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https://www.readbyqxmd.com/read/28802408/down-regulation-of-malate-synthase-in-mycobacterium-tuberculosis-h37ra-leads-to-reduced-stress-tolerance-persistence-and-survival-in-macrophages
#1
Kumar Sachin Singh, Rishabh Sharma, Deepa Keshari, Nirbhay Singh, Sudheer Kumar Singh
Malate synthase is a condensing enzyme responsible for conversion of glyoxylate to malate in the presence of acetyl-CoA. This reaction helps in bypassing the TCA cycle reactions involving carbon loss and leads to diverting some of the carbon skeletons to gluconeogenic events while rest can continue to provide TCA cycle intermediates. Malate synthase (GlcB) is encoded by MRA_1848 of Mycobacterium tuberculosis H37Ra (Mtb-Ra). We developed a knockdown (KD) Mtb-Ra strain by down-regulating GlcB. The survival studies suggested increased susceptibility to oxidative and nitrosative stress as well as to rifampicin...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802000/pmepa1-induced-by-rankl-p38-mapk-pathway-has-a-novel-role-in-osteoclastogenesis
#2
Noboru Funakubo, Xianghe Xu, Toshio Kukita, Seiji Nakamura, Hiroshi Miyamoto, Akiko Kukita
Osteoclasts are multinucleated cells formed by fusion of preosteoclasts (POCs) derived from cells of the monocyte/macrophage lineage. We have reported a culture system that supports the formation of POCs from stroma-depleted rat bone marrow cells. Global gene expression analysis of this culture system identified genes highly expressed in POCs. Here, we have analyzed the expression and function of one of these highly expressed genes, prostate transmembrane protein androgen induced 1 (Pmepa1), a target of TGF-β and binds Nedd4 ubiquitin ligase, which plays a role in intracellular trafficking...
August 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28795851/selective-induction-of-apoptosis-in-mcf7-cancer-cell-by-targeted-liposomes-functionalized-with-mannose-6-phosphate
#3
Cristina Minnelli, Laura Cianfruglia, Emiliano Laudadio, Roberta Galeazzi, Michela Pisani, Emanuela Crucianelli, Davide Bizzaro, Tatiana Armeni, Giovanna Mobbili
Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalization and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28793886/cathepsin-s-degraded-decorin-are-elevated-in-fibrotic-lung-disorders-development-and-biological-validation-of-a-new-serum-biomarker
#4
S N Kehlet, C L Bager, N Willumsen, B Dasgupta, C Brodmerkel, M Curran, S Brix, D J Leeming, M A Karsdal
BACKGROUND: Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue homeostasis contributing to extracellular matrix remodeling diseases. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific fragment of degraded decorin, which has potential as a novel non-invasive serum biomarker for fibrotic lung disorders...
August 9, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28791438/vps52-induces-apoptosis-via-cathepsin-d-in-gastric-cancer
#5
Jian Zhang, Ying Lin, Xichun Hu, Zheng Wu, Weijian Guo
Vacuolar protein sorting (VPS) genes encode a class of proteins involved in vesicular trafficking. Growing evidence suggests that VPS proteins play roles in tumor biology. Vacuolar protein sorting 52 (VPS52) is involved in retrograde transport of endosomes, and its roles in cancers have not been explored. This study investigated the genetic alterations, protein changes, biological role, and molecular mechanism of VPS52 in gastric cancer. Loss of heterozygosity of VPS52 was detected in 52.9% (9/17) of gastric cancer samples...
August 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28782357/beyond-a-carrier-graphene-quantum-dots-as-a-probe-for-programmatically-monitoring-anti-cancer-drug-delivery-release-and-response
#6
Hui Ding, Fan Zhang, Chaochao Zhao, Yanlin Lv, Guanghui Ma, Wei Wei, Zhiyuan Tian
On the basis of the unique physicochemical properties of graphene quantum dots (GQDs), we developed a novel type of theranostic agent by loading anticancer drug doxorubicin (DOX) to GQD's surface and conjugating Cy5.5 (Cy) dye to GQD though a cathepsin D-responsive (P) peptide. Such type of agents demonstrated superior therapeutic performance both in vitro and in vivo because of the improved tissue penetration and cellular uptake. More importantly, they are capable of functioning as probes for programmed tracking the delivery and release of anticancer drug as well as drug-induced cancer cell apoptosis through GQD's, DOX's, and Cy's charateristic fluorescence, respectively...
August 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28772283/the-interplay-of-matrix-metalloproteinase-8-transforming-growth-factor-%C3%AE-1-and-vascular-endothelial-growth-factor-c-cooperatively-contributes-to-the-aggressiveness-of-oral-tongue-squamous-cell-carcinoma
#7
Pirjo Åström, Krista Juurikka, Elin S Hadler-Olsen, Gunbjørg Svineng, Nilva K Cervigne, Ricardo D Coletta, Juha Risteli, Joonas H Kauppila, Sini Skarp, Samuel Kuttner, Ana Oteiza, Meeri Sutinen, Tuula Salo
BACKGROUND: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC). METHODS: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples...
August 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28767721/development-and-clinical-testing-of-individual-immunoassays-for-the-quantification-of-serum-glycoproteins-to-diagnose-prostate-cancer
#8
Kathrin Endt, Jens Goepfert, Aurelius Omlin, Alcibiade Athanasiou, Pierre Tennstedt, Anna Guenther, Maurizio Rainisio, Daniel S Engeler, Thomas Steuber, Silke Gillessen, Thomas Joos, Ralph Schiess
Prostate Cancer (PCa) diagnosis is currently hampered by the high false-positive rate of PSA evaluations, which consequently may lead to overtreatment. Non-invasive methods with increased specificity and sensitivity are needed to improve diagnosis of significant PCa. We developed and technically validated four individual immunoassays for cathepsin D (CTSD), intercellular adhesion molecule 1 (ICAM1), olfactomedin 4 (OLFM4), and thrombospondin 1 (THBS1). These glycoproteins, previously identified by mass spectrometry using a Pten mouse model, were measured in clinical serum samples for testing the capability of discriminating PCa positive and negative samples...
2017: PloS One
https://www.readbyqxmd.com/read/28762847/inhibition-of-nlrp3-inflammasome-a-new-protective-mechanism-of-cinnamaldehyde-in-endotoxin-poisoning-of-mice
#9
Feng Xu, Feng Wang, Taoqun Wen, Wentao Sang, Dejian Wang, Nan Zeng
CONTEXT: Cinnamaldehyde (CA) has a protective effect in endotoxin poisoning of mice, but there is no direct evidence for the protective effect of CA through inhibition of NLRP3 inflammasome activation in endotoxin poisoning of mice. OBJECTIVE: We aimed to investigate the protective mechanism of CA in endotoxin poisoned mice through NLRP3 inflammasome. MATERIALS AND METHODS: First, we evaluated the anti-inflammatory effect of CA in phorbol-12-myristate acetate-differentiated THP-1 cells through the NLRP3 inflammasome...
August 1, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28757214/vulnerability-of-marsh-frog-pelophylax-ridibundus-to-the-typical-wastewater-effluents-ibuprofen-triclosan-and-estrone-detected-by-multi-biomarker-approach
#10
Halina I Falfushynska, Lesya L Gnatyshyna, Oksana Horyn, Oksana B Stoliar
Pharmaceutical and personal care products (PPCPs) are the environmental pollutants of growing concern. The aim of this study was to indicate the effects of typical PPCPs on the marsh frog Pelophylax ridibundus. We treated male frogs with waterborne ibuprofen (IBU, 250ng·L(-1)), triclosan (TCS, 500ng·L(-1)), or estrone (E1, 100ng·L(-1)) for 14days. Common vulnerability of the frogs was detected from dramatic decrease of Zn, total and metalated metallothionein (MT) concentrations, Zn/Cu ratio, the elevation of activity of glutathione-S-transferase, cathepsin D and DNA instability in the liver, the depletion of cholinesterase in the brain and cortisol in the blood plasma in all exposures...
July 27, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28756483/identification-of-structure-stabilizing-interactions-in-enzymes-a-novel-mechanism-to-impact-enzyme-activity
#11
Marisol Serrano, Veronica Gonzalez, Supriyo Ray, Maria D Chavez, Mahesh Narayan
Cruzain, a cysteine protease in the cathepsin family, is pivotal to the life-cycle of Trypanosoma cruzi, the etiological agent in Chagas disease. Current inhibitors of cruzain suffer from drawbacks involving gastrointestinal and neurological side effects and as a result have spurred the search for alternative anti-trypanocidals. Through sequence alignment studies and intra-residue interaction analysis of the pro-protein of cruzain (pro-cruzain), we have identified a host of non-active site residues that are conserved among the cathepsins...
July 29, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28754864/foxm1-facilitates-gastric-cancer-cell-migration-and-invasion-by-inducing-cathepsin-d
#12
Li Yang, Ming Cui, Liang Zhang, Lei Song
Forkhead box M1 (FOXM1) has been reported as a vital transcription factor in different human malignancies. To date, the mechanisms of FOXM1 in modulating the invasion and metastasis of gastric cancer cells have not been elucidated. In the present study, we found that overexpression of FOXM1 prompted cell migration and invasion of gastric cancer, and increased the expression of Cathepsin D (Cath-D). However, FOXM1 siRNA repressed cell migration and invasion, and also decreased the expression of Cath-D in gastric cancer cells...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28744986/complete-recovery-of-fulminant-peripartum-cardiomyopathy-on-mechanical-circulatory-support-combined-with-high-dose-bromocriptine-therapy
#13
Patrick Horn, Diyar Saeed, Payam Akhyari, Denise Hilfiker-Kleiner, Malte Kelm, Ralf Westenfeld
Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure due to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found. We report a case of a woman with PPCM who developed a critical cardiogenic shock with repeated cardiopulmonary resuscitation. We show for the first time that mechanical circulatory support combined with high-dose bromocriptine therapy to suppress systemic prolactin levels may serve as an effective therapeutic option in patients with fulminant PPCM and cardiogenic shock...
July 25, 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28740333/mold-alkaloid-cytochalasin-d-modifies-the-morphology-and-secretion-of-fmlp-lps-or-pma-stimulated-neutrophils-upon-adhesion-to-fibronectin
#14
Svetlana I Galkina, Natalia V Fedorova, Marina V Serebryakova, Evgenii A Arifulin, Vladimir I Stadnichuk, Ludmila A Baratova, Galina F Sud'ina
Neutrophils play an essential role in innate immunity due to their ability to migrate into infected tissues and kill microbes with bactericides located in their secretory granules. Neutrophil transmigration and degranulation are tightly regulated by actin cytoskeleton. Invading pathogens produce alkaloids that cause the depolymerization of actin, such as the mold alkaloid cytochalasin D. We studied the effect of cytochalasin D on the morphology and secretion of fMLP-, LPS-, or PMA-stimulated human neutrophils upon adhesion to fibronectin...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28736174/effects-of-cigarette-smoke-extracts-on-cell-cycle-cell-migration-and-endocrine-activity-in-human-placental-cells
#15
Cho-Won Kim, Hae-Miru Lee, Kyuhong Lee, Bumseok Kim, Moo-Yeol Lee, Kyung-Chul Choi
Maternal smoking during pregnancy is known to be related to adverse pregnancy results associated with trophoblast proliferation and cell cycle progression. Moreover, many previous studies have shown that cigarette smoke is correlated with human chorionic gonadotropin beta (hCG-β) subunit produced from syncytiotrophoblasts during pregnancy. Thus, we further investigated whether cigarette smoke extract (CSE) affects the cell proliferation, migration and endocrine hormone activity of JEG-3 human placental cancer cells...
July 20, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28733353/use-of-proteomics-to-investigate-kidney-function-decline-over-5-years
#16
Axel C Carlsson, Erik Ingelsson, Johan Sundström, Juan Jesus Carrero, Stefan Gustafsson, Tobias Feldreich, Markus Stenemo, Anders Larsson, Lars Lind, Johan Ärnlöv
BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR...
July 21, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28726323/characterization-of-a-cathepsin-d-protease-from-cho-cell-free-medium-and-mitigation-of-its-impact-on-the-stability-of-a-recombinant-therapeutic-protein
#17
Amareth Lim, Brandon L Doyle, Gerard M Kelly, Angelia M Reed-Bogan, Lawrence H Breen, Parviz A Shamlou, Peter K Lambooy
During purification process development of a recombinant therapeutic protein, an endoproteolytic activity endogenous to the Chinese hamster ovary (CHO) cells and leading to degradation at particular hydrophobic amino acid residues (e.g., Phe and Trp) was observed when processing at acidic pH. The presence of residual levels of protease activity in purified protein batches affected the inherent activity of the product when stored as a solution. In order to develop a robust purification strategy to minimize this undesirable impact, identification and characterization of this protease was essential to ultimately ensure that a solution formulation was stable for many years...
July 20, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28720501/numb-positively-regulates-autophagic-flux-via-regulating-lysosomal-function
#18
Haiyan Sun, Yi Liu, Lei Zhang, Ximing Shao, Ke Liu, Zhihao Ding, Xianming Liu, Huashun Li, Hongchang Li
Autophagy is a lysosome-dependent catabolic process involving in the degradation and recycling of unnecessary or damaged proteins and organelles. Emerging evidence indicates that autophagy dysfunction is closely related to various human diseases including cancer, aging, myopathies and neurodegenerative disorders. Here, using genetic knockdown, we uncover the role of Numb, an endocytic adaptor protein, in regulating the late steps of autophagy. We found that Numb depletion led to the accumulation of autophagic vacuole, as verified by RFP-LC3 staining combined with transmission electron microscopy...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28720327/asymmetric-synthesis-and-evaluation-of-epoxy-%C3%AE-acyloxycarboxamides-as-selective-inhibitors-of-cathepsin-l
#19
Deborah A Dos Santos, Anna Maria Deobald, Vivian E Cornelio, Roberta M D Ávila, Renata C Cornea, Gilberto C R Bernasconi, Marcio W Paixão, Paulo C Vieira, Arlene G Corrêa
Cathepsin L plays important roles in physiological processes as well as in the development of many pathologies. Recently the attentions were turned to its association with tumor progress what makes essential the development of more potent and selective inhibitors. In this work, epoxipeptidomimetics were investigated as new cathepsin inhibitors. This class of compounds is straightforward obtained by using a green one-pot asymmetric epoxidation/Passerini 3-MCR. A small library of 17 compounds was evaluated against cathepsin L, and among them LSPN423 showed to be the most potent...
June 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28713240/the-coordinated-action-of-calcineurin-and-cathepsin-d-protects-against-%C3%AE-synuclein-toxicity
#20
Andreas Aufschnaiter, Lukas Habernig, Verena Kohler, Jutta Diessl, Didac Carmona-Gutierrez, Tobias Eisenberg, Walter Keller, Sabrina Büttner
The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca(2+) homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear...
2017: Frontiers in Molecular Neuroscience
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