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https://www.readbyqxmd.com/read/28921911/update-of-antitubercular-prodrugs-in-a-molecular-perspective-mechanisms-of-action-bioactivation-pathways-and-associated-resistances
#1
Vania Bernardes Genisson, Julie Laborde, Céline Deraeve
The place of prodrugs in the current antitubercular therapeutic arsenal is preponderant, since two of the four first-line antitubercular agents, isoniazid (INH) and pyrazinamide (PZA), need to be activated by Mycobacterium tuberculosis before exerting their activity. In addition, six other prodrugs can be found in the second- and third-line therapeutic regimens, namely ethionamide (ETH), prothionamide (PTH), p-aminosalicylic acid (PAS), thiacetazone (TAC), isoxyl (ISO) and the recently approved delamanid. The emergence of mycobacterial strains resistant to one or several antitubercular agents is one of the main issues of the antitubercular therapy...
September 16, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28921394/combination-therapy-with-pirfenidone-plus-prednisolone-ameliorates-paraquat-induced-pulmonary-fibrosis
#2
Rokhsana Rasooli, Fatemeh Pourgholamhosein, Younes Kamali, Fatemeh Nabipour, Ali Mandegary
Pirfenidone is known to slow the decline in vital capacity and increase survival in idiopathic pulmonary fibrosis (IPF). Besides, administration of glucocorticoids, e.g., prednisolone has been the conventional strategy to the treatment of patients with this disease, although their efficacy is under debate. Since multiple coactivated pathways are involved in the pathogenesis of IPF, combination therapy is a foundation strategy to cover many more synergetic mechanisms and increase response. The aim of the present study was to compare the therapeutic efficacy of prednisolone plus pirfenidone with pirfenidone alone in PQ-induced lung fibrosis...
September 18, 2017: Inflammation
https://www.readbyqxmd.com/read/28921056/oxidative-stress-in-atherosclerosis
#3
REVIEW
Ajoe John Kattoor, Naga Venkata K Pothineni, Deepak Palagiri, Jawahar L Mehta
PURPOSE OF REVIEW: Atherosclerosis is now considered a chronic inflammatory disease. Oxidative stress induced by generation of excess reactive oxygen species has emerged as a critical, final common mechanism in atherosclerosis. Reactive oxygen species (ROS) are a group of small reactive molecules that play critical roles in the regulation of various cell functions and biological processes. Although essential for vascular homeostasis, uncontrolled production of ROS is implicated in vascular injury...
September 18, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#4
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28920713/estradiol-decreases-blood-pressure-in-association-with-redox-regulation-in-preeclampsia
#5
Goran M Babic, Snezana D Markovic, Mirjana Varjacic, Natasa Z Djordjevic, Tamara Nikolic, Isidora Stojic, Vladimir Jakovljevic
In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2(-)), and peroxynitrite (ONOO(-)) were conducted before and during the therapy...
September 18, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28920117/hiv-haart-associated-oxidative-stress-is-detectable-by-metabonomics
#6
REVIEW
Aurelia A Williams, Lungile J Sitole, Debra Meyer
Chronic human immunodeficiency virus (HIV) infection, separately and in combination with highly active antiretroviral therapy (HAART) is closely associated with oxidative stress (OS). Most studies demonstrating redox imbalances in HIV-infected individuals have done so using conventional biochemical methodologies. The limited simultaneous detection of multiple OS markers within one sample is a major drawback of these methodologies and can be addressed through the use of metabonomics. HIV-metabonomic studies utilizing biofluids from HAART cohorts as the investigative source, are on the increase...
September 18, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28919892/serum-mediated-oxidative-stress-from-systemic-sclerosis-patients-affects-mesenchymal-stem-cell-function
#7
Guillaume Fonteneau, Claire Bony, Radjiv Goulabchand, Alexandre T J Maria, Alain Le Quellec, Sophie Rivière, Christian Jorgensen, Philippe Guilpain, Danièle Noël
OBJECTIVES: Properties of mesenchymal stromal/stem cells (MSCs) from systemic sclerosis (SSc) patients have been reported to be altered. MSC-based therapy may therefore rely on the use of allogeneic MSCs from healthy subjects. Here, we investigated whether heterologous MSCs could exhibit altered properties following exposure to oxidative environment of SSc sera. METHODS: Human bone marrow-derived MSCs were cultured in the presence of various sera: control human serum AB (SAB), SAB with HOCl-induced AOPPs at 400 or 1,000 µmol/L (SAB400 or SAB1000, respectively), or H2O2-induced AOPPs or SSc patient serum (PS)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919753/combination-of-graphene-oxide-silver-nanoparticle-nanocomposites-and-cisplatin-enhances-apoptosis-and-autophagy-in-human-cervical-cancer-cells
#8
Yu-Guo Yuan, Sangiliyandi Gurunathan
BACKGROUND: Cisplatin (Cis) is a widely used chemotherapeutic drug for treating a variety of cancers, due to its ability to induce cell death in cancer cells significantly. Recently, graphene and its modified nanocomposites have gained much interest in cancer therapy, due to their unique physicochemical properties. The objective of this study was to investigate the combination effect of Cis and a reduced graphene oxide-silver nanoparticle nanocomposite (rGO-AgNPs) in human cervical cancer (HeLa) cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28919744/composite-iron-oxide-prussian-blue-nanoparticles-for-magnetically-guided-t1-weighted-magnetic-resonance-imaging-and-photothermal-therapy-of-tumors
#9
Shraddha S Kale, Rachel A Burga, Elizabeth E Sweeney, Zungho Zun, Raymond W Sze, Anthony Tuesca, J Anand Subramony, Rohan Fernandes
Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4 nanoparticles and gadolinium-containing Prussian blue nanoparticles...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28919740/low-toxic-maghemite-nanoparticles-for-theranostic-applications
#10
Elena A Kuchma, Peter V Zolotukhin, Anna A Belanova, Mikhail A Soldatov, Tatiana A Lastovina, Stanislav P Kubrin, Anatoliy V Nikolsky, Lidia I Mirmikova, Alexander V Soldatov
BACKGROUND: Iron oxide nanoparticles have numerous and versatile biological properties, ranging from direct and immediate biochemical effects to prolonged influences on tissues. Most applications have strict requirements with respect to the chemical and physical properties of such agents. Therefore, developing rational design methods of synthesis of iron oxide nanoparticles remains of vital importance in nanobiomedicine. METHODS: Low toxic superparamagnetic iron oxide nanoparticles (SPIONs) for theranostic applications in oncology having spherical shape and maghemite structure were produced using the fast microwave synthesis technique and were fully characterized by several complementary methods (transmission electron microscopy [TEM], X-ray diffraction [XRD], dynamic light scattering [DLS], X-ray photoelectron spectroscopy [XPS], X-ray absorption near edge structure [XANES], Mossbauer spectroscopy, and HeLa cells toxicity testing)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28919632/cd36-in-chronic-kidney-disease-novel-insights-and-therapeutic-opportunities
#11
REVIEW
Xiaochun Yang, Daryl M Okamura, Xifeng Lu, Yaxi Chen, John Moorhead, Zac Varghese, Xiong Z Ruan
CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates the binding and cellular uptake of long-chain fatty acids, oxidized lipids and phospholipids, advanced oxidation protein products, thrombospondin and advanced glycation end products, and has roles in lipid accumulation, inflammatory signalling, energy reprogramming, apoptosis and kidney fibrosis. Renal CD36 is mainly expressed in tubular epithelial cells, podocytes and mesangial cells, and is markedly upregulated in the setting of chronic kidney disease (CKD)...
September 18, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28919507/tissue-engineered-magnetic-cell-sheet-patches-for-advanced-strategies-in-tendon-regeneration
#12
Ana I Gonçalves, Márcia T Rodrigues, Manuela E Gomes
Tendons are powerful 3D biomechanically structures combining a few cells in an intrincated and highly hierarchical niche environment. When tendon homeostasis is compromised, restoration of functionality upon injury is limited and requires alternatives to current augmentation or replacement strategies. Cell sheet technologies are a powerful tool for the fabrication of living extracellular-rich patches towards regeneration of tenotopic defects. Thus, we originally propose the development of magnetically responsive tenogenic patches through magnetic cell sheet (magCSs) technology that enable the remote control upon implantation of the tendon-mimicking constructs...
September 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28919220/peucedanum-japonicum-extract-attenuates-allergic-airway-inflammation-by-inhibiting-th2-cell-activation-and-production-of-pro-inflammatory-mediators
#13
Jin Mi Chun, A-Reum Lee, Hyo Seon Kim, A Yeong Lee, Gyo Jeong Gu, Byeong Cheol Moon, Bo-In Kwon
ETHNOPHARMACOLOGICAL RELEVANCE: The root of Peucedanum japonicum Thunb is traditionally used to treat coughs, colds, headache and inflammatory diseases in Korea and Japan. Its effects on allergic lung inflammation have not been investigated. AIM OF THE STUDY: To investigate the anti-asthmatic effects of Peucedanum japonicum extract (PJE) using a murine model of asthma and a lipopolysaccharide (LPS)-stimulated macrophage cell line. MATERIALS AND METHODS: Mice underwent two rounds of sensitization with ovalbumin 1 week apart followed by four intranasal ovalbumin challenges on days 13-16...
September 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28918598/triacsin-c-reduces-lipid-droplet-formation-and-induces-mitochondrial-biogenesis-in-primary-rat-hepatocytes
#14
Carlos R P Dechandt, Felippe H Zuccolotto-Dos-Reis, Bruno G Teodoro, Anna Maria A P Fernandes, Marcos N Eberlin, Isis C Kettelhut, Carlos Curti, Luciane C Alberici
Intracellular long-chain acyl-CoA synthetases (ACSL) activate fatty acids to produce acyl-CoA, which undergoes β-oxidation and participates in the synthesis of esterified lipids such as triacylglycerol (TAG). Imbalances in these metabolic routes are closely associated with the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Triacsin C is one of the few compounds that inhibit TAG accumulation into lipid droplets (LD) by suppressing ACSL activity. Here we report that treatment of primary rat hepatocytes with triacsin C at concentrations lower than the IC50 (4...
September 16, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28918342/the-potential-effect-of-ultra-long-insulin-degludec-on-glycemic-variability
#15
REVIEW
M Rodacki, R M Carvalho, L Zajdenverg
Despite the therapeutic advances in the treatment of diabetes, metabolic control instability due to glycemic variability (GV) is frequently observed in patients with diabetes on intensive insulin therapy and is associated with hyperglycemic peaks and hypoglycemic episodes. Hyperglycemia associated with GV has been implicated in the development of chronic complications due to its pro-oxidative consequences. On the other hand, hypoglycemia can be associated with increased cardiovascular risk secondarily to adrenergic activation...
June 30, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28918123/carnosic-acid-induces-apoptosis-of-hepatocellular-carcinoma-cells-via-ros-mediated-mitochondrial-pathway
#16
Xinrui Zhang, Yiling Chen, Guangsheng Cai, Xin Li, Di Wang
Carnosic acid (CA), an important bioactive phenolic diterpene mainly found in labiate plants, exerts various biological functions, including antioxidant, anti-inflammatory, antitumor, and neuroprotective activities. In the present study, we proved the deleterious effects of CA against hepatocellular carcinoma (HCC) in both in vitro and in vivo models. In vitro, CA significantly decreased cell viability, inhibited cell proliferation and migration, enhanced apoptosis, and increased caspase-3, -8, and -9 activities in HepG2 and SMMC-7721 cells...
September 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28917803/atp-mediated-rolling-circle-amplification-and-opening-dna-gate-for-drug-delivery-to-cell
#17
Yujie Wang, Xinxin Shang, Jia Liu, Yingshu Guo
Here, we have developed a facile fluorometric system for the detection of adenosine triphosphate (ATP) by a rolling circle amplification (RCA) based on proximity ligation mediated amplification, and simultaneously achieved the release of the anticancer drug doxorubicin (DOX) through the mesoporous silicon system. Once the ATP molecule is present, the linker DNA will be released from the graphene oxide (GO) surface and hybridized to the template DNA of the GO surface joining with ligation enzyme. RCA reaction is followed by the addition of the phi29 DNA polymerase...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28917625/reduced-neuroprotective-potential-of-the-mesenchymal-stromal-cell-secretome-with-ex-vivo-expansion-age-and-progressive-multiple-sclerosis
#18
Pamela Sarkar, Juliana Redondo, Kevin Kemp, Mark Ginty, Alastair Wilkins, Neil J Scolding, Claire M Rice
BACKGROUND: Clinical trials using ex vivo expansion of autologous mesenchymal stromal cells (MSCs) are in progress for several neurological diseases including multiple sclerosis (MS). Given that environment alters MSC function, we examined whether in vitro expansion, increasing donor age and progressive MS affect the neuroprotective properties of the MSC secretome. METHODS: Comparative analyses of neuronal survival in the presence of MSC-conditioned medium (MSCcm) isolated from control subjects (C-MSCcm) and those with MS (MS-MSCcm) were performed following (1) trophic factor withdrawal and (2) nitric oxide-induced neurotoxicity...
September 13, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#19
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916656/chemotherapy-induced-macrophage-infiltration-into-tumors-enhances-nanographene-based-photodynamic-therapy
#20
Yang Zhao, Chenran Zhang, Liquan Gao, Xinhe Yu, Jianhao Lai, Dehua Lu, Rui Bao, Yanpu Wang, Bing Jia, Fan Wang, Zhaofei Liu
Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation...
September 15, 2017: Cancer Research
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