Fundamental Understanding of Growth and Inhibition of Calcium Oxalate Kidney Stones

对草酸钙肾结石生长和抑制的基本了解

• 批准号: 1710049
• 负责人: Reza Shahbazian- Yassar
• 金额: $ 39万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710049&HistoricalAwards=false
• 关键词: Fundamental; Understanding; Growth; Inhibition; Calcium

Non-Technical:Millions of Americans are afflicted by kidney stones and related diseases. Currently the sciences involved in the formation, composition and growth of kidney stones are not known. Hence, there are no well developed treatments, and how to prevent their formation and growth. Current treatments for the prevention of this disease using different inhibitors show inconsistent results among patients who often have similar symptoms. Calcium oxalate (CaOx) crystals are the main constituents of kidney stones. These crystals undergo nucleation and growth starting from atomic scale, and progresses to millimeter or centimeter scales. Most of the available therapeutic treatments are designed to address the presence of crystals that may be detected through standard imaging techniques. At this stage of the crystal growth, these crystals become very stable and are difficult to breakdown or dissolve. The proposed research aims to understand the sciences involved in the nucleation and growth of crystals with the goal to understand the chemical and physical changes to these crystals at nanoscales. Understanding the nanoscale crystallization of CaOx, and the mechanisms through which different crystal structures are formed could provide clues why some medications are effective in treating only some kidney stone patients. The proposed advanced microscopic studies could provide insight into kidney stone formation and growth, and sciences from these studies could in turn develop novel prevention and treatment protocols, if this research is successful. Additionally, these materials research studies would be invaluable in other sciences for which crystal formation and growth are critical, such as polymers, pharmaceuticals, food products, geosciences and electro optic materials. Through the course of this research, particular attention will be given in recruiting and mentoring female and underrepresented students to work in the principal investigators' research laboratory. In addition, the research findings of this project will be incorporated in relevant undergraduate and graduate classes to further stimulate a new generation of students with the fundamental knowledge to engage in this field. To increase public awareness, the PIs plans to disseminate the new results of this project through social media, press coverage, and news releases.Technical:The goal of this project is to gain a better understanding of the basic sciences in the formation mechanisms of calcium oxalate (CaOx) minerals that are responsible for kidney stone disease. This disease affects approximately 20 million people in the United States. The current treatments show inconsistent results for these patients indicating that more fundamental understanding must be gained on how these crystals formed and how one can prevent the growth of such minerals. Using liquid electron microscopy with subnanometer scale resolution, this program will study the formation of calcium oxalate crystals in liquid solution. A unique advantage of this study is the ability to monitor the local chemical and structural evolutions with the state-of-the art aberration-corrected transmission electron microscopy equipped with imaging and spectrometers sensitive to single atoms. The proposed research is expected to yield a new understanding on the growth kinetics of Calcium crystals under different environmental conditions. The scientific broader impact of these studies could benefit further understanding in crystal formation and growth of polymers, pharmaceuticals, food products, geosciences and electro optic materials. The broader impacts with respect to outreach activities of this award would be the inclusion of students at both undergraduate and graduate level in training and education on the state-of-the art microscopy techniques for health sciences in improving the quality of life. As part of the planned outreach activities, minority and underrepresented students will be included for scientific visits and hands-on experience in the lab activities. The finding of this research will be incorporated in a bioengineering graduate course that has been developed for senior undergraduate and graduate students. The PIs are committed to recruit female/minority students for undergraduate education through well-established outreach programs at the University of Illinois at Chicago.

非技术：数百万美国人患有肾结石和相关疾病。目前，有关肾结石形成、组成和生长的科学尚不清楚。因此，没有很好的治疗方法，以及如何防止它们的形成和生长。目前使用不同抑制剂预防这种疾病的治疗方法在通常具有相似症状的患者中显示出不一致的结果。草酸钙（CaOx）晶体是肾结石的主要成分。这些晶体经历成核和生长，从原子尺度开始，发展到毫米或厘米尺度。大多数可用的治疗方法都是针对可以通过标准成像技术检测到的晶体的存在而设计的。在晶体生长的这个阶段，这些晶体变得非常稳定，很难分解或溶解。本研究旨在了解与晶体成核和生长有关的科学，以了解这些晶体在纳米尺度上的化学和物理变化。了解CaOx的纳米级结晶，以及不同晶体结构形成的机制，可以为某些药物仅对某些肾结石患者有效提供线索。如果这项研究成功的话，这些先进的显微研究可以为肾结石的形成和生长提供深入的了解，而这些研究的科学反过来可以开发出新的预防和治疗方案。此外，这些材料的研究在其他对晶体形成和生长至关重要的科学领域，如聚合物、制药、食品、地球科学和电光材料，将是无价的。在这项研究的过程中，将特别注意招募和指导女性和代表性不足的学生在主要研究人员的研究实验室工作。此外，该项目的研究成果将被纳入相关的本科和研究生课程，以进一步激发具有基础知识的新一代学生从事该领域的工作。为了提高公众意识，ppi计划通过社交媒体、新闻报道和新闻稿来传播该项目的新成果。技术：该项目的目标是更好地了解导致肾结石疾病的草酸钙（CaOx）矿物质形成机制的基础科学。在美国，这种疾病影响了大约2000万人。目前对这些患者的治疗结果并不一致，这表明必须对这些晶体如何形成以及如何防止这些矿物质的生长有更基本的了解。利用亚纳米级分辨率的液体电子显微镜，本项目将研究液体溶液中草酸钙晶体的形成。本研究的一个独特优势是能够监测局部化学和结构的演变与国家的最先进的像差校正透射电子显微镜配备的成像和光谱敏感的单原子。本研究有望对钙晶体在不同环境条件下的生长动力学有新的认识。这些研究对科学的广泛影响可能有助于进一步了解聚合物、药品、食品、地球科学和电光材料的晶体形成和生长。就该奖项的推广活动而言，其更广泛的影响将是使本科生和研究生都能参加有关用于改善生活质量的卫生科学的最先进显微镜技术的培训和教育。作为计划外展活动的一部分，少数民族和代表性不足的学生将被包括在科学访问和实验室活动的实践经验。这项研究的发现将被纳入为高年级本科生和研究生开发的生物工程研究生课程。私立学院致力于通过伊利诺伊大学芝加哥分校完善的外展项目招收女性/少数族裔学生接受本科教育。

项目成果

In Situ Transmission Electron Microscopy Explores a New Nanoscale Pathway for Direct Gypsum Formation in Aqueous Solution

• DOI: 10.1021/acsanm.8b00739
• 发表时间: 2018-10-01
• 期刊: ACS APPLIED NANO MATERIALS
• 影响因子: 5.9
• 作者: He, Kun;Nie, Anmin;Shahbazian-Yassar, Reza
• 通讯作者: Shahbazian-Yassar, Reza

In situ visualization of the superior nanomechanical flexibility of individual hydroxyapatite nanobelts

单个羟基磷灰石纳米带卓越的纳米机械灵活性的原位可视化

• DOI: 10.1039/c7ce01852e
• 发表时间: 2018
• 期刊: CrystEngComm
• 影响因子: 3.1
• 作者: Qi, Mei-li;Huang, Zhennan;Yao, Wentao;Long, Fei;Cheng, Meng;Song, Boao;Banner, David;Shahbazian-Yassar, Reza;Lu, Yu-peng;Shokuhfar, Tolou
• 通讯作者: Shokuhfar, Tolou

In Situ Graphene Liquid Cell Investigation of Metal Ion Modifiers of Calcium Oxalate

草酸钙金属离子改性剂的原位石墨烯液体电池研究

• DOI: 10.1017/s1431927621002245
• 发表时间: 2021
• 期刊: Microscopy and Microanalysis
• 影响因子: 2.8
• 作者: Sorokina, Lioudmila;Phakatkar, Abhijit;Shahbazian-Yassar, Reza;Shokuhfar, Tolou
• 通讯作者: Shokuhfar, Tolou

Counterions present in syntheses induce the precipitation of two different populations of Sr-containing hydroxyapatite crystals

合成中存在的抗衡离子诱导两种不同的含 Sr 羟基磷灰石晶体的沉淀

• DOI: 10.1016/j.ceramint.2019.10.177
• 发表时间: 2020
• 期刊: Ceramics International
• 影响因子: 5.2
• 作者: Silva, L.M.;Menezes, D.S.;Narayanan, S.;Shokuhfar, T.;Shahbazian-Yassar, R.;Dalmônico, G.M.L.;Werckmann, J.;Farina, M.;dos Santos, E.A.
• 通讯作者: dos Santos, E.A.

TEM Studies on Antibacterial Mechanisms of Black Phosphorous Nanosheets

• DOI: 10.2147/ijn.s237816
• 发表时间: 2020-01-01
• 期刊: INTERNATIONAL JOURNAL OF NANOMEDICINE
• 影响因子: 8
• 作者: Phakatkar, Abhijit H.;Firlar, Emre;Shokuhfar, Tolou
• 通讯作者: Shokuhfar, Tolou