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https://www.readbyqxmd.com/read/28225294/role-of-rock-isoforms-in-regulation-of-stiffness-induced-myofibroblast-differentiation-in-lung-fibrosis
#1
Su S Htwe, Byung H Cha, Kan Yue, Ali Khademhosseini, Alan J Knox, Amir M Ghaemmaghami
Fibrosis is a major cause of progressive organ dysfunction in several chronic pulmonary diseases. Rho associated coiled-coil forming kinase (ROCK) has shown to be involved in myofibroblast differentiation driven by altered matrix stiffness in fibrotic state. There are two known ROCK isoforms in human, ROCK1 (ROKβ) and ROCK2 (ROKα), but specific role of each isoform in myofibroblast differentiation in lung fibrosis remains unknown. To study this, we developed a Gelatin methacryloyl (GelMA) hydrogel based culture system with different stiffness levels relevant to healthy and fibrotic lungs...
February 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28224650/androgen-receptor-splice-variants-are-not-substrates-of-nonsense-mediated-decay
#2
Atinuke S Ajiboye, David Esopi, Srinivasan Yegnasubramanian, Samuel R Denmeade
BACKGROUND: Androgen receptor (AR) splice variants have been clinically associated with progressive cancer, castration-resistance, and resistance to AR antagonists and androgen synthesis inhibitors. AR variants can be generated by genomic alterations and alternative splicing, and their expression is androgen-regulated. There has been a suggestion that AR variants bearing premature termination codons and coding for truncated proteins should be regulated by the nonsense-mediated decay (NMD) mRNA surveillance pathway, suggesting that either the NMD pathway is dysfunctional in variant-expressing cell lines or that variants are somehow able to evade degradation by NMD...
February 22, 2017: Prostate
https://www.readbyqxmd.com/read/28224429/slc38a1-promotes-proliferation-and-migration-of-human-colorectal-cancer-cells
#3
Fen-Fang Zhou, Wei Xie, Shuang-Qian Chen, Xiao-Kang Wang, Qing Liu, Xue-Kai Pan, Fei Su, Mao-Hui Feng
Current studies have demonstrated that SLC38A1 proteins play a causal role in neoplastic cell transformation. The twofold aim of this study was to provide insight into whether a variance in the expression of SLC38A1 exists between human colorectal cancer and healthy human tissues and to determine how silencing or overexpressing the SLC38A1 gene could affect the proliferation, viability and migration of colorectal cancer cells. Immunohistochemical staining was used to analyze the expression of SLC38A1 in colorectal cancer tissues and adjacent normal mucosa in 77 patients who underwent surgical resection...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28224224/aminopeptidase-n5-apn5-as-a-putative%C3%A2-functional-receptor-of-cry1ac-toxin-in-the-larvae-of-athetis-lepigone
#4
Li-Yu Wang, Shao-Hua Gu, Zi-Yan Nangong, Ping Song, Qin-Ying Wang
Athetis lepigone was a new lepidopteran pest and caused severe damage to maize crops in China. We have detected that Cry1Ac protoxin and toxin were highly active against the larvae of A. lepigone. However, there is no report about the mode of action of Bt Cry1Ac toxin against this pest until now. A 110 kDa APN5 protein from BBMV of A. lepigone was identified as the binding receptor of Cry1Ac toxin using Ligand blotting. The Cry1Ac receptor APN5 was cloned from A. lepigone larval midgut mRNA and named as AlAPN5 (GenBank accession no...
February 21, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28223799/hypoxia-responsive-ionizable-liposome-delivery-sirna-for-glioma-therapy
#5
Hong-Mei Liu, Ya-Fei Zhang, Yan-Dong Xie, Yi-Fan Cai, Bai-Yang Li, Wen Li, Ling-Yu Zeng, Yu-Ling Li, Ru-Tong Yu
Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'(1),O(1)-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28223544/hdac8-functions-in-spindle-assembly-during-mouse-oocyte-meiosis
#6
Kemei Zhang, Yajuan Lu, Chaohua Jiang, Wei Liu, Jing Shu, Xueqin Chen, Yingjiao Shi, Ensheng Wang, Li Wang, Qinbo Hu, Yibo Dai, Bo Xiong
HDAC8 is a class I histone deacetylase that functions in a variety of biological processes through its non-histone substrates. However, its roles during oocyte meiosis remain elusive. Here, we document that HDAC8 localizes at spindle poles and positively participates in the regulation of microtubule organization and spindle assembly in mouse oocytes. Depletion of HDAC8 by siRNA-based gene silencing results in various spindle defects and chromosome misalignment during oocyte meiotic maturation, accompanied by impaired kinetochore-microtubule attachments...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223541/targeting-growth-hormone-receptor-in-human-melanoma-cells-attenuates-tumor-progression-and-epithelial-mesenchymal-transition-via-suppression-of-multiple-oncogenic-pathways
#7
Reetobrata Basu, Shiyong Wu, John J Kopchick
Recent reports have confirmed highest levels of growth hormone (GH) receptor (GHR) transcripts in melanoma, one of the most aggressive forms of human cancer. Yet the mechanism of GH action in melanoma remains mostly unknown. Here, using human malignant melanoma cells, we examined the effects of GH excess or siRNA mediated GHR knock-down (GHRKD) on tumor proliferation, migration and invasion. GH promoted melanoma progression while GHRKD attenuated the same. Western blot analysis revealed drastic modulation of multiple oncogenic signaling pathways (JAK2, STAT1, STAT3, STAT5, AKT, mTOR, SRC and ERK1/2) following addition of GH or GHRKD...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223424/hsp70-inhibition-synergistically-enhances-the-effects-of-magnetic-fluid-hyperthermia-in-ovarian-cancer
#8
Karem A Court, Hiroto Hatakeyama, Sherry Y Wu, Mangala S Lingegowda, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Lee Ju-Seog, Carlos Rinaldi, Eduardo J Juan, Anil K Sood, Madeline Torres-Lugo
Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223335/cooperation-of-musashi-2-numb-mdm2-and-p53-in-drug-resistance-and-malignant-biology-of-pancreatic-cancer
#9
Weiwei Sheng, Ming Dong, Chuanping Chen, Zixin Wang, Yunwei Li, Kewei Wang, Yuji Li, Jianping Zhou
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2-mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and invivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28223137/human-clec16a-regulates-autophagy-through-modulating-mtor-activity
#10
Rachel Chun Yee Tam, Michelle Wing Man Li, Yan Pan Gao, Yuen Ting Pang, Sheng Yan, Wei Ge, Chak Sing Lau, Vera Sau Fong Chan
CLEC16A is genetically linked with multiple autoimmune disorders but its functional relevance in autoimmunity remains obscure. Recent evidence has signposted the emerging role of autophagy in autoimmune disease development. Here, by ectopic expression and siRNA silencing, we show that CLEC16A has an inhibitory role in starvation-induced autophagy in human cells. Combining quantitative proteomics and immunoblotting analyses, we found that CLEC16A likely regulates autophagy by activating mTOR pathway. Overexpression of CLEC16A was found to sensitize cells towards the availability of nutrients, resulting in a heightened mTOR activity, which in turn diminished LC3 autophagic activity following nutrient deprivation...
February 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28223132/ternary-complexes-of-folate-peg-appended-dendrimer-g4-%C3%AE-cyclodextrin-conjugate-sirna-and-low-molecular-weight-polysaccharide-sacran-as-a-novel-tumor-selective-sirna-delivery-system
#11
Ayumu Ohyama, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima
We previously developed a tumor-selective siRNA carrier by preparing polyamidoamine dendrimer (generation 4, G4) conjugates with α-cyclodextrin and folate-polyethylene glycol (Fol-PαC (G4)). In the present study, we developed ternary complexes of Fol-PαC (G4)/siRNA with low-molecular-weight-sacrans to achieve more effective siRNA transfer activity. Among the different molecular-weight sacrans, i.e. sacran 100, 1000 and 10000 (MW 44,889Da, 943,692Da and 1,488,281Da, respectively), sacran 100 significantly increased the cellular uptake and the RNAi effects of Fol-PαC (G4)/siRNA binary complex with negligible cytotoxicity in KB cells (folate receptor-α positive cells)...
February 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28223126/targeted-inhibition-of-hdac8-increases-the-doxorubicin-sensitivity-of-neuroblastoma-cells-via-up-regulation-of-mir-137
#12
Gang Zhao, Guoliang Wang, Hongmin Bai, Tiandong Li, Fanghe Gong, Huan Yang, Jinchong Wen, Weimin Wang
Histone deacetylases (HDACs) have been suggested to be potential therapeutic targets for cancer treatment. Recent studies revealed that HDAC8 expression was associated with poor prognostic markers and poor overall survival rate of neuroblastoma (NB). Our present study revealed that among the four members of class I HDACs, HDAC8 is significantly over expressed in NB cells as compared with the normal fibroblast 3T3 cells or primary normal human astrocytes (NHA) cells. Targeted inhibition of HDAC8 by its specific siRNA (si-HDAC8) can inhibit the in vitro growth of NB cells...
February 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28223028/short-interfering-rnas-targeting-a-vampire-bat-related-rabies-virus-phosphoprotein-mrna
#13
Ekaterina Alexandrovna Durymanova Ono, Sueli Akemi Taniwaki, Paulo Brandão
The aim of this study was to assess the in vitro and in vivo effects of short-interfering RNAs (siRNAs) against rabies virus phosphoprotein (P) mRNA in a post-infection treatment for rabies as an extension of a previous report (Braz J Microbiol. 2013 Nov 15;44(3):879-82). To this end, rabies virus strain RABV-4005 (related to the Desmodus rotundus vampire bat) were used to inoculate BHK-21 cells and mice, and the transfection with each of the siRNAs was made with Lipofectamine-2000™. In vitro results showed that siRNA 360 was able to inhibit the replication of strain RABV-4005 with a 1log decrease in virus titter and 5...
February 5, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28222767/knockdown-of-slc41a1-magnesium-transporter-promotes-mineralization-and-attenuates-magnesium-inhibition-during-osteogenesis-of-mesenchymal-stromal-cells
#14
Yu-Tzu Tsao, Ya-Yi Shih, Yu-An Liu, Yi-Shiuan Liu, Oscar K Lee
BACKGROUND: Magnesium is essential for numerous physiological functions. Magnesium exists mostly in bone and the amount is dynamically regulated by skeletal remodeling. Accelerating bone mass loss occurs when magnesium intake is insufficient; whereas high magnesium could lead to mineralization defects. However, the underlying magnesium regulatory mechanisms remain elusive. In the present study, we investigated the effects of high extracellular magnesium concentration on osteogenic differentiation of mesenchymal stromal/stem cells (MSCs) and the role of magnesium transporter SLC41A1 in the mineralization process...
February 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28222718/abnormal-epigenetic-changes-during-differentiation-of-human-skeletal-muscle-stem-cells-from-obese-subjects
#15
Cajsa Davegårdh, Christa Broholm, Alexander Perfilyev, Tora Henriksen, Sonia García-Calzón, Lone Peijs, Ninna Schiøler Hansen, Petr Volkov, Rasmus Kjøbsted, Jørgen F P Wojtaszewski, Maria Pedersen, Bente Klarlund Pedersen, Dov B Ballak, Charles A Dinarello, Bas Heinhuis, Leo A B Joosten, Emma Nilsson, Allan Vaag, Camilla Scheele, Charlotte Ling
BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals...
February 22, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28222632/cryptotanshinone-potentiates-the-antitumor-effects-of-doxorubicin-on-gastric-cancer-cells-via-inhibition-of-stat3-activity
#16
Jiye Wang, Guangji Zhang, Chunyan Dai, Xiufei Gao, Jianbin Wu, Li Shen, Zhe Chen, Pei Liu
Objective To investigate the synergistic effects of cryptotanshinone (CPT) and doxorubicin (DOXO) on induction of apoptosis in human gastric cancer cells and the mechanisms. Methods Cell proliferation and apoptosis were detected using the CCK8 assay and AnnexinV/PI staining, respectively. Western blotting was used to determine the levels and phosphorylation of proteins encoded by STAT3-regulated genes and the cleaved forms of caspases and PARP. Results CPT significantly potentiated the antiproliferative effect of DOXO in gastric cancer cell lines...
February 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28222172/rhoa-promotes-epidermal-stem-cell-proliferation-via-pkn1-cyclin-d1-signaling
#17
Fan Wang, Rixing Zhan, Liang Chen, Xia Dai, Wenping Wang, Rui Guo, Xiaoge Li, Zhe Li, Liang Wang, Shupeng Huang, Jie Shen, Shirong Li, Chuan Cao
OBJECTIVE: Epidermal stem cells (ESCs) play a critical role in wound healing, but the mechanism underlying ESC proliferation is not well defined. Here, we explore the effects of RhoA on ESC proliferation and the possible underlying mechanism. METHODS: Human ESCs were enriched by rapid adhesion to collagen IV. RhoA(+/+)(G14V), RhoA(-/-)(T19N) and pGFP control plasmids were transfected into human ESCs. The effect of RhoA on cell proliferation was detected by cell proliferation and DNA synthesis assays...
2017: PloS One
https://www.readbyqxmd.com/read/28222068/inhibition-of-cdk5-induces-cell-death-of-tumor-initiating-cells
#18
Melanie M Mandl, Siwei Zhang, Melanie Ulrich, Elisa Schmoeckel, Doris Mayr, Angelika M Vollmar, Johanna Liebl
BACKGROUND: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. METHODS: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28220627/downregulation-of-mirna-141-in-breast-cancer-cells-is-associated-with-cell-migration-and-invasion-involvement-of-anp32e-targeting
#19
Ping Li, Tao Xu, Xin Zhou, Liangying Liao, Guolian Pang, Wan Luo, Lu Han, Jiankun Zhang, Xianyong Luo, Xiaobing Xie, Kuichun Zhu
MicroRNAs (miRNAs) regulate many cellular activities, including cancer development, progression, and metastasis. Some miRNAs are involved in breast cancer (BC) migration and invasion, thus affect patients' prognosis. Microarray analysis was performed to compare miRNA expression in BC tissues, and results confirmed by qPCR. BC cell migration and invasion were studied in vitro with MDA-MB-231 cells using microplate transwell assays. miRNA targeting was investigated using luciferase assays, qPCR, and Western blot analysis in cells with overexpression of miRNA mimics...
February 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28220341/adenovirus-mediated-small-interfering-rna-targeting-tak1-ameliorates-joint-inflammation-with-collagen-induced-arthritis-in-mice
#20
Xinjing Luo, Yongfeng Chen, Guoju Lv, Zhidong Zhou, Jie Chen, Xuanrong Mo, Jiangwen Xie
Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice...
February 21, 2017: Inflammation
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