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https://www.readbyqxmd.com/read/28808383/chemopreventive-potential-of-major-flavonoid-compound-of-methanolic-bark-extract-of-saraca-asoca-roxb-in-benzene-induced-toxicity-of-acute-myeloid-leukemia-mice
#1
Manas Kumar Mukhopadhyay, Mithun Shaw, Debjani Nath
BACKGROUND: Saraca asoca (SA) (Roxb.) is one of the folk medicinal plants found in India, Bangladesh, and Sri Lanka. Its major biological activity appears due to the presence of flavonoid group of compounds in its bark extract. OBJECTIVE: In this study, our research aims to analyze the chemopreventive effect of flavonoids, especially a natural phenol catechin present in the bark methanolic extract of SA on acute myeloid leukemia (AML) mice. MATERIALS AND METHODS: The total bark extract was partitioned and analyzed on thin-layer chromatography (TLC) plate...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808351/inhibition-of-the-mevalonate-pathway-augments-the-activity-of-pitavastatin-against-ovarian-cancer-cells
#2
Marwan Ibrahim Abdullah, Mohammed Najim Abed, Alan Richardson
Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously shown that pitavastatin induces regression of ovarian cancer xenografts in mice. To evaluate whether the response of ovarian cancer cells to pitavastatin is potentiated by farnesyl diphosphate synthase inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations of pitavastatin with zoledronic acid, risedronate and GGTI-2133 in a panel of ovarian cancer cells. Pitavastatin (IC50 = 0.6-14 μM), zoledronic acid (IC50 = 21-57 μM), risedronate (IC50 > 100 μM) or GGTI-2133 (IC50 > 25 μM) inhibited the growth of ovarian cancer cell cultures...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800131/atg2a-b-deficiency-switches-cytoprotective-autophagy-to-non-canonical-caspase-8-activation-and-apoptosis
#3
Zhenyuan Tang, Yoshinori Takahashi, Chong Chen, Ying Liu, Haiyan He, Nikolaos Tsotakos, Jacob M Serfass, Melat T Gebru, Han Chen, Megan M Young, Hong-Gang Wang
Autophagosomal membranes are emerging as platforms for various cell survival and death signaling networks beyond autophagy. While autophagy-dependent cell death has been reported in response to a variety of stimuli, the underlying molecular mechanisms remain far from clear. Here, we demonstrate that inhibition of autophagosome completion by Atg2A/B deletion accumulates immature autophagosomal membranes that promote non-canonical caspase-8 activation in response to nutrient starvation via an intracellular death-inducing signaling complex (iDISC)...
August 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28799566/shrna-mediated-silencing-of-htert-suppresses-proliferation-and-promotes-apoptosis-in-osteosarcoma-cells
#4
P Chen, W-L Gu, M-Z Gong, J Wang, D-Q Li
In this study, we aim to explore the effects of short hairpin RNAs (shRNAs) targeting human telomerase reverse transcriptase (hTERT) on the proliferation and apoptosis of osteosarcoma cells. After the synthesis of shRNA that target hTERT, osteosarcoma cells were assigned into three experimental groups-shRNA group, scramble group and blank group. The transcription and expressions of the hTERT gene in transfected cells were measured with quantitative real-time polymerase chain reaction and western blotting. Cell proliferation in each group was detected by Cell Counting Kit-8 assay...
August 11, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28771586/inhibition-of-caspase-1-or-gasdermin-d-enable-caspase-8-activation-in-the-naip5-nlrc4-asc-inflammasome
#5
Danielle P A Mascarenhas, Daiane M Cerqueira, Marcelo S F Pereira, Fernanda V S Castanheira, Talita D Fernandes, Graziele Z Manin, Larissa D Cunha, Dario S Zamboni
Legionella pneumophila is a Gram-negative, flagellated bacterium that survives in phagocytes and causes Legionnaires' disease. Upon infection of mammalian macrophages, cytosolic flagellin triggers the activation of Naip/NLRC4 inflammasome, which culminates in pyroptosis and restriction of bacterial replication. Although NLRC4 and caspase-1 participate in the same inflammasome, Nlrc4-/- mice and their macrophages are more permissive to L. pneumophila replication compared with Casp1/11-/-. This feature supports the existence of a pathway that is NLRC4-dependent and caspase-1/11-independent...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28767087/novel-methylselenoesters-as-antiproliferative-agents
#6
Nuria Díaz-Argelich, Ignacio Encío, Daniel Plano, Aristi P Fernandes, Juan Antonio Palop, Carmen Sanmartín
Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH₃SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH₃SeH. The fifteen compounds follow Lipinski's Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid...
August 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28766061/lysophosphatidic-acid-enhances-human-umbilical-cord-mesenchymal-stem-cell-viability-without-differentiation-via-lpa-receptor-mediating-manner
#7
Narengerile Li, Ya-Li Yan, Sachaofu Fu, Rui-Juan Li, Peng-Fei Zhao, Xi-Yuan Xu, Jing-Ping Yang, Alatangaole Damirin
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential stromal cells which are regarded as the most feasible stem cell group in cell therapy. The maintenance of cell survival without differentiation is important in cell transplantation and stem cell therapy. However, negative factors exist in cell transplantation. Lysophosphatidic acid (LPA) is a non-antigenic small molecule phospholipid which induced several fundamental cellular responses, such as cell proliferation, apoptosis and migration. In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy...
August 1, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28760991/presumptive-trp-channel-ced-11-promotes-cell-volume-decrease-and-facilitates-degradation-of-apoptotic-cells-in-caenorhabditis-elegans
#8
Kaitlin Driscoll, Gillian M Stanfield, Rita Droste, H Robert Horvitz
Apoptotic cells undergo a series of morphological changes. These changes are dependent on caspase cleavage of downstream targets, but which targets are significant and how they facilitate the death process are not well understood. In Caenorhabditis elegans an increase in the refractility of the dying cell is a hallmark morphological change that is caspase dependent. We identify a presumptive transient receptor potential (TRP) cation channel, CED-11, that acts in the dying cell to promote the increase in apoptotic cell refractility...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760936/caspase-11-plays-a-protective-role-in-pulmonary-a-baumannii-infection
#9
Wei Wang, Yue Shao, Shengjun Li, Na Xin, Tingxian Ma, Chenghai Zhao, Min Song
Activation of caspase-11 by some gram negative bacteria triggers caspase-1/IL-1β pathway independent of canonical inflammasomes. Acinetobacter baumannii (A. baumannii) are gram negative, conditional pathogenic bacteria, which can lead to severe pulmonary infection in hospitalized patients. A. baumannii were revealed to activate canonical and noncanonical inflammasome pathway in bone marrow-derived macrophages (BMDMs). Pulmonary infection of caspase-11(-/-) mice with A. baumannii showed that caspase-11 deficiency impaired A...
July 31, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28756208/activation-of-aldh1a1-in-mda-mb-468-breast-cancer-cells-that-over-express-cyp2j2-protects-against-paclitaxel-dependent-cell-death-mediated-by-reactive-oxygen-species
#10
Sarah E Allison, Yongjuan Chen, Nenad Petrovic, Jian Zhang, Kirsi Bourget, Peter I Mackenzie, Michael Murray
Cytochrome P450 2J2 (CYP2J2) expression is elevated in breast and other tumours, and is known to be protective against cytotoxic agents that may be used in cancer chemotherapy. This study evaluated the mechanisms by which MDA-MB-468 breast cancer cells that stably expressed CYP2J2 (MDA-2J2 cells) were protected against killing by the anti-cancer agent paclitaxel. Compared to control cells caspase-3/7 activation by paclitaxel was lower in MDA-2J2 cells, while cell proliferation and colony formation following paclitaxel treatment were increased...
July 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28752106/in-vivo-analysis-of-neutrophil-infiltration-during-lps-induced-peritonitis
#11
Lucia de Almeida, Andrea Dorfleutner, Christian Stehlik
Bacterial lipopolysaccharide (LPS) is present in the outer membrane of Gram-negative bacteria and functions as pathogen-associated molecular pattern (PAMP) (Whitfield and Trent, 2014). LPS therefore is a potent activator of inflammatory responses leading to cytokine release and neutrophils recruitment. The lipid A moiety of LPS activates the complex consisting of the LPS binding protein (LBP), CD14, MD-2 and Toll-like receptor 4 (TLR4) and the non-canonical inflammasome-linked caspases-4, 5 and 11, which in turn activate the canonical NLRP3 inflammasome (Shi et al...
October 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28746866/aim2-engages-active-but-unprocessed-caspase-1-to-induce-noncanonical-activation-of-the-nlrp3-inflammasome
#12
Larissa D Cunha, Alexandre L N Silva, Juliana M Ribeiro, Danielle P A Mascarenhas, Gustavo F S Quirino, Leonardo L Santos, Richard A Flavell, Dario S Zamboni
Inflammasomes are multimeric protein complexes that initiate inflammatory cascades. Their activation is a hallmark of many infectious or inflammatory diseases. Their composition and activity are specified by proinflammatory stimuli. For example, the NLRP3 inflammasome is activated in response to cell damage and K(+) efflux, whereas the AIM2 inflammasome is activated in response to cytosolic DNA. We used Legionella pneumophila, an intracellular bacterial pathogen that activates multiple inflammasomes, to elucidate the molecular mechanisms regulating inflammasome activation during infection...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28742842/new-hydrazonoindolin-2-ones-synthesis-exploration-of-the-possible-anti-proliferative-mechanism-of-action-and-encapsulation-into-plga-microspheres
#13
Mohamed I Attia, Wagdy M Eldehna, Samar A Afifi, Adam B Keeton, Gary A Piazza, Hatem A Abdel-Aziz
The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8...
2017: PloS One
https://www.readbyqxmd.com/read/28740491/nod-like-receptor-p3-inflammasome-controls-protective-th1-th17-immunity-against-pulmonary-paracoccidioidomycosis
#14
Claudia Feriotti, Eliseu Frank de Araújo, Flavio Vieira Loures, Tania Alves da Costa, Nayane Alves de Lima Galdino, Dario Simões Zamboni, Vera Lucia Garcia Calich
The NOD-like receptor P3 (NLRP3) inflammasome is an intracellular multimeric complex that triggers the activation of inflammatory caspases and the maturation of IL-1β and IL-18, important cytokines for the innate immune response against pathogens. The functional NLRP3 inflammasome complex consists of NLRP3, the adaptor protein apoptosis-associated speck-like protein, and caspase-1. Various molecular mechanisms were associated with NLRP3 activation including the presence of extracellular ATP, recognized by the cell surface P2X7 receptor (P2X7R)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28728976/effect-of-alkylaminophenols-on-growth-inhibition-and-apoptosis-of-bone-cancer-cells
#15
Phuong Doan, Tien Nguyen, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu
In this work, we report the anticancer properties of a series of 11 chemically synthesized alkylaminophenols against human osteosarcoma U2OS tumor cell line. Several assays including cytotoxicity, inhibitor kinetic study, cell migration, Annexin-V/PI double staining, reactive oxygen species (ROS) and caspase 3/7 assays were conducted on this cell line. Cytotoxic 2-((3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol was determined to have an IC50 value of 36.6μM against U2OS cells and it also inhibits the cell growth in time-dependent manner...
July 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28726636/live-cell-visualization-of-gasdermin-d-driven-pyroptotic-cell-death
#16
Joseph K Rathkey, Bryan L Benson, Steven M Chirieleison, Jie Yang, Tsan S Xiao, George R Dubyak, Alex Y Huang, Derek W Abbott
Pyroptosis is a form of cell death important in defenses against pathogens, but which can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, gasdermin D (GSDMD), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28704759/novel-pyrazolopyrimidines-synthesis-in%C3%A2-vitro-cytotoxic-activity-and-mechanistic-investigation
#17
Ghaneya S Hassan, Doaa E Abdel Rahman, Yassin M Nissan, Esraa A Abdelmajeed, Tamer M Abdelghany
A series of novel pyrazolo[3,4-d]pyrimidines bearing benzenesulfonamide moiety 5a-f, 6 and 7 were synthesized. Cytotoxic screening was conducted against MCF-7 and HepG2. 6-(4-Methoxyphenyl)-4-oxopyrazolopyrimidine derivative 5e and 4-imino-6-oxopyrazolopyrimidine derivative 6 revealed potent cytotoxic activity with IC50 1.4 μM (MCF-7) and 0.4 μM (HepG2), respectively compared to that of doxorubicin, (IC50 = 1.02 μM and 0.9 μM, respectively). Compounds 5e and 6 were subjected to cell cycle analysis and apoptosis assay after 24 h and 48 h treatment...
July 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28701883/20s-protopanaxadiol-an-aglycosylated-ginsenoside-metabolite-induces-hepatic-stellate-cell-apoptosis-through-liver-kinase-b1-amp-activated-protein-kinase-activation
#18
Sang Mi Park, Eun Hye Jung, Jae Kwang Kim, Kyung Hwan Jegal, Chung A Park, Il Je Cho, Sang Chan Kim
BACKGROUND: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. METHODS: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28695629/caspase-11-non-canonical-inflammasome-a-critical-sensor-of-intracellular-lps-in-macrophage-mediated-inflammatory-responses
#19
REVIEW
Young-Su Yi
Inflammatory responses mediated by macrophages are part of the innate immune system, whose role is to protect against invading pathogens. Lipopolysaccharide (LPS) found in the outer membrane of Gram-negative bacteria stimulate an inflammatory response by macrophages. During the inflammatory response, extracellular LPS are recognized by Toll-like receptor 4 (TLR4), one of the pattern recognition receptors (PRRs) that activates inflammatory signaling pathways and leads to the production of inflammatory mediators...
July 10, 2017: Immunology
https://www.readbyqxmd.com/read/28682956/diphenyleneiodonium-mitigates-bupivacaine-induced-sciatic-nerve-damage-in-a-diabetic-neuropathy-rat-model-by-attenuating-oxidative-stress
#20
Zhong-Hua Ji, Zhong-Jie Liu, Zi-Ting Liu, Wei Zhao, Brian A Williams, Hong-Fei Zhang, Le Li, Shi-Yuan Xu
BACKGROUND: Increased oxidative stress has been linked to local anesthetic-induced nerve injury in a diabetic neuropathy (DN) rat model. The current study explores the effects of diphenyleneiodonium (DPI) chloride, an NADPH oxidase (NOX) inhibitor, on bupivacaine-induced sciatic nerve injury in DN rats. METHODS: A rat DN model was established through high-fat diet feeding and streptozotocin injection. The model was confirmed via testing (i) blood glucose, (ii) hindpaw allodynia responses to von Frey (VF) monofilaments, (iii) paw withdrawal thermal latency (PWTL), and (iv) nerve conduction velocity (NCV)...
August 2017: Anesthesia and Analgesia
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