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https://www.readbyqxmd.com/read/28704759/novel-pyrazolopyrimidines-synthesis-in%C3%A2-vitro-cytotoxic-activity-and-mechanistic-investigation
#1
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
#2
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
#3
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
#4
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)...
July 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28681618/regulation-of-p53-and-survivin-by-prodigiosin-compound-derived-from-serratia-marcescens-contribute-to-caspase-3-dependent-apoptosis-in-acute-lymphoblastic-leukemia-cells
#5
M R Sam, R S Pourpak
Tumor suppressor p53 and proto-oncogene survivin are challenging targets for anticancer drugs in acute lymphoblastic leukemia (ALL) which are associated with chemoresistance. Yet, no p53 and survivin-modulating drug with low toxicity and high efficacy has been approved for clinical application in ALL. Consequently, the search for novel compounds which target p53 or survivin is needed to further advance ALL treatment. Prodigiosin, a secondary metabolite of Serratia marcescens induces apoptosis in cancer cells with no toxicity on normal cells...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28679691/metastatic-triple-negative-breast-cancer-patient-with-tp53-tumor-mutation-experienced-11-months-progression-free-survival-on-bortezomib-monotherapy-without-adverse-events-after-ending-standard-treatments-with-grade-3-adverse-events
#6
Tobias Meißner, Adam Mark, Casey Williams, Wolfgang E Berdel, Stephanie Wiebe, Andrea Kerkhoff, Eva Wardelmann, Timo Gaiser, Carsten Müller-Tidow, Philip Rosenstiel, Norbert Arnold, Brian Leyland-Jones, Andre Franke, Martin Stanulla, Michael Forster
A triple-negative breast cancer patient had no hereditary BRCA1, BRCA2, or TP53 risk variants. After exhaustion of standard treatments, she underwent experimental treatments and whole-exome sequencing of tumor, blood, and a metastasis. Well-tolerated experimental bortezomib monotherapy was administered for a progression-free period of 11 mo. After progression, treatments were changed and the exome data were evaluated, expanded with RNA and exome sequencing of a late-stage metastasis. In the final stage, eribulin alone and in combination with anthracyclines were administered...
July 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28665136/coordination-driven-self-assembly-using-ditopic-pyridyl-pyrazolyl-donor-and-p-cymene-ru-ii-acceptors-2-catenane-synthesis-and-anticancer-activities
#7
Jae-Ho Jo, Nem Singh, Donghyuk Kim, Se Min Cho, Anurag Mishra, Hyunuk Kim, Se Chan Kang, Ki-Whan Chi
Coordination-driven self-assembly of m-bis[3-(4-pyridyl)pyrazolyl]xylene (L) and [(p-cymene)2Ru2(OO∩OO)2(OTf)2] (A1) (OO∩OO = 6,11-dioxido-5,12-naphthacenedione) in methanol resulted in a mixture of [2]catenane 1 and macrocycle 2, and self-assembly in nitromethane resulted in pure macrocycle 2, whereas the coordination-driven self-assembly of L and similar acceptors [(p-cymene)2Ru2(OO∩OO)2(OTf)2] [OO∩OO = 5,8-dioxido-1,4-naphthoquinonnato (A2); 2,5-dioxido-1,4-benzoquinonato (A3); oxalato (A4)] resulted in the formations of monomeric macrocycles 3-5, respectively...
July 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28662964/synthesis-and-biological-activity-of-cyclolinopeptide-a-analogues-modified-with-%C3%AE-4-bis-homo-phenylalanine
#8
Karol Jędrzejczak, Paweł Hrynczyszyn, Małgorzata Szczesio, Jolanta Artym, Tomasz Jastrząbek, Maja Kocięba, Marek Główka, Krzysztof Huben, Iwona Kochanowska, Michał Zimecki, Janusz Zabrocki, Stefan Jankowski, Beata Kolesińska
Cyclolinopeptide A (CLA), an immunosuppressive nonapeptide derived from linen seeds, was modified with S or R-γ(4)-bis(homo-phenylalanine) in positions 3 or 4, or both 3 and 4. These modifications changed the flexibility of new analogues and distribution of intramolecular hydrogen bonds. Analogues 11 c(Pro(1)-Pro(2)-Phe(3)-S-γ(4)-hhPhe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)), 13 c(Pro(1)-Pro(2)-S-γ(4)-hhPhe(3)-R-γ(4)-hhPhe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)) and 15 c(Pro(1)-Pro(2)-R-γ(4)-hhPhe(3)-Phe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)) existed as a mixture of stable cis/trans isomers of Pro-Pro peptide bond...
June 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28654176/multiple-pseudomonas-species-secrete-exolysin-like-toxins-and-provoke-caspase-1-dependent-macrophage-death
#9
REVIEW
Pauline Basso, Pierre Wallet, Sylvie Elsen, Emmanuelle Soleilhac, Thomas Henry, Eric Faudry, Ina Attrée
Pathogenic bacteria secrete protein toxins that provoke apoptosis or necrosis of eukaryotic cells. Here, we developed a live-imaging method, based on incorporation of a DNA-intercalating dye into membrane-damaged host cells, to study the kinetics of primary bone marrow-derived macrophages (BMDMs) mortality induced by opportunistic pathogen Pseudomonas aeruginosa expressing either Type III Secretion System (T3SS) toxins or the pore-forming toxin, Exolysin (ExlA). We found that ExlA promotes the activation of Caspase-1 and maturation of interleukin-1β...
June 27, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28644062/4-nerolidylcatechol-apoptosis-by-mitochondrial-mechanisms-with-reduction-in-cyclin-d1-at-g0-g1-stage-of-the-chronic-myelogenous-k562-cell-line
#10
Polyana Lopes Benfica, Renato Ivan de Ávila, Bruna Dos Santos Rodrigues, Alane Pereira Cortez, Aline Carvalho Batista, Marilisa Pedroso Nogueira Gaeti, Eliana Martins Lima, Kênnia Rocha Rezende, Marize Campos Valadares
CONTEXT: 4-Nerolidylcatechol (4-NRC) has showed antitumor potential through apoptosis. However, its apoptotic mechanisms are still unclear, especially in leukemic cells. OBJECTIVES: To evaluate the cytotoxic potential of 4-NRC and its cell death pathways in p53-null K562 leukemic cells. MATERIALS AND METHODS: Cytotoxicity of 4-NRC (4.17-534.5 μM) over 24 h of exposure was evaluated by MTT assay. 4-NRC-induced apoptosis in K562 cells was investigated by phosphatidylserine (PS) externalization, cell cycle, sub-G1, mitochondrial evaluation, cytochrome c, cyclin D1 and intracellular reactive oxygen species (ROS) levels, and caspase activity analysis...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28636534/novel-tropolones-induce-the-unfolded-protein-response-pathway-and-apoptosis-in-multiple-myeloma-cells
#11
Staci L Haney, Cheryl Allen, Michelle L Varney, Kaitlyn M Dykstra, Eric R Falcone, Sean H Colligan, Qiang Hu, Alyssa M Aldridge, Dennis L Wright, Andrew J Wiemer, Sarah A Holstein
Tropolones are small organic compounds with metal-directing moieties. Tropolones inhibit the proliferation of cancer cell lines, possibly through their effects on metalloenzymes such as select histone deacetylases (HDACs). Pan-HDAC inhibitors are therapeutically beneficial in the treatment of multiple myeloma, however there is interest in the use of more selective HDAC inhibitor therapy to minimize adverse side effects. We hypothesized that tropolones might have anti-myeloma activities. To this end, a series of novel α-substituted tropolones were evaluated for effects on multiple myeloma cells...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627343/-study-on-the-role-of-autophagy-in-heme-oxygenase-1-preventing-hepatic-ischemia-reperfusion-injury-in-rats
#12
Sheng Lan, Jintai Li, Yi Liu
OBJECTIVE: To identify the role of autopahgy in the protective mechanism of heme oxygenase 1 (HO-1) against hepatic ischemia/reperfusion (I/R) injury. METHODS: Forty healthy male Sprague-Dawley (SD) rats were randomly (random number table) divided into five groups (n = 8 in each group), namely sham group, model group, cobalt protoporphyrin (CoPP) group, zinc protoporphyrin (ZnPP) group and 6-amino-3-methylpurine (3-MA) group. Partial hepatic I/R model was established by clamping the pedicles of left and median lobes for 1 hour and reopening for 6 hours in rats, and the rats in sham group were only received celiotomp without hepatic I/R...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28622490/lawsonia-intracellularis-in-pigs-progression-of-lesions-and-involvement-of-apoptosis
#13
Roberto M C Guedes, Mariana A Machuca, Maria A Quiroga, Carlos E Real Pereira, Talita P Resende, Connie J Gebhart
The purpose of this study was to follow the progression of gross and histologic lesions and apoptosis events in Lawsonia intracellularis-infected enterocytes through the course of the disease, proliferative enteropathy (PE). Thirty 5-week-old pigs were divided into 2 groups: 20 challenged and 10 control animals. Groups of 3 pigs, 2 challenged and 1 control, were euthanized at 1, 3, 5, 8, 11, 15, 19, 24, 29, and 35 days after inoculation. Complete necropsies were performed with gross evaluation. Tissue samples from different sites of the gastrointestinal tract and other visceral organs were collected for routine histologic staining and for immunohistochemistry (IHC) for L...
July 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28621234/icarisid-ii-inhibits-the-proliferation-of-human-osteosarcoma-cells-by-inducing-apoptosis-and-cell-cycle-arrest
#14
Yuanyuan Tang, Mao Xie, Neng Jiang, Feifei Huang, Xiao Zhang, Ruishan Li, Jingjing Lu, Shijie Liao, Yun Liu
Icarisid II, one of the main active components of Herba Epimedii extracts, shows potent antitumor activity in various cancer cell lines, including osteosarcoma cells. However, the anticancer mechanism of icarisid II against osteosarcoma U2OS needs further exploration. This study aims to investigate further antitumor effects of icarisid II on human osteosarcoma cells and elucidate the underlying mechanism. We cultivated human osteosarcoma USO2 cells in vitro using different concentrations of icarisid II (0-30 µM)...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28619981/ibrutinib-unmasks-critical-role-of-bruton-tyrosine-kinase-in-primary-cns-lymphoma
#15
Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Daniel Rohle, Marc K Rosenblum, Agnes Viale, Viviane Tabar, Cameron W Brennan, Igor T Gavrilovic, Thomas J Kaley, Craig Nolan, Antonio M P Omuro, Elena Pentsova, Alissa A Thomas, Elina Tsyvkin, Ariela Noy, M Lia Palomba, Paul A Hamlin, Craig Sauter, Craig H Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C Lallana, Vaios Hatzoglou, Anne S Reiner, Philip Gutin, Jason T Huse, Katherine Panageas, Thomas G Graeber, Nikolaus Schultz, Lisa M DeAngelis, Ingo K Mellinghoff
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with Nuclear factor kappa B (NF-κB). The role of BTK in primary CNS lymphoma (PCNSL) is unknown. We performed a Phase 1 clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS Lymphoma. Clinical responses to ibrutinib occurred in 10/13 (77%) PCNSL patients, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of Caspase Recruitment Domain Family Member 11, a known ibrutinib resistance mechanism...
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28619472/gasdermins-effectors-of-pyroptosis
#16
REVIEW
Stephen B Kovacs, Edward A Miao
Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane that drive swelling and membrane rupture. Gasdermin D is one of six (in humans) gasdermin family members; several other gasdermins have also been shown to form pores that cause pyroptosis after cleavage to activate their PFDs...
June 12, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28614717/microbiota-normalization-reveals-that-canonical-caspase-1-activation-exacerbates-chemically-induced-intestinal-inflammation
#17
Adrian J Błażejewski, Sophie Thiemann, Alexander Schenk, Marina C Pils, Eric J C Gálvez, Urmi Roy, Ulrike Heise, Marcel R de Zoete, Richard A Flavell, Till Strowig
Inflammasomes play a central role in regulating intestinal barrier function and immunity during steady state and disease. Because the discoveries of a passenger mutation and a colitogenic microbiota in the widely used caspase-1-deficient mouse strain have cast doubt on previously identified direct functions of caspase-1, we reassessed the role of caspase-1 in the intestine. To this end, we generated Casp1(-/-) and Casp11(-/-) mice and rederived them into an enhanced barrier facility to standardize the microbiota...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612844/nlrp3-inflammasome-pathway-has-a-critical-role-in-the-host-immunity-against-clinically-relevant-acinetobacter-baumannii-pulmonary-infection
#18
N Dikshit, S D Kale, H J Khameneh, V Balamuralidhar, C Y Tang, P Kumar, T P Lim, T T Tan, A L Kwa, A Mortellaro, B Sukumaran
The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1β (IL-1β) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28611572/4r-cembranoid-improves-outcomes-after-6-hydroxydopamine-challenge-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#19
Jing Hu, P A Ferchmin, Ann M Hemmerle, Kim B Seroogy, Vesna A Eterovic, Jiukuan Hao
(1S, 2E, 4R, 6R,-7E, 11E)-2, 7, 11-cembratriene-4, 6-diol (4R) is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA) and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP). Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD) and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA)-induced injury models...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28610850/dietary-myo-inositol-deficiency-decreased-the-growth-performances-and-impaired-intestinal-physical-barrier-function-partly-relating-to-nrf2-jnk-e2f4-and-mlck-signaling-in-young-grass-carp-ctenopharyngodon-idella
#20
Shuang-An Li, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xu Tang, He-Qun Shi, Xiao-Qiu Zhou
In this study, we investigated the effects of dietary myo-inositol on the growth and intestinal physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.83 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila for 14 days. The results indicated that compared with optimal myo-inositol levels, myo-inositol deficiency (27...
August 2017: Fish & Shellfish Immunology
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