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https://www.readbyqxmd.com/read/29352525/an-mrm-based-cytokeratin-marker-assay-as-a-tool-for-cancer-studies-application-to-lung-cancer-pleural-effusions
#1
Anna Perzanowska, Agnieszka Fatalska, Grzegorz Wojtas, Andrzej Lewandowicz, Agata Michalak, Grzegorz Krasowski, Christoph H Borchers, Michal Dadlez, Dominik Domanski
PURPOSE: The goal of this work was to develop an LC-MRM assay for the quantitative analysis of a set of established and diagnostically important cytokeratin (CK) markers used in cancer diagnosis, prognosis and therapy monitoring. Secondly, the potential of this assay in lung cancer diagnosis through pleural effusion (PE) analysis was examined. EXPERIMENTAL DESIGN: A multiplexed MRM assay was developed for 17 CKs and their select caspase-cleaved fragments. Isotope-labeled standard peptides were used for high assay specificity and absolute peptide quantitation; with robust standard-flow LC coupled to a latest-generation triple-quadrupole instrument for high sensitivity...
January 19, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29352519/nafamostat-mesilate-attenuates-inflammation-and-apoptosis-and-promotes-locomotor-recovery-after-spinal-cord-injury
#2
Hui-Quan Duan, Qiu-Li Wu, Xue Yao, Bao-You Fan, Hong-Yu Shi, Chen-Xi Zhao, Yan Zhang, Bo Li, Chao Sun, Xiao-Hong Kong, Xin-Fu Zhou, Shi-Qing Feng
AIM: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI. METHODS: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29352269/phosphorylation-by-protein-kinase-a-disassembles-the-caspase-9-core
#3
Banyuhay P Serrano, Jeanne A Hardy
Caspases, the cysteine proteases which facilitate the faithful execution of apoptosis, are tightly regulated by a number of mechanisms including phosphorylation. In response to cAMP, PKA phosphorylates caspase-9 at three sites preventing caspase-9 activation, and suppressing apoptosis progression. Phosphorylation of caspase-9 by PKA at the functionally relevant site Ser-183 acts as an upstream block of the apoptotic cascade, directly inactivating caspase-9 by a two-stage mechanism. First, Ser-183 phosphorylation prevents caspase-9 self-processing and directly blocks substrate binding...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#4
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352265/type-i-ifn-operates-pyroptosis-and-necroptosis-during-multidrug-resistant-a-baumannii-infection
#5
Yang Li, Xiaomin Guo, Chunmiao Hu, Yan Du, Chuansheng Guo, Di Wang, Weiheng Zhao, Gonghua Huang, Chunliang Li, Qiumin Lu, Ren Lai, Tao Xu, Xiaopeng Qi
Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumannii is a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352251/differential-effects-of-sumo1-and-sumo3-on-pkr-activation-and-stability
#6
Ghizlane Maarifi, Faten El Asmi, Mohamed Ali Maroui, Laurent Dianoux, Mounira K Chelbi-Alix
Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is a serine/threonine kinase that exerts its own phosphorylation and the phosphorylation of the α subunit of the protein synthesis initiation factor eIF-2α. PKR was identified as a target of SUMOylation and the triple PKR-SUMO deficient mutant on Lysine residues K60-K150-K440 has reduced PKR activity. We report that SUMO1 and SUMO3 expression exert differential effects on PKR localization, activation and stability. SUMO1 or SUMO3 did not alter the repartition of PKR in the cytoplasm and the nucleus...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352186/glycolysis-promotes-caspase-3-activation-in-lipid-rafts-in-t-cells
#7
Michael A Secinaro, Karen A Fortner, Oliver Dienz, Angela Logan, Michael P Murphy, Vikas Anathy, Jonathan E Boyson, Ralph C Budd
Resting T cells undergo a rapid metabolic shift to glycolysis upon activation in the presence of interleukin (IL)-2, in contrast to oxidative mitochondrial respiration with IL-15. Paralleling these different metabolic states are striking differences in susceptibility to restimulation-induced cell death (RICD); glycolytic effector T cells are highly sensitive to RICD, whereas non-glycolytic T cells are resistant. It is unclear whether the metabolic state of a T cell is linked to its susceptibility to RICD. Our findings reveal that IL-2-driven glycolysis promotes caspase-3 activity and increases sensitivity to RICD...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352134/pseudoalteromonas-haloplanktis-tac125-produces-4-hydroxybenzoic-acid-that-induces-pyroptosis-in-human-a459-lung-adenocarcinoma-cells
#8
Filomena Sannino, Clementina Sansone, Christian Galasso, Sara Kildgaard, Pietro Tedesco, Renato Fani, Gennaro Marino, Donatella de Pascale, Adrianna Ianora, Ermenegilda Parrilli, Thomas Ostenfeld Larsen, Giovanna Romano, Maria Luisa Tutino
In order to exploit the rich reservoir of marine cold-adapted bacteria as a source of bioactive metabolites, ethyl acetate crude extracts of thirteen polar marine bacteria were tested for their antiproliferative activity on A549 lung epithelial cancer cells. The crude extract from Pseudoalteromonas haloplanktis TAC125 was the most active in inhibiting cell proliferation. Extensive bioassay-guided purification and mass spectrometric characterization allowed the identification of 4-hydroxybenzoic acid (4-HBA) as the molecule responsible for this bioactivity...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352133/molecular-and-physiological-roles-of-the-adaptor-protein-card9-in-immunity
#9
REVIEW
Xiaoming Zhong, Bin Chen, Liang Yang, Zhiwen Yang
CARD9 is a caspase recruitment domain-containing signaling protein that plays a critical role in innate and adaptive immunity. It has been widely demonstrated that CARD9 adaptor allows pattern recognition receptors to induce NF-κB and MAPK activation, which initiates a "downstream" inflammation cytokine cascade and provides effective protection against microbial invasion, especially fungal infection. Here our aim is to update existing paradigms and summarize the most recent findings on the CARD9 signaling pathway, revealing significant mechanistic insights into the pathogenesis of CARD9 deficiency...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352129/molecular-characterization-of-the-grape-seeds-extract-s-effect-against-chemically-induced-liver-cancer-in-vivo-and-in-vitro-analyses
#10
Alaaeldin Ahmed Hamza, Gehan Hussein Heeba, Hanan Mohamed Elwy, Chandraprabha Murali, Raafat El-Awady, Amr Amin
The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352110/melatonin-inhibits-apoptotic-cell-death-induced-by-vibrio-vulnificus-vvha-via-melatonin-receptor-2-coupling-with-ncf-1
#11
Sei-Jung Lee, Hyun Jik Lee, Young Hyun Jung, Jun Sung Kim, Sang Ho Choi, Ho Jae Han
Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial (HCT116) cells induced by the hemolysin (VvhA) produced by V. vulnificus. Melatonin (1 μM) significantly inhibited apoptosis induced by the recombinant protein (r) VvhA, which had been inhibited by the knockdown of MT2...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351316/dexmedetomidine-reduces-lipopolysaccharide-induced-neuroinflammation-sickness-behavior-and-anhedonia
#12
Ching-Hua Yeh, Liang-Po Hsieh, Ming-Chung Lin, Tsui-Shan Wei, Hui-Ching Lin, Chia-Cheng Chang, Chung-Hsi Hsing
BACKGROUND: Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex) has anti-inflammatory effect. We investigated the effects of Dex on lipopolysaccharide (LPS)-induced neuroinflammation and sickness behavior in mice. MATERIALS AND METHODS: BALB/c mice were intraperitoneally (i.p.) injected with Dex (50 ug/kg) or vehicle. One hour later, the mice were injected (i...
2018: PloS One
https://www.readbyqxmd.com/read/29351226/curcumin-attenuates-on-carbon-tetrachloride-induced-acute-liver-injury-in-mice-via-modulation-of-the-nrf2-ho-1-and-tgf-%C3%AE-1-smad3-pathway
#13
Xinyan Peng, Chongshan Dai, Quanwen Liu, Junke Li, Jingru Qiu
This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl₄)-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl₄ exposure. At 24 h, curcumin-attenuated CCl₄ induced elevated serum transaminase activities and histopathological damage in the mouse's liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl₄-induced oxidative stress, characterized by decreased malondialdehyde (MDA) formations, and increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) content, followed by a decrease in caspase-9 and -3 activities...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29351194/involvement-of-bax-and-bcl-2-in-induction-of-apoptosis-by-essential-oils-of-three-lebanese-salvia-species-in-human-prostate-cancer-cells
#14
Alessandra Russo, Venera Cardile, Adriana C E Graziano, Rosanna Avola, Maurizio Bruno, Daniela Rigano
Prostate cancer is one of the most common forms of cancer in men, and research to find more effective and less toxic drugs has become necessary. In the frame of our ongoing program on traditionally used Salvia species from the Mediterranean Area, here we report the biological activities of Salvia aurea, S. judaica and S. viscosa essential oils against human prostate cancer cells (DU-145). The cell viability was measured by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) release was used to quantify necrosis cell death...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351079/syphacia-muris-infection-in-rats-attenuates-colorectal-carcinogenesis-through-oxidative-stress-and-gene-expression-alterations-implications-for-modulatory-effects-by-bryostatin-1
#15
Elsayed I Salim, Samar F Harras, Aisha G Abdalla, Mohmmed H Mona
Accumulating evidence suggest that some infectious agents may interfere in the natural progression of neoplasia. This study examined the association between chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan, Bugulane ritina, was investigated against this combined effect.DMH administration has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal carcinogenesis, while the S...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29350920/crystal-structures-and-human-leukemia-cell-apoptosis-inducible-activities-of-parthenolide-analogues-isolated-from-piptocoma-rufescens
#16
Yulin Ren, Judith C Gallucci, Xinxin Li, Lichao Chen, Jianhua Yu, A Douglas Kinghorn
The molecular structures of three parthenolide analogues, (-)-goyazensolide (1), (-)-15-deoxygoyazensolide (2), and (-)-ereglomerulide (3), isolated from the leaves of Piptocoma rufescens in a previous study were determined by X-ray analysis, and the absolute configuration of (-)-goyazensolide (1) was confirmed crystallographically using Cu Kα radiation at low temperature. Compounds 1-3, (+)-rufesolide A (4), and commercial parthenolide were found to be growth inhibitory toward MOLM-13 and EOL-1 human acute myeloid leukemia cells using PKC412 (midostaurin) as the positive control, with 1-3 being more active than parthenolide...
January 19, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29350771/recombinant-relaxin-protects-liver-transplants-from-ischemia-damage-via-hepatocyte-glucocorticoid-receptor-from-bench-to-bedside
#17
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29350405/reactive-oxygen-species-induced-parthanatos-of-immunocytes-by-human-cytomegalovirus-associated-substance
#18
Jung Heon Kim, Jiyeon Kim, Jin Roh, Chan-Sik Park, Ju-Young Seoh, Eung-Soo Hwang
Previous studies examined various immune evasion strategies of human cytomegalovirus (HCMV) to understand HCMV pathogenesis. Although the mechanism that underlies immunocyte destruction near HCMV-infected lesions has yet to be established, we show that substances produced by HCMV-infected cells induce death in several types of immunocytes, but not in fibroblasts or astrocytomas. These substances contain HCMV proteins and were termed HCMV-associated insoluble substance (HCMVAIS). We characterized this mechanism of cell death induced by HCMVAIS to understand the death of immunocytes near HCMV-infected lesions...
January 19, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29349707/piperazine-clubbed-with-2-azetidinone-derivatives-suppresses-proliferation-migration-and-induces-apoptosis-in-human-cervical-cancer-hela-cells-through-oxidative-stress-mediated-intrinsic-mitochondrial-pathway
#19
Rashmin Khanam, Raj Kumar, Iram Iqbal Hejazi, Syed Shahabuddin, Ramovatar Meena, Vikrant Jayant, Prabhat Kumar, Abdul Roouf Bhat, Fareeda Athar
Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis...
January 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29349609/caspase-1-mediated-pyroptosis-of-the-predominance-for-driving-cd4-formula-see-text-t-cells-death-a-nonlocal-spatial-mathematical-model
#20
Wei Wang, Tongqian Zhang
Caspase-1-mediated pyroptosis is the predominance for driving CD4[Formula: see text] T cells death. Dying infected CD4[Formula: see text] T cells can release inflammatory signals which attract more uninfected CD4[Formula: see text] T cells to die. This paper is devoted to developing a diffusive mathematical model which can make useful contributions to understanding caspase-1-mediated pyroptosis by inflammatory cytokines IL-1[Formula: see text] released from infected cells in the within-host environment. The well-posedness of solutions, basic reproduction number, threshold dynamics are investigated for spatially heterogeneous infection...
January 18, 2018: Bulletin of Mathematical Biology
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