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2023 IEEE EMBS R9 Conference, EMBS R9 2023

作者： Gonzalez-Lujan, F.J. Osuna-Carrasco, L.P. De La Torre-Valdovinos, B. Aguilar-Garcia, I.G. Toro-Castillo, C. Trevino, M. CUCEI University of Guadalajara Translational Bioengineering Department Mexico Master of Science in Bioengineering and Intelligent Computing Program CUCEI Campus at University of Guadalajara Jalisco44430 Mexico CUCS Molecular Biology and Genomics Department University of Guadalajara Mexico

ISBN: (纸本)9798350381092

The proposed study proves the option to have a different treatment displayed on quantitative and qualitative parameters of kinematics and pain tests, by experiments with mice groups during walk and mobility analysis with kinematics parameters and pain sensation using Von Frey filaments in acute osteoarthritis knee (AOAK) model. This would allow us to have enough information to recommend or not recommend a new based treatment that can be compared to another successful treatment for osteoarthritis. Clinical Relevance - Therefore, with this study it is proposed to be able to analyze different compounds from opioids, steroids, and non-steroid anti-inflammatories (NSAIDs) like cannabinoid components, avoiding with that the dependance pathology and renal damage in patients treated with one of this kind of common treatments and thus be able to determine their viability on a in vivo model to recommend their study in instances closer to a clinical model. © 2023 IEEE.

关键词： Kinematics

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Regulation of Leukaemia Associated Rho GEF (LARG/ARHGEF12)

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Small GTPases 2022年第1期13卷 196-204页

作者： Ghanem, Neda Z. Matter, Michelle L. Ramos, Joe W. Cancer Biology Program University of Hawaii Cancer Center University of Hawaii at Mānoa Honolulu United States Molecular Biosciences and BioEngineering Graduate Program University of Hawaii at Mānoa Honolulu United States

The Ras homologous (Rho) protein family of GTPases (RhoA, RhoB and RhoC) are the members of the Ras superfamily and regulate cellular processes such as cell migration, proliferation, polarization, adhesion, gene transcription and cytoskeletal structure. Rho GTPases function as molecular switches that cycle between GTP-bound (active state) and GDP-bound (inactive state) forms. Leukaemia-associated RhoGEF (LARG) is a guanine nucleotide exchange factor (GEF) that activates RhoA subfamily GTPases by promoting the exchange of GDP for GTP. LARG is selective for RhoA subfamily GTPases and is an essential regulator of cell migration and invasion. Here, we describe the mechanisms by which LARG is regulated to facilitate the understanding of how LARG mediates functions like cell motility and to provide insight for better therapeutic targeting of these functions. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

关键词： ARHGEF12 GTPase LARG migration Rho RhoGef signal transduction

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Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning

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molecular Therapy 2025年第5期33卷 1937-1945页

作者： Nisanov, Alan M. Rivera de Jesús, Julio A. Schaffer, David V. Department of Chemistry University of California Berkeley Berkeley 94720 CA United States Department of Chemical and Biomolecular Engineering University of California Berkeley Berkeley 94720 CA United States Department of Bioengineering University of California Berkeley Berkeley 94720 CA United States Graduate Program in Bioengineering University of California Berkeley San Francisco and University of California Berkeley 94720 CA United States Department of Neurological Surgery University of California San Francisco 94143 CA United States Department of Molecular and Cell Biology University of California Berkeley Berkeley 94720 CA United States

Adeno-associated virus (AAV) has emerged as a highly promising vector for human gene therapy due to its favorable safety profile, versatility, and ability to transduce a wide range of tissues. However, natural AAV serotypes have shortcomings, including suboptimal transduction efficiency, pre-existing immunity, and a lack of tissue specificity, that hinder their therapeutic potential. To address these challenges, significant efforts are being applied to engineer novel AAV capsids. Rational design leverages structural insights to enhance capsid properties, directed evolution enables unbiased selection of superior variants, and machine learning accelerates discovery by computational analysis of high-throughput screening results to enable predictive algorithms. These strategies have yielded novel capsids with improved transduction efficiency, reduced immunogenicity, and enhanced tissue targeting. Future advances that continue to integrate such multi-disciplinary approaches will further drive the clinical translation of AAV-based therapies. © 2025 The Authors

关键词： AAV directed evolution gene therapy high-throughput screening machine learning next generation sequencing NGS rational design

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Nanoparticle-based sustained drug delivery for the treatment of ocular neovascular diseases

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ACTA OPHTHALMOLOGICA 2024年第S279期102卷

作者： Durak, Saliha Kutlu, Ozlem Cetinel, Sibel Nanotechnology Research and Application Center (SUNUM) Sabanci University Istanbul Turkey Faculty of Engineering and Natural Sciences Molecular Biology Genetics and Bioengineering Program Sabanci University Istanbul Turkey

Aims/Purpose: Nanoparticles have shown great potential as a drug delivery system for the treatment of neovascular ocular diseases characterized by the growth of abnormal blood vessels in the retina. The current standard of therapy for neovascular ocular diseases involves administering monoclonal antibody-based anti-VEGF drugs via intravitreal injections on a periodic basis. The short half-lives of these drugs necessitate frequent injections, which can limit the effectiveness of the treatments. Hence, there is a need to develop new approaches for enhanced bioavailability and sustained and long-lasting delivery of anti-VEGF drugs. The aim of this study was to utilize poly (glycerol sebacate) (PGS) nanoparticles to achieve an extended release of anti-VEGF (anti-vascular endothelial growth factor) drugs, with the objective of reducing the frequency of intravitreal injections required for treatment. Methods: Double emulsion solvent evaporation method was utilized for the synthesis of PGS nanoparticles. Nanoparticle size and polydispersity index (PDI) were determined with dynamic light scattering method. Results: Nanoparticles were synthesized with a size of approximately 150 nm and PDI less than 0.3. The encapsulation efficiency of nanoparticles loaded with anti-VEGF drugs was found to be 74%. The 30% drug release from nanoparticles in the first 2 months indicates that nanoparticles are a promising candidate for sustained drug release applications. Cell-viability studies showed that anti-VEGF drug-loaded nanoparticles did not exhibit toxicity to ARPE-19 cells, but they did exhibit anti-angiogenesis properties by inhibiting the growth of HUVEC cells in a concentration-dependent manner. Conclusions: The development of new-generation materials for the storage and preservation of anti-VEGF drugs, as well as their enhancement with prolonged release, will considerably improve the efficacy of long-term treatment strategies for ocular neovascular diseases.

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Quantitative Imaging of ⁵⁵CO and ¹⁸F-Labeled Tracers in a Single 'Multiplexed' Pet Imaging Session 22

Quantitative Imaging of <sup>55</sup>CO and <sup>18</sup>F-L...

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22nd IEEE International Symposium on Biomedical Imaging, ISBI 2025

作者： Zou, Sarah J. Lim, Irene Foster, Jackson W. Chinn, Garry Houson, Hailey A. Lapi, Suzanne E. Rao, Jianghong Levin, Craig S. Bates College Chemistry and Biochemistry Department United States University of Alabama at Birmingham Department of Radiology United States Stanford University Department of Radiology and Molecular Imaging Program at Stanford (MIPS) United States Stanford University Department of Bioengineering United States Stanford University Department of Physics United States

ISBN: (纸本)9798331520526

In this study, we explore the use of Cobalt-55 as a radioisotope for multiplexed PET (mPET) by utilizing its emission of a prompt gamma-ray in cascade with a positron during decay. We leverage the prompt-gamma signal to generate triple coincidences for a Co-55-labeled tracer, allowing us to distinguish it from a tracer labeled with a pure positron emitter F-18, which yields a two photon coincidence. By employing this triple versus double coincidence detection and signal processing methodology, we show the potential to separate and quantify the Co-55 signal from that of F-18. Phantom studies showed strong linear correlation (R2=0.99) between Co-55 double and triple coincidence counts and total Co-55 activity. Finally, we highlight the capability of this method to quantify overlapping and non-overlapping hot spots within a warm background to within a 3 to 15% error range. Moreover, we demonstrate the feasibility of simultaneously imaging two tracers in vivo during a single PET session using mice. © 2025 IEEE.

关键词： Co-55 Dual-isotope PET Multiplexed PET Preclinical PET Imaging triple coincidence

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Study of Novel Photodetectors and Electronics to Enhance Coincidence Time Resolution of BGO-based PET Detectors

Study of Novel Photodetectors and Electronics to Enhance Coi...

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2022 IEEE Nuclear Science Symposium, Medical Imaging Conference, and Room Temperature Semiconductor Detector Conference, IEEE NSS MIC RTSD 2022

作者： Gonzalez-Montoro, Andrea Pourashraf, Shirin Cates, Joshua W Levin, Craig S Stanford University Department of Radiology StanfordCA94305 United States Lawrence Berkeley National Laboratory Applied Nuclear Physics Program BerkeleyCA94720 United States Stanford University Departments of Radiology Molecular Imaging Program Bioengineering Physics and Electrical Engineering CA94305 United States

ISBN: (纸本)9781665488723

Developing high sensitivity multiparametric medical imaging tools constitutes one of the main research topics in radionuclide *** time-of-flight positron emission tomography (TOF-PET) scanners have shown potential in this context. One of the most attractive solutions that have been proposed to improve the coincidence time resolution (CTR) of TOF-PET scanners includes exploiting the small population of promptly emitted light photons (i.e., Cherenkov photons). Bismuth germanate (BGO) is a legacy detection material for PET which exhibits a moderate Cherenkov yield. which new advancements in ultra-violet (UV) light sensitive photosensor technologies and associated detection techniques can exploit for fast timing. It has been demonstrated that exploiting the BGO-Cherenkov component may simultaneously facilitate high 511 keV photon detection sensitivity with excellent CTR, thus enabling high sensitivity, low cost TOF-PET systems. Accessing the timing information from these Cherenkov photons requires enhanced photodetector technology combined with low noise and fast readout electronics, as well as specific data post-processing *** this summary, we report the CTR evaluation of different length BGO crystals coupled to UV enhanced SiPMs and custom designed electronics. Average CTR values of 156 ± 6, 188 ± 5, 228 ± 8 and 297 ± 8 ps CTR FWHM have been achieved for 3 × 3 × 3, × 5, × 10, and × 15 mm3 BGO crystal with chemically processed surface finishes. © 2022 IEEE.

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Electronic Readout for a 100 ps CTR PET Detector with 24:1 Multiplexing Ratio of Timing Channels

Electronic Readout for a 100 ps CTR PET Detector with 24:1 M...

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2022 IEEE Nuclear Science Symposium, Medical Imaging Conference, and Room Temperature Semiconductor Detector Conference, IEEE NSS MIC RTSD 2022

作者： Pourashraf, Shirin Gonzalez-Montoro, Andrea Innes, Derek Cates, Joshua W. Levin, Craig S. Stanford University Department of Radiology StanfordCA94305 United States Lawrence Berkeley National Laboratory Applied Nuclear Physics Program BerkeleyCA94720 United States Stanford University Molecular Imaging Program Departments of Radiology Bioengineering Physics and Electrical Engineering StanfordCA94305 United States

ISBN: (纸本)9781665488723

We have designed a novel electronic readout with 24:1 multiplexing ratio of the timing channels that achieves 100 ps coincidence time resolution. The detector layer units comprise 2×4 arrays of 3×3×10 mm3 "LGSO"crystals side-coupled to 6×4 arrays of 3×3 mm2 SiPMs. To achieve low power dissipation and scalability of this readout design, its effective area is implemented in only 13.3 mm using compact and power efficient electronic components. The measured CTR of the 24:1 multiplexed timing channels (or 8:1 LVDS signals) was 107.0 ± 3.6 ps FWHM using a22Na point-source and a very low timing jitter FPGA-based TDC. © 2022 IEEE.

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Evaluation of Pharmacological Treatment in Acute Osteo Arthrosis Model by Means of Kinematic Analysis and Pain Threshold

Evaluation of Pharmacological Treatment in Acute Osteo Arthr...

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EMBS R9 Conference, IEEE

作者： F. J. Gonzalez-Lujan L. P. Osuna-Carrasco B. De la Torre-Valdovinos I. G. Aguilar-García C. Toro-Castillo M. Treviño Translational Bioengineering Department CUCEI University of Guadalajara Master of Science in Bioengineering and Intelligent Computing program CUCEI campus at University of Guadalajara Jalisco Molecular Biology and Genomics Department CUCS University of Guadalajara Neuroscience Institute CUCBA University of Guadalajara

ISBN: (数字)9798350381092

ISBN: (纸本)9798350381108

The proposed study proves the option to have a different treatment displayed on quantitative and qualitative parameters of kinematics and pain tests, by experiments with mice groups during walk and mobility analysis with kinematics parameters and pain sensation using Von Frey filaments in acute osteoarthritis knee (AOAK) model. This would allow us to have enough information to recommend or not recommend a new based treatment that can be compared to another successful treatment for osteoarthritis. Clinical Relevance — Therefore, with this study it is proposed to be able to analyze different compounds from opioids, steroids, and non-steroid anti-inflammatories (NSAIDs) like cannabinoid components, avoiding with that the dependance pathology and renal damage in patients treated with one of this kind of common treatments and thus be able to determine their viability on a in vivo model to recommend their study in instances closer to a clinical model.

关键词： Knee Analytical models Pathology In vivo Pain Kinematics Opioids

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Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer

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Genes & Diseases 2022年第2期9卷 393-400页

作者： Yi Zuo Shaoqiu Chen Lingling Yan Ling Hu Scott Bowler Emory Zitello Gang Huang Youping Deng Tianyou Hospital Affiliated to Wuhan University of Science and TechnologyWuhan 430064PR China Department of Quantitative Health Sciences John A.Burns School of MedicineUniversity of Hawaii at ManoaHonoluluHI 96813USA Molecular Biosciences and Bioengineering Program College of Tropical Agriculture and Human ResourcesUniversity of Hawaii at ManoaHonoluluHI 96822USA Shanghai Key Laboratory for Molecular Imaging Shanghai University of Medicine and Health SciencesShanghai 201318PR China

Liver cancer presents divergent clinical *** remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis,especially since tRNA-derived small RNAs(tsRNA)have rarely been *** this study,a random forests(RF)diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation(IV).A LASSO model was used to developed a seven-tsRNA-based risk score signature for liver cancer *** performance was evaluated by a receiver operating characteristic curve(ROC curve)and Precision-Recall curve(PR curve).The five-tsRNA-based RF diagnosis model had area under the receiver operating characteristic curve(AUROC)88%and area under the precision–recall curve(AUPR)87%in the discovery cohort and 87%and 86%in IV-AUROC and IV-AUPR,*** seven-tsRNA-based prognostic model predicts the overall survival of liver cancer patients(Hazard Ratio 2.02,95%CI 1.36–3.00,P<0.001),independent of standard clinicopathological prognostic ***,the model successfully categorizes patients into high-low risk *** and prognostic modeling can be reliably utilized in the diagnosis of liver cancer and high-low risk classification of patients based upon tsRNA characterization.

关键词： Diagnosis Liver cancer Prognosis Random forests tRNA-derived small RNAs

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SAME-CELL, SINGLE-CELL DETECTION OF PROTEIN ISOFORMS AND NUCLEIC ACIDS 25

SAME-CELL, SINGLE-CELL DETECTION OF PROTEIN ISOFORMS AND NUC...

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25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021

作者： Gomez Martinez, Ana E. Rosas-Canyelles, Elisabet Modzelewski, Andrew J. Geldert, Alisha Gopal, Anjali He, Lin Herr, Amy E. Department of Bioengineering University of California Berkeley BerkeleyCA United States UC Berkeley-UCSF Graduate Program in Bioengineering United States Division of Cellular and Developmental Biology Department of Molecular & Cell Biology University of California BerkeleyCA United States

ISBN: (纸本)9781733419031

Single-cell 'omics is advancing rapidly, but there are gaps in linking nucleic acids to proteins in their myriad forms. To surmount this gap, we describe a microfluidic device that reports information on nucleic acids and proteoforms, or proteins that arise from a variety of modifications to nucleic acids or proteins, which are detected by immunoblotting (triBlot). The triBlot fractionates nuclei from the cytoplasm, allowing analysis of cytoplasmic proteoforms. Then, nuclei-laden regions are laser excised to perform PCR/RT-qPCR. We correlate DNA, mRNA, and protein expression from the same few cells, a step forward in 'omics that measure diverse protein forms. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

关键词： Proteins

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