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https://www.readbyqxmd.com/read/29786956/rho-kinase-and-protein-kinase-c-pathways-are-responsible-for-enhanced-carbachol-contraction-in-permeabilized-detrusor-in-a-rat-model-of-cystitis
#1
Merve Denizalti, N Tugba Durlu-Kandilci, G Simsek, T Emrah Bozkurt, Inci Sahin-Erdemli
Interstitial cystitis is a syndrome characterized by detrusor overactivity and chronic inflammation of the bladder. The mechanisms responsible for the altered smooth muscle contractility remain poorly understood. The aim of the study was to investigate the role of intracellular signalling pathways in carbachol-induced detrusor contraction in a rat model of interstitial cystitis. Cyclophosphamide (150 mg/kg, dissolved in saline) was injected to rats (Sprague-Dawley, female, 200-250 g) intraperitoneally once a day on days 1, 4 and 7 to induce interstitial cystitis...
May 22, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29786744/mir%C3%A2-133b-regulates-proliferation-and-apoptosis-in-high%C3%A2-glucose%C3%A2-induced-human-retinal-endothelial-cells-by-targeting-ras-homolog-family-member-a
#2
Jun Yao, Jihong Wang, Yong Yao, Kelei Wang, Qianqian Zhou, Ying Tang
The aim of the present study was to investigate the role of microRNA (miR)‑133b in high‑glucose‑induced human retinal endothelial cells (hRECs), particularly regarding its potential targeting of ras homolog family member A (RhoA). To establish the high‑glucose‑induced diabetic retinopathy (DR) model, hRECs were cultured in high‑glucose medium for 1, 2 and 3 days. An Annexin allophycocyanin (APC)/7‑aminoactinomycin D (7‑AAD) staining assay was performed to measure the apoptosis of hRECs. Next, the cells were transfected with miR‑133b inhibitors or mimics, and the cell proliferation and apoptosis were measured by MTT and Annexin‑APC/7‑AAD staining assays, respectively...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29784011/extremely-low-frequency-electromagnetic-fields-promote-mesenchymal-stem-cell-migration-by-increasing-intracellular-ca-2-and-activating-the-fak-rho-gtpases-signaling-pathways-in-vitro
#3
Yingchi Zhang, Jiyuan Yan, Haoran Xu, Yong Yang, Wenkai Li, Hua Wu, Chaoxu Liu
BACKGROUND: The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. METHODS: We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29781749/oncogenic-pkc-%C3%AE-activates-vimentin-during-epithelial-mesenchymal-transition-in-melanoma-a-study-based-on-pkc-%C3%AE-and-pkc-%C3%AE-specific-inhibitors
#4
Wishrawana S Ratnayake, Christopher A Apostolatos, André H Apostolatos, Ryan J Schutte, Monica A Huynh, David A Ostrov, Mildred Acevedo-Duncan
Melanoma is one of the fastest growing cancers in the United States and is accompanied with a poor prognosis owing to tumors being resistant to most therapies. Atypical protein kinase Cs (aPKC) are involved in malignancy in many cancers. We previously reported that aPKCs play a key role in melanoma's cell motility by regulating cell signaling pathways which induce epithelial-mesenchymal Transition (EMT). We tested three novel inhibitors; [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1T) along with its nucleoside analog 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S) which are specific to protein kinase C-iota (PKC-ι) and 8-hydroxy-1,3,6-naphthalenetrisulfonic acid (ζ-Stat) which is specific to PKC-zeta (PKC-ζ) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes...
May 21, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#5
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777544/gingipains-disrupt-f-actin-and-cause-osteoblast-apoptosis-via-integrin-%C3%AE-1
#6
Q Qiu, F Zhang, J Wu, N Xu, M Liang
BACKGROUND AND OBJECTIVE: The aim of this study was to explore the cellular mechanisms underlying gingipain-caused changes in cell morphology and apoptosis of osteoblasts. MATERIAL AND METHODS: Human calvarial osteoblasts and mouse osteoblasts MC3T3-E1 were treated with gingipain extracts from Porphyromonas gingivalis stain W83. Apoptosis was detected with annexin V and propidium iodide flow cytometry analysis or terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining...
May 18, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29776664/rhod-localization-and-function-is-dependent-on-its-gtp-gdp-bound-state-and-unique-n-terminal-motif
#7
Magdalena Blom, Katarina Reis, Pontus Aspenström
The atypical Rho GTPase RhoD has previously been shown to have a major impact on the organization and function of the actin filament system. However, when first discovered, RhoD was found to regulate endosome trafficking and dynamics and we therefore sought to investigate this regulation in more detail. We found that exogenously expressed RhoD in human fibroblasts localized to vesicles and the plasma membrane and that the active GTP-bound conformation was required for the plasma membrane localization but not for vesicle localization...
May 16, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29773874/mutations-in-six-nephrosis-genes-delineate-a-pathogenic-pathway-amenable-to-treatment
#8
Shazia Ashraf, Hiroki Kudo, Jia Rao, Atsuo Kikuchi, Eugen Widmeier, Jennifer A Lawson, Weizhen Tan, Tobias Hermle, Jillian K Warejko, Shirlee Shril, Merlin Airik, Tilman Jobst-Schwan, Svjetlana Lovric, Daniela A Braun, Heon Yung Gee, David Schapiro, Amar J Majmundar, Carolin E Sadowski, Werner L Pabst, Ankana Daga, Amelie T van der Ven, Johanna M Schmidt, Boon Chuan Low, Anjali Bansal Gupta, Brajendra K Tripathi, Jenny Wong, Kirk Campbell, Kay Metcalfe, Denny Schanze, Tetsuya Niihori, Hiroshi Kaito, Kandai Nozu, Hiroyasu Tsukaguchi, Ryojiro Tanaka, Kiyoshi Hamahira, Yasuko Kobayashi, Takumi Takizawa, Ryo Funayama, Keiko Nakayama, Yoko Aoki, Naonori Kumagai, Kazumoto Iijima, Henry Fehrenbach, Jameela A Kari, Sherif El Desoky, Sawsan Jalalah, Radovan Bogdanovic, Nataša Stajić, Hildegard Zappel, Assel Rakhmetova, Sharon-Rose Wassmer, Therese Jungraithmayr, Juergen Strehlau, Aravind Selvin Kumar, Arvind Bagga, Neveen A Soliman, Shrikant M Mane, Lewis Kaufman, Douglas R Lowy, Mohamad A Jairajpuri, Richard P Lifton, York Pei, Martin Zenker, Shigeo Kure, Friedhelm Hildebrandt
No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29772566/the-epigenetic-factor-kdm2b-regulates-emt-and-small-gtpases-in-colon-tumor-cells
#9
Nefeli Zacharopoulou, Anna Tsapara, Galatea Kallergi, Evi Schmid, Saad Alkahtani, Saud Alarifi, Philip N Tsichlis, Sotirios C Kampranis, Christos Stournaras
BACKGROUND/AIMS: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. METHODS: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins...
May 14, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#10
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29769144/contributions-of-the-rhoa-guanine-nucleotide-exchange-factor-net1-to-polyoma-middle-t-antigen-mediated-mammary-gland-tumorigenesis-and-metastasis
#11
Yan Zuo, Arzu Ulu, Jeffrey T Chang, Jeffrey A Frost
BACKGROUND: The RhoA activating protein Net1 contributes to breast cancer cell proliferation, motility, and invasion in vitro, yet little is known about its roles in mammary gland tumorigenesis and metastasis. METHODS: Net1 knockout (KO) mice were bred to mice with mammary gland specific expression of the polyoma middle T antigen (PyMT) oncogene. Mammary gland tumorigenesis and lung metastasis were monitored. Individual tumors were assessed for proliferation, apoptosis, angiogenesis, RhoA activation, and activation of PyMT-dependent signaling pathways...
May 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29769011/evolving-strategies-for-the-treatment-of-t-cell-lymphoma-a-systematic-review-and-recent-patents
#12
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29765526/esophageal-cancer-cells-resistant-to-t-dm1-display-alterations-in-cell-adhesion-and-the-prostaglandin-pathway
#13
Juliette Sauveur, Eva-Laure Matera, Kamel Chettab, Philippe Valet, Jerome Guitton, Ariel Savina, Charles Dumontet
Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate that specifically targets HER2 thanks to its antibody component trastuzumab. In spite of responses to this novel agent, acquired resistance to treatment remains a major obstacle. Prolonged in vitro exposure of the gastroesophageal junction cancer cell line OE-19 to T-DM1, in the absence or presence of ciclosporin A resulted in the selection of two resistant cell lines to T-DM1. T-DM1-resistant cells presented an increased expression of adhesion genes, altered spreading and higher sensitivity to anoikis than parental cells...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765517/targeting-the-mevalonate-pathway-is-a-novel-therapeutic-approach-to-inhibit-oncogenic-foxm1-transcription-factor-in-human-hepatocellular-carcinoma
#14
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Hidetoshi Eguchi, Hisakazu Ogita, Yuichiro Doki, Masaki Mori, Tomohide Tatsumi, Tetsuo Takehara
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765417/zinc-promotes-adipose-derived-mesenchymal-stem-cell-proliferation-and-differentiation-towards-a-neuronal-fate
#15
Mi-Young Moon, Hyun Jung Kim, Bo Young Choi, Min Sohn, Tae Nyoung Chung, Sang Won Suh
Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs) are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29764980/interplay-of-cell-cell-contacts-and-rhoa-mrtf-a-signaling-regulates-cardiomyocyte-identity
#16
Tatjana Dorn, Jessica Kornherr, Elvira I Parrotta, Dorota Zawada, Harold Ayetey, Gianluca Santamaria, Laura Iop, Elisa Mastantuono, Daniel Sinnecker, Alexander Goedel, Ralf J Dirschinger, Ilaria My, Svenja Laue, Tarik Bozoglu, Christian Baarlink, Tilman Ziegler, Elisabeth Graf, Rabea Hinkel, Giovanni Cuda, Stefan Kääb, Andrew A Grace, Robert Grosse, Christian Kupatt, Thomas Meitinger, Austin G Smith, Karl-Ludwig Laugwitz, Alessandra Moretti
Cell-cell and cell-matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29761173/liver-enriched-transcription-factor-expression-relates-to-chronic-hepatic-failure-in-humans
#17
Jorge Guzman-Lepe, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J Fox, Kazuki Takeishi, Alejandro Soto-Gutierrez
The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29753262/effect-of-oxidation-processing-on-the-preparation-of-post-hydrothermolysis-acid-from-cotton-stalk
#18
Caiwei Wang, Shouyu Zhang, Shunyan Wu, Zhongyao Cao, Yifan Zhang, Hao Li, Fenghao Jiang, Junfu Lyu
The typical properties and yield of the refined hydrothermolytic acid (RHTA) and refined hydrothermolytic oxidation acid (RHOA) respectively prepared from cotton stalk by the hydrothermolysis process with and without hydrogen peroxide at 180-280 °C were investigated. The pH of RHOA at 180-260 °C is lower than that of RHTA. The yield of RHOA prepared at 180-280 °C is higher than that of RHTA except 230 °C. Besides, the variation trend of RHOA yield at 180-260 °C is in accordance with that of RHTA yield at 200-280 °C...
May 4, 2018: Bioresource Technology
https://www.readbyqxmd.com/read/29752492/novel-antidepressant-effects-of-paeonol-alleviate-neuronal-injury-with-concomitant-alterations-in-bdnf-rac1-and-rhoa-levels-in-chronic-unpredictable-mild-stress-rats
#19
Xiu-Ling Zhu, Jing-Jing Chen, Fei Han, Chuan Pan, Ting-Ting Zhuang, Ya-Fei Cai, Ya-Ping Lu
RATIONALE: Increasing evidence has suggested that major depressive disorder (MDD) is highly associated with brain-derived neurotrophic factor (BDNF) levels, dendrites atrophy, and loss of dendritic spines, especially in emotion-associated brain regions including the hippocampus. Paeonol is a kind of polyphenols natural product with a variety of therapeutic effects. Recent studies have reported its antidepressant effects. However, it is unclear what signaling pathways contribute to improve MDD...
May 12, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29752407/integrin-%C3%AE-v%C3%AE-3-associated-daam1-is-essential-for-collagen-induced-invadopodia-extension-and-cell-haptotaxis-in-breast-cancer-cells
#20
Ting Yan, Ailiang Zhang, Fangfang Shi, Fei Chang, Jie Mei, Yongjian Liu, Yichao Zhu
The formin protein dishevelled-associated activator of morphogenesis 1 (DAAM1) polymerizes straight actin filaments and mediates migration of cancer cells. However, how DAAM1 governs cell haptotaxis in response to collagen remains unexplored in breast cancer cells. We hypothesized that DAAM1 mediates invadopodia extension and cell haptotaxis in response to type IV collagen in association with integrin receptors. Using Boyden chamber membranes coated with type IV collagen, we show here that type IV collagen activates both DAAM1 and  Ras homolog family member A (RHOA)  and promotes haptotaxis of MDA-MB-231 and MDA-MB-453 breast cancer cells, a process abolished by treatment with the integrin αvβ3 inhibitor cyclo(-RGDfK)...
May 11, 2018: Journal of Biological Chemistry
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