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Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes

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Genes & Diseases 2023年第4期10卷 1641-1656页

作者： Kexin Li Xun Sun Hudie Li Hailan Ma Meng Zhou Kazumasa Minami Keisuke Tamari Kazuhiko Ogawa Pankita HPandya MReza Saadatzadeh Melissa AKacena Karen EPollok Bai-Yan Li hiroki yokota Department of Pharmacology School of PharmacyHarbin Medical UniversityHarbinHeilongjiang 150081China Department of Biomedical Engineering Indiana University Purdue University IndianapolisIndianapolisIN 46202USA Department of Radiation Oncology Osaka University Graduate School of MedicineSuitaOsaka 565-0871Japan Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA Department of Pediatrics Indiana University School of MedicineIndianapolisIN 46202USA Department of Orthopaedic Surgery Indiana University School of MedicineIndianapolisIN 46202USA Indiana Center for Musculoskeletal Health Indiana University School of MedicineIndianapolisIN 46202USA

Cancer cells tend to develop resistance to chemotherapy and enhance aggressive-ness.A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic *** on this strategy,induced tumor-suppressing cells(iTSCs)have been generated from tumor cells and mesenchymal stem ***,we examined the possi-bility of generating iTSCs from lymphocytes by activating PKA signaling for suppressing the pro-gression of osteosarcoma(OS).While lymphocyte-derived CM did not present anti-tumor capabilities,the activation of PKA converted them into *** PKA conversely gener-ated tumor-promotive *** a mouse model,PKA-activated CM suppressed tumorinduced bone *** analysis revealed that moesin(MSN)and calreticulin(Calr),which are highly expressed intracellular proteins in many cancers,were enriched in PKA-activated CM,and they acted as extracellular tumor suppressors through CD44,CD47,and *** study presented a unique option for cancer treatment by generating iTSCs that secret tumor-suppressive proteins such as MSN and *** envision that identifying these tu-mor suppressors and predicting their binding partners such as CD44,which is an FDA-approved oncogenic target to be inhibited,may contribute to developing targeted protein therapy.

关键词： Calreticulin Lymphocytes Moesin Osteosarcoma PKA Proteome

Genomics in Space Life Sciences

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Genomics, Proteomics & Bioinformatics 2008年第1期6卷 1-3页

作者： Jade Q. Clement hiroki yokota Department of Chemistry and NASA University Research Center for Biotechnology and Environmental Health Texas Southern UniversityHouston TX 77004 USA Department of Biomedical Engineering / Department of Anatomy and Cell Biology Indiana University-Purdue University IndianapolisIndianapolis IN 46202 USA

Since the early days of manned spaceflight, hazardous effects of the space environment on living organisms have been disputed. With the continuous manning of the International Space Station, the planned Chinese space station, and renewed interest in returning to the Moon and sending manned flights to Mars, identifying and addressing the potential outcomes of long-term space exposures is critically important.

关键词： gene Genomics in Space Life Sciences

Model-based Comparative Prediction of Transcription-Factor Binding Motifs in Anabolic Responses in Bone

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Genomics, Proteomics & Bioinformatics 2007年第3期5卷 158-165页

作者： Andy B. Chen Kazunori Hamamura Guohua Wang Weirong Xing Subburaman Mohan hiroki yokota Yunlong Liu Departments of Biomedical Engineering/Anatomy and Cell Biology Indiana University-Purdue University Indianapolis Indianapolis IN 45202 USA Division of Biostatistics Department of Medicine Center for Computational Biology and Bioinformatics Indiana University School of Medicine Indianapolis IN 46202 USA School of Computer Science and Technology Harbin Institute of Technology Harbin 150001 China Musculoskeletal Disease Center JP Pettis Memorial Veterans Administration Medical Center Loma Linda CA 92357 USA

Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs （TFBMs） through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins （BMPs） are two known treatments to strengthen bone. We addressed a question： Is there any TFBM that stimulates both ＂anabolic responses of mechanical loading＂ and ＂BMP-mediated osteogenic signaling＂？ Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor （PPAR）. The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.

关键词： microarray transcription-factor binding motif mechanical loading bone morphogenic protein ant algorithm

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机械振动的心血管生物学效应研究综述

西安体育学院学报 2010年第6期27卷 709-715页

作者：马雪田振军 hiroki yokota 陕西师范大学体育学院暨运动生物学研究所西安71006 Departments of Biomedical Engineering Indiana University Purdue University Indianapolis

目前机械振动作为干预手段,在运动员肌肉力量训练、多发性硬化症、帕金森氏综合症、促进骨折愈合、预防骨质疏松等诸领域内得到广泛应用。并且低频振动作为康复治疗手段用于如减肥(作用于脂肪及较厚部位的体表,促使脂肪分解)、消除疲劳... 详细信息

目前机械振动作为干预手段,在运动员肌肉力量训练、多发性硬化症、帕金森氏综合症、促进骨折愈合、预防骨质疏松等诸领域内得到广泛应用。并且低频振动作为康复治疗手段用于如减肥(作用于脂肪及较厚部位的体表,促使脂肪分解)、消除疲劳(作用于足底或足踝部放松全身)、消除肌痉挛(作用于痉挛肌局部,加速清除局部代谢产物)等方面。采用回顾性研究和前瞻性分析相结合的方法就机械振动对心血管系统的影响进行文献梳理与总结,希望这些研究能为振动训练参数的制定提供参考,在提高训练效果的同时避免对运动员造成不必要的伤害。

关键词：机械振动心血管生物学振动训练

Bicuspidization Using the Open-Sleeve Technique for Congenital Aortic Stenosis during Infancy

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Congenital Heart Disease 2024年第2期19卷 177-183页

作者： Toshi Maeda hiroki Ito Keiichi Hirose Kisaburo Sakamoto Departments of Cardiovascular Surgery Mt.Fuji Shizuoka Children’s HospitalShizuoka420-8660Japan

Congenital aortic stenosis(cAS)frequently requires intervention during the neonatal or infantile ***,surgical repair is challenging because of the narrow surgical *** performed bicuspidization using the open-sleeve technique for cAS with a unicuspid aortic valve in two ***,the patients were doing well without reintervention for the aortic valve for 8 and 6 years,*** aortic annular diameter increased along with somatic *** for neonates or infancy can be performed safely using the open-sleeve technique as its midterm results have been satisfactory.

关键词： Aortic valve repair infant bicuspidization open-sleeve technique

Development of an Artificial Finger-Like Knee Loading Device to Promote Bone Health

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Journal of Biomedical Science and Engineering 2017年第11期10卷 550-561页

作者： Sandeep Korupolu Stanley Chien hiroki yokota Sohel Anwar Department of Mechanical Engineering Indiana University Purdue University Indianapolis (IUPUI) Indianapolis IN USA Department of Electrical and Computer Engineering Indiana University Purdue University Indianapolis (IUPUI) Indianapolis IN USA Department of Biomedical Engineering Indiana University Purdue University Indianapolis (IUPUI) Indianapolis IN USA

This study presents the development of an innovative artificial finger-like device that provides position specific mechanical loads at the end of the long bone and induces mechanotransduction in bone. Bone cells such as osteoblasts are the mechanosensitive cells that regulate bone remodelling. When they receive gentle, periodic mechanical loads, new bone formation is promoted. The proposed device is an under-actuated multi-fingered artificial hand with 4 fingers, each having two phalanges. These fingers are connected by mechanical linkages and operated by a worm gearing mechanism. With the help of 3D printing technology, a prototype device was built mostly using plastic materials. The experimental validation results show that the device is capable of generating necessary forces at the desired frequencies, which are suitable for the stimulation of bone cells and the promotion of bone formation. It is recommended that the device be tested in a clinical study for confirming its safety and efficacy with patients.

关键词： Osteoblasts Mechanical Loading Artificial Hand Bone Growth

Improved Protein Transfer Efficiency and Signal Intensity in BlotMan Using Pulse Width Modulation

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Journal of Biomedical Science and Engineering 2016年第5期9卷 269-279页

作者： Thuc Nhi Truongvo Feixue Zheng Stanley Chien hiroki yokota Department of Biomedical Engineering Indiana University Purdue University Indianapolis Indianapolis IN USA YC Bioelectric LLC Indianapolis IN USA Department of Electrical and Computer Engineering Indiana University Purdue University Indianapolis Indianapolis IN USA

BlotMan is a protein blotting device that allows generating multiple membranes from a single polyacrylamide gel. To transfer all proteins uniformly with the same efficiency regardless of protein size, BlotMan employs pulse-width-modulated (PWM) voltage that applies a higher average voltage to a larger protein species. BlotMan can be controlled not only by its custom-made interface but also by a smart phone via Bluetooth technology. In this study, we examined effects of PWM signals (50%, 60%, and 80% duty cycle) on transfer efficiency and signal intensity in comparison to a constant voltage signal (100% duty cycle). The result revealed that in response to the same average voltage of 150 V, a lower duty cycle with a higher maximum voltage increased transfer efficiency as well as sharpness of transferred proteins. We validated BlotMan’s capability using a chondrosarcoma cell line (SW1353 cells) and a breast cancer cell line (MDA-MB231 cells) in response to antitumor chemical agents. BlotMan successfully generated 5 membranes from a single gel and detected 5 protein species such as c-Src, eukaryotic translation initiation factor 2 alpha (eIF2), phosphorylated eIF2, lamin B, and actin. Collectively, we demonstrated herein that BlotMan reduces an amount of protein samples by generating multiple membranes from a single gel and improving signal intensity with PWM voltage signals.

关键词： Pulse Width Modulation (PWM) Western Blotting Protein Transfer

Voltage profile generation for simultaneous multi-protein detection in western blot analysis

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Journal of Biomedical Science and Engineering 2012年第9期5卷 542-547页

作者： Matthew Blair Mina Wanis Gaurav Swarnkar hiroki yokota Stanley Chien Department of Biomedical Engineering Indiana University-Purdue University Indianapolis Indianapolis USA Department of Electrical and Computer Engineering Indiana University-Purdue University Indianapolis Indianapolis USA

Western blotting is a popular technique for examining expression levels of proteins using gel-based electrophoretic fractionation followed by blotting and antibody reactions. Although this is a mature technique, one of the major limitations is the need to prepare an individual electrophoretic gel for each of the protein species to be analyzed. Since most analyses require the detection of multiple protein species, a procedure that allows utilization of a single gel for detecting multiple protein species should significantly save time and resources. In this paper, we developed a novel multiprotein detection device, which enabled simultaneous detection of several proteins species from a single electrophoretic gel. In this device, a protein transfer unit utilized a multi-anode plate that generated a non-uniform voltage profile. This voltage profile enabled uniform transfer regardless of molecular mass of proteins. In vitro experiments using samples, isolated from boneforming osteoblast cells, showed that the expression levels of 5 - 7 different proteins were detectable in the presence and absence of mechanical stimulation that activated genes necessary for bone formation. The result supports the notion that through simultaneous detection of multiple protein species, the described device contributes to reduction in procedural time and sample amounts, as well as a removal of variations among multiple gels.

关键词： Western Blot Protein Transfer Voltage Control Multiple Membranes

Do changes in intracoronary pressure aid coronary spasm diagnosis using the spasm provocation test?

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World Journal of Cardiology 2024年第1期16卷 16-26页

作者： hiroki Teragawa Chikage Oshita Yuko Uchimura Department of Cardiovascular Medicine JR Hiroshima HospitalHiroshima 732-0057Japan

BACKGROUND Although the spasm provocation test(SPT)can diagnose coronary spasms,it would be helpful if it could also predict their *** To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the *** Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery *** each SPT,the pressure wire was advanced into the distal portion of the right coronary artery(RCA)and left anterior descending coronary artery,and the ratio of intracoronary pressure to aortic pressure(Pd/Pa)was *** spasm was defined as an arterial narrowing of>90%in response to the administration of acetylcholine(ACh),with chest symptoms and/or ischemic electrocardiographic *** was administered to the RCA at low,moderate,or high doses of 20,50,or 80μg,respectively,and to the left coronary artery(LCA)at low,moderate,or high doses of 50,100,or 200μg,*** arteries with coronary spasms at low doses of ACh were defined as group L,and those with coronary spasms at moderate or high doses were defined as group *** who did not occur coronary spasms at any ACh dose were designated as group *** Among the 132 coronary arteries assessed using a pressure wire,there were 49 in group N,25 in group L,and 58 in group *** Pd/Pa was the lowest in group L(P=0.001).The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N(P<0.001).A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95,with a sensitivity of 0.600(15/25)and a specificity of 0.713(76/107)and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was−0.04,with a sensitivity of 0.741(43/58)and a specificity of 0.694(34/49).CONCLUSION These findings suggest that indices of intracoronary pressure during SPT may be useful means for

关键词： Acetylcholine Coronary spasm Intracoronary pressure Pressure wire Spasm provocation test Vasospastic angina