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Huafeng Wang, Huan Zhang, Yuqing Zhang, Dan Wang, Xixi Cheng, Fengrui Yang, Qi Zhang, Zhenyi Xue, Yan Li, Lijuan Zhang, Luhong Yang, Guolin Miao, Daiqing Li, Zhiyu Guan, Yurong Da, Zhi Yao, Fei Gao, Liang Qiao, Li Kong, Rongxin Zhang
Plumbagin is a quinonoid constituent extracted from Plumbago genus, and it exhibits diverse pharmacological effects. This study thoroughly investigated the effects of plumbagin on thioacetamide-induced acute and chronic liver injury. Results shown that plumbagin increased survival rate, reduced liver congestion and inflammation, and decreased macrophages and neutrophils in the fulminant hepatic failure model, and remarkably diminished liver fibrosis and inflammation in the chronic liver injury model. Furthermore, plumbagin significantly suppress the HSCs/myofibroblasts activation by reduced expression of markers α-SMA and COL-1/3, and reduced macrophage in liver...
October 14, 2016: Oncotarget
Niloy Bhattacharjee, Sujata Barma, Nandita Konwar, Saikat Dewanjee, Prasenjit Manna
Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals...
August 25, 2016: European Journal of Pharmacology
Wenjuan Yao, Lei Huang, Qinju Sun, Lifeng Yang, Lian Tang, Guoliang Meng, Xiaole Xu, Wei Zhang
Macrophage foam cell formation triggered by oxLDL is an important event that occurs during the development of atherosclerosis. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) exhibits significant anti-atherosclerotic activity. Herein we used U937 cells induced by PMA and oxLDL in vitro to investigate the inhibitory effects of TSG on U937 differentiation and macrophage foam cell formation. TSG pretreatment markedly inhibited cell differentiation induced by PMA, macrophage apoptosis and foam cell formation induced by oxLDL...
August 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yuji Miyamoto, Diana L Hanna, Wu Zhang, Hideo Baba, Heinz-Josef Lenz
Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival...
August 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Takumi Yamane, Aimi Muramatsu, Sawako Yoshino, Sho Matsui, Mari Shimura, Yoshimasa Tsujii, Ken Iwatsuki, Kazuo Kobayashi-Hattori, Yuichi Oishi
Although mammalian target of rapamycin (mTOR) mediates a wide variety of biological functions, little information is available on the effect of mTOR on the functions of skin cells. In this study, we investigated effects of mTOR inhibition by rapamycin on ceramide synthesis in the skin of rats and human keratinocytes and its regulatory mechanisms. The phosphorylation of p70 S6 kinase, which indicates mTOR activation, was induced in the skin of rats fed a high-fat diet, but this abnormality was reversed by supplementation with rapamycin...
April 2016: FEBS Open Bio
Jun-Mei Lu, Chang-Ying Wang, Changlong Hu, Yan-Jia Fang, Yan-Ai Mei
GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K(+) currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca(2+) concentration ([Ca(2+)]i) in response to membrane depolarization, as determined by Ca(2+) imaging...
July 1, 2016: Biochemical Journal
Huixing Chen, Lan Zhou, Xiaorong Wu, Rongbing Li, Jiling Wen, Jianjun Sha, Xiaofei Wen
Despite recent advances in our understanding of the biological behavior of prostate cancer (PCa), PCa is becoming the most common malignancy in men worldwide. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in prostate carcinogenesis. Inflammatory cytokines (CCR9, IL-6, and TLR3) regulate PI3K/AKT signaling during apoptosis of PCa cells, and PI3K/AKT signaling participates with androgen-, 1alpha,25(OH)2-vitamin D3-, and prostaglandin-associated mechanisms and is regulated by ErbB, EGFR, and the HER family during cell growth...
2016: Frontiers in Bioscience (Landmark Edition)
Antonella Vetuschi, Giovanni Latella, Simona Pompili, Eugenio Gaudio, Roberta Sferra
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic, progressive and relapsing inflammatory disorders of unknown etiology. UC is characterized by inflammation of the large bowel mucosa and submucosa, whereas in CD inflammation is transmural and may involve various sites of the gastrointestinal tract. Superficial mucosal lesions are most prone to heal, whereas deep ulcers or transmural fissures may heal with more difficulty and may be followed by the development of fibrosis and strictures requiring surgery...
2014: Italian Journal of Anatomy and Embryology, Archivio Italiano di Anatomia Ed Embriologia
Michele Simbolo, Matteo Fassan, Andrea Mafficini, Rita T Lawlor, Andrea Ruzzenente, Aldo Scarpa
Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms characterized by a dismal prognosis. At variance with most solid tumors, no effective molecular targeted agent has been currently approved for BTCs treatment and their molecular landscape has only been recently investigated. Comprehensive mutational profiling studies identified IDH1/2 and BAP1 as characteristic of intrahepatic cholangiocarcinomas, while extrahepatic cholangiocarcinomas and gallbladder carcinomas were characterized by frequent KRAS and TP53 alterations...
2016: Frontiers in Bioscience (Landmark Edition)
Sunetra Das, Natalie L Pitts, Megan R Mudron, David S Durica, Donald L Mykles
In decapod crustaceans, arthropod steroid hormones or ecdysteroids regulate molting. These hormones are synthesized and released from a pair of molting glands called the Y-organs (YO). Cyclic nucleotide, mTOR, and TGFβ/Smad signaling pathways mediate molt cycle-dependent phase transitions in the YO. To further identify the genes involved in the regulation of molting, a YO transcriptome was generated from three biological replicates of intermolt blackback land crab, Gecarcinus lateralis. Illumina sequencing of cDNA libraries generated 227,811,829 100-base pair (bp) paired-end reads; following trimming, 90% of the reads were used for further analyses...
March 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Ranjan Das, Shanhua Xu, Tuyet Thi Nguyen, Xianglan Quan, Seong-Kyung Choi, Soo-Jin Kim, Eun Young Lee, Seung-Kuy Cha, Kyu-Sang Park
TGF-β is a pleiotropic cytokine that accumulates during kidney injuries, resulting in various renal diseases. We have reported previously that TGF-β1 induces the selective up-regulation of mitochondrial Nox4, playing critical roles in podocyte apoptosis. Here we investigated the regulatory mechanism of Nox4 up-regulation by mTORC1 activation on TGF-β1-induced apoptosis in immortalized podocytes. TGF-β1 treatment markedly increased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets p70S6K and 4EBP1...
December 25, 2015: Journal of Biological Chemistry
Md Shaifur Rahman, Naznin Akhtar, Hossen Mohammad Jamil, Rajat Suvra Banik, Sikder M Asaduzzaman
Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals...
2015: Bone Research
Zhijie Wang, Zhirong Shen, Zhenxiang Li, Jianchun Duan, Shuai Fu, Zhentao Liu, Hua Bai, Zemin Zhang, Jun Zhao, Xiaodong Wang, Jie Wang
The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non-small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K...
August 11, 2015: Proceedings of the National Academy of Sciences of the United States of America
Xuefeng Xu, Huaping Dai, Jing Geng, Xuan Wan, Xiaoxi Huang, Fei Li, Dianhua Jiang, Chen Wang
Excessive production of connective tissue growth factor (CTGF, CCN2) and increased motor ability of the activated fibroblast phenotype contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, molecules and signal pathways regulating CCN2 expression and migration of lung fibroblasts are still elusive. We hypothesize that rapamycin, via binding and blocking mammalian target of rapamycin (mTOR) complex (mTORC), affects CCN2 expression and migration of lung fibroblasts in vitro. Primary normal and fibrotic human lung fibroblasts were isolated from lung tissues of three patients with primary spontaneous pneumothorax and three with IPF...
August 2015: Laboratory Investigation; a Journal of Technical Methods and Pathology
Brandon J Metge, Aparna Mitra, Dongquan Chen, Lalita A Shevde, Rajeev S Samant
We have previously reported that expression of NMI (N-myc and STAT interactor) is compromised in invasive breast cancers. We also demonstrated that loss of NMI expression promotes epithelial-mesenchymal-transition and results in enhanced invasive ability of breast cancer cells. Additionally we had demonstrated that restoration of NMI expression reduced breast cancer xenograft growth and downregulated Wnt and TGFβ/SMAD signaling. Here we present our observations that NMI expression drives autophagy. Our studies were promoted by our observation that NMI expressing breast cancer cells showed autophagic vacuoles and LC3 processing...
2015: Scientific Reports
Palanivel Chitra, Gowrikumar Saiprasad, Ramar Manikandan, Ganapasam Sudhandiran
UNLABELLED: Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disorder of unknown aetiology. Transforming growth factor-β1 (TGF-β1)-mediated Smad and non-Smad signaling cascades are considered as central players in accelerating pulmonary fibrosis. We earlier reported berberine's amelioration against TGF-β1-mediated pro-fibrotic effects in bleomycin-induced pulmonary fibrosis. The present study aimed to determine the regulatory role of berberine on abrogated Smad 2/3 and FAK-dependent PI3K/Akt-mTOR signaling cascades in bleomycin-induced pulmonary fibrosis...
September 2015: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Jung-Il Kang, Sang-Cheol Kim, Min-Kyoung Kim, Hye-Jin Boo, Eun-Ji Kim, Guang-Jin Im, Young Ho Kim, Jin-Won Hyun, Ji-Hoon Kang, Young-Sang Koh, Deok-Bae Park, Eun-Sook Yoo, Hee-Kyoung Kang
Androgenetic alopecia involves the action of dihydrotestosterone (DHT) on dermal papilla cells (DPCs) that line the base of the hair follicle. However, the mechanism of DHT action is not completely understood. The effects of DHT on DPCs, regulatory cells that function in follicle growth and the hair cycle, were examined in immortalized cells derived from rat vibrissa follicles. DHT did not affect the proliferation of immortalized DPCs. However, flow cytometry analysis revealed that DHT increased cell-cycle arrest in these cells, which was accompanied by an increase in the p27(kip1) level and by decreases in cyclin E, cyclin D1, and cyclin-dependent kinase 2 levels...
June 15, 2015: European Journal of Pharmacology
Maruf Hasan, Bernhard Neumann, Steffen Haupeltshofer, Sarah Stahlke, Massimo Claudio Fantini, Klemens Angstwurm, Ulrich Bogdahn, Ingo Kleiter
Although transforming growth factor-β (TGF-β) has been shown to positively regulate the development of murine T helper type 17 (Th17) cells, which of the intracellular signaling pathways are involved is controversial. We examined Smad-dependent and -independent signaling molecules downstream of the TGF-β receptor (TGFβR) involved in Th17 differentiation of naive murine CD4(+)CD62L(+) T cells. During Th17 differentiation of wild-type T cells, Smad2/3 was phosphorylated, indicating activation of the canonical Smad pathway...
August 2015: Immunology and Cell Biology
Caihong Wei, Hangxing Ren, Lingyang Xu, Li Li, Ruizao Liu, Li Zhang, Fuping Zhao, Jian Lu, Xiaoning Zhang, Lixin Du
Myostatin and Pax7 have been well documented individually, however, the mechanism by which Myostatin regulates Pax7 is seldom reported. Here, based on muscle transcriptome analysis in Texel (Myostatin mutant) and Ujumqin (wild type) sheep across the five fetal stages, we constructed and examined the Myostatin-Pax7 pathways in muscle. Then we validated the signals by RNAi in the proliferating and differentiating sheep myoblasts in vitro at mRNA, protein, and cell morphological levels. We reveal that Myostatin signals to Pax7 at least through Ezh2, Src, and Akt during the sheep myoblast proliferation and differentiation...
2015: PloS One
Anna Sebestyén, Ágnes Márk, Melinda Hajdu, Noémi Nagy, Anna Molnár, Gyula Végső, Gábor Barna, László Kopper
TGF-β1 (transforming growth factor beta 1) is a negative regulator of lymphocytes, inhibiting proliferation and switching on the apoptotic program in normal lymphoid cells. Lymphoma cells often lose their sensitivity to proapoptotic/anti-proliferative regulators such as TGF-β1. Rapamycin can influence both mTOR (mammalian target of rapamycin) and TGF-β signaling, and through these pathways it is able to enhance TGF-β induced anti-proliferative and apoptotic responses. In the present work we investigated the effect of rapamycin and TGF-β1 combination on cell growth and on TGF-β and mTOR signalling events in lymphoma cells...
June 2015: Cytokine
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