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https://www.readbyqxmd.com/read/29331278/impact-of-treatment-with-a-protein-tyrosine-kinase-inhibitor-genistein-on-acute-and-chronic-experimental-schistosoma-mansoni-infection
#1
Maysa Mohamed Kamel Sobhy, Soheir Sayed Mahmoud, Shaimaa Helmy El-Sayed, Enas Mohamed Ali Rizk, Amira Raafat, Mohamed Sherif Ismail Negm
Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease...
January 10, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29301325/extracorporeal-shock-wave-therapy-alters-the-expression-of-fibrosis-related-molecules-in-fibroblast-derived-from-human-hypertrophic-scar
#2
Hui Song Cui, A Ram Hong, June-Bum Kim, Joo Hyang Yu, Yoon Soo Cho, So Young Joo, Cheong Hoon Seo
Extracorporeal shock wave therapy (ESWT) considerably improves the appearance and symptoms of post-burn hypertrophic scars (HTS). However, the mechanism underlying the observed beneficial effects is not well understood. The objective of this study was to elucidate the mechanism underlying changes in cellular and molecular biology that is induced by ESWT of fibroblasts derived from scar tissue (HTSFs). We cultured primary dermal fibroblasts derived from human HTS and exposed these cells to 1000 impulses of 0...
January 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29299971/the-role-of-the-fas-fasl-signaling-pathway-in-environmental-toxicant-induced-testicular-cell-apoptosis-an-update
#3
Mei Wang, Ping Su
The Fas/FasL signaling pathway is one of the major pathways that regulate apoptosis. Increasing studies have shown that the activation of the Fas/FasL signaling pathway is closely associated with testicular cell apoptosis. However, the mechanism involved is still unclear. We discuss recent findings regarding the molecular mechanisms by which environmental toxicants induce testicular pathology via Fas/FasL signaling. These findings suggest that Fas/FasL signaling is employed to impact the sensitivity (a response to external factors) of germ cells, disrupt steroidogenic hormone and cytokine metabolism mediated by Sertoli cells, and elicit the activation of NFAT (nuclear factor of activated T-cells) in Leydig cell apoptosis...
January 4, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29283464/tgf-%C3%AE-2-and-tgf-%C3%AE-3-from-cultured-%C3%AE-amyloid-treated-or-3xtg-ad-derived-astrocytes-may-mediate-astrocyte-neuronal-communication
#4
Laura Tapella, Matteo Cerruti, Isabella Biocotino, Alessio Stevano, Francesca Rocchio, Pier Luigi Canonico, Mariagrazia Grilli, Armando A Genazzani, Dmitry Lim
Astrocytes participate in the development and resolution of neuroinflammation in numerous ways, including the release of cytokines and growth factors. Among many, astrocytes release transforming growth factors beta (TGF-β) TGF-β1, TGF-β2 and TGF-β3. TGF-β1 is the most studied isoform, while production and release of TGF-β2 and 3 by astrocytes has been poorly characterized. Here we report that purified cultures of hippocampal astrocytes produce mainly TGF-β3 followed by TGF-β2 and TGF-β1. Furthermore, astrocytes release principally the active form of TGF-β3 over the other two...
December 28, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29282682/targeted-therapies-against-growth-factor-signaling-in-breast-cancer
#5
Juan Du, Yu Yu, Jun Zhan, Hongquan Zhang
Breast cancer is the most prevalent female malignancy throughout the world. Conventional treatment strategies for breast cancer consist of chemotherapy, radiation, surgery, chemoradiation, hormone therapy, and targeted therapies. Among them, targeted therapies show advantages to reduce cost and toxicity for being possible for individualized treatments based on the intrinsic subtypes of breast cancer. With deeper understanding of key signaling pathways concerning tumor growth and survival, growth factor-controlled signaling pathways are frequently dysregulated in the development and progression of breast cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29250925/cucurbitacin-b-attenuates-ccl4-induced-hepatic-fibrosis-in-mice-through-inhibition-of-stat-3
#6
Alaliaa M Sallam, Ahmed Esmat, Ashraf B Abdel-Naim
Liver fibrosis is a major health concern worldwide. Inhibitors of Signal Transducer and Activator of Transcription 3 (STAT3) have been reported to attenuate experimental liver fibrosis. Therefore, the aim of current study was to investigate the potential ameliorative effect of cucurbitacin-B (Cucu-B) against CCl4 -induced liver fibrosis in mice. Treatment with Cucu-B (5 mg/kg) preserved hepatocellular membrane integrity and amended the metabolic function as indicated by preventing the rise of serum liver function markers...
December 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29224245/regulation-of-c-myc-transcriptional-activity-by-transforming-growth-factor-beta-1-stimulated-clone-22
#7
Ling Zheng, Hiroyuki Suzuki, Yuka Nakajo, Akinobu Nakano, Mitsuyasu Kato
C-MYC stimulates cell proliferation through the suppression of cyclin-dependent kinase (CDK) inhibitors including P15 (CDKN2B) and P21 (CDKN1A). It also activates E-box-mediated transcription of various target genes including telomerase reverse transcriptase (TERT) that is involved in cellular immortality and tumorigenesis. Transforming growth factor-beta 1 (TGF-β1)-stimulated clone 22 (TSC-22/TSC22D1) encodes a highly conserved leucine zipper protein that is induced by various stimuli, including TGF-β. TSC-22 inhibits cell growth in mammalian cells and in Xenopus embryos...
December 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/29215776/tgf-%C3%AE-transactivates-egfr-and-facilitates-breast-cancer-migration-and-invasion-through-canonical-smad3-and-erk-sp1-signaling-pathway
#8
Yuanyuan Zhao, Jing Ma, Yanling Fan, Zhiyong Wang, Ran Tian, Wei Ji, Fei Zhang, Ruifang Niu
Transforming growth factor-beta (TGF-β) functions as a potent proliferation inhibitor and apoptosis inducer in the early stages of breast cancer, yet promotes cancer aggressiveness in the advanced stages. The dual effect of TGF-β on cancer development is known as TGF-β paradox, and the remarkable functional conversion of TGF-β is a pivotal and controversial phenomenon that has been widely investigated for decades. This phenomenon may be attributed to the crosstalk between TGF-β signaling and other pathways, including epidermal growth factor receptor (EGFR) signaling during cancer progression...
December 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29215720/gsk3%C3%AE-regulates-ameloblast-differentiation-via-wnt-and-tgf-%C3%AE-pathways
#9
Yaling Yang, Ziyue Li, Guoqing Chen, Jie Li, Hui Li, Mei Yu, Weiping Zhang, Weihua Guo, Weidong Tian
Wnt and TGF-β signaling pathways participate in regulating a variety of cell fates during organogenesis, including tooth development. Despite well-documented, the specific mechanisms, especially how these two pathways act coordinately in regulating enamel development, remain unknown. In this study, we identified Glycogen Synthase Kinase 3 beta (GSK3β), a negative regulator of Wnt signal pathway, participated in ameloblast differentiation via Wnt and TGF-β pathways during enamel development. In vitro rat mandible culture treated with specific GSK3β inhibitor SB415286 displayed enamel defects, accompanied by disrupted ameloblasts polarization, while odontoblasts and dentin appeared to be unaffected...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29211497/the-rho-kinase-isoforms-rock1-and-rock2-each-contribute-to-the-development-of-experimental-pulmonary-fibrosis
#10
Rachel S Knipe, Clemens K Probst, David Lagares, Alicia Franklin, Jillian J Spinney, Patricia L Brazee, Paula Grasberger, Linlin Zhang, Katharine E Black, Norihiko Sakai, Barry S Shea, James K Liao, Benjamin D Medoff, Andrew M Tager
Pulmonary fibrosis is thought to result from dysregulated wound repair after repetitive lung injury. Many cellular responses to injury involve rearrangements of the actin cytoskeleton mediated by the two isoforms of the Rho-associated coiled coil forming protein kinase, ROCK1 and ROCK2. Additionally, profibrotic mediators such as transforming growth factor-beta (TGF-β), thrombin and lysophosphatidic acid (LPA) act through receptors that activate ROCK. Inhibition of ROCK activation may be a potent therapeutic strategy for human pulmonary fibrosis...
December 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29208458/inhibition-of-tgf-%C3%AE-pathway-reverts-extracellular-matrix-remodeling-in-t-cruzi-infected-cardiac-spheroids
#11
Patrícia M Ferrão, Líndice M Nisimura, Otacílio C Moreira, Marcelo G Land, Mirian C Pereira, Leila de Mendonça-Lima, Tania C Araujo-Jorge, Mariana C Waghabi, Luciana R Garzoni
Chagasic cardiomyopathy (CC) is the main manifestation of Chagas Disease (CD). CC is a progressive dysfunctional illness, in which transforming growth factor beta (TGF-β) plays a central role in fibrogenesis and hypertrophy. In the present study, we tested in a three-dimensional (3D) model of cardiac cells culture (named cardiac spheroids), capable of mimicking the aspects of fibrosis and hypertrophy observed in CC, the role of TGF-β pathway inhibition in restoring extracellular matrix (ECM) balance disrupted by T...
December 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29186693/osteocyte-intrinsic-tgf-%C3%AE-signaling-regulates-bone-quality-through-perilacunar-canalicular-remodeling
#12
Neha S Dole, Courtney M Mazur, Claire Acevedo, Justin P Lopez, David A Monteiro, Tristan W Fowler, Bernd Gludovatz, Flynn Walsh, Jenna N Regan, Sara Messina, Daniel S Evans, Thomas F Lang, Bin Zhang, Robert O Ritchie, Khalid S Mohammad, Tamara Alliston
Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR)...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29163548/emodin-alleviates-sodium-taurocholate-induced-pancreatic-acinar-cell-injury-via-microrna-30a-5p-mediated-inhibition-of-high-temperature-requirement-a-transforming-growth-factor-beta-1-inflammatory-signaling
#13
Hong Xiang, Xufeng Tao, Shilin Xia, Jialin Qu, Huiyi Song, Jianjun Liu, Dong Shang
Pancreatitis is an inflammatory disease that is responsible for substantial morbidity and mortality, and it can induce pancreatic necrosis that starts within pancreatic acinar cells in severe cases. Emodin, a pleiotropic natural product isolated from the Chinese herb Rheum palmatum L., has effective anti-inflammatory activities. In this paper, we investigated the protective effects and molecular mechanism of emodin against sodium taurocholate (STC)-induced pancreatic acinar cells injury in vitro and in vivo; and the results showed that emodin could significantly alleviate STC-induced pancreatic acinar cells injury through decreasing trypsin, amylase and the release of inflammatory factors (tumor necrosis factor alpha, interleukin-1β, and interleukin-6)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163160/aberrant-wnt-beta-catenin-pathway-activation-in-dialysate-induced-peritoneal-fibrosis
#14
Yuanyuan Guo, Lin Sun, Li Xiao, Rong Gou, Yudong Fang, Yan Liang, Ruiqiang Wang, Ningjun Li, Fuyou Liu, Lin Tang
Peritoneal dialysis (PD)-associated peritoneal fibrosis is a chronic progress which induces ultrafiltration failure. It remains a challenge to prevent the progression of PD-associated fibrosis in clinic practice. Wnt/β-catenin pathway plays important role in many severe fibrotic diseases, here we investigated its contribution to the development of peritoneal damage. We isolated mesothelial cells (MC) from the effluent of PD patients and found that the expressions of Wnt1, Wnt5a, β-catenin, and LEF1 were increased in patients with more than 1-year PD compared with patients who just started with PD (<1 month)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#15
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29140729/gene-expression-and-gene-associations-during-the-development-of-heart-failure-with-preserved-ejection-fraction-in-the-dahl-salt-sensitive-model-of-hypertension
#16
Jeffrey Yim, Hyokeun Cho, Simon W Rabkin
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9...
November 15, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29101624/genistein-attenuates-pathological-cardiac-hypertrophy-in-vivo-and-in-vitro
#17
Y Meng, Y Zhang, Z Ma, H Zhou, J Ni, H Liao, Q Tang
BACKGROUND: We investigated the effects and underlying mechanisms of genistein on pathological cardiac hypertrophy in vivo and in vitro. MATERIALS AND METHODS: A cardiac hypertrophy model was developed by aortic banding (AB). C57/BL6 mice were randomly assigned to sham + vehicle (CON), sham + genistein (GEN), AB + vehicle (AB), and AB + genistein groups. Genistein (40 mg/kg/day) was administered by gavage for 7 weeks. After assessing the echocardiographic and hemodynamic parameters, mouse hearts were harvested for histopathological and molecular biological analysis...
November 3, 2017: Herz
https://www.readbyqxmd.com/read/29098682/relation-of-nodal-expression-to-the-specification-of-the-dorsal-ventral-axis-and-tissue-patterning-in-the-starfish-patiria-pectinifera
#18
Hiroki Sasaki, Tetsuya Kominami
In this study, we attempted to reveal fundamental aspects of starfish embryogenesis, particularly embryonic axis specification or determination, in Patiria pectinifera. We first cloned PpNodal, which is known to play an important role in the specification of the embryonic axis in a wide range of animals, and studied its expression profile. PpNodal expression was first detected at the mid-blastula stage and showed a single peak around the onset of gastrulation. These features of Nodal expression were shifted to later stages by several hours, compared with those of sea urchin embryos...
November 2, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/29037070/melatonin-promotes-self-renewal-of-nestin-positive-pancreatic-stem-cells-through-activation-of-the-mt2-erk-smad-nestin-axis
#19
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promotion of self-renewal in pancreatic stem cells remain unknown. In this study, we incubated murine pancreatic stem cells (PSCs) with various concentrations of melatonin (0.01, 0.1, 1, 10 or 100 μM) to screen for the optimum culture medium for increasing cell proliferation. We found that 10 μM melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in PSCs via melatonin receptor 2 (MT2)...
October 16, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29034312/tgf-%C3%AE-inhibition-improves-oncolytic-herpes-viroimmunotherapy-in-murine-models-of-rhabdomyosarcoma
#20
Brian Hutzen, Chun-Yu Chen, Pin-Yi Wang, Les Sprague, Hayley M Swain, Julia Love, Joe Conner, Louis Boon, Timothy P Cripe
Oncolytic viruses are an emerging class of cancer therapeutics that couple cytotoxicity with the induction of an anti-tumor immune response. Host-virus interactions are complex and modulated by a tumor microenvironment whose immunosuppressive activities can limit the effectiveness of cancer immunotherapies. In an effort to improve this aspect of oncolytic virotherapy, we combined the oncolytic herpes virus HSV1716 with the transforming growth factor beta receptor 1 (TGF-βR1) inhibitor A8301 to treat syngeneic models of murine rhabdomyosarcoma...
December 15, 2017: Molecular Therapy Oncolytics
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