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Eun-Young Nam, Sun Ah Kim, Heejung Kim, Su-Hyun Kim, Jae-Hyun Han, Ju-Hee Lee, Dong-Il Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Evodiae Fructus (EF) is the dried, unripe fruit of Evodia rutaecarpa Benth., and one of the main components of traditional herbal prescriptions issued for the treatment of sterility caused by irregular menstruation in Korea. However, scientific evidence regarding the efficacy and action mechanism of EF is lacking. AIM OF THE STUDY: In this study, the authors established an in vitro screening tool to identify promising new drug candidates in herbal medicines for the prevention and treatment of premature ovarian failure...
October 18, 2016: Journal of Ethnopharmacology
Lei Wu, Hua Feng, Jinhua Hu, Xiangguo Tian, Chunqing Zhang
Due to the low cost and favorable safety profile, valproic acid (VPA) has been considered as a potential candidate drug for therapy of various cancers. Our present study revealed that VPA, at the concentration (1mM) which has no effect on cell proliferation, can significantly increase the in vitro migration and invasion of hepatocarcinoma (HCC) HepG2 and Huh7 cells via induction of epithelial mesenchymal transition (EMT). VPA treatment can significantly increase the mRNA and protein expression of Snail, the key transcription factor of EMT...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhaoyang Hu, Sheng Hu, Shuai Yang, Mou Chen, Ping Zhang, Jin Liu, Geoffrey W Abbott
BACKGROUND: Preconditioning stimuli conducted in remote organs can protect the heart against subsequent ischemic injury, but effects on arrhythmogenesis and sudden cardiac death (SCD) are unclear. Here, we investigated the effect of remote liver ischemia preconditioning (RLIPC) on ischemia/reperfusion (I/R)-induced cardiac arrhythmia and sudden cardiac death (SCD) in vivo, and determined the potential role of ERK/GSK-3βsignaling. METHODS/RESULTS: Male Sprague Dawley rats were randomized to sham-operated, control, or RLIPC groups...
2016: PloS One
Vincent Ronfard, Alain Vertes, Michael May, Anne Dupraz, Mark van Dyke, Yves Bayon
"Evaluating the Past & Present of Regenerative Medicine (RM)" was the first part of an Industry Symposium dedicated to the subject during the 2015 World TERMIS Congress in Boston. This working session presented a critical review of the current RM landscape in Europe and North America with possible projections for the future. Interestingly, the RM development cycle seems to obey the Gartner hype cycle, now at the enlightenment phase, after past exaggerated expectations and discouragements, as suggested by increasing numbers of clinical trials and recent market approvals of RM solutions in both Europe (Glybera & Holoclar® from Chiesi Pharma and Strimvelis® from GSK) and Japan (Remestemcel-L from Mesoblast® )...
October 20, 2016: Tissue Engineering. Part B, Reviews
Chun Ma, Violetta Karwacki-Neisius, Haoran Tang, Wenjing Li, Zhennan Shi, Haolin Hu, Wenqi Xu, Zhentian Wang, Lingchun Kong, Ruitu Lv, Zheng Fan, Wenhao Zhou, Pengyuan Yang, Feizhen Wu, Jianbo Diao, Li Tan, Yujiang Geno Shi, Fei Lan, Yang Shi
Nono is a component of the para-speckle, which stores and processes RNA. Mouse embryonic stem cells (mESCs) lack para-speckles, leaving the function of Nono in mESCs unclear. Here, we find that Nono functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We report that Nono loss results in robust self-renewing mESCs with epigenomic and transcriptomic features resembling the 2i (GSK and Erk inhibitors)-induced "ground state." Erk interacts with and is required for Nono localization to a subset of bivalent genes that have high levels of poised RNA polymerase...
October 18, 2016: Cell Reports
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Lewan Parker, Itamar Levinger, Aya Mousa, Kirsten Howlett, Barbora de Courten
Vitamin D has been suggested to play a role in glucose metabolism. However, previous findings are contradictory and mechanistic pathways remain unclear. We examined the relationship between plasma 25-hydroxyvitamin D (25(OH)D), insulin sensitivity, and insulin signaling in skeletal muscle and adipose tissue. Seventeen healthy adults (Body mass index: 26 ± 4; Age: 30 ± 12 years) underwent a hyperinsulinemic-euglycemic clamp, and resting skeletal muscle and adipose tissue biopsies. In this cohort, the plasma 25(OH)D concentration was not associated with insulin sensitivity (r = 0...
October 13, 2016: Nutrients
Wenwen Wang, Yanqin Yang, Zhewen Xiong, Jiamin Kong, Xinlu Fu, Feihai Shen, Zhiying Huang
Triptolide (TP), a diterpene triepoxide, is a major active component of Tripterygium wilfordii extracts, which are prepared as tablets and has been used clinically for the treatment of inflammation and autoimmune disorders. However, TP's therapeutic potential is limited by severe adverse effects. In a previous study, we reported that TP induced mitochondria dependent apoptosis in cardiomyocytes. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays important roles in the necrosis and apoptosis of cardiomyocytes...
October 14, 2016: Toxicology and Applied Pharmacology
Lezi Chen, Quan Chen, Guosan Deng, Wenbin Xie, Jihong Lian, Mian Wang, Huilan Zhu
Recent studies suggest that forced activation of AMP-activated protein kinase (AMPK) could inhibit melanoma cell proliferation. In this report, we evaluated the anti-melanoma cell activity by a novel small-molecular AMPK activator, GSK621. Treatment of GSK621 decreased survival and proliferation of human melanoma cells (A375, WM-115 and SK-Mel-2 lines), which was accompanied by activation of caspase-3/-9 and apoptosis. Reversely, caspase inhibitors attenuated GSK621-induced cytotoxicity against melanoma cells...
October 14, 2016: Biochemical and Biophysical Research Communications
Young-Lan Park, Sun-Young Park, Seung-Hyun Lee, Rul-Bin Kim, Joong-Keun Kim, Sung-Yoon Rew, Dae-Seong Myung, Sung-Bum Cho, Wan-Sik Lee, Hyun-Soo Kim, Young-Eun Joo
Filamin A interacting protein 1-like (FILIP1L) expression, which is decreased in various cancers, may inhibit carcinogenesis. In this study, we evaluated the effects of FILIP1L on oncogenic behavior and prognosis in colorectal cancer. siRNA-mediated FILIP1L knockdown enhanced tumor cell migration and invasion and inhibited apoptosis and cell cycle arrest in COLO205 cells. pcDNA-myc vector-mediated FILIP1L overexpression suppressed tumor cell migration and invasion and induced apoptosis and cell cycle arrest in HCT116 cells...
October 14, 2016: Oncotarget
Jia Guo, Lili Yang, Yingjin Qiao, Zhangsuo Liu
Epithelial-mesenchymal transition (EMT) is important for diabetic nephropathy (DN). Podocytes are specialized epithelial cells, which form a major component of the glomerular filtration barrier. Podocyte damage has been suggested to be the primary mechanism behind the albuminuria associated with DN. The present study aimed to determine the function of glycogen synthase kinase (GSK)‑3β in EMT and barrier dysfunction of mouse podocytes exposed to high glucose (HG) conditions. Matured and differentiated podocytes were treated with normal glucose (NG), HG or NG + mannitol...
September 26, 2016: Molecular Medicine Reports
Jatin Machhi, Navnit Prajapati, Ashutosh Tripathi, Zalak S Parikh, Ashish M Kanhed, Kirti Patel, Prakash P Pillai, Rajani Giridhar, Mange Ram Yadav
Excitotoxicty, a key pathogenic event is characteristic of the onset and development of neurodegeneration. The glutamatergic neurotransmission mediated through different glutamate receptor subtypes plays a pivotal role in the onset of excitotoxicity. The role of NMDA receptor (NMDAR), a glutamate receptor subtype, has been well established in the excitotoxicity pathogenesis. NMDAR overactivation triggers excessive calcium influx resulting in excitotoxic neuronal cell death. In the present study, a series of benzazepine derivatives, with the core structure of 3-methyltetrahydro-3H-benzazepin-2-one, were synthesised in our laboratory and their NMDAR antagonist activity was determined against NMDA-induced excitotoxicity using SH-SY5Y cells...
October 15, 2016: Molecular Neurobiology
Nagendra Yaluri, Shalem Modi, Tarja Kokkola
Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor widely used for the treatment of hypercholesterolemia. Recent data indicates that simvastatin increases the risk of new-onset diabetes by impairing both insulin secretion and insulin sensitivity. However, systematic evaluation of mechanistic pathways is lacking. We aimed to explore the effects of simvastatin on glucose uptake and underlying mechanisms using L6 skeletal muscle myotubes. We performed our experiments at basal and insulin-stimulated conditions, at normal (5...
October 12, 2016: Biochemical and Biophysical Research Communications
Rohit Mathur, Lalit Sehgal, Ondrej Havranek, Stefan Köhrer, Tamer Khashab, Neeraj Jain, Jan A Burger, Sattva S Neelapu, R Eric Davis, Felipe Samaniego
Histone methylation and demethylation regulates B-cell development, and their deregulation correlates with tumor chemoresistance in diffuse large B-cell lymphoma, limiting curative rates. Since histone methylation status correlates with disease aggressiveness and relapse, we investigated the therapeutic potential of inhibiting histone 3 Lys27 demethylase KDM6B, in-vitro, using the small molecule inhibitor GSK-J4. KDM6B is overexpressed in the DLBCL germinal center B-cell subtype, and higher KDM6B levels are associated with worse survival in DLBCL patients treated with R-CHOP...
October 14, 2016: Haematologica
Jian Zheng, Zhen Liu, Weishan Li, Jiaxin Tang, Dongwei Zhang, Xiaobo Tang
OBJECTIVE Inflammation and apoptosis are two key factors contributing to secondary brain injury after intracerebral hemorrhage (ICH). The objective of this study was to evaluate the effects of lithium posttreatment on behavior, brain atrophy, inflammation, and perihematomal cell death. Furthermore, the authors aimed to determine the role of the pro-apoptotic glycogen synthase kinase-3β (GSK-3β) after experimental ICH. METHODS Male Sprague-Dawley rats (n = 108) were subjected to intracerebral infusion of semicoagulated autologous blood...
October 14, 2016: Journal of Neurosurgery
Shantaé M Thornton, James E Krolopp, Marcia J Abbott
Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed "myokines," has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPARα and/or PPARδ as targets of IL-15 signaling...
2016: PPAR Research
Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Adbulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing form of liver disease, and if left untreated can result in non-alcoholic steatohepatitis (NASH) ultimately resulting in liver cirrhosis and failure. Biliverdin reductase-A (BVRA) is a multi-functioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA can function as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase-3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
October 10, 2016: Journal of Biological Chemistry
Hee Kyong Oh, Se Jin Jeon, Sunhee Lee, Hyung Eun Lee, Eunji Kim, Se Jin Park, Ha Neul Kim, Won Yong Jung, Jae Hoon Cheong, Dae Sik Jang, Jong Hoon Ryu
Swertisin, a plant-derived C-glucosylflavone, is known to have antidiabetic, anti-inflammatory and antioxidant effects. In the present study, we investigated in mice the effects of swertisin on glutamatergic dysfunction induced by dizocilpine (MK-801), a non-competitive N-methyl-D-aspartate receptor antagonist. In the Acoustic Startle Response test, their MK-801-induced (given 0.2 mg/kg i.p.) pre-pulse inhibition deficit was significantly attenuated by the administration of swertisin (30 mg/kg p.o.). In the Novel Object Recognition Test, the recognition memory impairments that were induced by MK-801 (0...
October 11, 2016: Journal of Psychopharmacology
Xu Ling-Zhi, Xu De-Feng, Han Ying, Liu Li-Jing, Sun Cheng-Yu, Deng Jia-Hui, Zhang Ruo-Xi, Yuan Ming, Zhang Su-Zhen, Li Zhi-Meng, Xu Yi, Li Jin-Sheng, Xie Su-Hua, Li Su-Xia, Zhang Hong-Yan, Lu Lin
BACKGROUND: Morinda officinalis oligosaccharides (MOs) have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test (FST) in mice. However, the mechanisms that underlie the antidepressant-like effects of MOs are unclear. METHODS: Chronic unpredictable stress (CUS) and FST were used to explore the antidepressant-like effects of MOs and resilience to stress in rats. The PI3K inhibitor LY294002 was microinjected in the medial prefrontal cortex (mPFC) to explore the role of GSK-3β in the antidepressant-like effects of MOs...
October 11, 2016: International Journal of Neuropsychopharmacology
Steven W Yancey, Hector G Ortega, Oliver N Keene, Bhabita Mayer, Necdet B Gunsoy, Christopher E Brightling, Eugene R Bleecker, Pranabashis Haldar, Ian D Pavord
BACKGROUND: Studies show that mepolizumab can reduce the frequency of clinically significant exacerbations in patients with severe eosinophilic asthma, compared with placebo. However, important events such as hospitalizations and emergency room visits are rare and difficult to characterize in single studies. OBJECTIVE: We sought to compare hospitalization or hospitalization and/or emergency room visit rates in patients with severe eosinophilic asthma treated with mepolizumab or placebo in addition to standard of care for at least 24 weeks...
October 4, 2016: Journal of Allergy and Clinical Immunology
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