Journal of Biological Engineering最新文献

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Light scattering-based screening method for rapid evaluating antibiotic effects on bacteria using laser speckle imaging. 基于光散射的激光散斑成像快速评价抗生素对细菌作用的筛选方法。
IF 6.5 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-26 DOI: 10.1186/s13036-025-00542-8
Donghyeok Kim, Seongjoon Moon, Jongseo Lee, Kyoungman Cho, Changhan Lee, Jonghee Yoon
{"title":"Light scattering-based screening method for rapid evaluating antibiotic effects on bacteria using laser speckle imaging.","authors":"Donghyeok Kim, Seongjoon Moon, Jongseo Lee, Kyoungman Cho, Changhan Lee, Jonghee Yoon","doi":"10.1186/s13036-025-00542-8","DOIUrl":"10.1186/s13036-025-00542-8","url":null,"abstract":"<p><p>Rapid and timely selection of appropriate antibiotics minimizes treatment delays, enhances patient care, and improves infection control. The antibiotic disk diffusion method (Kirby-Bauer test) is the most widely used growth-based technique for assessing bacterial susceptibility due to its simplicity and reliability. However, conventional growth-based methods typically require over 12 h of incubation for visible inspection, making them unsuitable for situations requiring urgent treatment. In this study, we developed a novel laser speckle imaging (LSI) system that measures light scattering properties in a medium, along with an advanced image processing method for the quantitative assessment of antimicrobial effects based on bacterial activity. The LSI system utilizes an optical diffuser with controlled rotations to generate multiple independent speckle illumination patterns. The image processing algorithm analyzes correlation contrast in time-series laser speckle images, enabling more precise bacterial activity detection compared to conventional LSI techniques. The proposed method successfully detected effective antibiotics within 3h for both Gram-negative and Gram-positive bacteria, a capability not achievable using traditional bacterial growth-based antimicrobial susceptibility tests. This approach has the potential to serve as a versatile, rapid, and clinically viable tool for identifying effective antibiotics in patients with bacterial infections, significantly improving diagnostic efficiency in clinical settings.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"68"},"PeriodicalIF":6.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting rheumatoid arthritis: a molecular perspective on biologic therapies and clinical progress. 靶向类风湿性关节炎:分子生物学治疗和临床进展。
IF 6.5 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-24 DOI: 10.1186/s13036-025-00534-8
Ankit Jain, Mamta Bishnoi, Shiv Kumar Prajapati, Sweta Acharya, Sumedha Kapre, Gautam Singhvi, Srinath Palakurthi
{"title":"Targeting rheumatoid arthritis: a molecular perspective on biologic therapies and clinical progress.","authors":"Ankit Jain, Mamta Bishnoi, Shiv Kumar Prajapati, Sweta Acharya, Sumedha Kapre, Gautam Singhvi, Srinath Palakurthi","doi":"10.1186/s13036-025-00534-8","DOIUrl":"10.1186/s13036-025-00534-8","url":null,"abstract":"<p><p>To surpass challenges with traditional approaches to treat Rheumatoid arthritis (RA), an improved understanding of molecular-level pathogenesis brought forth targeted therapy with biologics as a great promise in halting the progression of RA. Novel biologics are being designed with the help of synthetic fusion proteins, monoclonal antibodies, and protein fragments, with or without drugs, to target various signaling pathways, including TNF-α, IL-6, JAK, Th-17, IL-family, GM-CSF, B-cell, and T-cell signaling. The journey of biologics in RA management began in 1998 with etanercept (Enbrel<sup>®</sup>). Since then, regulatory bodies have endorsed various biologics and many more are in different clinical stages. This review aims to explore RA by examining current clinical studies with focus on emerging development on molecular-level pathogenesis, prevalent conventional treatment options and their limitations, as well as recent advancements in biologically engineered therapeutics. It also includes a few relevant case studies to support these findings. Despite the progress, challenges remain, such as high costs and the need for safer, more effective delivery methods. The document also touches on the historical perspective of RA, its pathophysiology, and the role of synovial fluid pharmacokinetics in treatment effectiveness. The importance of early diagnosis and well-controlled treatment strategies for RA is paramount. The potential of emerging biological and targeted treatments to facilitate a treat-to-target approach in RA management is substantial. This review explores the key molecular pathways of rheumatoid arthritis and includes detailed figures for better understanding. It also highlights the promising potential of biologically engineered therapeutics, supported by evidence from case studies and clinical trials.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"67"},"PeriodicalIF":6.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel PNIPAM-Modified polyurethane/carboxymethyl cellulose photo-thermoresponsive hydrogel loaded with gemcitabine to suppress esophageal cancer cells via VEGF-mediated angiogenic pathway inhibition. 一种新型pnipam改性聚氨酯/羧甲基纤维素光热响应水凝胶负载吉西他滨通过vegf介导的血管生成途径抑制食管癌细胞。
IF 6.5 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-23 DOI: 10.1186/s13036-025-00530-y
Shirong Wu, Huachuan Zhang, Yu Zhang, Ya Zhao, Mengqi Xiang, Liqiong Hao, Jing Chen
{"title":"A novel PNIPAM-Modified polyurethane/carboxymethyl cellulose photo-thermoresponsive hydrogel loaded with gemcitabine to suppress esophageal cancer cells via VEGF-mediated angiogenic pathway inhibition.","authors":"Shirong Wu, Huachuan Zhang, Yu Zhang, Ya Zhao, Mengqi Xiang, Liqiong Hao, Jing Chen","doi":"10.1186/s13036-025-00530-y","DOIUrl":"10.1186/s13036-025-00530-y","url":null,"abstract":"","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"66"},"PeriodicalIF":6.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lactic acid bacteria as microbial cell factories for the in vivo delivery of therapeutic proteins as secretable TAT fusion products. 乳酸菌作为微生物细胞工厂,作为可分泌的TAT融合产物在体内递送治疗性蛋白。
IF 5.7 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-17 DOI: 10.1186/s13036-025-00538-4
Giorgio Medici, Giulia Candini, Nicola Mottolese, Beatrice Uguagliati, Federica Trebbi, Manuela Loi, Angelica Marina Bove, Spase Stojanov, Erika Esposito, Rosalba Vitagliano, Federica D'Amico, Silvia Turroni, Jessica Fiori, Aleš Berlec, Stefania Trazzi, Elisabetta Ciani
{"title":"Lactic acid bacteria as microbial cell factories for the in vivo delivery of therapeutic proteins as secretable TAT fusion products.","authors":"Giorgio Medici, Giulia Candini, Nicola Mottolese, Beatrice Uguagliati, Federica Trebbi, Manuela Loi, Angelica Marina Bove, Spase Stojanov, Erika Esposito, Rosalba Vitagliano, Federica D'Amico, Silvia Turroni, Jessica Fiori, Aleš Berlec, Stefania Trazzi, Elisabetta Ciani","doi":"10.1186/s13036-025-00538-4","DOIUrl":"10.1186/s13036-025-00538-4","url":null,"abstract":"<p><p>Protein-based therapeutics have garnered increasing attention across various medical fields for their substantial benefits to human health. Existing strategies for intracellular protein delivery, such as cell-penetrating peptide (CPP)-based approaches, including the transactivator of transcription (TAT) peptide, have shown promising results but also present limitations, particularly due to the need for recombinant protein manufacturing and daily invasive administration. To overcome such hindrances and develop delivery tools that are able to foster the production of the protein directly inside the body of patients, we engineered the lactic acid bacterium, Lactococcus lactis, to express and secrete TATκ-GFP protein. After oral administration of the recombinant L. lactis in mice, we found the presence of the TATκ-GFP protein not only in the intestinal wall but also in the mouse liver, heart, and brain. This provides the first evidence that a recombinant TATκ-fused protein, secreted by L. lactis in the mouse host gut, by virtue of the presence of the TATκ peptide, can efficiently pass from the intestinal wall to other organs. With future research and development, this technology based on lactic acid bacteria (LAB) as a platform for the production and delivery of therapeutic proteins could offer significant advancements in the field of therapeutic protein delivery.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"65"},"PeriodicalIF":5.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing the therapeutic efficacy of gemcitabine in bladder cancer through TGF-β1 inhibition and pluronic F-127-based microsphere delivery. 通过抑制TGF-β1和基于pluronic f -127的微球递送增强吉西他滨治疗膀胱癌的疗效。
IF 5.7 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-11 DOI: 10.1186/s13036-025-00535-7
Yaoyao Xiong, Yangle Li, Lingxiao Chen, Minfeng Chen, Wei He, Lin Qi
{"title":"Enhancing the therapeutic efficacy of gemcitabine in bladder cancer through TGF-β1 inhibition and pluronic F-127-based microsphere delivery.","authors":"Yaoyao Xiong, Yangle Li, Lingxiao Chen, Minfeng Chen, Wei He, Lin Qi","doi":"10.1186/s13036-025-00535-7","DOIUrl":"10.1186/s13036-025-00535-7","url":null,"abstract":"<p><p>Bladder cancer is prevalent and features significant recurrence and progression rates, necessitating effective treatment strategies. Gemcitabine, commonly used to treat non-muscle invasive bladder cancer (NMIBC), shows moderate efficacy and notable side effects. TGF-β, not only a key in epithelial-mesenchymal transition(EMT) but also in tumor development, offers a target for enhancing gemcitabine efficacy. The present research was designed to explore the impact of TGF-β1 inhibitors (LY2109761 and LY3200882) with or without gemcitabine on bladder cancer cells and to develop Pluronic F-127-based microspheres (MSs) for drug delivery. TGF-β1 inhibitors significantly reduced cell viability, promoted apoptosis, and inhibited invasion in bladder cancer cell lines 5637 and SW780, with LY3200882 showing superior efficacy. Combining LY3200882 with gemcitabine enhanced these effects, indicating a synergistic interaction. Drug-loaded MSs were prepared, characterized by smooth morphology and consistent size distribution, and demonstrated sustained drug release, sufficient physical integrity, and no significant cytotoxicity to normal human fibroblast cells. In vitro, gemcitabine encapsulated in MSs exhibited enhanced cytotoxicity, apoptosis induction, and invasion inhibition compared to non-encapsulated gemcitabine. In vivo, these MSs significantly reduced tumor weight and volume, with notable reductions in blood vessel and cancer cell density, and altered expression of proliferation and apoptosis markers, particularly in the gemcitabine + LY3200882 MSs group. Systemic and local bladder toxicity assessments in mice demonstrated the in vivo safety of drug-loaded MSs. This study concludes that combining TGF-β1 inhibitors with gemcitabine in Pluronic F-127-based MSs enhances therapeutic efficacy against bladder cancer, promoting apoptosis, inhibiting cell invasion, and reducing tumor growth and metastasis while maintaining safety.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"62"},"PeriodicalIF":5.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Directed evolution and modular integration of a high-affinity ICOS-L variant for potent T cell-mediated tumor elimination. 高亲和力ICOS-L变体的定向进化和模块化整合,用于有效的T细胞介导的肿瘤消除。
IF 5.7 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-11 DOI: 10.1186/s13036-025-00536-6
Ji Yeon Ha, Tae Wook Song, Petrina Jebamani, Sun-Gu Lee, Sang Taek Jung
{"title":"Directed evolution and modular integration of a high-affinity ICOS-L variant for potent T cell-mediated tumor elimination.","authors":"Ji Yeon Ha, Tae Wook Song, Petrina Jebamani, Sun-Gu Lee, Sang Taek Jung","doi":"10.1186/s13036-025-00536-6","DOIUrl":"10.1186/s13036-025-00536-6","url":null,"abstract":"<p><strong>Background: </strong>Advancing cancer immunotherapy requires engineering synthetic immunomodulators that integrate precise receptor targeting, tunable activity, and compatibility with modular biologic formats. The Inducible T-cell Co-Stimulator (ICOS) is a clinically validated co-stimulatory receptor whose engagement enhances T-cell function. However, the development of ICOS-targeting biologics has been hindered by limited receptor affinity and format-dependent agonist activity. To address this, we applied a protein engineering framework to optimize the ICOS ligand (ICOS-L) as a high-affinity, modular component for precision immune modulation.</p><p><strong>Results: </strong>Using yeast surface display-based directed evolution, we identified an ICOS-L variant (Y8) containing two synergistic mutations (Q51P and N57H) that improved human ICOS (hICOS) binding affinity by ~ 100-fold relative to wild-type. Structural modeling revealed that Q51P enhances backbone rigidity via a proline-induced conformational constraint, while N57H introduces a salt bridge with Asp86 in hICOS. These mutations reconfigure the receptor-binding interface to support high-affinity engagement. Functionally, Y8 induced potent T-cell proliferation and IFN-γ secretion. When genetically fused to pembrolizumab, Y8 further enhanced T-cell activation and tumor cell lysis, demonstrating synthetic synergy between PD-1 blockade and ICOS agonism. Among fusion formats, light-chain conjugation (pembrolizumab-L-Y8) exhibited superior functional output, highlighting the importance of geometric configuration in optimizing fusion-based agonism.</p><p><strong>Conclusion: </strong>This study establishes Y8 as a high-affinity ICOS-L variant with robust co-stimulatory function, capable of potentiating anti-PD-1 immunotherapy through modular fusion design. The integration of Y8 into therapeutic antibody scaffolds provides a versatile engineering framework for the development of next-generation immunomodulatory biologics, offering opportunities to overcome resistance and enhance clinical efficacy in cancer immunotherapy.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"63"},"PeriodicalIF":5.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erythrocyte based achiral micromotors for localized therapeutic delivery. 基于红细胞的非手性微型马达用于局部治疗递送。
IF 5.7 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-11 DOI: 10.1186/s13036-025-00537-5
Qi Wang, Jaideep Katuri, Narjes Dridi, Jamel Ali
{"title":"Erythrocyte based achiral micromotors for localized therapeutic delivery.","authors":"Qi Wang, Jaideep Katuri, Narjes Dridi, Jamel Ali","doi":"10.1186/s13036-025-00537-5","DOIUrl":"10.1186/s13036-025-00537-5","url":null,"abstract":"<p><p>Bio-hybrid micromotors, active structures composed of both biological and synthetic components, are promising for use in several biomedical applications including targeted drug delivery, tissue engineering, and biosensing. Among biological candidates, erythrocytes are well suited for use as the biological component of bio-hybrid micromotors due to their biocompatibility, mechanical deformability, and long circulation time. However, their symmetric shape and small size make controlled actuation of these devices particularly challenging. Here, we present a novel strategy to overcome these limitations by fabricating achiral erythrocyte micromotors with enhanced propulsion efficiency. Inspired by recent work on synthetic achiral microswimmers, we report two and three-cell micromotors fabricated through biotin-streptavidin binding. These self-assembled red blood cell (RBC) structures are then interfaced with magnetic beads enabling them to swim and roll under the propulsion of a single homogenous rotating magnetic field at a much greater velocity compared to single cell micromotors in both Newtonian and viscoelastic fluids. Further, to demonstrate biomedical application of these self-assembled micromotors, the chemotherapeutic agent doxorubicin is loaded into RBC achiral micromotors, which are magnetically directed to cancer cells within a microfluidic chamber, successfully delivering their anticancer payload. The fabrication and propulsion method reported here will aid in the development of future erythrocyte-based micromotors for drug delivery and cancer therapy.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"64"},"PeriodicalIF":5.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular matrix dysregulation in PCOS: pathogenesis, therapeutic strategies, and innovative technologies. 多囊卵巢综合征的细胞外基质失调:发病机制、治疗策略和创新技术。
IF 5.7 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-05 DOI: 10.1186/s13036-025-00533-9
Yunxi Liu, Jialei Zhu, Yingli Yang, Zhengyun Chen, Yong Zhou, Weidong Fei, Xian Zhang, Yongquan Zheng
{"title":"Extracellular matrix dysregulation in PCOS: pathogenesis, therapeutic strategies, and innovative technologies.","authors":"Yunxi Liu, Jialei Zhu, Yingli Yang, Zhengyun Chen, Yong Zhou, Weidong Fei, Xian Zhang, Yongquan Zheng","doi":"10.1186/s13036-025-00533-9","DOIUrl":"10.1186/s13036-025-00533-9","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS), the most common endocrine disease in women of reproductive age, severely impacts female fertility due to chronic anovulation and currently lacks effective clinical treatment strategies. The extracellular matrix (ECM) is a three-dimensional, non-cellular framework comprising molecules such as collagens, elastin, and laminin, which support the ovarian structure and provide extracellular signals to cells. Changes in ECM localization and composition can disturb local biochemical pathways, impair folliculogenesis, and reduce the fertility of women. This paper explores innovative therapeutic approaches for PCOS by investigating the mechanisms underlying PCOS pathogenesis due to ECM dysregulation. This includes ECM deposition-induced inflammation and fibrosis, impaired ECM degradation, altered mechanical forces in ECM remodeling, and disrupted interactions between granulosa cells and the ECM. In the second part, we present therapeutic strategies informed by these pathogenic mechanisms, integrating insights from basic and clinical research. More importantly, this paper introduces innovative therapies for POCS that regulate ECM. These therapeutic strategies represent future development directions. In the final section, we summarize the advantages, potential challenges, and prospects of ECM-based treatments for improving fertility in PCOS. Overall, this review underscores the emerging significance of ECM-targeted interventions in unraveling PCOS pathophysiology and paves the way for the development of more precise and effective fertility-preserving therapies.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"61"},"PeriodicalIF":5.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New approach methodologies for in vitro toxicity screening of nanomaterial using a pulmonary three-dimensional floating extracellular matrix model. 使用肺三维漂浮细胞外基质模型进行纳米材料体外毒性筛选的新方法。
IF 5.7 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-01 DOI: 10.1186/s13036-025-00532-w
Soojin Kim, Mi-Sun Choi, Hyun Jegal, Min Beom Heo, Minjeong Kwak, Hyun Kyong Shon, Seungwoo Song, Tae Geol Lee, Ji-Ho Park, Dong Woo Lee, Seokjoo Yoon, Jung-Hwa Oh
{"title":"New approach methodologies for in vitro toxicity screening of nanomaterial using a pulmonary three-dimensional floating extracellular matrix model.","authors":"Soojin Kim, Mi-Sun Choi, Hyun Jegal, Min Beom Heo, Minjeong Kwak, Hyun Kyong Shon, Seungwoo Song, Tae Geol Lee, Ji-Ho Park, Dong Woo Lee, Seokjoo Yoon, Jung-Hwa Oh","doi":"10.1186/s13036-025-00532-w","DOIUrl":"10.1186/s13036-025-00532-w","url":null,"abstract":"<p><strong>Background: </strong>Nanomaterials offer increasing applications across diverse sectors, including food science, medicine, and electronics. Environmental risk assessment is crucial for ensuring the safety and sustainability of nanomaterials. However, high-throughput screening (HTS) of their potential toxicity remains challenging owing to their unique physicochemical properties.</p><p><strong>Results: </strong>This study introduces a novel pulmonary three-dimensional (3D) floating extracellular matrix (ECM) model utilizing a 384-pillar/well platform for HTS of nanotoxicity. Compared with conventional HTS models based on two-dimensional (2D) cells, the 3D model developed in this study successfully addressed the issues related to the aggregation and sedimentation of nanoparticles and their possible optical interference with the toxicity assays. Using 20 nm silica nanoparticles (SiNPs), we assessed cell viability and nanoparticle uptake in both serum-containing and serum-free culture media. While the 2D model showed high SiNPs toxicity regardless of the media composition, the pulmonary 3D floating ECM model demonstrated variable toxicities that depended on the SiNPs behaviors under different conditions.</p><p><strong>Conclusions: </strong>By reducing the uncertainties associated with the sedimentation and optical interference of nanomaterials, our 3D model provided a more precise analysis of cytotoxicity. This study highlights the potential of using new approach methodologies and improved HTS approaches to enhance the efficiency and accuracy of risk assessment protocols for emerging nanomaterials.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"60"},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SsDiHal: discovery and engineering of a novel tryptophan dihalogenase. SsDiHal:一种新型色氨酸二卤酶的发现和工程。
IF 5.7 3区 生物学
Journal of Biological Engineering Pub Date : 2025-07-01 DOI: 10.1186/s13036-025-00518-8
Hassan Sher, Haley Hardtke, Wenzhu Tang, Jie Ren, Hayat Ullah, Xudong Zhou, Y Jessie Zhang, Jixun Zhan
{"title":"SsDiHal: discovery and engineering of a novel tryptophan dihalogenase.","authors":"Hassan Sher, Haley Hardtke, Wenzhu Tang, Jie Ren, Hayat Ullah, Xudong Zhou, Y Jessie Zhang, Jixun Zhan","doi":"10.1186/s13036-025-00518-8","DOIUrl":"10.1186/s13036-025-00518-8","url":null,"abstract":"<p><strong>Background: </strong>Halogenation plays a crucial role in enhancing the properties of small molecules, particularly by making them more effective for applications in agrochemicals and pharmaceuticals. Notably, approximately a quarter of current pharmaceuticals are halogenated. While chemical halogenation remains the most widely employed method for producing halogenated molecules, it has significant drawbacks, including extreme reaction conditions, heavy pollution, and the use of toxic reagents. In contrast, bio-halogenation offers a \"greener\" approach to generating halogenated compounds. However, its industrial application is limited due to the low activity and stability of naturally occurring halogenase enzymes.</p><p><strong>Results: </strong>In this study, we identified a novel tryptophan halogenase, SsDiHal, from Saccharothrix sp. NRRL B-16348 through genome mining. We found that SsDiHal catalyzes a two-step chlorination of tryptophan to sequentially yield 7-chlorotryptophan and 6,7-dichlorotryptophan, making SsDiHal the first naturally occurring tryptophan dihalogenase to be identified. Using a strcutral model of SsDiHal to guide mutagensis, several SsDiHal mutants were generated and tested for improved catalytic efficiency and altered regioselectivity. Compared to the halogenation activity of the wild type SsDiHal, the V53I, V53I/I83V and N470S mutants demonstrated significantly enhanced catalytic efficiency, with 7.7-, 4.16-, and 7.4-fold increases respectively, for the L-tryptophan substrate. While no change in regioselectivity was observed for the V53I, I83V, F112Y, and V53I/I83V mutants, a notable regioselectivity shift was found in the N470S mutant. Specifically, this mutant synthesized 6-chlorotryptophan as the first product, rather than the canonical 7-chlorotryptophan that is synthesized by wild type SsDiHal with no effect in its dihlogenation function.</p><p><strong>Conclusion: </strong>Overall, this work not only adds a novel dihalogenase to the growing field of halogenating enzymes but also demonstrates that leveraging a structrual model to guide engineering of halogenases can both enhance the catalytic efficiency and modify regioselectivity of the wild type enzyme. This work holds significant potential for green applications in the agrochemical and pharmaceutical industries.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"59"},"PeriodicalIF":5.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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