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https://www.readbyqxmd.com/read/28749412/multi-targeting-andrographolide-a-novel-nf-%C3%AE%C2%BAb-inhibitor-as-a-potential-therapeutic-agent-for-stroke
#1
REVIEW
Chih-Hao Yang, Ting-Lin Yen, Chia-Yuan Hsu, Philip-Aloysius Thomas, Joen-Rong Sheu, Thanasekaran Jayakumar
A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28749049/mineral-trioxide-aggregate-enhances-the-osteogenic-capacity-of-periodontal-ligament-stem-cells-via-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#2
Yanqiu Wang, Yixiang Zhou, Lin Jin, Xiyao Pang, Yadie Lu, Zilu Wang, Yan Yu, Jinhua Yu
INTRODUCTION: Mineral trioxide aggregate (MTA), as a bioactive material, has a widespread application in clinical practice. To date, the effects of MTA on the proliferation and differentiation of human periodontal ligament stem cells (hPDLSCs) remain unclear. MATERIALS AND METHODS: hPDLSCs were isolated from human periodontal ligament tissues and cultured with MTA conditioned media. Cell counting kit-8 (CCK-8) assay was performed to assess the proliferation capacity of MTA-treated hPDLSCs...
July 27, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28748642/noonan-syndrome-in-diverse-populations
#3
Paul Kruszka, Antonio R Porras, Yonit A Addissie, Angélica Moresco, Sofia Medrano, Gary T K Mok, Gordon K C Leung, Cedrik Tekendo-Ngongang, Annette Uwineza, Meow-Keong Thong, Premala Muthukumarasamy, Engela Honey, Ekanem N Ekure, Ogochukwu J Sokunbi, Nnenna Kalu, Kelly L Jones, Julie D Kaplan, Omar A Abdul-Rahman, Lisa M Vincent, Amber Love, Khadija Belhassan, Karim Ouldim, Ihssane El Bouchikhi, Anju Shukla, Katta M Girisha, Siddaramappa J Patil, Nirmala D Sirisena, Vajira H W Dissanayake, C Sampath Paththinige, Rupesh Mishra, Eva Klein-Zighelboim, Bertha E Gallardo Jugo, Miguel Chávez Pastor, Hugo H Abarca-Barriga, Steven A Skinner, Eloise J Prijoles, Eben Badoe, Ashleigh D Gill, Vorasuk Shotelersuk, Patroula Smpokou, Monisha S Kisling, Carlos R Ferreira, Leon Mutesa, Andre Megarbane, Antonie D Kline, Amy Kimball, Emmy Okello, Peter Lwabi, Twalib Aliku, Emmanuel Tenywa, Nonglak Boonchooduang, Pranoot Tanpaiboon, Antonio Richieri-Costa, Ambroise Wonkam, Brian H Y Chung, Roger E Stevenson, Marshall Summar, Kausik Mandal, Shubha R Phadke, María G Obregon, Marius G Linguraru, Maximilian Muenke
Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%...
July 27, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28748452/single-cell-transcriptomics-reveals-gene-signatures-and-alterations-associated-with-aging-in-distinct-neural-stem-progenitor-cell-subpopulations
#4
Zhanping Shi, Yanan Geng, Jiping Liu, Huina Zhang, Liqiang Zhou, Quan Lin, Juehua Yu, Kunshan Zhang, Jie Liu, Xinpei Gao, Chunxue Zhang, Yinan Yao, Chong Zhang, Yi E Sun
Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside...
July 26, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28748373/novel-combination-of-salinomycin-and-resveratrol-synergistically-enhances-the-anti-proliferative-and-pro-apoptotic-effects-on-human-breast-cancer-cells
#5
Jayant Dewangan, Divya Tandon, Sonal Srivastava, Ajeet Kumar Verma, Ashok Yapuri, Srikanta Kumar Rath
Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We further evaluated the molecular mechanism behind SAL and RES mediated cell death...
July 26, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28748356/pd-l1-induced-by-ifn-%C3%AE-from-tumor-associated-macrophages-via-the-jak-stat3-and-pi3k-akt-signaling-pathways-promoted-progression-of-lung-cancer
#6
Xiaohui Zhang, Yuanyuan Zeng, Qiuxia Qu, Jianjie Zhu, Zeyi Liu, Weiwei Ning, Hui Zeng, Nan Zhang, Wenwen Du, Cheng Chen, Jian-An Huang
BACKGROUND: Interferon-γ (IFN-γ) is conventionally regarded as an inflammatory cytokine that has a pivotal role in anti-infection and tumor immune surveillance. It has been used clinically to treat a variety of malignancies. However, increased evidence has suggested IFN-γ can act to induce tumor progression. The role of IFN-γ in regulating antitumor immunity appears to be complex and paradoxical. The mechanism underlying the dual aspects of IFN-γ function in antitumor immunity is not clear...
July 26, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28747866/polysaccharide-from-wheat-bran-induces-cytokine-expression-via-the-toll-like-receptor-4-mediated-p38-mapk-signaling-pathway-and-prevents-cyclophosphamide-induced-immunosuppression-in-mice
#7
Ting Shen, Gongcheng Wang, Long You, Liang Zhang, Haiwei Ren, Weicheng Hu, Qian Qiang, Xinfeng Wang, Lilian Ji, Zhengzhong Gu, Xiangxiang Zhao
Wheat bran-derived polysaccharides have attracted particular attention due to their immunomodulatory effects. However, the molecular mechanisms underlying their functions are poorly understood. The current study was designed to examine the effect of wheat bran polysaccharide (WBP) on RAW 264.7 cells and the underlying signaling pathways, which have not been explored. In addition, we also investigated the immuno-enhancement effects of WBP on cyclophosphamide (CTX)-induced immunosuppression in mice. WBP significantly increased the concentrations of intracellular nitric oxide (NO) and cytokines such as prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) in RAW 264...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28747712/2-oxoadenosine-induces-cytotoxicity-through-intracellular-accumulation-of-2-oxo-atp-and-depletion-of-atp-but-not-via-the-p38-mapk-pathway
#8
Shinji Asada, Eiko Ohta, Yoriko Akimoto, Nona Abolhassani, Daisuke Tsuchimoto, Yusaku Nakabeppu
2-Oxoadenosine (2-oxo-Ado), an oxidized form of adenosine, is cytotoxic and induces growth arrest and cell death, which has potential as an anti-cancer drug. However, it is not well understood how 2-oxo-Ado exerts its cytotoxicity. We examined the effects of 2-oxo-Ado on non-tumour cells, namely immortalized mouse embryonic fibroblast lines, and investigated mechanisms by which 2-oxo-Ado exerts its cytotoxicity. We found that cell death induced by 2-oxo-Ado is classical caspase-dependent apoptosis, and requires its sequential intracellular phosphorylation catalysed by adenosine kinase (ADK) and adenylate kinase 2, resulting in intracellular accumulation of 2-oxo-ATP accompanied by accumulation of 2-oxo-Ado in RNA and depletion of ATP...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747567/modulation-of-the-nur77-bcl-2-apoptotic-pathway-by-p38%C3%AE-mapk
#9
Jie Liu, Guang-Hui Wang, Ying-Hui Duan, Yi Dai, Yuzhou Bao, Mengjie Hu, Yu-Qi Zhou, Mingyu Li, Fuquan Jiang, Hu Zhou, Xin-Sheng Yao, Xiao-Kun Zhang
Orphan nuclear receptor Nur77 promotes apoptosis by targeting mitochondria through interaction with Bcl-2, an event that converts Bcl-2 from a survival to killer. However, how the Nur77-Bcl-2 apoptotic pathway is regulated remains largely unknown. In this study, we examined the regulation of the Nur77-Bcl-2 pathway by CCE9, a xanthone compound. Our results demonstrated that the apoptotic effect of CCE9 depended on its induction of Nur77 expression, cytoplasmic localization, and mitochondrial targeting. The activation of the Nur77-Bcl-2 pathway by CCE9 was associated with its activation of p38α MAPK...
July 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28746469/interleukin-27-augments-the-inhibitory-effects-of-sorafenib-on-bladder-cancer-cells
#10
J Y Cao, H S Yin, H S Li, X Q Yu, X Han
Both sorafenib and interleukin-27 (IL-27) are antineoplastic drugs. This study aimed to investigate the synergistic effect of these two drugs on bladder cancer cells. HTB-9 and T24 cells were stimulated with IL-27 (50 ng/mL), sorafenib (2 μM) or the synergistic action of these two drugs. The cells without treatment acted as control. Cell proliferation, apoptosis and invasion were measured by bromodeoxyuridine assay, flow cytometry and modified Boyden chamber, respectively. Simultaneously, both modified Boyden chamber and scratch assay were used to assess cell migration...
July 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28746311/prolonged-mek1-2-suppression-impairs-the-developmental-potential-of-embryonic-stem-cells
#11
Jiho Choi, Aaron J Huebner, Kendell Clement, Ryan M Walsh, Andrej Savol, Kaixuan Lin, Hongcang Gu, Bruno Di Stefano, Justin Brumbaugh, Sang-Yong Kim, Jafar Sharif, Christopher M Rose, Arman Mohammad, Junko Odajima, Jean Charron, Toshi Shioda, Andreas Gnirke, Steven Gygi, Haruhiko Koseki, Ruslan I Sadreyev, Andrew Xiao, Alexander Meissner, Konrad Hochedlinger
Concomitant activation of the Wnt pathway and suppression of Mapk signalling by two small molecule inhibitors (2i) in the presence of leukaemia inhibitory factor (LIF) (hereafter termed 2i/L) induces a naive state in mouse embryonic stem (ES) cells that resembles the inner cell mass (ICM) of the pre-implantation embryo. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naive ES cells in vitro affects their stability and functionality. Here we show that prolonged culture of male mouse ES cells in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential...
July 26, 2017: Nature
https://www.readbyqxmd.com/read/28745544/euptox-a-induces-g1-arrest-and-autophagy-via-p38-mapk-and-pi3k-akt-mtor-mediated-pathways-in-mouse-splenocytes
#12
Quan Mo, Liwen Hu, Jiahua Weng, Yong Zhang, Yancheng C Zhou, Ruiguang Xu, Zhicai C Zuo, Junliang Deng, Zhihua Ren, Zhijun J Zhong, Guangneng Peng, Xiang Nong, Yahui Wei, Yanchun Hu
Euptox A (9-oxo-10, 11-dehydroageraphorone), the main toxin isolated from Eupatorium adenophorum, is known to induce immunotoxicity in animals. However, the precise mechanism underlying the effects of Euptox A on splenocytes is unclear. Here, we aimed to investigate the molecular mechanisms underlying the effect of Euptox A in mouse spleens after its intragastric administration and found that Euptox A exhibits proautophagic effects in splenocytes. Euptox A markedly arrested the splenocytes in the G0/G1 phase, which was accompanied by inhibition of the expression of the positive regulators CDK4, CDK2, cyclin D1, PCNA, and E2F1, and promotion of the expression of the negative regulators p53, p21 Waf1/Cip1, p27 Kip1, and Chk1...
July 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28745435/mapk-15-is-a-ciliary-protein-required-for-pkd-2-localization-and-male-mating-behavior-in-caenorhabditis-elegans
#13
Brian P Piasecki, Thomas A Sasani, Alexander T Lessenger, Nicholas Huth, Shane Farrell
Cilia are conserved cellular structures that facilitate sensory-based processes, including those required for neuronal and kidney functions. Here, we show that the human mitogen activated kinase-15 (MAPK-15) ortholog in Caenorhabditis elegans encodes a ciliary protein. A strain harboring a mutation in the catalytic site of the kinase domain results in ciliary-specific defects in tail neurons of both hermaphrodite and male worms, manifesting in dye uptake, dendrite extension, and male mating behavior defects...
July 26, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28745322/p53-loss-does-not-permit-escape-from-braf-v600e-induced-senescence-in-a-mouse-model-of-lung-cancer
#14
S Garnett, K L Dutchak, R V McDonough, D Dankort
Lung cancer arises through the acquisition of a number of genetic lesions, with a preponderance of activating mutations in the canonical mitogen-activated protein kinase (MAPK) cascade (RTK-RAS-RAF-MEK). Braf(V600E) expression induces benign lung adenomas that fail to progress to adenocarcinoma because of oncogene-induced senescence (OIS). Braf(V600E) expression, coupled with simultaneous p53 ablation, permits bypass of senescence and progression to lung adenocarcinoma. However, spontaneous human tumors sustain mutations in a temporally separated manner...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28745127/modified-gold-based-sirna-nanotherapeutics-for-targeted-therapy-of-triple-negative-breast-cancer
#15
Reza Shahbazi, Elif Asik, Nermin Kahraman, Mustafa Turk, Bulent Ozpolat, Kezban Ulubayram
AIM: In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. MATERIALS & METHODS: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. RESULTS: We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model...
July 26, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28744771/anti-inflammatory-effects-of-stearidonic-acid-mediated-by-suppression-of-nf-%C3%AE%C2%BAb-and-map-kinase-pathways-in-macrophages
#16
Jeehye Sung, Heemang Jeon, In-Hwan Kim, Heon Sang Jeong, Junsoo Lee
Stearidonic acid (SDA, 18:4n-3) is an omega-3 polyunsaturated fatty acid present in oils derived from plants of the Boraginaceae family. In this study, we determined the anti-inflammatory effects of SDA isolated from echium oil on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. SDA significantly downregulated the levels of the inducible nitric oxide synthase (iNOS) protein, thereby suppressing the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. In addition, SDA inhibited the nuclear translocation and promoter activity of nuclear factor κB (NFκB) and the phosphorylation of mitogen-activated protein kinases (MAPK) such as extracellular signal regulated kinase 1/2, c-jun N terminal kinase, and p38 in LPS-stimulated RAW 264...
July 25, 2017: Lipids
https://www.readbyqxmd.com/read/28744712/vacuolar-protein-sorting-4b-vps4b-regulates-apoptosis-of-chondrocytes-via-p38-mitogen-activated-protein-kinases-mapk-in-osteoarthritis
#17
Libin Xu, Leilei Zhai, Qingtian Ge, Zhongbing Liu, Ran Tao
To aim of this study is to investigate the expression of VPS4B (vacuolar protein sorting 4B) in articular cartilage with osteoarthritis (OA) and to analyze the relationship between VPS4B and chondrocyte apoptosis. We established an OA rat model by the MLI (meniscal/ligamentous injury) modeling method, and we observed the expression of VPS4B in articular cartilage through immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Human SW1353 chondrosarcoma cells were treated with IL-1β to mimic the OA-like chondrocyte injury in vitro, and Western blot was employed to examine the IL-1β-induced expression of VPS4B, phosphorylated p38, and apoptotic markers, namely active caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP)...
July 25, 2017: Inflammation
https://www.readbyqxmd.com/read/28744650/role-of-nf-%C3%AE%C2%BAb-pi3k-mapk-erk-1-2-and-p38-in-erythropoietin-production-by-bone-marrow-nuclears-under-conditions-of-immobilization-stress
#18
L A Miroshnichenko, V V Zhdanov, E V Udut, T Yu Polyakova, G N Zyuz'kov, E V Simanina, E Yu Sherstoboev, L A Stavrova, V I Agafonov, M Yu Minakova, A V Chaikovskii, A M Dygai
The involvement of the studied signal cascades in the regulation of erythropoietin production by bone marrow nuclears under conditions of immobilization stress depends on the type of the hemopoiesis-inducing microenvironment cells and the period of blood system reaction to stress exposure. Secretory activity of monocytes is regulated mainly by PI3K improving cell resistance to disturbances. The functional role of signal cascades involved in the production of erythropoietin by T cells is determined by the stage of the common adaptation syndrome...
July 26, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28744016/anti-inflammatory-and-chondroprotective-effects-of-the-s-adenosylhomocysteine-hydrolase-inhibitor-3-deazaneplanocin-a-in-human-articular-chondrocytes
#19
Juliette Aury-Landas, Céline Bazille, Lyess Allas, Sara Bouhout, Christophe Chesneau, Sylvain Leclercq, Karim Boumédiene, Catherine Baugé
3-Deazaneplanocin A (DZNep) is an inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) known to inhibit EZH2, a histone methylase upregulated during osteoarthritis. In this study, we assessed its effects in human articular chondrocytes. Anti-inflammatory effects were assessed by Nitric Oxide (NO), Prostaglandin E2 (PGE2) and Metalloprotease (MMP) release in IL-1β-stimulated chondrocytes. MAPK and NFκB activation was analyzed by western blotting. Differentially expressed genes (DEG) regulated by DZNep were identified by whole-transcriptome microarray...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743999/selenocysteine-induces-apoptosis-in-human-glioma-cells-evidence-for-trxr1-targeted-inhibition-and-signaling-crosstalk
#20
Cun-Dong Fan, Xiao-Yan Fu, Zong-Yong Zhang, Ming-Zhi Cao, Jing-Yi Sun, Ming-Feng Yang, Xiao-Ting Fu, Shi-Jun Zhao, Lu-Rong Shao, Hui-Fang Zhang, Xiao-Yi Yang, Bao-Liang Sun
Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation...
July 25, 2017: Scientific Reports
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