' (MAPKs') play a crucial role in the development of human renal cell carcinoma. OBJECTIVE: The aim of the current study is to evaluate the antigenotoxic and anticancer role of β-sitosterol against renal carcinogen...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216438/porphyromonas-gingivalis-lipopolysaccharide-induces-pro-inflammatory-adipokine-secretion-and-oxidative-stress-by-regulating-toll-like-receptor-mediated-signaling-pathways-and-redox-enzymes-in-adipocytes
#9
Fanny Le Sage, Olivier Meilhac, Marie-Paule Gonthier
Gut microbiota LPS contributes to obesity-related chronic inflammation and oxidative stress, promoting insulin resistance. Periodontal disease also represents a risk factor for type 2 diabetes and is associated with obesity. This study compared the effect of LPS from P. gingivalis periodontopathogen and E. coli enterobacteria on inflammatory adipokine secretion and redox status of 3T3-L1 adipocytes. We found that both LPS activated TLR2- and TLR4-mediated signaling pathways involving MyD88 adaptor and NFκB transcription factor, leading to an increased secretion of leptin, resistin, IL-6 and MCP-1...
February 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28214973/a-multifunctional-alanine-rich-anti-inflammatory-peptide-bcp61-showed-potent-inhibitory-effects-by-inhibiting-both-nf-%C3%AE%C2%BAb-and-mapk-expression
#10
Yun Hee Choi, Yoon Seok Choi, Young Kyun Kim, Md Saifur Rahman, G C Pradeep, Jin Cheol Yoo, Joo-Won Suh
The purified BCP61 was reported to be a unique low-molecular-weight (MW) anti-microbial peptide because of its non-identical alanine-rich N-terminal sequence. In this study, we investigated the anti-inflammatory effects of BCP61 on induction of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. The treatment with BCP61, with varying concentrations of 10, 50, and 100 μg/mL, inhibited levels of expression of LPS-induced NF-κB and MAPKs (extracellular signal-related kinases (ERKs), c-Jun NH2-terminal kinase (JNK), and mitogen-activated protein (p38)) as well as production of pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)...
February 18, 2017: Inflammation
https://www.readbyqxmd.com/read/28214882/il-1%C3%AE-up-regulates-il-6-expression-in-bovine-granulosa-cells-via-mapks-and-nf-%C3%AE%C2%BAb-signaling-pathways
#11
Meng Yang, Xurong Wang, Lei Wang, Xuezhi Wang, Jianxi Li, Zhiqiang Yang
BACKGROUND/AIMS: IL-6 is one of the main cytokines in regulating ovarian follicular development and ovulation. However, the factors that regulate IL-6 expression in follicles are still unclear. The aim of this study was to elucidate the mechanisms underlying the effect of IL-1α on IL-6 expression in granulosa cells. METHODS: IL-6 expression after IL-1α with/without inhibitors treatment was analyzed by RT-qPCR and ELISA. The phosphorylation of proteins induced by IL-1α was analyzed by western blot...
January 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214858/hepatitis-b-virus-core-antigen-stimulates-il-6-expression-via-p38-erk-and-nf-%C3%AE%C2%BAb-pathways-in-hepatocytes
#12
Zhi Chen, Yang-Xia Li, Hai-Jing Fu, Yan-Li Ren, Ling Zou, Shi-Zhen Shen, Ping Chen, Ting Sun, Chun-Hong Huang
BACKGROUND: Hepatitis B virus (HBV) causes both acute and chronic liver injury. Viral proteins are involved in the pathological progress. Hepatitis B core antigen (HBcAg), a component of viral nucleocapsid, is not only essential for HBV lifecycle, but also exhibits strong immunogenicity. The cytoplasmic location of HBcAg in liver biopsy is associated with liver injury and inflammation, but the exact mechanisms remain to be elaborated. METHODS: Huh7, SMMC-7721 and L-02 cells were transfected with pEGFP-N1-HBcAg to establish an intracellular HBcAg expression model...
January 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214826/emodin-increases-expression-of-insulin-like-growth-factor-binding-protein-1-through-activation-of-mek-erk-ampk%C3%AE-and-interaction-of-ppar%C3%AE-and-sp1-in-lung-cancer
#13
Qing Tang, JingJing Wu, Fang Zheng, Swei Sunny Hann, YuQing Chen
BACKGROUND: Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#14
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signaling-and-promotes-lipid-accumulation-in-hepatocytes
#15
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signaling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28213093/enhanced-effect-of-geldanamycin-nanocomposite-against-breast-cancer-cells-growing-in-vitro-and-as-xenograft-with-vanquished-normal-cell-toxicity
#16
Suma Prabhu, Preeta Ananthanarayanan, Kannangar Aziz Sajida, Sharada Rai, Srinivas Mutalik, Satish Rao Bola Sadashiva
Despite enormous advances in remedies developed for breast cancer, an effective therapeutic strategy by targeting malignant cells with the least normal tissue toxicity is yet to be developed. Hsp90 is considered to be an important therapeutic target to inhibit cell proliferation. Geldanamycin (GDM), a potent inhibitor of Hsp90 was withdrawn from clinical trials due to its undesirable hepatotoxicity. We report a superparamagnetic iron oxide (SPION) based polymeric nanocomposite of GDM augmenting anticancer competence with decreased hepatic toxicity...
February 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28212583/role-of-topk-in-lipopolysaccharide-induced-breast-cancer-cell-migration-and-invasion
#17
Min-Ah Seol, Jung-Hwan Park, Ji Heun Jeong, Jungmook Lyu, Seung Yun Han, Sang-Muk Oh
Inflammation has been known to be linked to invasion or metastasis of breast cancer, which has poor prognosis, although the regulatory mechanism remains to be undiscovered. Here we show that T-LAK cell-originated protein kinase (TOPK) mediates pro-inflammatory endotoxin lipopolysaccharide (LPS)-induced breast cancer cell migration and invasion. The mRNA or protein level of TOPK, toll- like receptor4 (TLR4), interleukin (IL)-6, vascular endothelial growth factor (VEGF) or matrix metalloproteinase9 (MMP9) genes related to TLR4 signaling or tumor progression was induced by LPS treatment in MCF7 breast cancer cells, but the induction was abolished by stable knocking down of TOPK in MCF7 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211523/pedf-mediates-pathological-neovascularization-by-regulating-macrophage-recruitment-and-polarization-in-the-mouse-model-of-oxygen-induced-retinopathy
#18
Sha Gao, Changwei Li, Yanji Zhu, Yanuo Wang, Ailing Sui, Yisheng Zhong, Bing Xie, Xi Shen
Macrophages have been demonstrated to play a proangiogenic role in retinal pathological vascular growth. Pigment epithelium-derived factor (PEDF) works as a powerful endogenous angiogenesis inhibitor, but its role in macrophage recruitment and polarization is largely unknown. To explore the underlying mechanisms, we first evaluated macrophage polarization in the retinas of the oxygen-induced retinopathy (OIR) mouse model. Compared to that in normal controls, M1- and M2-like macrophages were all abundantly increased in the retinas of OIR mice...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209621/prominent-oncogenic-roles-of-evi1-in-breast-carcinoma
#19
Hui Wang, Thorsten Schaefer, Martina Konantz, Martin Braun, Zsuzsanna Varga, Anna M Paczulla, Selina Reich, Francis Jacob, Sven Perner, Holger Moch, Tanja Fehm, Lothar Kanz, Klaus Schulze-Osthoff, Claudia Lengerke
Overexpression of the EVI1 oncogene is associated typically with aggressive myeloid leukemia, but is also detectable in breast carcinoma (BC) where its contributions are unexplored. Analyzing a tissue microarray of 608 BC patient specimens, we documented EVI1 overexpression in both estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC. Here we report prognostic relevance of EVI1 overexpression in triple-negative BC (TNBC) but not in the HER2-positive BC subset. In human breast cancer cells, EVI1 silencing reduced proliferation, apoptosis resistance and tumorigenicity, effects rescued by estrogen supplementation in ER+ BC cells...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209487/lipoxin-a4-suppresses-osteoclastogenesis-in-raw264-7-cells-and-prevents-ovariectomy-induced-bone-loss
#20
Changyu Liu, Hanfeng Guan, Cong Cai, Feng Li, Jun Xiao
Lipoxin A4 (LXA4; 5S, 6R, 15Strihydroxy- 7,9,13-trans-11-eicosatetraenoic acid) is a metabolic product of arachidonic acid under the action of lipoxidase. This lipid molecule plays important roles in several biological functions, especially inflammatory processes. In vivo, LXA4 regulates the inflammatory response through several signaling pathways. Its mechanism suggests that it might have an effect on osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, it was here observed that LXA4 could significantly inhibit the formation and function of osteoclasts and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4)...
February 13, 2017: Experimental Cell Research
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