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https://www.readbyqxmd.com/read/28748751/update-on-nitazoxanide-a-multifunctional-chemotherapeutic-agent
#1
Anshul Shakya, Hans Raj Bhat, Surjit Kumar Ghosh
The thiazolide nitazoxanide (NTZ) is a broad-spectrum anti-infective drug that adversely affects viability, growth, and proliferation of a range of extracellular and intracellular protozoan, helminths, anaerobic and microaerophilic bacteria, and viruses. Current review compiled the potential chemotherapeutic efficacy of NTZ against a variety of such disease-causing macro and/or micro-organisms as well as neoplastic cells. The most accepted anti-infective mechanism of NTZ involves impairment of the energy metabolism in anaerobic pathogens by inhibition of the pyruvate: ferredoxin/flavodoxin oxidoreductase (PFOR)...
July 27, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28747473/dissecting-the-contributions-of-time-and-microbe-density-to-variation-in-immune-gene-expression
#2
Ann T Tate, Andrea L Graham
Widespread differential expression of immunological genes is a hallmark of the response to infection in almost all surveyed taxa. However, several challenges remain in the attempt to connect differences in gene expression with functional outcomes like parasite killing and host survival. For example, temporal gene expression patterns are not always monotonic (unidirectional slope), yielding results that qualitatively depend on the time point selected for analysis. They may also be correlated to microbe density, confounding the strength of an immune response and resistance to parasites...
July 26, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28747388/neuronal-p2x7-receptors-revisited-do-they-really-exist
#3
Peter Illes, Tahir Muhammad Khan, Patrizia Rubini
P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic receptors (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long intracellular C terminus regulating trafficking to the cell membrane, protein-protein interactions, and post-translational modification. Their C-terminal tail is especially important in enabling the transition from the nonselective ion channel mode to a membrane pore allowing the passage of large molecules. There is an ongoing dispute on the existence of neuronal P2X7Rs with consequences for our knowledge on their involvement in neuroinflammation, aggravating stroke, temporal lobe epilepsy, neuropathic pain, and various neurodegenerative diseases...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28745885/chemical-synthesis-demonstrates-dynamic-o-glycosylation-regulates-folding-and-functional-conformation-of-a-pivotal-egf12-domain-of-human-notch1-receptor
#4
Shun Hayakawa, Yasuhiro Yokoi, Hiroshi Hinou, Shin-Ichiro Nishimura
The interaction of human NOTCH1 receptor and its ligands is a crucial step to initiate the intracellular signal transductions, in which O-glycosylation of the extracellular EGF-like domain is known to modify this pathway that strongly affects multiple aspects of cell differentiation, development, and cancer biology. In spite of the emerging importance of O-glycosylation in the NOTCH signaling pathway, consequences of this dynamic O-glycosylation processes in ER/Golgi on the folding of functional EGF-like domains re-main unclear...
July 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28745764/control-of-targeting-ligand-display-by-ph-responsive-polymers-on-gold-nanoparticles-mediates-selective-entry-into-cancer-cells
#5
C Brazzale, F Mastrotto, P Moody, P D Watson, A Balasso, A Malfanti, G Mantovani, P Caliceti, C Alexander, A T Jones, S Salmaso
Selective targeting of cells for intracellular delivery of therapeutics represents a major challenge for pharmaceutical intervention in disease. Here we show pH-triggered receptor-mediated endocytosis of nanoparticles via surface ligand exposure. Gold nanoparticles were decorated with two polymers: a 2 kDa PEG with a terminal folate targeting ligand, and a di-block copolymer including a pH-responsive and a hydrophilic block. At the normal serum pH of 7.4, the pH-responsive block (apparent pKa of 7.1) displayed a hydrophilic extended conformation, shielding the PEG-folate ligands, which inhibited cellular uptake of the nanoparticles...
July 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28745311/outer-membrane-vesicle-associated-lipase-ftla-enhances-cellular-invasion-and-virulence-in-francisella-tularensis-lvs
#6
Fei Chen, Guolin Cui, Shuxia Wang, Manoj Kumar Mohan Nair, Lihong He, Xinyi Qi, Xiangmin Han, Hanqi Zhang, Jing-Ren Zhang, Jingliang Su
Francisella tularensis is a highly infectious intracellular pathogen that infects a wide range of host species and causes fatal pneumonic tularemia in humans. ftlA was identified as a potential virulence determinant of the F. tularensis live vaccine strain (LVS) in our previous transposon screen, but its function remained undefined. Here, we show that an unmarked deletion mutant of ftlA was avirulent in a pneumonia mouse model with a severely impaired capacity to infect host cells. Consistent with its sequence homology with GDSL lipase/esterase family proteins, the FtlA protein displayed lipolytic activity in both E...
July 26, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28743942/covalent-non-covalent-encapsulated-nanodrug-regulate-the-fate-of-intra-and-extracellular-trafficking-impact-on-cancer-and-normal-cells
#7
Sang-Woo Kim, Yeon Kyung Lee, Sang-Hyun Kim, Jun-Young Park, Dong Un Lee, Jungil Choi, Jeong Hee Hong, Sanghyo Kim, Dongwoo Khang
Drugs need to be designed to access the designated intracellular organelle compartments in order to maximize anticancer efficacy. This study identified that covalently conjugated, non-covalent polyethylene glycol coated and encapsulated nanodrugs selectively influence drug uptake, the intracellular and extracellular trafficking of cancer cells. The types of nano conjugation modulated intracellular dynamics associated with differential impact on anti-cancer efficacy, but also induced differential cytotoxicity on cancer versus normal cells...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743815/galectin-3-inhibits-galectin-8-parkin-mediated-ubiquitination-of-group-a-streptococcus
#8
Yi-Lin Cheng, Yan-Wei Wu, Chih-Feng Kuo, Shiou-Ling Lu, Fu-Tong Liu, Robert Anderson, Chiou-Feng Lin, Yi-Ling Liu, Wan-Yu Wang, Ying-Da Chen, Po-Xing Zheng, Jiunn-Jong Wu, Yee-Shin Lin
Group A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections. Although originally thought to be an extracellular bacterium, numerous studies have demonstrated that GAS can trigger internalization into nonimmune cells to escape from immune surveillance or antibiotic-mediated killing. Epithelial cells possess a defense mechanism involving autophagy-mediated targeting and killing of GAS within lysosome-fused autophagosomes. In endothelial cells, in contrast, we previously showed that autophagy is not sufficient for GAS killing...
July 25, 2017: MBio
https://www.readbyqxmd.com/read/28743484/oxidative-stress-enhances-and-modulates-protein-s-nitrosation-in-smooth-muscle-cells-exposed-to-s-nitrosoglutathione
#9
E Belcastro, W Wu, I Fries-Raeth, A Corti, A Pompella, P Leroy, I Lartaud, C Gaucher
Among S-nitrosothiols showing reversible binding between NO and -SH group, S-nitrosoglutathione (GSNO) represents potential therapeutics to treat cardiovascular diseases (CVD) associated with reduced nitric oxide (NO) availability. It also induces S-nitrosation of proteins, responsible for the main endogenous storage form of NO. Although oxidative stress parallels CVD development, little is known on the ability of GSNO to restore NO supply and storage in vascular tissues under oxidative stress conditions. Aortic rat smooth muscle cells (SMC) were stressed in vitro with a free radical generator (2,2'-azobis(2-amidinopropane) dihydrochloride, AAPH)...
July 22, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28743285/%C3%AE-adrenergic-receptor-camp-pka-signaling-contributes-to-the-intracellular-ca-2-release-by-tentacle-extract-from-the-jellyfish-cyanea-capillata
#10
Qianqian Wang, Hui Zhang, Bo Wang, Chao Wang, Liang Xiao, Liming Zhang
BACKGROUND: Intracellular Ca(2+) overload induced by extracellular Ca(2+) entry has previously been confirmed to be an important mechanism for the cardiotoxicity as well as the acute heart dysfunction induced by jellyfish venom, while the underlying mechanism remains to be elucidated. METHODS: Under extracellular Ca(2+)-free or Ca(2+)-containing conditions, the Ca(2+) fluorescence in isolated adult mouse cardiomyocytes pre-incubated with tentacle extract (TE) from the jellyfish Cyanea capillata and β blockers was scanned by laser scanning confocal microscope...
July 25, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28743063/glutamate-pathways-of-the-beta-cell-and-the-control-of-insulin-secretion
#11
REVIEW
Pierre Maechler
Pancreatic beta-cells secrete insulin in response to circulating glucose, thereby maintaining euglycemia. Inside the beta-cell, glucose is transformed into intracellular signals stimulating exocytosis. While calcium is an obligatory messenger, this ion is not sufficient to promote the full secretory response. Accordingly, glucose metabolism produces the additive factor glutamate that participates to an amplifying pathway of the calcium signal. Although intracellular glutamate potentiates insulin secretion, extracellular glutamate may activate ionotropic receptors...
July 12, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28742793/intracrine-vegf-signalling-mediates-colorectal-cancer-cell-migration-and-invasion
#12
Rajat Bhattacharya, Fan Fan, Rui Wang, Xiangcang Ye, Ling Xia, Delphine Boulbes, Lee M Ellis
BACKGROUND: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) are key regulators of angiogenesis, affecting endothelial cell survival and function. However, the effect of VEGF-VEGFR signalling on tumour cell function is not well understood. Our previous studies in colorectal cancer (CRC) cells have demonstrated an intracrine VEGF/VEGFR1 signalling mechanism that mediates CRC cell survival and chemo-sensitivity. Since extracellular VEGF signalling regulates migration of endothelial cells and various tumour cells, we attempted to determine whether intracrine VEGF signalling affects CRC cell motility...
July 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28742508/clinical-characterization-of-a-novel-calcium-sensing-receptor-genetic-alteration-in-a-greek-patient-with-autosomal-dominant-hypocalcemia-type-1
#13
Anna Papadopoulou, Evangelia Gole, Katerina Melachroinou, Theoni Trangas, Evaggelia Bountouvi, Anastasios Papadimitriou
OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor (CaSR) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical characteristics and the bone mineral density (BMD) progression from early childhood to late puberty in a patient with ADH. DESIGN: Genetic analysis of the CaSR gene was performed in a patient who presented in the neonatal period with hypocalcemic seizures and biochemical features of ADH...
April 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#14
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28741346/occurrence-state-and-molecular-structure-analysis-of-extracellular-proteins-with-implications-to-the-dewaterability-of-waste-activated-sludge
#15
Boran Wu, Bing-Jie Ni, Kristine Horvat, Liyan Song, Xiaoli Chai, Xiaohu Dai, Devinder Mahajan
The occurrence state and molecular structure of extracellular proteins were analyzed to reveal the influencing factors on the water-holding capacities of protein-like substances in waste activated sludge (WAS). The gelation process of extracellular proteins verified that advanced oxidation processes (AOPs) for WAS dewaterability improvement eliminated the water affinity of extracellular proteins and prevented these macromolecules to form stable colloidal aggregation. Isobaric tags for relative and absolute quantitation proteomics identified that most of extracellular proteins were originally derived from intracellular part and the proteins originally located at extracellular part were mainly membrane-associated...
July 25, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28740491/nod-like-receptor-p3-inflammasome-controls-protective-th1-th17-immunity-against-pulmonary-paracoccidioidomycosis
#16
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/28738309/irradiation-by-blue-light-in-the-presence-of-a-photoacid-confers-changes-to-colony-morphology-of-the-plant-pathogen-colletotrichum-gloeosporioides
#17
Ron Simkovitch, Oren Gajst, Einat Zelinger, Oded Yarden, Dan Huppert
We used the photoacid 8-hydroxy-1,3,6-pyrenetrisulfonate (HPTS) that converts blue photons to acidic protons in water, with an efficiency of close to 100%, and determined that this treatment conferred changes to colony morphology of the plant pathogen Colletotrichum gloeosporioides. The time elapsed until hyphal collapse is noticed depends on both the laser intensity in mW/cm(2), and the concentration of HPTS in the Agar hydrogel. The time elapsed until hyphal collapse is noticed varies by only ±8% at HPTS concentrations of 500μM and at lower concentrations of HPTS the variance increases as the inverse of the concentration...
June 28, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28737766/endothelial-fibrosis-induced-by-suppressed-stat3-expression-mediated-by-signaling-involving-the-tgf-%C3%AE-1-alk5-smad-pathway
#18
Alvaro Becerra, Macarena Rojas, Alejandro Vallejos, Vicente Villegas, Lorena Pérez, Claudio Cabello-Verrugio, Felipe Simon
During systemic inflammatory pathologies, mediators of inflammation circulate in the bloodstream and interact with endothelial cells (ECs), resulting in endothelial dysfunction that maintains and enhances the pathological condition. Inflammatory mediators change the protein expression profile of ECs, which become activated fibroblasts via endothelial-to-mesenchymal transition. This process is characterized by downregulated endothelial proteins and strongly upregulated fibrotic-specific genes and extracellular matrix-forming proteins...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28737753/metabolic-control-of-the-scaffold-protein-tks5-in-tissue-invasive-proinflammatory-t-cells
#19
Yi Shen, Zhenke Wen, Yinyin Li, Eric L Matteson, Jison Hong, Jörg J Goronzy, Cornelia M Weyand
Pathogenic T cells in individuals with rheumatoid arthritis (RA) infiltrate non-lymphoid tissue sites, maneuver through extracellular matrix and form lasting inflammatory microstructures. Here we found that RA T cells abundantly express the podosome scaffolding protein TKS5, which enables them to form tissue-invasive membrane structures. TKS5 overexpression was regulated by the intracellular metabolic environment of RA T cells-specifically, by reduced glycolytic flux that led to deficiencies in ATP and pyruvate...
July 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28737376/insight-into-c-di-gmp-regulation-in-anammox-aggregation-in-response-to-alternating-feed-loadings
#20
Yongzhao Guo, Sitong Liu, Xi Tang, Chao Wang, Zhao Niu, Ying Feng
Substrate concentrations generally fluctuate in wastewaters. However, how anammox biomass behaves to overcome the stress of alternating feed loadings remains unclear. Here, we combined long-term reactor operation, batch tests, 16S rRNA transcript sequencing, and metabolomics analysis to investigate the aggregation of anammox biomass under the regulation of c-di-GMP, a key second messenger, in response to alternating feed loadings. We demonstrated that the aggregation process was significantly faster under alternating loadings and was significantly correlated with higher levels of c-di-GMP and extracellular polymeric substances (EPS) production...
July 24, 2017: Environmental Science & Technology
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