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  1. AU="David, Nathaniel E"
  2. AU=Rammes G
  3. AU="Esbenshade, Tim"
  4. AU="Yu, S-J"
  5. AU="de Oliveira, Arao Belitardo"
  6. AU="H Charles Manning"
  7. AU=Raman Siva P
  8. AU="Gederaas, Odrun A"
  9. AU="Cho, Won-Ki"
  10. AU="Juranic Lisnic, Vanda"
  11. AU="Junzhou Wu"
  12. AU="Kevin M Haigis"
  13. AU="Brühl, Marius"
  14. AU="Hawash, Mohammed"
  15. AU="Kalra, Sarathi"
  16. AU=Schwab Frank
  17. AU="Tzung-Chi Huang"
  18. AU="Nisa, Maherun"
  19. AU="Resnick, Adam C"
  20. AU="Thomas, Brodie"
  21. AU="Yaming Wang"
  22. AU="Lee, Chun‐Tsu"
  23. AU="Albert Gargallo‐Garriga"
  24. AU="Serwin, Natalia Maria"
  25. AU="La Rosa, Stefano"
  26. AU="Yin-Yin Xie"
  27. AU=White David P
  28. AU="Maria Teresa Viadero"
  29. AU="Wingeter, Márcia A"
  30. AU="Stein, Joshua D"
  31. AU="De Vecchis, Liana"
  32. AU="Chapman, Janet"
  33. AU="Umlai, Umm-Kulthum Ismail"
  34. AU="Reddi, Jyoti M"
  35. AU=Zeissig Sebastian
  36. AU="Valentini, Mariaconsuelo"

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  1. Artikel ; Online: Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results.

    Crespo-Garcia, Sergio / Fournier, Frédérik / Diaz-Marin, Roberto / Klier, Sharon / Ragusa, Derek / Masaki, Lauren / Cagnone, Gael / Blot, Guillaume / Hafiane, Ikhlas / Dejda, Agnieszka / Rizk, Rana / Juneau, Rachel / Buscarlet, Manuel / Chorfi, Sarah / Patel, Priyanka / Beltran, Pedro J / Joyal, Jean-Sebastien / Rezende, Flavio A / Hata, Masayuki /
    Nguyen, Alex / Sullivan, Lynne / Damiano, Jason / Wilson, Ariel M / Mallette, Frédérick A / David, Nathaniel E / Ghosh, Anirvan / Tsuruda, Pamela R / Dananberg, Jamie / Sapieha, Przemyslaw

    Nature medicine

    2024  Band 30, Heft 2, Seite(n) 443–454

    Abstract: Compromised vascular endothelial barrier function is a salient feature of diabetic complications such as sight-threatening diabetic macular edema (DME). Current standards of care for DME manage aspects of the disease, but require frequent intravitreal ... ...

    Abstract Compromised vascular endothelial barrier function is a salient feature of diabetic complications such as sight-threatening diabetic macular edema (DME). Current standards of care for DME manage aspects of the disease, but require frequent intravitreal administration and are poorly effective in large subsets of patients. Here we provide evidence that an elevated burden of senescent cells in the retina triggers cardinal features of DME pathology and conduct an initial test of senolytic therapy in patients with DME. In cell culture models, sustained hyperglycemia provoked cellular senescence in subsets of vascular endothelial cells displaying perturbed transendothelial junctions associated with poor barrier function and leading to micro-inflammation. Pharmacological elimination of senescent cells in a mouse model of DME reduces diabetes-induced retinal vascular leakage and preserves retinal function. We then conducted a phase 1 single ascending dose safety study of UBX1325 (foselutoclax), a senolytic small-molecule inhibitor of BCL-xL, in patients with advanced DME for whom anti-vascular endothelial growth factor therapy was no longer considered beneficial. The primary objective of assessment of safety and tolerability of UBX1325 was achieved. Collectively, our data suggest that therapeutic targeting of senescent cells in the diabetic retina with a BCL-xL inhibitor may provide a long-lasting, disease-modifying intervention for DME. This hypothesis will need to be verified in larger clinical trials. ClinicalTrials.gov identifier: NCT04537884 .
    Mesh-Begriff(e) Animals ; Mice ; Humans ; Macular Edema/drug therapy ; Macular Edema/etiology ; Diabetic Retinopathy/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Endothelial Cells ; Senotherapeutics ; Cellular Senescence ; Diabetes Mellitus
    Chemische Substanzen Angiogenesis Inhibitors ; Senotherapeutics
    Sprache Englisch
    Erscheinungsdatum 2024-02-06
    Erscheinungsland United States
    Dokumenttyp Clinical Trial, Phase I ; Journal Article
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-024-02802-4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Carbon black functionalized with hyperbranched polymers: synthesis, characterization, and application in reversible CO2 capture

    He, Hongkun / David, Nathaniel E / Konkolewicz, Dominik / Matyjaszewski, Krzysztof / Rappold, Timothy / Sugar, Glenn / Yacatto, Karin / Zhong, Mingjiang

    Journal of materials chemistry A. 2013 May 21, v. 1, no. 23

    2013  

    Abstract: The functionalization of carbon black by grafting of hyperbranched polymers from the surface via self-condensing atom transfer radical polymerization (SC-ATRP) is reported. The surfaces of the pristine carbon black were modified with ATRP initiators ... ...

    Abstract The functionalization of carbon black by grafting of hyperbranched polymers from the surface via self-condensing atom transfer radical polymerization (SC-ATRP) is reported. The surfaces of the pristine carbon black were modified with ATRP initiators using two different methods. The first method uses acid oxidation to place COOH groups on the carbon black surface, followed by the esterification to give ATRP initiators bound to the carbon black surface. Alternatively, ATRP initiators bearing both azido and bromine groups were placed directly on the carbon black surface by nitrene chemistry. The hyperbranched poly(p-chloromethylstyrene) (PCMS) was grafted from the ATRP initiator modified carbon black surfaces using the inimer of p-chloromethylstyrene, and CuCl/CuCl2/N,N,N′,N′′,N′′-pentamethyldiethylenetriamine (PMDETA) as the catalytic system in N,N-dimethylformamide (DMF). In addition, a one-pot two-step method was developed to graft crosslinked polymers from the carbon black surfaces. The polymerization process was well controlled and the fraction of the grafted polymers on carbon black could be adjusted by changing the polymerization time. The resulting samples were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The hyperbranched polymers on the carbon black surfaces were quaternized to give an ammonium group on the polymer, and a chloride counterion was subsequently exchanged to give a hydroxide counterion. Under these basic conditions, the ATRP initiators should be attached to the surface using nitrene chemistry rather than acid oxidation, to avoid the hydrolysis of the ester groups that link the grafted polymers to the carbon black surface. The ammonium hydroxide functionalized carbon black materials were utilized for the reversible absorption and desorption of CO2 from ambient air, providing improved absorption/desorption kinetics compared with the commercially available Excellion membrane.
    Schlagwörter absorption ; air ; ammonium ; ammonium hydroxide ; bromine ; carbon dioxide ; catalytic activity ; chlorides ; crosslinking ; desorption ; dimethylformamide ; esterification ; hydrolysis ; oxidation ; polymerization ; polymers ; scanning electron microscopy ; soot ; thermogravimetry ; transmission electron microscopy
    Sprache Englisch
    Erscheinungsverlauf 2013-0521
    Umfang p. 6810-6821.
    Erscheinungsort The Royal Society of Chemistry
    Dokumenttyp Artikel
    ZDB-ID 2702232-8
    ISSN 2050-7496 ; 2050-7488
    ISSN (online) 2050-7496
    ISSN 2050-7488
    DOI 10.1039/c3ta10699c
    Datenquelle NAL Katalog (AGRICOLA)

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  3. Artikel ; Online: Tissue-selective effects of injected deoxycholate.

    Thuangtong, Rattapon / Bentow, Jason J / Knopp, Kristeene / Mahmood, Nadir A / David, Nathaniel E / Kolodney, Michael S

    Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.

    2010  Band 36, Heft 6, Seite(n) 899–908

    Abstract: Background: Recent studies suggest that the principal active ingredient in phosphatidylcholine-containing injectable fat-reduction formulations is actually deoxycholate (DC). This bile acid acts as a detergent to rapidly disrupt cell membranes. Thus, it ...

    Abstract Background: Recent studies suggest that the principal active ingredient in phosphatidylcholine-containing injectable fat-reduction formulations is actually deoxycholate (DC). This bile acid acts as a detergent to rapidly disrupt cell membranes. Thus, it is not obvious why DC would preferentially target fat.
    Objective: To investigate possible mechanisms for the selectivity of DC for fat tissue using in vivo and in vitro models.
    Methods and materials: Histology, drug distribution studies, and cell viability assays were used to examine possible mechanisms contributing to DC selectivity.
    Results: In vitro, DC caused the lysis of all cell types tested within the tested concentration range. DC injected into fat tissue caused adipocyte death, whereas other cell types appeared less affected. Physiological concentrations of albumin or protein-rich tissues decrease the ability of DC to lyse cells. Furthermore, DC relocated to the gastrointestinal tract in animals within hours of injection. This suggests that similar mechanisms may be present in humans.
    Conclusion: We report observations that provide a possible explanation for the in vivo preferential fat targeting by DC. Fat tissue, being deficient in cell-associated proteins and interstitial albumin, may be unable to sufficiently neutralize the detergent activity of DC, possibly making fat uniquely sensitive to DC.
    Mesh-Begriff(e) Adipocytes/drug effects ; Animals ; Cell Culture Techniques ; Cholagogues and Choleretics/administration & dosage ; Cholagogues and Choleretics/pharmacology ; Deoxycholic Acid/administration & dosage ; Deoxycholic Acid/pharmacology ; Fibroblasts/drug effects ; Humans ; Injections, Subcutaneous ; Keratinocytes/drug effects ; Mice ; Mice, Obese ; Models, Animal ; Muscle Cells/drug effects ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Skin/drug effects ; Skin/metabolism ; Skin/pathology ; Subcutaneous Fat/drug effects ; Subcutaneous Fat/metabolism ; Subcutaneous Fat/pathology
    Chemische Substanzen Cholagogues and Choleretics ; Deoxycholic Acid (005990WHZZ)
    Sprache Englisch
    Erscheinungsdatum 2010-06
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1227586-4
    ISSN 1524-4725 ; 1076-0512
    ISSN (online) 1524-4725
    ISSN 1076-0512
    DOI 10.1111/j.1524-4725.2010.01566.x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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