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https://www.readbyqxmd.com/read/28106491/effect-of-an-mg132-sustained-drug-delivery-capsular-ring-on-the-inhibition-of-posterior-capsule-opacification-in-a-rabbit-model
#1
Xuan Bao, Min Hou, Yingyan Qin, Furong Luo, Fu Shang, Mingxing Wu
PURPOSE: To design an MG132-sustained drug delivery capsular ring (SDDCR) and investigate its effect on the inhibition of posterior capsule opacification (PCO) in a rabbit model. METHODS: The SDDCRs were prepared by forming a slice of film made by the mixture of poly lactic-co-glycolic acid (PLGA) and MG132 on the surface of capsular tension rings (CTRs). The drug-loading capacity, entrapment efficiency, and in vitro release of the drug-containing film were detected...
January 20, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28100501/mdm2-mediates-fibroblast-activation-and-renal-tubulointerstitial-fibrosis-via-p53-independent-pathway
#2
Chen Ye, Hui Tang, Zheng Zhao, Chun-Tao Lei, Chao-Qun You, Jiao Zhang, Pan Gao, Fang-Fang He, Shan Chen, Yumei Wang, Chun Zhang, Hua Su
It is well-recognized that Murine Double Minute gene 2 (MDM2) plays a critical role in cell proliferation and inflammatory processes during tumorigenesis. Also it is reported that MDM2 is expressed in glomeruli and involved in podocyte injury. However, whether MDM2 is implicated in renal fibrosis remains unclear. Here we investigated the role of MDM2 in tubulointerstitial fibrosis (TIF). By immunohistochemical staining and western blotting we confirmed that MDM2 is up-regulated in tubulointerstitial compartment in TIF patients and Unilateral Urethral Obstruction (UUO) mice, which mainly originates from myofibroblasts...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28098164/uncovering-the-sumoylation-and-ubiquitylation-crosstalk-in-human-cells-using-sequential-peptide-immunopurification
#3
Frédéric Lamoliatte, Francis P McManus, Ghizlane Maarifi, Mounira K Chelbi-Alix, Pierre Thibault
Crosstalk between the SUMO and ubiquitin pathways has recently been reported. However, no approach currently exists to determine the interrelationship between these modifications. Here, we report an optimized immunoaffinity method that permits the study of both protein ubiquitylation and SUMOylation from a single sample. This method enables the unprecedented identification of 10,388 SUMO sites in HEK293 cells. The sequential use of SUMO and ubiquitin remnant immunoaffinity purification facilitates the dynamic profiling of SUMOylated and ubiquitylated proteins in HEK293 cells treated with the proteasome inhibitor MG132...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28088021/sanguinarine-induced-oxidative-stress-and-apoptosis-like-programmed-cell-death-al-pcd-in-root-meristem-cells-of-allium-cepa
#4
Aneta Żabka, Konrad Winnicki, Justyna Teresa Polit, Janusz Maszewski
A vast number of studies on plant cell systems clearly indicate that various biotic and abiotic stresses give rise to the uncontrolled increase in the level of reactive oxygen species (ROS). Excess concentrations of ROS result in damage to proteins, lipids, carbohydrates, and DNA, which may lead, in consequence, to the apoptotic cell death. The current study investigates the effects of sanguinarine (SAN), a natural alkaloid derived from the roots of Sanguinaria canadensis, on root apical meristem cells of Allium cepa...
January 4, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28087276/drosophila-argonaute2-turnover-is-regulated-by-the-ubiquitin-proteasome-pathway
#5
Madoka Chinen, Elissa P Lei
Argonaute (AGO) proteins play a central role in the RNA interference (RNAi) pathway, which is a cytoplasmic mechanism important for post-transcriptional regulation of gene expression. In Drosophila, AGO2 also functions in the nucleus to regulate chromatin insulator activity and transcription. Although there are a number of studies focused on AGO2 function, the regulation of AGO2 turnover is not well understood. We found that mutation of T1149 or R1158 in the conserved PIWI domain causes AGO2 protein instability, but only T1149 affects RNAi activity...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28086832/norcantharidin-inhibits-cell-growth-by-suppressing-the-expression-and-phosphorylation-of-both-egfr-and-c-met-in-human-colon-cancer-cells
#6
Peiju Qiu, Siwen Wang, Ming Liu, He Ma, Xuan Zeng, Meng Zhang, Lingling Xu, Yidi Cui, Huixin Xu, Yang Tang, Yanli He, Lijuan Zhang
BACKGROUND: Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study. METHODS: Two human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28073696/spop-promotes-sirt2-degradation-and-suppresses-non-small-cell-lung-cancer-cell-growth
#7
Jie Luo, Yu-Chen Bao, Xian-Xiu Ji, Bin Chen, Qin-Fang Deng, Song-Wen Zhou
SIRT2 is a NAD-dependent deacetylase and inhibition of SIRT2 has a broad anticancer activity. Here we report that SPOP binds to SIRT2 and mediates its degradation by the 26S proteasome, which can be blocked by MG132 treatment. We also found that the levels of SPOP significantly decreased, while the levels of SIRT2 significantly increased in non-small cell lung cancer (NSCLC) cell lines, compared to normal bronchial epithelial cell line and NSCLC specimens, compared to the paired non-tumor lung tissue. Furthermore, SPOP can suppress NSCLC cell growth...
January 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28052875/liver-x-receptor-%C3%AE-lxr%C3%AE-increases-aqp2-protein-level-via-a-post-transcriptional-mechanism-in-renal-collecting-ducts
#8
Wen Su, Shi-Zheng Huang, Min Gao, Xiao-Mu Kong, Jan-Ake Gustafsson, Su-Juan Xu, Bing Wang, Feng Zheng, Li-Hong Chen, Nan-Ping Wang, You-Fei Guan, Xiao-Yan Zhang
Liver X Receptors (LXRs) including LXRα and LXRβ are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRβ but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRβ regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRβ-/- mice exhibited a reduced response to dDAVP stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28035387/therapeutic-mechanisms-of-ibuprofen-prednisone-and-betamethasone-in-osteoarthritis
#9
Fenglong Sun, Yaohua Zhang, Qiang Li
The present study aimed to investigate the therapeutic mechanisms of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids in osteoarthritis (OA). The CHON‑002 human chondrocyte cell line was used in the study. The levels of the cytokines, interleukin (IL)‑1β, IL‑6, IL‑8 and IL‑10, released by cells treated with tumor necrosis factor‑α (TNF‑α) were determined by ELISA. Levels of collagen I, aggrecan, matrix metalloproteinase (MMP)‑1, MMP‑13, signal transducer and activator of transcription (STAT) 3, nuclear factor‑κB (NF‑κB) subunit p65 and inhibitory subunit of NF‑κB (IκB) following treatment with IL‑1β, IL‑6, IL‑8 or IL‑10 were assessed by western blot...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28009721/propofol-provides-cardiac-protection-by-suppressing-the-proteasome-degradation-of-caveolin-3-in-ischemic-reperfused-rat-hearts
#10
Afang Zhu, Xin Wei, Yali Zhang, Tao You, Shanglong Yao, Shiying Yuan, Haodong Xu, Faqian Li, Weike Mao
The mechanisms underlying propofol's cardioprotective role remain elusive. Caveolin-3 (Cav-3) has been shown to mediate both opioids- and volatile anesthetics-induced cardioprotection against ischemia/reperfusion (I/R) injury. We hypothesize that the cardioprotective role of propofol is mediated through Cav-3 and its regulation of PI3K/Akt/GSK3β signal pathway. Rats or H9c2 cardiomyocytes were exposed to propofol prior to I/R or simulated ischemia/reperfusion (SI/R). Propofol pretreatment significantly decreased left ventricle (LV) infarct size in vivo (P < 0...
December 17, 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28000177/geniposide-accelerates-proteasome-degradation-of-txnip-to-inhibit-insulin-secretion-in-pancreatic-%C3%AE-cells
#11
C Y Liu, Y N Hao, F Yin, Y L Zhang, J H Liu
PURPOSE: To analyze the role of geniposide in the protein degradation of Txnip and to determine the impact of Txnip on geniposide-regulated GSIS in pancreatic INS-1 cells. METHODS: The content of Txnip protein was measured by western blot; insulin content and glucose uptake were determined by ELISA; and knockdown of Txnip was the method of RNA interference. RESULTS: Glucose induces a rapid increase in Txnip protein, and geniposide accelerates the degradation of Txnip via proteasome pathway in the presence of high glucose (25 mM) in INS-1 pancreatic β-cells...
December 20, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27993609/chlorpyrifos-induces-endoplasmic-reticulum-stress-in-jeg-3-cells
#12
Luciana Reyna, Jésica Flores-Martín, Magali E Ridano, Graciela M Panzetta-Dutari, Susana Genti-Raimondi
Chlorpyrifos (CPF) is an organophosphorous pesticide widely used in agricultural, industrial, and household applications. We have previously shown that JEG-3 cells are able to attenuate the oxidative stress induced by CPF through the adaptive activation of the Nrf2/ARE pathway. Considering that there is a relationship between oxidative stress and endoplasmic reticulum stress (ER), herein we investigated whether CPF also induces ER stress in JEG-3 cells. Cells were exposed to 50μM or 100μM CPF during 24h in conditions where cell viability was not altered...
December 16, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27983979/ibandronate-concomitantly-blocks-immobilization-induced-bone-and-muscle-atrophy
#13
Ryuichi Watanabe, Nobuyuki Fujita, Satoshi Takeda, Yuiko Sato, Tami Kobayashi, Mayu Morita, Takatsugu Oike, Kana Miyamoto, Yoshihiro Matsumoto, Morio Matsumoto, Masaya Nakamura, Takeshi Miyamoto
Both bone and muscle volume is concomitantly reduced under immobilization conditions; however, no single drug is currently available to block these outcomes simultaneously. Bisphosphonates are utilized clinically to inhibit osteoclast-dependent bone resorption, but their effects on muscle are largely unknown. Here we show that skeletal muscle is a direct target of the bisphosphonate ibandronate (IBN) and that reduced muscle volume and induction of Atrogin-1 and MuRF1, both atrogenes, are significantly inhibited by IBN administration in vivo using a mouse model of muscle atrophy...
October 27, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27983599/using-crispr-cas9-mediated-gla-gene-knockout-as-an-in-vitro-drug-screening-model-for-fabry-disease
#14
Hui-Yung Song, Huai-Chih Chiang, Wei-Lien Tseng, Ping Wu, Chian-Shiu Chien, Hsin-Bang Leu, Yi-Ping Yang, Mong-Lien Wang, Yuh-Jyh Jong, Chung-Hsuan Chen, Wen-Chung Yu, Shih-Hwa Chiou
The CRISPR/Cas9 Genome-editing system has revealed promising potential for generating gene mutation, deletion, and correction in human cells. Application of this powerful tool in Fabry disease (FD), however, still needs to be explored. Enzyme replacement therapy (ERT), a regular administration of recombinant human α Gal A (rhα-GLA), is a currently available and effective treatment to clear the accumulated Gb3 in FD patients. However, the short half-life of rhα-GLA in human body limits its application. Moreover, lack of an appropriate in vitro disease model restricted the high-throughput screening of drugs for improving ERT efficacy...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27973439/down-regulation-of-ca-2-activated-k%C3%A2-%C2%BA-channel-kca1-1-in-human-breast-cancer-mda-mb-453-cells-treated-with-vitamin-d-receptor-agonists
#15
Anowara Khatun, Mayu Fujimoto, Hiroaki Kito, Satomi Niwa, Takayoshi Suzuki, Susumu Ohya
Vitamin D (VD) reduces the risk of breast cancer and improves disease prognoses. Potential VD analogs are being developed as therapeutic agents for breast cancer treatments. The large-conductance Ca(2+)-activated K⁺ channel KCa1.1 regulates intracellular Ca(2+) signaling pathways and is associated with high grade tumors and poor prognoses. In the present study, we examined the effects of treatments with VD receptor (VDR) agonists on the expression and activity of KCa1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, flow cytometry, and voltage-sensitive dye imaging...
December 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27932549/proteolytic-degradation-of-heat-shock-protein-a2-occurs-in-response-to-oxidative-stress-in-male-germ-cells-of-the-mouse
#16
Elizabeth G Bromfield, R John Aitken, Eileen A McLaughlin, Brett Nixon
STUDY QUESTION: Does oxidative stress compromise the protein expression of heat shock protein A2 (HSPA2) in the developing germ cells of the mouse testis? SUMMARY ANSWER: Oxidative stress leads to the modification of HSPA2 by the lipid aldehyde 4-hydroxynonenal (4HNE) and initiates its degradation via the ubiquitin-proteasome system. WHAT IS KNOWN ALREADY: Previous work has revealed a deficiency in HSPA2 protein expression within the spermatozoa of infertile men that have failed fertilization in a clinical setting...
December 8, 2016: Molecular Human Reproduction
https://www.readbyqxmd.com/read/27911270/saha-and-or-mg132-reverse-the-aggressive-phenotypes-of-glioma-cells-an-in-vitro-and-vivo-study
#17
Xue-Feng Yang, Zhi-Juan Zhao, Jia-Jie Liu, Xiang-Hong Yang, Yang Gao, Shuang Zhao, Shuai Shi, Ke-Qiang Huang, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes' assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901482/hyperglycemia-triggers-hipk2-protein-degradation
#18
Silvia Baldari, Alessia Garufi, Marisa Granato, Laura Cuomo, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888613/psmc2-is-up-regulated-in-osteosarcoma-and-regulates-osteosarcoma-cell-proliferation-apoptosis-and-migration
#19
Mingzhi Song, Yong Wang, Zhen Zhang, Shouyu Wang
Proteasome 26S subunit ATPase 2 (PSMC2) is a recently identified gene potentially associated with certain human carcinogenesis. However, the expressional correlation and functional importance of PSMC2 in osteosarcoma is still unclear. Current study was focused on elucidating the significance of PSMC2 on malignant behaviors in osteosarcoma including proliferation, apoptosis, colony formation, migration as well as invasion. The high protein levels of PSMC2 in osteosarcoma samples were identified by tissue microarrays analysis...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27875574/chidamide-inhibits-aerobic-metabolism-to-induce-pancreatic-cancer-cell-growth-arrest-by-promoting-mcl-1-degradation
#20
Mu He, Zhixin Qiao, Yanbing Wang, Qiyuan Kuai, Changlan Li, Yu Wang, Xingwei Jiang, Xuanlin Wang, Weijing Li, Min He, Suping Ren, Qun Yu
Pancreatic cancer is a fatal malignancy worldwide and urgently requires valid therapies. Previous research showed that the HDAC inhibitor chidamide is a promising anti-cancer agent in pancreatic cancer cell lines. In this study, we elucidate a probable underlying anti-cancer mechanism of chidamide involving the degradation of Mcl-1. Mcl-1 is frequently upregulated in human cancers, which has been demonstrated to participate in oxidative phosphorylation, in addition to its anti-apoptotic actions as a Bcl-2 family member...
2016: PloS One
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