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https://www.readbyqxmd.com/read/28651331/il-1%C3%AE-up-regulates-star-and-progesterone-production-through-the-erk1-2-and-p38-mediated-creb-signaling-pathways-in-human-granulosa-lutein-cells
#1
Xuan Dang, Qinling Zhu, Yaqiong He, Yuan Wang, Yao Lu, Xiaoxue Li, Jia Qi, Hasiximuke Wu, Yun Sun
The pro-inflammatory cytokine interleukin-1β (IL-1β) may be involved in several ovulation-associated events, such as proteases synthesis, prostaglandin production and steroidogenesis in granulosa cells. However, the exact effect of IL-1β on progesterone synthesis in granulosa cells and the underlying mechanism remain unclear. By using cultured granulosa-lutein cells collected from women undergoing in vitro fertilization or intracytoplasmic sperm injection, we found that IL-1β up-regulated steroidogenic acute regulatory protein (StAR) expression and progesterone synthesis in granulosa-lutein cells, which was comparable with luteinizing hormone (LH) effect and could be abolished by an IL-1 receptor antagonist...
June 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28651235/alpinumisoflavone-inhibits-osteoclast-differentiation-and-exerts-anti-osteoporotic-effect-in-ovariectomized-mice
#2
Wei Cong, Chao Zhou, Jun Yin
Alpinumisoflavone (AIF), a naturally occurring flavonoid compound exacted from Derris eriocarpa, has been found to have a number of pharmacological activities. However, its role in bone disorder has not been investigated. The aim of this study is to evaluate the osteoprotective effect of AIF on ovariectomy-induced bone loss in mice model and related underlying mechanisms. Our study provides experimental evidence that AIF could regulate the remodeling process of bone and exert osteoprotective effect against ovariectomy-induced bone loss...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28650663/overexpression-and-lowexpression-of-selenoprotein-s-impact-ochratoxin-a-induced-porcine-cytotoxicity-and-apoptosis-in-vitro
#3
Fang Gan, Zhihua Hu, Yajiao Zhou, Kehe Huang
Our previous study demonstrated that selenium could alleviate ochratoxin A (OTA)-induced nephrotoxicity in PK15 cells. Selenoprotein S (SelS) has antioxidant activities, but it is unclear whether SelS plays a role in the alleviating effects of selenium on OTA-induced nephrotoxicity. We previously have stably transfected pig pCDNA3.1-SelS to PK15 cells to over-express SelS. Here, we demonstrated that SelS overexpression alleviated OTA-induced cytotoxicity and apoptosis as demonstrated by cell viabilities, LDH activities, Annexin V-bing, caspase 3 activities and apoptotic nuclei...
June 26, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28650427/roflumilast-reverses-polymicrobial-sepsis-induced-liver-damage-by-inhibiting-inflammation-in-mice
#4
Hongfang Feng, Jiajia Chen, Haitao Wang, Yufang Cheng, Zhengqiang Zou, Qiuping Zhong, Jiangping Xu
Sepsis is a life-threatening syndrome accompanied by an overwhelming inflammatory response and organ dysfunction. Selective targeting of phosphodiesterase 4 (PDE4) is currently being investigated as an effective therapeutic approach for inflammation-associated diseases. Roflumilast is a selective PDE4 inhibitor, used for the treatment of severe chronic obstructive pulmonary disease in clinic. However, its role in the treatment of sepsis-induced liver damage remains unclear. In the present study, we evaluated the effects of roflumilast in mice with cecal ligation and puncture-induced sepsis, and investigated the underlying mechanism...
June 26, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28649665/tgf-%C3%AE-target-genes-are-differentially-regulated-in-corneal-epithelial-cells-and-fibroblasts
#5
Xiaoqing Guo, Audrey E K Hutcheon, Jennifer A Tran, James D Zieske
PURPOSE: Transforming growth factor-beta (TGF-β) activates the canonical Smad pathway, which includes the Smad family of proteins and SARA (Smad Anchor for Receptor Activation) and other less understood pathways, including one involving p38(MAPK). The goal of the current research was to determine if corneal epithelial cells and fibroblasts used the classical or alternative TGF-β-signaling pathways. To examine this question, we made use of Trx-SARA, which inhibits native SARA, thus blocking the Smad pathway...
2017: New Front Ophthalmol
https://www.readbyqxmd.com/read/28649128/lx2343-alleviates-cognitive-impairments-in-ad-model-rats-by-inhibiting-oxidative-stress-induced-neuronal-apoptosis-and-tauopathy
#6
Xiao-Dan Guo, Guang-Long Sun, Ting-Ting Zhou, Yi-Yang Wang, Xin Xu, Xiao-Fan Shi, Zhi-Yuan Zhu, Vatcharin Rukachaisirikul, Li-Hong Hu, Xu Shen
Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress (OS) and tauopathy is believed to be one of the major players in AD development. Here, we demonstrated the capability of the small molecule N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) to ameliorate the cognitive dysfunction of AD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28648642/hpi-amf-inhibition-halts-the-development-of-the-aggressive-phenotype-of-breast-cancer-stem-cells
#7
Juan Carlos Gallardo-Pérez, Alhelí Adán-Ladrón de Guevara, Alvaro Marín-Hernández, Rafael Moreno-Sánchez, Sara Rodríguez-Enríquez
Cancer stem cells are responsible for tumor recurrence and metastasis. A new highly reproducible procedure for human breast cancer MCF-7 stem cells (BCSC) isolation and selection was developed by using a combination of hypoxia/hypoglycemia plus taxol and adriamycin for 24h. The BCSC enriched fraction (i) expressed (2-15 times) the typical stemness protein markers CD44+, ALDH1A3 and Oct 3/4; (ii) increased its clonogenicity index (20-times), invasiveness profile (>70%), migration capacity (100%) and ability to form mammospheres, compared to its non-metastatic MCF-7 counterpart...
June 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28648405/anti-inflammatory-activity-of-coptisine-free-base-in-mice-through-inhibition-of-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#8
Han-Bin Chen, Chao-Dan Luo, Jia-Li Liang, Zhen-Biao Zhang, Guo-Sheng Lin, Jia-Zhen Wu, Cai-Lan Li, Li-Hua Tan, Xiao-Bo Yang, Zi-Ren Su, Jian-Hui Xie, Hui-Fang Zeng
Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema...
June 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28647884/fluoxetine-induces-apoptosis-through-endoplasmic-reticulum-stress-via-mitogen-activated-protein-kinase-activation-and-histone-hyperacetylation-in-sk-n-be-2-m17-human-neuroblastoma-cells
#9
Ji Hyun Choi, Yeon Ju Jeong, Ah-Ran Yu, Kyung-Sik Yoon, Wonchae Choe, Joohun Ha, Sung Soo Kim, Eui-Ju Yeo, Insug Kang
Fluoxetine (FLX) is an antidepressant drug that belongs to the class of selective serotonin reuptake inhibitors. FLX is known to induce apoptosis in multiple types of cancer cells. In this study, the molecular mechanisms underlying the anti-cancer effects of FLX were investigated in SK-N-BE(2)-M17 human neuroblastoma cells. FLX induced apoptotic cell death, activation of caspase-4, -9, and -3, and expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP)...
June 24, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28647652/kinase-activity-in-recurring-primary-skull-base-chordomas-and-chondrosarcomas-identification-of-novel-pathways-of-oncogenesis-and-potential-drug-targets
#10
Philip Tatman, Joshua Osbun, Youssef Yakkioui, Sumanpret Kaur, Carolina Parada, Tina Busald, Donald Born, Owais Ahmad, Jing Zhang, Manuel Ferreira
OBJECTIVE: Chordomas and chondrosarcomas are tumors that can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within five years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the FDA for chordomas or chondrosarcomas. The high propensity for recurrence and lack of definitive adjuvant therapy necessitates additional basic science research to identify molecular anomalies associated with recurrent disease...
June 21, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28646487/immunotoxic-effects-of-thymus-in-mice-following-exposure-to-nanoparticulate-tio2
#11
Fashui Hong, Yaoming Zhou, Yingjun Zhou, Ling Wang
Titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in industry, medicine, and daily life, and have shown potential toxic effects for animals or humans. We noted that the effects of TiO2 NPs on the immune system and its mechanism of action in animals or humans have not been elucidated. Thus, mice were exposed to the TiO2 NPs (0, 1.25, 2.5, or 5 mg kg(-1) body weight) for 9 consecutive months. Exposure to TiO2 NPs was accumulated in the thymus, leading to a decrease in body weight and increases in the weight of the thymus or thymus indices...
June 24, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28646091/stress-specific-p38-map-kinase-activation-is-sufficient-to-drive-egf-receptor-endocytosis-but-not-nuclear-translocation
#12
Alejandra Tomas, Sylwia Jones, Simon O Vaughan, Daniel Hochhauser, Clare E Futter
P38 MAP kinase-dependent EGF receptor (EGFR) endocytosis is induced by stress. Ligand and stresses like X-rays, reportedly promote nuclear traffic of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression and so did not represent nuclear EGFR...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28644955/turning-on-proteasomes
#13
Jan Henrik Krahn, Farnusch Kaschani, Markus Kaiser
While proteasome inhibitors are now well-established research tools and chemotherapeutics, proteasome activators are much less explored. In this issue of Cell Chemical Biology, in a study from the groups of Berkers and Ovaa (Leestemaker et al., 2017), a chemical screen was used to identify a p38 MAPK inhibitor as a proteasome activator. This compound furthermore enhanced clearance of protein aggregates, thereby implicating alternative chemotherapeutic options for treating neurodegenerative diseases.
June 22, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28644396/runx1-plays-an-important-role-in-mediating-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells-line-c3h10t1-2-murine-multi-lineage-cells-lines-c2c12-and-mefs
#14
Caixia Ji, Xiaohua Liu, Li Xu, Tingting Yu, Chaoqun Dong, Jinyong Luo
As one of the least studied bone morphogenetic proteins (BMPs), BMP9 is highly capable of promoting osteogenic differentiation. However, the underlying mechanism involved remains largely unknown. Recent studies have demonstrated that RUNX1 (runt-related transcription factor 1) is essential in osteoblast/chondrocyte maturation. In this study, we investigated the function of RUNX1 in BMP9-induced osteogenic of murine mesenchymal stem cell line (C3H10T1/2) and murine multi-lineage cell lines (C2C12 and MEFs). Our data showed that BMP9 promoted the endogenous expression of RUNX1 in C3H10T1/2, C2C12 and MEFs...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28643937/proinflammatory-effects-and-mechanisms-of-calprotectin-on-human-gingival-fibroblasts
#15
H Gao, J Hou, H Meng, X Zhang, Y Zheng, L Peng
BACKGROUND AND OBJECTIVE: Calprotectin (S100A8/A9) is a heterodimer of S100A8 and S100A9 and is associated with multiple inflammatory diseases, including Crohn's disease, rheumatoid arthritis and periodontitis. Levels of calprotectin are elevated in the gingival crevicular fluid of patients with periodontitis; however, the effects of calprotectin on human gingival fibroblasts (HGFs) remain unknown. This study investigated the proinflammatory activity of calprotectin on HGFs and the functional receptors and signaling pathways engaged by calprotectin...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28643892/calcitriol-exerts-an-anti-tumor-effect-in-osteosarcoma-by-inducing-the-endoplasmic-reticulum-er-stress-response
#16
Takatsune Shimizu, Walied A Kamel, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Akihiro Muto, Hideyuki Saya
Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of FDA-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS)...
June 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28642873/serum-amyloid-a-induces-a-vascular-smooth-muscle-cell-phenotype-switch-through-the-p38-mapk-signaling-pathway
#17
Xincai Zhang, Jinqin Chen, Shixun Wang
Atherosclerosis is an important pathological condition which is accompanied by a vascular smooth muscle cell (VSMC) phenotype switch toward a synthetic phenotype. As an acute-phase protein, Serum Amyloid A (SAA) is thought to have a close relationship to atherosclerosis development. However, no study has investigated the direct effect of SAA on the VSMC phenotype switch, as well as the underlying mechanisms. The purpose of our study was to explore the effect of SAA on the VSMC phenotype switch and the potential mechanisms involved...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642802/perk-dependent-defective-tcr-mediated-activation-of-cd4-t-cells-in-end-stage-renal-disease-patients
#18
Ling Huang, Nicolle H R Litjens, Nynke M Kannegieter, Mariska Klepper, Carla C Baan, Michiel G H Betjes
BACKGROUND: Patients with end-stage renal disease (ESRD) have an impaired immune response with a prematurely aged T-cell system. Mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) and p38, regulate diverse cellular programs by transferring extracellular signals into an intracellular response. T cell receptor (TCR)-induced phosphorylation of ERK (pERK) may show an age-associated decline, which can be reversed by inhibiting dual specific phosphatase (DUSP) 6, a cytoplasmic phosphatase with substrate specificity to dephosphorylate pERK...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28642704/quercetin-a-lead-compound-against-type-2-diabetes-ameliorates-glucose-uptake-via-ampk-pathway-in-skeletal-muscle-cell-line
#19
R Dhanya, A D Arya, P Nisha, P Jayamurthy
Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642198/treatment-of-intestinal-fibrosis-in-experimental-inflammatory-bowel-disease-by-the-pleiotropic-actions-of-a-local-rho-kinase-inhibitor
#20
Tom Holvoet, Sarah Devriese, Karolien Castermans, Sandro Boland, Dirk Leysen, Yves-Paul Vandewynckel, Lindsey Devisscher, Lien Van den Bossche, Sophie Van Welden, Melissa Dullaers, Roosmarijn E Vandenbroucke, Riet De Rycke, Karel Geboes, Arnaud Bourin, Olivier Defert, Pieter Hindryckx, Martine De Vos, Debby Laukens
BACKGROUND: Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ1-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side-effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. METHODS: Fibrosis was assessed in mouse models using dextran sulfate sodium and adoptive T cell transfer...
June 19, 2017: Gastroenterology
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