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Mihu, M.R.; Cabral, V.; Pattabhi, R.; Tar, M.T.; Davies, K.P.; Friedman, A.J.; Martinez, L.R.; Nosanchuk, J.D. |
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Title |
Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model |
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Journal Article |
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Year |
2017 |
Publication  |
Antimicrobial Agents and Chemotherapy |
Abbreviated Journal |
Antimicrob Agents Chemother |
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Volume |
61 |
Issue |
1 |
Pages |
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Keywords |
Animals; Anti-Bacterial Agents/chemistry/*pharmacology; Bacterial Adhesion/drug effects; Biofilms/*drug effects/growth & development; Catheter-Related Infections/*drug therapy/microbiology; Central Venous Catheters; Chitosan/chemistry/pharmacology; Delayed-Action Preparations; Disease Models, Animal; Female; Glucose/chemistry; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects/growth & development/ultrastructure; Nanoparticles/*administration & dosage/chemistry; Nitric Oxide/chemical synthesis/*pharmacology; Oxidation-Reduction; Plankton/drug effects/growth & development; Rats; Rats, Sprague-Dawley; Sodium Nitrite/chemistry; Staphylococcal Infections/*drug therapy/microbiology; Staphylococcus aureus; antimicrobials; biofilms; nanoparticles; nitric oxide |
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Abstract |
Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices. |
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Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA |
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0066-4804 |
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PMID:27821454 |
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Call Number |
ref @ user @ |
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100161 |
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Author |
de Morais Sato, P.; Unsain, R.F.; Gittelsohn, J.; Sanches Tavares da Silva, J.G.; Goncalves Perez, I.C.; Baeza Scagliusi, F. |
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Title |
Strategies used by overweight and obese low-income mothers to feed their families in urban Brazil |
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Journal Article |
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Year |
2017 |
Publication |
Appetite |
Abbreviated Journal |
Appetite |
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Volume |
111 |
Issue |
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Pages |
63-70 |
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Keywords |
Brazil; Food insecurity; Low-income; Obesity; Overweight; Women |
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Abstract |
OBJECTIVE: To describe and compare strategies adopted by overweight and obese low-income mothers living in different vulnerable contexts to deal with food constraints and feed their families. DESIGN: Qualitative in-depth interviews. Data were analyzed with exploratory content analysis and the number of segments per theme was used to compare neighborhoods. SETTING: Three low-income neighborhoods in Santos, Brazil. PARTICIPANTS: A purposive sample of 21 overweight or obese mothers. RESULTS: We identified three main types of strategies, namely, food acquisition, cooking, and eating. Food acquisition included social support and food-sourcing strategies. Social support strategies ranged from macro (governmental programs) to micro (family) levels. Food-sourcing strategies involved price research and use of credit to buy foods. Cooking approaches included optimizing food (e.g., adding water to beans), avoiding wastefulness, and substitutions (e.g., using water instead of milk when making cakes). Eating themes ranged from lack of quantity to lack of quality. Strategies to deal with the lack of food were affected by family dynamics, such as prioritizing provision of fruits to children. Food choices (e.g., low consumption of fruits and high consumption of fatty meats) derived from strategies may help promote overweight and obesity. Furthermore, for participants, financial constraints were perceived as barriers to following nutritionists' recommendations and weight loss. CONCLUSIONS: This study highlights the barriers that low-income women face in adopting a healthy diet and sheds light on the importance of the symbolic value of food, even in the context of food insecurity. Finally, it suggests that environmental aspects could increase the accessibility to fruits and vegetables. These findings could be used to inform the planning and implementation of interventions. |
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Department of Nutrition, School of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715 – Sao Paulo/SP – CEP 01255-000, Sao Paulo/SP, Brazil |
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0195-6663 |
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PMID:28034737 |
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Call Number |
ref @ user @ |
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97449 |
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Author |
de Morais Sato, P.; Unsain, R.F.; Gittelsohn, J.; Sanches Tavares da Silva, J.G.; Goncalves Perez, I.C.; Baeza Scagliusi, F. |
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Title |
Strategies used by overweight and obese low-income mothers to feed their families in urban Brazil |
Type |
Journal Article |
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Year |
2017 |
Publication |
Appetite |
Abbreviated Journal |
Appetite |
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Volume |
111 |
Issue |
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Pages |
63-70 |
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Keywords |
Brazil; Food insecurity; Low-income; Obesity; Overweight; Women |
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Abstract |
OBJECTIVE: To describe and compare strategies adopted by overweight and obese low-income mothers living in different vulnerable contexts to deal with food constraints and feed their families. DESIGN: Qualitative in-depth interviews. Data were analyzed with exploratory content analysis and the number of segments per theme was used to compare neighborhoods. SETTING: Three low-income neighborhoods in Santos, Brazil. PARTICIPANTS: A purposive sample of 21 overweight or obese mothers. RESULTS: We identified three main types of strategies, namely, food acquisition, cooking, and eating. Food acquisition included social support and food-sourcing strategies. Social support strategies ranged from macro (governmental programs) to micro (family) levels. Food-sourcing strategies involved price research and use of credit to buy foods. Cooking approaches included optimizing food (e.g., adding water to beans), avoiding wastefulness, and substitutions (e.g., using water instead of milk when making cakes). Eating themes ranged from lack of quantity to lack of quality. Strategies to deal with the lack of food were affected by family dynamics, such as prioritizing provision of fruits to children. Food choices (e.g., low consumption of fruits and high consumption of fatty meats) derived from strategies may help promote overweight and obesity. Furthermore, for participants, financial constraints were perceived as barriers to following nutritionists' recommendations and weight loss. CONCLUSIONS: This study highlights the barriers that low-income women face in adopting a healthy diet and sheds light on the importance of the symbolic value of food, even in the context of food insecurity. Finally, it suggests that environmental aspects could increase the accessibility to fruits and vegetables. These findings could be used to inform the planning and implementation of interventions. |
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Department of Nutrition, School of Public Health, University of Sao Paulo, Av. Dr. Arnaldo, 715 – Sao Paulo/SP – CEP 01255-000, Sao Paulo/SP, Brazil |
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0195-6663 |
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PMID:28034737 |
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no |
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Call Number |
ref @ user @ |
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98033 |
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Author |
Hira, V.V.V.; Verbovsek, U.; Breznik, B.; Srdic, M.; Novinec, M.; Kakar, H.; Wormer, J.; der Swaan, B.V.; Lenarcic, B.; Juliano, L.; Mehta, S.; Van Noorden, C.J.F.; Lah, T.T. |
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Title |
Cathepsin K cleavage of SDF-1alpha inhibits its chemotactic activity towards glioblastoma stem-like cells |
Type |
Journal Article |
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Year |
2017 |
Publication |
Biochimica et Biophysica Acta |
Abbreviated Journal |
Biochim Biophys Acta |
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Volume |
1864 |
Issue |
3 |
Pages |
594-603 |
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Keywords |
Amino Acid Sequence; Cathepsin K/genetics/*metabolism; Cell Line, Tumor; Chemokine CXCL12/chemistry/genetics/*metabolism; Chemotaxis; Gene Expression; Heterocyclic Compounds/pharmacology; Humans; Neoplastic Stem Cells/*metabolism/pathology; Neuroglia/*metabolism/pathology; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Proteolysis; Receptors, CXCR/genetics/metabolism; Receptors, CXCR4/antagonists & inhibitors/genetics/*metabolism; Stem Cell Niche/genetics; *Cathepsin K; *Glioma stem-like cells; *Niche; *Stromal-derived factor-1alpha |
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Abstract |
Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1alpha (SDF-1alpha), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1alpha is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches. Furthermore, we aimed to prove that SDF-1alpha cleavage by CatK inactivates SDF-1alpha and inhibits the invasion of GSLCs. We performed mass spectrometric analysis of cleavage products of SDF-1alpha after proteolysis by CatK. We demonstrated that CatK cleaves SDF-1alpha at 3 sites in the N-terminus, which is the region of SDF-1alpha that binds to its receptors. Confocal imaging of human GBM tissue sections confirmed co-localization of SDF-1alpha and CatK in GSLC niches. In accordance, 2D and 3D invasion experiments using CXCR4/CXCR7-expressing GSLCs and GBM cells showed that SDF-1alpha had chemotactic activity whereas CatK cleavage products of SDF-1alpha did not. Besides, CXCR4 inhibitor plerixafor inhibited invasion of CXCR4/CXCR7-expressing GSLCs. In conclusion, CatK can cleave and inactivate SDF-1alpha. This implies that CatK activity facilitates migration of GSLCs out of niches. We propose that activation of CatK may be a promising strategy to prevent homing of GSLCs in niches and thus render these cells sensitive to chemotherapy and radiation. |
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Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Vecna pot 111, 1000 Ljubljana, Slovenia; Jozef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia; Department of Biochemistry, Faculty of Chemistry and Chemical Engineering, University of Ljubljana, Vecna pot 113, 1000 Ljubljana, Slovenia |
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0006-3002 |
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PMID:28040478 |
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no |
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Call Number |
ref @ user @ |
Serial |
96615 |
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Author |
Heffernan, J.M.; McNamara, J.B.; Borwege, S.; Vernon, B.L.; Sanai, N.; Mehta, S.; Sirianni, R.W. |
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Title |
PNIPAAm-co-Jeffamine(R) (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells |
Type |
Journal Article |
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Year |
2017 |
Publication |
Biomaterials |
Abbreviated Journal |
Biomaterials |
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Volume |
143 |
Issue |
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Pages |
149-158 |
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Keywords |
Brain tumor initiating cells; Cancer stem cells; Radioresistance; Temperature responsive polymer scaffolds; Tissue engineering |
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Abstract |
Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population. In this work, we engineered 3D scaffolds from temperature responsive poly(N-isopropylacrylamide-co-Jeffamine M-1000(R) acrylamide), or PNJ copolymers, as a platform for enriching stem-specific phenotypes in two molecularly distinct human patient-derived GSC cell lines. Notably, we observed that, compared to conventional neurosphere cultures, PNJ cultured GSCs maintained multipotency and exhibited enhanced self-renewal capacity. Concurrent increases in expression of proteins known to regulate self-renewal, invasion, and stem maintenance in GSCs (NESTIN, EGFR, CD44) suggest that PNJ scaffolds effectively enrich the GSC population. We further observed that PNJ cultured GSCs exhibited increased resistance to radiation treatment compared to GSCs cultured in standard neurosphere conditions. GSC radioresistance is supported in vivo by niche microenvironments, and this remains a significant barrier to effectively treating these highly tumorigenic cells. Taken in sum, these data indicate that the microenvironment created by synthetic PNJ scaffolds models niche enrichment of GSCs in patient-derived GBM cell lines, and presents tissue engineering opportunities for studying clinically important behaviors such as radioresistance in vitro. |
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Address |
Barrow Brain Tumor Research Center, Barrow Neurological Institute, 350 W Thomas Ave, Phoenix, AZ, 85013, USA; School of Biological and Health Systems Engineering, Arizona State University, PO Box 879709, Tempe, AZ, 85287, USA. Electronic address: rachael.sirianni@dignityhealth.org |
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0142-9612 |
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Notes |
PMID:28802102 |
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Call Number |
ref @ user @ |
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96570 |
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