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.

非技术性：数以百万计的美国人遭受肾结石和相关疾病的困扰。目前尚不清楚参与肾结石的形成，组成和生长的科学。因此，没有发达的治疗方法，以及如何防止其形成和成长。目前使用不同抑制剂预防这种疾病的治疗方法表明，在经常出现相似症状的患者中，结果不一致。草酸钙（CAOX）晶体是肾结石的主要成分。这些晶体从原子量表开始经历成核和生长，并发展为毫米或厘米尺度。大多数可用的治疗方法旨在解决可以通过标准成像技术检测到的晶体的存在。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。拟议的研究旨在了解晶体成核和生长的科学，目的是了解纳米级这些晶体的化学和物理变化。了解CAOX的纳米级结晶以及形成不同晶体结构的机制可以提供线索，为什么某些药物仅治疗一些肾结石患者。拟议的高级微观研究可以提供对肾结石形成和生长的见解，如果这项研究成功，这些研究的科学反过来又可以开发新颖的预防和治疗方案。此外，在其他科学中，这些材料研究将是无价的，这些科学对晶体形成和生长至关重要，例如聚合物，药品，食品，地球科学和电子光学材料。通过这项研究的过程，将特别关注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，该项目的研究结果将纳入相关的本科和研究生班，以进一步刺激新一代学生，并具有从事这一领域的基本知识。为了提高公众意识，PIS计划通过社交媒体，新闻报道和新闻发布来传播该项目的新结果。技术：该项目的目的是更好地了解Ocium Ocium Ocium calcium calcium ociim ociim callation机制（CAOX）矿物质的基本科学，这些矿物是负责肾脏石头疾病的矿物质。在美国，这种疾病影响了大约2000万人。目前的治疗表明，这些患者的结果不一致，表明必须在这些晶体如何形成以及如何防止这种矿物质的生长上获得更多的基本理解。使用液体电子显微镜和亚纳光尺度分辨率，该程序将研究液体溶液中草酸钙晶体的形成。这项研究的一个独特优势是能够使用具有成像和光谱仪对单个原子敏感的最先进的矫正电子显微镜来监测局部化学和结构演变。预计拟议的研究将对不同环境条件下钙晶体的生长动力学产生新的了解。这些研究的科学广泛影响可以使人们对聚合物，药品，食品，地球科学和电光材料的晶体形成和生长的进一步了解。关于该奖项的外展活动的更广泛的影响是，在本科和研究生水平的学生中包括在改善生活质量方面的最先进的显微镜技术方面的培训和教育。作为计划的外展活动的一部分，将包括少数群体和代表性不足的学生，以进行实验室活动的科学访问和动手经验。这项研究的发现将纳入为高级本科生和研究生开发的生物工程研究生课程。 PIS致力于通过伊利诺伊大学芝加哥大学良好的外展计划招募女/少数族裔学生接受本科教育。

项目成果

Nanocomposite materials in orthopedic applications

• DOI: 10.1007/s11705-018-1764-1
• 发表时间: 2019-03-01
• 期刊: FRONTIERS OF CHEMICAL SCIENCE AND ENGINEERING
• 影响因子: 4.5
• 作者: Shirdar, Mostafa R.;Farajpour, Nasim;Shokuhfar, Tolou
• 通讯作者: Shokuhfar, Tolou

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

In-Situ TEM Studies on Nanoparticle Interactions with Bacterial Cells

纳米颗粒与细菌细胞相互作用的原位 TEM 研究

• DOI: 10.1017/s1431927622004676
• 发表时间: 2022
• 期刊: Microscopy and Microanalysis
• 影响因子: 2.8
• 作者: Phakatkar, Abhijit H.;Ghildiyal, Pankaj;Wang, Yujie;Zachariah, Michael R.;Shokuhfar, Tolou;Shahbazian-Yassar, Reza
• 通讯作者: Shahbazian-Yassar, Reza