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Characterization of the interaction of nanobubble ultrasound contrast agents with human blood components

生物活性材料(英文) 2023年第1期19卷 642-652页

作者： michaela b.cooley Eric C.Abenojar Dana Wegierak Anirban Sen Gupta Michael C.Kolios Agata A.Exner Department of biomedical Engineering Case Western Reserve UniversityClevelandOH44106United States Department of Radiology Case Western Reserve UniversityClevelandOH44106United States Department of Physics Ryerson UniversityTorontoOntarioM5B 2K3Canada Institute for biomedical Engineering and Science Technology A Partnership Between Ryerson University and St.Michael’s HospitalTorontoOntarioM5B 1T8Canada

Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in *** sub-micron particles are approximately 10x smaller than clinically available *** allows them to effectively traverse compromised physiological barriers and circulate for extended periods of *** various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been ***,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic *** observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PbS),plasma,or red blood cell solutions(RbCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 *** contrast,nanobubbles in PbS had a stable signal with negligible change in intensity(􀀀1.7±3.2%)over 8 *** the same conditions,microbubbles made with the same lipid formulation showed a􀀀56.8±6.1%decrease in enhancement in whole *** confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RbCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RbCs in the presence of plasma may be a possible mechanism for the observed *** phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RbC interaction with nanoparticles could be exploited to improve delivery efficiency.

关键词： Nanobubbles Ultrasound contrast agents Red blood cells Hitchhiking Ultrasound Drug delivery

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Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral

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International Journal of Oral Science 2023年第4期15卷 676-690页

作者： Hyun-Yi Kim Victoria cooley Eun-Jung Kim Shujin Li Jong-Min Lee Dina Sheyfer Wenjun Liu Ophir D.Klein Derk Joester Han-Sung Jung NGeneS Inc. Ansan-siGyeonggi-doKorea Department of Materials Science and Engineering Northwestern UniversityEvanstonILUSA X-ray Science Division Advanced Photon SourceArgonne National LaboratoryLemontILUSA Division in Anatomy and Developmental biology Department of Oral BiologyOral Science Research CenterBK21 FOUR ProjectYonsei University College of DentistrySeoulKorea Department of Orofacial Sciences and Program in Craniofacial biology University of CaliforniaSan FranciscoCAUSA Department of Pediatrics Cedars-Sinai Guerin Children’sLos AngelesCAUSA

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel,a hierarchically structured tissue comprised of highly elongated hydroxylapatite(OHAp)*** unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet,partly due to limitations with in vitro experimental ***,we demonstrate the ability to generate mineralizing dental epithelial organoids(DEOs)from adult dental epithelial stem cells(aDESCs)isolated from mouse incisor *** expressed ameloblast markers,could be maintained for more than five months(11 passages)in vitro in media containing modulators of Wnt,Egf,bmp,Fgf and Notch signaling pathways,and were amenable to *** transplanted underneath murine kidney capsules,organoids produced OHAp crystallites similar in composition,size,and shape to mineralized dental tissues,including some enamel-like elongated *** are thus a powerful in vitro model to study mineralization process by dental epithelium,which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.

关键词： epithelium maintained specialized

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Turner综合征大血管异常的发生率及磁共振血管造影特征

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世界核心医学期刊文摘（心脏病学分册） 2005年第3期1卷 28-29页

作者： Ho V.b. bakalov V.K. cooley M. 王永兴 Dept. of Radiol./Radiological Sci. Uniformed Serv. Univ. Hlth. Sciences 4301 Jones Bridge Rd Bethesda MD 20814 United States Dr.

background-Turner syndrome(TS) is associated with aortic coarctation and dissection; hence, echocardiographic evaluation of all patients is currently recommended. X-ray angiography in clinically symptomatic patients has suggested a range of other vascular anomalies, but the true prevalence of such lesions in TS is unknown. To better understand the prevalence and pathogenesis of cardiovascular defects in TS, we prospectively evaluated a group of asymptomatic adult volunteers with TS using magnetic resonance(MR) angiography. Methods and Results-A total of 85 adults with TS and 27 normal female adult volunteers underwent gadolinium-enhanced 3D MR angiography. A high prevalence of aortic anomalies was seen in women with TS, including elongation of the transverse arch(49%), aortic coarctation(12%), and aberrant right subclavian artery(8%). Venous anomalies were also prominent, including persistent left superior vena cava (13%) and partial anomalous pulmonary venous return(13%). None of these anomalies were found in healthy female controls. The constellation of elongation of the transverse arch, aortic coarctation, and persistent left superior vena cava was significantly associated with women with TS. Neck webbing and increased thoracic anterior-to-posterior dimension diameters were strong predictors for arterial and venous anomalies. Conclusions-Thoracic vascular anomalies are common in TS, occurring in ≈50%of a group not preselected for cardiovascular disease. The highly significant association between neck webbing, increased chest diameter, and these vascular anomalies suggests that in utero, centrally localized lymphatic obstruction may contribute to these cardiovascular deformities in TS. Improved recognition of these often-undetected vascular lesions may be important for identification of patients in need of closer cardiovascular monitoring.

关键词： Turner综合征磁共振血管造影主动脉弓延长锁骨下动脉超声心动图心血管病变左上腔静脉血管造影检查静脉畸形无症状

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Delivering an mRNA vaccine using a lymphatic drug delivery device improves humoral and cellular immunity against SARS-CoV-2

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Journal of Molecular Cell biology 2022年第6期14卷 47-56页

作者： Runqiang Chen Hui Xie Sahba Khorsandzadeh Madison Smith Namir Shaabani Qidong Hu Xiaoxuan Lyu Hua Wang Wan-lin Lim Haotian Sun Henry Ji brian cooley Russell Ross David M.Francis Sorrento Therapeutics Inc.San DiegoCA 92121USA Sofusa a Division of Sorrento TherapeuticsAtlantaGA 30350USA

The exploration and identification of safe and effective vaccines for the SARS-CoV-2 pandemic have captured the world's attention and remains an ongoing issue due to concerns of balancing protection against emerging variants of concern while also generating long-lasting immunity. Here, we report the synthesis of a novel messenger ribonucleic acid encoding the spike protein in a lipid nanoparticle formulation (STI-7264) that generates robust humoral and cellular immunity following immunization of C57bl6 mice. In an effort to improve immunity, a clinically focused lymphatic drug delivery device (MuVaxx) was engineered to modulate immune cells at the injection site (epidermis and dermis) and draining lymph node (LN) and tested to measure adaptive immunity. Using MuVaxx, immune responses were elicited and maintained at a 10-fold dose reduction compared to traditional intramuscular (IM) administration as measured by anti-spike antibodies, cytokine-producing CD8 T cells, neutralizing antibodies against the Washington (wild type) strain and South African (beta) variants, and LN-resident spike-specific memory b cells. Remarkably, a 4-fold-elevated T cell response was observed in MuVaxx-administered vaccination compared to that of IM-administered vaccination. Thus, these data support further investigation into STI-7264 and lymphatic-mediated delivery using MuVaxx for SARS-CoV-2 and VoC vaccines.

关键词： COVID-19 lymph nodes lymphatics vaccines drug delivery

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KIR b单倍型无关供者造血干细胞移植可提高急性髓细胞白血病患者的无复发存活率

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中华移植杂志（电子版） 2009年第3期3卷 149-149页

作者： cooley S Trachtenberg E bergemann TL 曹玲来晓瑜

急性髓细胞白血病(AML)患者接受无关供者造血干细胞移植(HSCT)后的存活率与移植相关死亡率和复发率密切相关.由供者杀伤细胞免疫球蛋白样受体(killer- cell immunoglobulin- like receptor,KIR)和受者HLA共同介导的自然杀伤细胞同种异... 详细信息

急性髓细胞白血病(AML)患者接受无关供者造血干细胞移植(HSCT)后的存活率与移植相关死亡率和复发率密切相关.由供者杀伤细胞免疫球蛋白样受体(killer- cell immunoglobulin- like receptor,KIR)和受者HLA共同介导的自然杀伤细胞同种异基因反应性可改善受者存活率、促进植入、减少移植物抗宿主病的发生和降低复发率,关系着AML患者的HSCT能否成功.

关键词：急性髓细胞白血病造血干细胞移植受者存活率无关供者复发率白血病患者杀伤细胞免疫球蛋白样受体单倍型

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