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https://www.readbyqxmd.com/read/29139477/a-dietary-flavone-confers-communicable-protection-against-colitis-through-nlrp6-signaling-independently-of-inflammasome-activation
#1
K Radulovic, S Normand, A Rehman, A Delanoye-Crespin, J Chatagnon, M Delacre, N Waldschmitt, L F Poulin, J Iovanna, B Ryffel, P Rosenstiel, M Chamaillard
Flavones represent a class of polyphenols that are found in many plant-derived food sources. Herein, we provide evidence that the anti-inflammatory and antiproliferative effect of the flavone apigenin relies on the regulation of the gut microbiota by the NOD-like receptor family pyrin domain containing 6 (Nlrp6). When challenged by dextran sulfate sodium (DSS) in drinking water, mice were protected against colitis upon cohousing with apigenin-treated animals. In contrast, the protective effect was lost in the absence of Nlrp6...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29130929/tnf-regulates-transcription-of-nlrp3-inflammasome-components-and-inflammatory-molecules-in-cryopyrinopathies
#2
Matthew D McGeough, Alexander Wree, Maria E Inzaugarat, Ariela Haimovich, Casey D Johnson, Carla A Peña, Raphaela Goldbach-Mansky, Lori Broderick, Ariel E Feldstein, Hal M Hoffman
The NLRP3 inflammasome is a protein complex responsible for caspase-1-dependent maturation of the proinflammatory cytokines IL-1β and IL-18. Gain-of-function missense mutations in NLRP3 cause the disease spectrum known as the cryopyrin-associated periodic syndromes (CAPS). In this study, we generated Nlrp3-knockin mice on various KO backgrounds including Il1b/Il18-, caspase-1-, caspase-11- (Casp1/11-), and Tnf-deficient strains. The Nlrp3L351P Il1b-/- Il18-/- mutant mice survived and grew normally until adulthood and, at 6 months of age, exhibited marked splenomegaly and leukophilia...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29102767/curcuzedoalide-contributes-to-the-cytotoxicity-of-curcuma-zedoaria-rhizomes-against-human-gastric-cancer-ags-cells-through-induction-of-apoptosis
#3
Eun Bee Jung, Tuy An Trinh, Tae Kyoung Lee, Noriko Yamabe, Ki Sung Kang, Ji Hoon Song, Sungyoul Choi, Sang Hyun Lee, Tae Su Jang, Ki Hyun Kim, Gwi Seo Hwang
ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma zedoaria Roscoe (Zingiberaceae), also known as white turmeric or zedoaria, has been used in Ayurveda and traditional Chinese medicine to treat various cancers, and it possesses several sesquiterpenoid compounds. OBJECTIVE: This study aimed to evaluate the therapeutic effects of a methanolic (MeOH) extract of C. zedoaria rhizomes, as well as its active constituents, against gastric cancer, which is a frequently diagnosed cancer in South Korea...
November 1, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29100294/novel-tropolones-induce-the-unfolded-protein-response-pathway-and-apoptosis-in-multiple-myeloma-cells
#4
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...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093011/primary-immunoprevention-of-epithelial-ovarian-carcinoma-by-vaccination-against-the-extracellular-domain-of-anti-m%C3%A3-llerian-hormone-receptor-ii
#5
Suparna Mazumder, Justin M Johnson, Valerie Swank, Nina Dvorina, Elizabeth Martelli, Jennifer Ko, Vincent K Tuohy
Epithelial ovarian carcinoma (EOC) is the most prevalent form of ovarian cancer in the United States, representing approximately 85% of all cases and causing more deaths than any other gynecologic malignancy. We propose that optimized control of EOC requires the incorporation of a vaccine capable of inducing safe and effective preemptive immunity in cancer-free women. In addition, we hypothesize that ovarian-specific self-proteins that are "retired" from autoimmune-inducing expression levels as ovaries age but are expressed at high levels in emerging EOC may serve as vaccine targets for mediating safe and effective primary immunoprevention...
November 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29089761/targeted-delivery-of-ginsenoside-compound-k-using-tpgs-peg-pcl-mixed-micelles-for-effective-treatment-of-lung-cancer
#6
Lei Yang, Zhenghai Zhang, Jian Hou, Xin Jin, Zhongcheng Ke, Dan Liu, Mei Du, Xiaobing Jia, Huixia Lv
Ginsenoside compound K (CK) is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded d-alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone) mixed micelles (CK-M) is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29075257/the-p2x7-receptor-mediates-toxoplasma-gondii-control-in-macrophages-through-canonical-nlrp3-inflammasome-activation-and-reactive-oxygen-species-production
#7
Aline Cristina Abreu Moreira-Souza, Cássio Luiz Coutinho Almeida-da-Silva, Thuany Prado Rangel, Gabrielle da Costa Rocha, Maria Bellio, Dario Simões Zamboni, Rossiane Claudia Vommaro, Robson Coutinho-Silva
Toxoplasma gondii (T. gondii) is the protozoan parasite that causes toxoplasmosis, a potentially fatal disease to immunocompromised patients, and which affects approximately 30% of the world's population. Previously, we showed that purinergic signaling via the P2X7 receptor contributes to T. gondii elimination in macrophages, through reactive oxygen species (ROS) production and lysosome fusion with the parasitophorous vacuole. Moreover, we demonstrated that P2X7 receptor activation promotes the production of anti-parasitic pro-inflammatory cytokines during early T...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29074603/concurrent-inhibition-of-pim-and-flt3-kinases-enhances-apoptosis-of-flt3-itd-acute-myeloid-leukemia-cells-through-increased-mcl-1-proteasomal-degradation
#8
Shivani Kapoor, Karthika Natarajan, Patrick R Baldwin, Kshama A Doshi, Rena G Lapidus, Trevor J Mathias, Mario Scarpa, Rossana Trotta, Eduardo Davila, Manfred Kraus, Dennis Huszar, Adriana E Tron, Danilo Perrotti, Maria R Baer
PURPOSE: fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29070105/-embelin-reverses-the-multi-drug-resistance-of-k562-d-to-daunorubicin-independently-of-p-gp-and-mdr1-mrna
#9
Hui-Nan Jiang, Zhuo-Gang Liu, Rong Hu
OBJECTIVE: To investigate the mechanism of reversing drug resistance of K562/D cells to daunorubicin by Embelin and its relationship with P-gp and MDR1 mRNA. METHODS: MTT assay was used to detect and compare the cell proliferation rate of treating with DNR alone and DNR combined with Embelin. Flow cytometry with Annexin V-FITC/PI double staining was used to detect cell apoptosis rate, Western blot was used to detect the expression of XIAP,Caspase-3,BCL-2,BAX and P-gp of K562/D cells after using DNR alone and combining with Embelin...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29066624/active-site-adjacent-phosphorylation-at-tyr-397-by-c-abl-kinase-inactivates-caspase-9
#10
Banyuhay P Serrano, Hannah S Szydlo, Dominique R Alfandari, Jeanne A Hardy
Caspase-9 (casp-9) is an initiator caspase and plays a central role in activating apoptotic cell death. Control of all caspases is tightly regulated by a series of phosphorylation events enacted by several different kinases. Caspase-9 is the most heavily phosphorylated of all caspases, with phosphorylation of at least 11 distinct residues in all three caspase-9 domains by nine kinases. Caspase-9 phosphorylation by the non-receptor tyrosine kinase c-Abl at Tyr-153 reportedly leads to caspase-9 activation. All other phosphorylation events on caspases have been shown to block their proteolytic function by a number of mechanisms, so we sought to unravel the molecular mechanism of the putative caspase-9 activation by phosphorylation...
October 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29063417/propofol-does-not-reduce-pyroptosis-of-enterocytes-and-intestinal-epithelial-injury-after-lipopolysaccharide-challenge
#11
Xu-Yu Zhang, Xi Chen, Hu-Fei Zhang, Su Guan, Shi-Hong Wen, Wen-Qi Huang, Zi-Meng Liu
BACKGROUND: To date, mechanisms of sepsis-induced intestinal epithelial injury are not well known. P2X7 receptor (P2X7R) regulates pyroptosis of lymphocytes, and propofol is usually used for sedation in septic patients. AIMS: We aimed to determine the occurrence of enterocyte pyroptosis mediated by P2X7R and to explore the effects of propofol on pyroptosis and intestinal epithelial injury after lipopolysaccharide (LPS) challenge. METHODS: A novel regimen of LPS challenge was applied in vitro and in vivo...
October 23, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29061850/the-brucella-effector-protein-tcpb-induces-degradation-of-inflammatory-caspases-and-thereby-subverts-noncanonical-inflammasome-activation-in-macrophages
#12
Padmaja Jakka, Swapna Namani, Subathra Murugan, Nivedita Rai, Girish Radhakrishnan
The inflammasome contains intracellular receptors that recognize various pathogen-associated molecular patterns and play crucial roles in innate immune responses to invading pathogens. Noncanonical inflammasome activation is mediated by caspase 4/11, which recognizes intracellular LPS and promotes pyroptosis and secretion of proinflammatory cytokines. Brucella species are infectious intracellular pathogens that replicate in professional and nonprofessional phagocytic cells and subvert immune responses for chronic persistence in the host...
October 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29052227/adjuvant-pretreatment-with-alum-protects-neonatal-mice-in-sepsis-through-myeloid-cell-activation
#13
Jaimar C Rincon, Angela L Cuenca, Steven L Raymond, Brittany Mathias, Dina C Nacionales, Ricardo Ungaro, Philip A Efron, James L Wynn, Lyle L Moldawer, Shawn D Larson
The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Especially in the premature neonate where outcomes from sepsis are so dismal, pretreatment strategies to prevent sepsis have received inadequate consideration. Aluminum-based adjuvants (alum) are currently used in many pediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pre-treatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis...
October 20, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29040208/an-update-on-gain-of-function-mutations-in-primary-immunodeficiency-diseases
#14
Rekha D Jhamnani, Sergio D Rosenzweig
PURPOSE OF REVIEW: Most primary immunodeficiencies described since 1952 were associated with loss-of-function defects. With the advent and popularization of unbiased next-generation sequencing diagnostic approaches followed by functional validation techniques, many gain-of-function mutations leading to immunodeficiency have also been identified. This review highlights the updates on pathophysiology mechanisms and new therapeutic approaches involving primary immunodeficiencies because of gain-of-function mutations...
December 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29038261/coadministration-of-minocycline-with-colistin-in-critically-ill-patients-is-associated-with-reduced-frequency-of-acute-renal-failure-a-retrospective-cohort-analysis
#15
Thomas P Lodise, Weihong Fan, David C Griffith, Michael N Dudley, Katherine A Sulham
Nonclinical studies have suggested oxidative damage, caspase-mediated apoptosis, and inducible nitric oxide synthase levels may be involved in the pathogenesis of colistin (CST)-associated acute renal failure. Synergistic antibacterial activity of minocycline (MIN) with polymyxins has been demonstrated in vitro, and MIN inhibits caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the hypothesis that coadministration of CST with MIN (CST-MIN) may reduce incidence of acute renal failure. A multicenter retrospective cohort study was conducted using the Premier Research database to examine the impact of CST-MIN on acute renal failure...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29038248/lipopolysaccharide-potentiates-insulin-driven-hypoglycemic-shock
#16
Jon A Hagar, Matthew L Edin, Fred B Lih, Lance R Thurlow, Beverly H Koller, Bruce A Cairns, Darryl C Zeldin, Edward A Miao
Critically ill patients typically present with hyperglycemia. Treatment with conventional insulin therapy (targeting 144-180 mg/dl) improves patient survival; however, intensive insulin therapy (IIT) targeting normal blood glucose levels (81-108 mg/dl) increases the incidence of moderate and severe hypoglycemia, and increases mortality. Septic patients are especially prone to IIT-induced hypoglycemia, but the mechanism remains unknown. Here, we show that codelivery of insulin with otherwise sublethal doses of LPS induced hypoglycemic shock in mice within 1-2 h...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29017836/emerging-insights-into-noncanonical-inflammasome-recognition-of-microbes
#17
REVIEW
Ashley J Russo, Bharat Behl, Ishita Banerjee, Vijay A K Rathinam
Inflammasomes are cytosolic multi-molecular complexes that sense intracellular microbial danger signals and metabolic perturbations. Inflammasome activation leads to the activation of caspase-1 and the release of pro-inflammatory cytokines IL-1β and IL-18 accompanied by cell death. An inflammasome-based surveillance machinery for Gram-negative bacterial infections has been recently discovered. This noncanonical inflammasome relies on sensing the cytosolic presence of lipopolysaccharide (LPS) of Gram-negative bacteria via inflammatory caspases such as caspase-4, -5, and -11...
October 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29017653/-effects-of-hmgb1-inhibition-on-endoplasmic-reticulum-stress-after-myocardial-ischemia-reperfusion-injury-in-rats
#18
Lusha E, Jinglong Nan
OBJECTIVE: To investigate the effect of high mobility group protein B1 (HMGB1) inhibition on endoplasmic reticulum stress (ERS) after myocardial ischemia/reperfusion (I/R) in rats. METHODS: Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group, I/R model group, Gene silencing (HMGB1-siRNA) group, and empty vector (Scrambled-siRNA) group. Coronary blood flow of the rats were ligated for 30 minutes, relaxed the ligament line for 2 hours, to establish I/R injury model; not ligation with the sham operation group...
October 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29016810/mir-30c-5p-regulates-macrophage-mediated-inflammation-and-pro-atherosclerosis-pathways
#19
Giulio Ceolotto, Alessandra Giannella, Mattia Albiero, Maniselvan Kuppusamy, Claudia Radu, Paolo Simioni, Katia Garlaschelli, Andrea Baragetti, Alberico Luigi Catapano, Elisabetta Iori, Gian Paolo Fadini, Angelo Avogaro, Saula Vigili de Kreutzenberg
Aims: Atherosclerosis is an inflammatory disease wherein cholesterol-loaded macrophages play a major role. MicroRNAs and microparticles propagate inflammatory pathways and are involved in cardiovascular disease. We aimed to screen and validate circulating microRNAs correlated with atherosclerosis development in humans, and to dissect the molecular mechanisms associated with atherogenesis using in vitro and in vivo approaches. Methods and results: A panel of 179 secreted microRNAs was screened in plasma samples of patients with and without atherosclerosis, and validated cross-sectionally and prospectively in patients followed for up to 11 years...
November 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28991049/stearoyl-lysophosphatidylcholine-inhibits-endotoxin-induced-caspase-11-activation
#20
Wenbo Li, Wei Zhang, Meihong Deng, Patricia Loughran, Yiting Tang, Hong Liao, Xianying Zhang, Jian Liu, Timothy R Billiar, Ben Lu
Stearoyl lysophosphatidylcholine (LPC) exerts protective effect during endotoxemia and in experimental sepsis, but the underlying mechanism is unclear. Here, we demonstrated that stearoyl LPC could block caspase-11 mediated macrophage pyroptosis. In vitro, stearoyl LPC significantly decreased caspase-11 activation and pyroptosis induced by LPS plus CTB independent of the receptor G2A. Stearoyl LPC did not affect LPS uptake by mouse peritoneal macrophages but, did significantly inhibit the interaction between LPS and caspase-11...
October 4, 2017: Shock
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