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https://www.readbyqxmd.com/read/29214694/myelodysplastic-syndromes-2018-update-on-diagnosis-risk-stratification-and-management
#1
Guillermo Montalban-Bravo, Guillermo Garcia-Manero
DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29205851/regulated-cell-death-of-lymphoma-cells-after-graded-mitochondrial-damage-is-differentially-affected-by-drugs-targeting-cell-stress-responses
#2
Tomás Lombardo, Martín Gil Folgar, Luciana Salaverry, Estela Rey-Roldán, Elida M Alvarez, María C Carreras, Laura Kornblihtt, Guillermo A Blanco
Collapse of the mitochondrial membrane potential (MMP) is often considered the initiation of regulated cell death (RCD). Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) is an uncoupler of the electron transport chain (ETC) that facilitates the translocation of protons into the mitochondrial matrix leading to the collapse of the MMP. Several cell stress responses such as mitophagy, mitochondrial biogenesis and the ubiquitin proteasome system, may differentially contribute to restrain the initiation of RCD depending on the extent of mitochondrial damage...
December 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29180254/reclaiming-hijacked-phagosomes-hybrid-nano-in-micro-encapsulated-miap-peptide-ensures-host-directed-therapy-by-specifically-augmenting-phagosome-maturation-and-apoptosis-in-tb-infected-macrophage-cells
#3
Ankur Sharma, Kalpesh Vaghasiya, Pushpa Gupta, Umesh Datta Gupta, Rahul Kumar Verma
TB-Superbugs have emerged as one of the most challenging global health threat due to the decrease in effectiveness of conventional antibiotics. Meanwhile, Host defense peptides (HDP) have evolved as an alternative to classical therapeutics with lesser susceptibility of resistance. We describe the potential of nano-encapsulated synthetic Magainin-I analog peptide (MIAP) as Host Directed Therapy against TB. Micron-sized inhalable platform "Porous Nanoparticle Aggregates Particles (PNAP)" with nano-scale physiognomies were developed to improve the delivery of MIAP-peptide to the lungs and enhance its stability...
November 24, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29179729/deficiency-of-innate-like-t-lymphocytes-in-chronic-obstructive-pulmonary-disease
#4
Mariann Szabó, Veronika Sárosi, Zoltán Balikó, Kornélia Bodó, Nelli Farkas, Tímea Berki, Péter Engelmann
BACKGROUND: Based on the phenotypic and functional characteristics unconventional T-lymphocytes such as invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells link the innate and adaptive immune responses. Up to now data are scarce about their involvement in pulmonary disorders including chronic obstructive pulmonary disease (COPD). This study explores simultaneously the frequencies of iNKT and MAIT cells in the peripheral blood and sputum of stable and exacerbating COPD patients...
November 28, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29177837/high-throughput-flow-cytometry-screening-of-multidrug-efflux-systems
#5
Mark K Haynes, Matthew Garcia, Ryan Peters, Anna Waller, Pietro Tedesco, Oleg Ursu, Cristian G Bologa, Radleigh G Santos, Clemencia Pinilla, Terry H Wu, Julie A Lovchik, Tudor I Oprea, Larry A Sklar, George P Tegos
The resistance nodulation cell division (RND) family of proteins are inner membrane transporters that associate with periplasmic adaptor proteins and outer membrane porins to affect substrate transport from the cytosol and periplasm in Gram-negative bacteria. Various structurally diverse compounds are substrates of RND transporters. Along with their notable role in antibiotic resistance, these transporters are essential for niche colonization, quorum sensing, and virulence as well as for the removal of fatty acids and bile salts...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29152587/a-synthetic-community-system-for-probing-microbial-interactions-driven-by-exometabolites
#6
John L Chodkowski, Ashley Shade
Though most microorganisms live within a community, we have modest knowledge about microbial interactions and their implications for community properties and ecosystem functions. To advance understanding of microbial interactions, we describe a straightforward synthetic community system that can be used to interrogate exometabolite interactions among microorganisms. The filter plate system (also known as the Transwell system) physically separates microbial populations, but allows for chemical interactions via a shared medium reservoir...
November 2017: MSystems
https://www.readbyqxmd.com/read/29127762/anti-invasive-and-antiproliferative-effects-of-pleurotus-ostreatus-extract-on-acute-leukemia-cell-lines
#7
Alireza Ebrahimi, Amir Atashi, Masoud Soleimani, Maedeh Mashhadikhan, Ahmadreza Barahimi, Amirhossein Maghari
BACKGROUND: Currently, mushrooms have been used in traditional and folk medicines for their therapeutic activities, such as antibiotic, antitumor, anti-inflammatory, anticancer, antileukemic and immunomodulatory actions. This investigation evaluates the anti-invasive, antiproliferative and cytotoxic effects of Pleurotus ostreatus (Pleurotaceae) on leukemia cell lines. METHODS: The proliferation of KG-1 cells was measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with gradient dilutions of P...
November 11, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29127049/predicting-mutant-selection-in-competition-experiments-with-ciprofloxacin-exposed-escherichia-coli
#8
David D Khan, Pernilla Lagerbäck, Christer Malmberg, Anders N Kristoffersson, Erik Gullberg, Cao Sha, Otto Cars, Dan I Andersson, Diarmaid Hughes, Elisabet I Nielsen, Lena E Friberg
Predicting competition between antibiotic susceptible wild-type and less susceptible mutant bacteria is valuable for understanding how drug concentrations influence emergence of resistance. Pharmacokinetic-pharmacodynamic (PKPD) models predicting the rate and extent of takeover of resistant bacteria during different antibiotic pressures can thereby be a valuable tool in improving treatment regimens. The aim of this study was to evaluate a previously developed mechanism-based PKPD model for its ability to predict in vitro mixed-population experiments with competition between E...
November 7, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29126235/clinical-significance-of-interferon-%C3%AE-neutralizing-autoantibodies-against-disseminated-nontuberculous-mycobacterial-disease
#9
Ami Aoki, Takuro Sakagami, Kazutaka Yoshizawa, Kenjiro Shima, Mio Toyama, Yoshinari Tanabe, Hiroshi Moro, Nobumasa Aoki, Satoshi Watanabe, Toshiyuki Koya, Takashi Hasegawa, Kozo Morimoto, Atsuyuki Kurashima, Yoshihiko Hoshino, Bruce C Trapnell, Toshiaki Kikuchi
Background: Interferon-γ neutralizing autoantibodies (nIFNγ-autoAb) are reported in patients with disseminated nontuberculous mycobacteria (NTM) infection and may function by increasing the infection risk. Notwithstanding, the prevalence of nIFNγ-autoAb as well as the clinical presentation, diagnosis, and natural history, of disseminated NTM infection in these patients is poorly understood. Methods: In this retrospective observational study, data and sera for 331 Japanese subjects with mycobacterial infection were collected and analyzed...
November 8, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29099326/disarming-staphylococcus-aureus-from-destroying-human-cells-by-simultaneously-neutralizing-six-cytotoxins-with-two-human-monoclonal-antibodies
#10
Harald Rouha, Susanne Weber, Philipp Janesch, Barbara Maierhofer, Karin Gross, Ivana Dolezilkova, Irina Mirkina, Zehra C Visram, Stefan Malafa, Lukas Stulik, Adriana Badarau, Eszter Nagy
Pathogenesis of Staphylococcus aureus is increasingly recognized to be driven by powerful toxins. Staphylococcus aureus employs up to six pore-forming toxins to subvert the human host defense and to promote bacterial invasion: alpha-hemolysin that disrupts epithelial and endothelial barriers and five leukocidins that lyse phagocytes involved in bacterial clearance. Previously, we described two human monoclonal antibodies (mAbs), ASN-1 that neutralizes alpha-hemolysin and four leukocidins (LukSF-PV, LukED, HlgAB, HlgCB), and ASN-2 that inactivates the 5(th) leukocidin, LukGH...
November 3, 2017: Virulence
https://www.readbyqxmd.com/read/29091578/dual-label-flow-cytometry-based-host-cell-adhesion-assay-to-ascertain-the-prospect-of-probiotic-lactobacillus-plantarum-in-niche-specific-antibacterial-therapy
#11
Sandipan Mukherjee, Aiyagari Ramesh
Host cell adhesion assays that provide quantitative insight on the potential of lactic acid bacteria (LAB) to inhibit adhesion of intestinal pathogens can be leveraged for the development of niche-specific anti-adhesion therapy. Herein, we report a dual-colour flow cytometry (FCM) analysis to assess the ability of probiotic Lactobacillus plantarum strains to impede adhesion of Enterococcus faecalis, Listeria monocytogenes and Staphylococcus aureus onto HT-29 cells. FCM in conjunction with a hierarchical cluster analysis could discern the anti-adhesion potential of L...
November 1, 2017: Microbiology
https://www.readbyqxmd.com/read/29089598/cellular-uptake-of-modified-aminoglycosides
#12
Kaivin Hadidi, Ezequiel Wexselblatt, Jeffrey D Esko, Yitzhak Tor
The uptake of modified amino- and guanidino-glycosides derived from kanamycin, tobramycin and neomycin in native and mutant CHO cells is examined using confocal microscopy and flow cytometry, illustrating the significance of multivalency for mammalian cell internalization of carriers that specifically interact with cell surface heparan sulfate proteoglycans.The Journal of Antibiotics advance online publication, 1 November 2017; doi:10.1038/ja.2017.131.
November 1, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/29052983/in-vivo-biochemistry-single-cell-dynamics-of-cyclic-di-gmp-in-e-coli-in-response-to-zinc-overload
#13
Jongchan Yeo, Andrew B Dippel, Xin C Wang, Ming C Hammond
Intracellular signaling enzymes drive critical changes in cellular physiology and gene expression, but their endogenous activities in vivo remain highly challenging to study in real-time and for individual cells. Here we show that flow cytometry can be performed in complex media to monitor single-cell population distributions and dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. These in vivo biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which exhibit high fluorescence turn-on in response to cyclic di-GMP...
October 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/29046671/generation-of-persister-cells-of-pseudomonas-aeruginosa-and-staphylococcus-aureus-by-chemical-treatment-and-evaluation-of-their-susceptibility-to-membrane-targeting-agents
#14
Lucia Grassi, Mariagrazia Di Luca, Giuseppantonio Maisetta, Andrea C Rinaldi, Semih Esin, Andrej Trampuz, Giovanna Batoni
Persister cells (PCs) are a subset of dormant, phenotypic variants of regular bacteria, highly tolerant to antibiotics. Generation of PCs in vivo may account for the recalcitrance of most chronic infections to antimicrobial treatment and demands for the identification of new antimicrobial agents able to target such cells. The present study explored the possibility to obtain in vitro PCs of Pseudomonas aeruginosa and Staphylococcus aureus at high efficiency through chemical treatment, and to test their susceptibility to structurally different antimicrobial peptides (AMPs) and two clinically used peptide-based antibiotics, colistin and daptomycin...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29043783/marine-mammal-microbiota-yields-novel-antibiotic-with-potent-activity-against-clostridium-difficile
#15
Jessica L Ochoa, Laura M Sanchez, Byoung-Mo Koo, Jennifer S Doherty, Manohary Rajendram, Kerwyn Casey Huang, Carol A Gross, Roger G Linington
The recent explosion of research on the microbiota has highlighted the important interplay between commensal microorganisms and the health of their cognate hosts. Metabolites isolated from commensal bacteria have been demonstrated to possess a range of antimicrobial activities, and it is widely believed that some of these metabolites modulate host behavior, affecting predisposition to disease and pathogen invasion. Our access to the local marine mammal stranding network and previous successes in mining the fish microbiota poised us to test the hypothesis that the marine mammal microbiota is a novel source of commensal bacteria-produced bioactive metabolites...
October 18, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29042988/toll-like-receptor-2-and-dectin-1-function-as-promising-biomarker-for-aspergillus-fumigatus-infection
#16
Peng-Peng Zhang, Xiao-Feng Xin, Xiao-Yong Xu, Li-Ping Fang, Jie Wu, Yi Shi
In recent years, along with the wide application of organ transplantation and immunosuppressive agents, as well as the abuse of broad spectrum antibiotics, the incidence of invasive fungal infections has been increasing gradually. The present study aimed to identify novel biomarkers in cells infected with Aspergillus fumigatus. Human umbilical vein endothelial cells (HUVECs) were infected with Aspergillus fumigatus and then harvested at different time-points (0, 1, 2, 4 and 6 h). The expression Toll-like receptor 2 (TLR2) and dectin-1 expression were examined using flow cytometry and western blotting, and fluorescence-based microscopy was used to evaluate their distribution...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29018116/quinolone-resistance-reversion-by-targeting-the-sos-response
#17
E Recacha, J Machuca, P Díaz de Alba, M Ramos-Güelfo, F Docobo-Pérez, J Rodriguez-Beltrán, J Blázquez, A Pascual, J M Rodríguez-Martínez
Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies...
October 10, 2017: MBio
https://www.readbyqxmd.com/read/29017327/enhancing-the-bactericidal-efficacy-of-nanostructured-multifunctional-surface-using-an-ultrathin-metal-coating
#18
Abinash Tripathy, Syama Sreedharan, Chetana Bhaskarla, Shamik Majumdar, Sudheer Kumar Peneti, Dipankar Nandi, Prosenjit Sen
Insects and plants exhibit bactericidal behavior through nanostructures, which leads to physical contact killing that does not require antibiotics or chemicals. Also, certain metallic ions (e.g., Ag(+) and Cu(2+)) are well-known to kill bacteria by disrupting their cellular functionalities. The aim of this study is to explore the improvement in bactericidal activity by combining extreme physical structure with surface chemistry. We have fabricated tall (8-9 μm high) nanostructures on silicon surfaces (NSS) having sharp tips (35-110 nm) using a single-step, maskless deep reactive ion etching technique inspired by dragonfly wing...
October 23, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28960193/an-early-report-a-modified-porphyrin-linked-metronidazole-targeting-intracellular-porphyromonas-gingivalis-in-cultured-oral-epithelial-cells
#19
Ping Ye, Jiho Chang, Lin Feng Foo, Benjamin C-M Yap
Porphyromonas gingivalis (P. gingivalis) has a strong association with the pathogenesis of periodontal disease. Recurrence of periodontal disease following therapy is attributed to numerous factors, and of growing interest is the potential problem of intracellular bacteria that are able to persist and multiply within the host cell, thereby facilitating relapse of infection. The effect of antibiotic therapy in controlling P. gingivalis is questionable. Accordingly, while metronidazole is very effective against anaerobic extracellular P...
September 2017: International Journal of Oral Science
https://www.readbyqxmd.com/read/28955313/antibacterial-effect-of-potassium-tetraborate-tetrahydrate-against-soft-rot-disease-agent-pectobacterium-carotovorum-in-tomato
#20
Firas A Ahmed, Mohammad Arif, Anne M Alvarez
Soft rot caused by Pectobacterium carotovorum is one of most common bacterial diseases occurring in fruits and vegetables worldwide, yet consumer-acceptable options for post-harvest disease management are still insufficient. We evaluated the effect of potassium tetraborate tetrahydrate (B4K2O7.4H2O) (PTB) on the growth of P. carotovorum using strain BA17 as a representative of high virulence. Complete inhibition of bacterial growth was achieved by treatment with PTB at 100 mM both at pH 9.2 and after adjustment to pH 7...
2017: Frontiers in Microbiology
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