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https://www.readbyqxmd.com/read/28929337/escherichia-coli-aggravates-endoplasmic-reticulum-stress-and-triggers-chop-dependent-apoptosis-in-weaned-pigs
#1
Qian Jiang, Shuai Chen, Wenkai Ren, Gang Liu, Kang Yao, Guoyao Wu, Yulong Yin
Intestinal cells can sense the presence of pathogens and trigger many important signaling pathways to maintain tissue homeostasis and normal function. Escherichia coli and lipopolysaccharides (LPS) are the main pathogenic factors of intestinal disease in pigs. However, the roles of endoplasmic reticulum stress (ERS) and its mediated apoptosis in intestinal malfunction induced by E. coli or LPS remain unclear. In the present study, we aimed to evaluate whether ERS could be activated by E. coli fed to piglets and whether the underlying mechanisms of this disease process could be exploited...
September 19, 2017: Amino Acids
https://www.readbyqxmd.com/read/28928892/the-targeted-antitumor-effects-of-c-pc-cmc-cd59sp-nanoparticles-on-hela-cells-in-vitro-and-in-vivo
#2
Yujuan Wang, Liangqian Jiang, Qifeng Yin, Huihui Liu, Guoxiang Liu, Guoteng Zhu, Bing Li
The novel C-PC/CMC-CD59sp-NPs were made by carbocymethyl chitosan (CMC) loading C-phycocyanin (C-PC) with the lead of CD59 specific ligand peptide (CD59sp) for targeting, and the characteristics and targeted anti-tumor mechanism were explored in order to realize the targeted therapy of C-PC on the growth of HeLa cells both in vitro and vivo. The targeting nanoparticles were synthesized by ionic-gelation method, and the optimal condition was selected out by orthogonal analysis. The properties of nanoparticles were observed by laser particle analyzer and dynamic light scattering (DLS) and Fourier Transform Infrared Spectrometer (FTIR)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28927146/impacts-of-survivin-and-caspase-3-on-apoptosis-and-angiogenesis-in-oral-cancer
#3
Shuxia Li, Yanqi Yang, Yanping Ding, Xiaofei Tang, Zheng Sun
The present study aimed to investigate the impact of survivin and caspase-3 on apoptosis and angiogenesis in oral cancer. A total of 16 oral leukoplakia cases accompanied by low-moderate epithelial dysplasia, 12 cases of oral leukoplakia accompanied by severe epithelial dysplasia, 17 cases of high-moderate differentiated oral squamous cell carcinoma and 10 cases of normal oral mucosa were selected. Immunohistochemistry was used to detect the expression levels of survivin, caspase-3, and caspase inhibitor factor VIII in lesions from each group...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925739/synthesis-of-piperazine-based-thiazolidinones-as-vegfr2-tyrosine-kinase-inhibitors-inducing-apoptosis
#4
Mostafa Mm El-Miligy, Heba A Abd El Razik, Marwa M Abu-Serie
AIM: VEGFR2 tyrosine kinase is a main target in suppressing cancer growth and metastasis. Materials & methods: Piperazine-based thiazolidinones were synthesized and screened for their anticancer and VEGFR2 tyrosine kinase inhibitory activity. Results: Compounds 11, 13 and 16 displayed potent anticancer activity against HepG-2 with IC50 values 0.03-0.06 μM. They were safe on normal human fibroblasts with selectivity indices 8.09, 11.40 and 4.37, respectively. Also, these compounds showed VEGFR2 tyrosine kinase inhibitory activities more than the reference staurosporine with IC50 values <0...
September 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28923386/structure-based-design-synthesis-and-biological-evaluation-of-withaferin-a-analogues-as-potent-apoptotic-inducers
#5
Gabriel G Llanos, Liliana M Araujo, Ignacio A Jiménez, Laila M Moujir, Jaime Rodríguez, Carlos Jiménez, Isabel L Bazzocchi
Apoptosis inducers represent an attractive approach for the discovery and development of anticancer agents. Herein, we report on the development by molecular fine tuning of a withaferin A-based library of 63 compounds (2-64), 53 of them reported for the first time. Their antiproliferative evaluation on HeLa, A-549 and MCF-7 human tumor cell lines identified fifteen analogues displaying higher activity (IC50 values ranging 0.3-4.8 μM) than the lead (IC50 values ranging 1.3-10.1 μM) either in lag or log growth phases...
September 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28916158/pyrrolizines-design-synthesis-anticancer-evaluation-and-investigation-of-the-potential-mechanism-of-action
#6
Ahmed M Gouda, Ahmed H Abdelazeem, Hany A Omar, Ashraf N Abdalla, Mohammed A S Abourehab, Hamed I Ali
A novel set of pyrrolizine-5-carboxamides has been synthesized and evaluated for their anticancer potential against human breast MCF-7, lung carcinoma A549 and hepatoma Hep3B cancer cell lines. Compound 10c was the most active against MCF-7 with IC50 value of 4.72µM, while compound 12b was the most active against A549 and Hep3B cell lines. Moreover, kinases/COXs inhibition and apoptosis induction were suggested as potential molecular mechanisms for the anticancer activity of the novel pyrrolizines based on their structural features...
August 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28901492/interactions-between-hematopoietic-progenitor-kinase-1-and-its-adaptor-proteins-review
#7
Qing Zhang, Shu Ding, Huilin Zhang
Hematopoietic progenitor kinase 1 (HPK1), also known as mitogen‑activated protein kinase kinase kinase kinase 1 is a serine/threonine protein kinase. It is involved in various cellular events, including mitogen‑activated protein kinase signaling, nuclear factor‑κB signaling, cytokine signaling, cellular proliferation and apoptosis, T cell receptor/B cell receptor signaling and T/B/dendritic cell‑mediated immune responses. Therefore, HPK1 has variety of roles in immunity, and is associated with the pathogenesis of autoimmune diseases, cancer, and the inflammatory response...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28895072/role-of-the-inflammasome-related-cytokines-il-1-and-il-18-during-infection-with-murine-coronavirus
#8
Zachary B Zalinger, Ruth Elliott, Susan R Weiss
The inflammasome, a cytosolic protein complex that mediates the processing and secretion of pro-inflammatory cytokines, is one of the first responders during viral infection. The cytokines secreted following inflammasome activation, which include IL-1 and IL-18, regulate cells of both the innate and adaptive immune system, guiding the subsequent immune responses. In this study, we used murine coronavirus, mouse hepatitis virus (MHV), infection of the central nervous system and liver to assess of the role of the inflammasome and its related cytokines on pathogenesis and host defense during viral infection...
September 11, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28877257/rosmarinic-acid-potentiates-carnosic-acid-induced-apoptosis-in-lung-fibroblasts
#9
Sana Bahri, Frédérique Mies, Ridha Ben Ali, Mona Mlika, Saloua Jameleddine, Kathleen Mc Entee, Vadim Shlyonsky
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11...
2017: PloS One
https://www.readbyqxmd.com/read/28875942/inflammasome-dependent-mechanisms-involved-in-sensing-and-restriction-of-bacterial-replication
#10
Warrison A Andrade, Dario S Zamboni
Inflammasomes are multiprotein platforms assembled in the cytosol in response to pathogens and cell stress. Inflammasomes are recognized by their important role on defenses against bacterial infections and have been also implicated in a range of human inflammatory disorders. Intracellular sensors such as NLRP1, NLRP3, NLRC4, AIM2 and Pyrin induce assembly of inflammasomes, while caspase-11 induces the non-canonical pathway for activation of the NLRP3 inflammasome. The formation of the inflammasome leads to caspase-1 activation that triggers pyroptosis and activation of interleukin-1β (IL-1β) and IL-18...
September 6, 2017: Current Issues in Molecular Biology
https://www.readbyqxmd.com/read/28868328/creating-a-raw264-7-crispr-cas9-genome-wide-library
#11
Brooke A Napier, Denise M Monack
The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome editing tools are used in mammalian cells to knock-out specific genes of interest to elucidate gene function. The CRISPR-Cas9 system requires that the mammalian cell expresses Cas9 endonuclease, guide RNA (gRNA) to lead the endonuclease to the gene of interest, and the PAM sequence that links the Cas9 to the gRNA. CRISPR-Cas9 genome wide libraries are used to screen the effect of each gene in the genome on the cellular phenotype of interest, in an unbiased high-throughput manner...
May 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28846926/cirtical-role-for-salmonella-effector-sopb-in-regulating-inflammasome-activation
#12
Gui-Qiu Hu, Pei-Xuan Song, Wei Chen, Shuai Qi, Shui-Xing Yu, Chong-Tao Du, Xu-Ming Deng, Hong-Sheng Ouyang, Yong-Jun Yang
OBJECTIVE: Salmonella is known to evolve many mechanisms to avoid or delay inflammasome activation which remain largely unknown. In this study, we investigated whether the SopB protein critical to bacteria virulence capacity was an effector that involved in the regulation of inflammasome activation. METHODS: BMDMs from NLRC4-, NLRP3-, caspase-1/-11-, IFI16- and AIM2-deficient mice were pretreated with LPS, and subsequently stimulated with a series of SopB-related strains of Salmonella, inflammasome induced cell death, IL-1β secretion, cleaved caspase-1 production and ASC speckle formation were detected...
August 25, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28837200/carboxylate-isosteres-for-caspase-inhibitors-the-acylsulfonamide-case-revisited
#13
Y Adriaenssens, D Jiménez Fernández, L Vande Walle, F Elvas, J Joossens, A Lambeir, K Augustyns, M Lamkanfi, P Van der Veken
As part of an ongoing effort to discover inhibitors of caspase-1 with an optimized selectivity and biopharmaceutical profile, acylsulfonamides were explored as carboxylate isosteres for caspase inhibitors. Acylsulfonamide analogues of the clinically investigated caspase-1 inhibitor VRT-043198 and of the pan-caspase inhibitor Z-VAD-CHO were synthesized. The isostere-containing analogues with an aldehyde warhead had inhibitory potencies comparable to the carboxylate references. In addition, the conformational and tautomeric characteristics of these molecules were determined using (1)H- and (13)C-based NMR...
September 13, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28827028/the-s1p1-receptor-selective-agonist-cym-5442-protects-retinal-ganglion-cells-in-endothelin-1-induced-retinal-ganglion-cell-loss
#14
Román Blanco, Gema Martínez-Navarrete, Francisco J Valiente-Soriano, Marcelino Avilés-Trigueros, Consuelo Pérez-Rico, Ana Serrano-Puebla, Patricia Boya, Eduardo Fernández, Manuel Vidal-Sanz, Pedro de la Villa
We investigated the feasibility and efficacy of using a specific sphingosine 1-phosphate (S1P1) receptor agonist, CYM-5442, to slow or block retinal ganglion cell (RGC) loss in endothelin-1 (ET-1) induced RGC loss. A single intravitreal injection of ET-1 (20pmol/ul), a potent vasoactive peptide that produces retinal vessels vasoconstriction, was used to induce and characterize RGC-specific cell death. CYM-5442 (1 mgr/kg) or vehicle was administered intraperitoneally for five consecutive days after ET-1-induced RGC loss...
August 4, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28814241/the-emerging-picture-of-cdk11-genetic-functional-and-medicinal-aspects
#15
Nikolas Ferreira Dos Santos Paparidis, Fernanda Canduri
Cyclin-dependent kinase 11 is a relatively neglected member of the transcriptional CDKs subfamily, despite possibly being the most versatile CDK in this group. Different CDK11 variants are known to play essential roles in major cellular processes as mRNA transcription (CDK11p110), mitosis (CDK11p58), and apoptosis (CDK11p46 and CDK11p60). Each CDK11 species targets a particular set of substrates related to its functional background, but all isoforms originate from the CDC2L gene complex in human chromosome 1p36...
August 14, 2017: Current Medicinal Chemistry
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
#16
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
#17
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
#18
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
#19
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 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
#20
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
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