Bioengineering & Translational Medicine最新文献

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Enhancement of spinal cord injury repair in rats using photo-crosslinked GelMA hydrogel combined with mitochondrial transplantation 光交联GelMA水凝胶联合线粒体移植增强大鼠脊髓损伤修复
IF 5.7 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-07-03 DOI: 10.1002/btm2.70040
Wenyong Gao, Can Tang, Diancheng Hang, Hao Chen, Dongsheng Li, Youjie Yan, Wuchang Wang, Hao Peng, Xianmin Wang, Enpeng Zhang, Min Wei, Hengzhu Zhang, Xiaodong Wang
{"title":"Enhancement of spinal cord injury repair in rats using photo-crosslinked GelMA hydrogel combined with mitochondrial transplantation","authors":"Wenyong Gao,&nbsp;Can Tang,&nbsp;Diancheng Hang,&nbsp;Hao Chen,&nbsp;Dongsheng Li,&nbsp;Youjie Yan,&nbsp;Wuchang Wang,&nbsp;Hao Peng,&nbsp;Xianmin Wang,&nbsp;Enpeng Zhang,&nbsp;Min Wei,&nbsp;Hengzhu Zhang,&nbsp;Xiaodong Wang","doi":"10.1002/btm2.70040","DOIUrl":"10.1002/btm2.70040","url":null,"abstract":"<p>Acute spinal cord injury (SCI) induces mitochondrial oxidative stress, cellular bioenergetic crises, impaired protein degradation, and subsequent degeneration, resulting in increased neuronal vulnerability. Transplantation of exogenous mitochondria to the injury site mitigates cellular energy crises and counteracts neurodegeneration; however, the limited efficacy of mitochondrial transplantation alone constrains its therapeutic potential. In this study, we established a right-sided spinal cord hemisection model at the T10 thoracic segment in rats and transplanted a methacrylate-based gelatin (GelMA) hydrogel containing active mitochondria at the injury site to assess its therapeutic effects and underlying mechanisms. Our findings indicate that GelMA hydrogel combined with mitochondrial transplantation provides superior therapeutic benefits for SCI compared to mitochondrial transplantation alone. GelMA hydrogel enables sustained mitochondrial release at the injury site, supplying energy, upregulating NF200 expression, and promoting axonal regeneration. Additionally, it enhances M2 macrophage accumulation and improves the local inflammatory microenvironment. The structural framework of GelMA hydrogel further supports axonal regeneration. Footprint gait analysis and Basso, Beattie, and Bresnahan (BBB) motor scoring demonstrated that GelMA hydrogel combined with mitochondrial transplantation significantly improves motor function in the right hind limb of rats with SCI. Consequently, GelMA hydrogel combined with mitochondrial transplantation offers a viable and promising approach for treating spinal cord injury.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","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 vesicles from glucocorticoids‐preconditioned synovial mesenchymal stem cells exert antiarthritic effects by downregulating the mRNA m6A modification of NLRP3 in macrophages through miR‐212‐5p 糖皮质激素预处理的滑膜间充质干细胞细胞外囊泡通过miR - 212 - 5p下调巨噬细胞NLRP3 mRNA的m6A修饰,从而发挥抗关节炎作用
IF 7.4 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-07-02 DOI: 10.1002/btm2.70042
Xiaolong Shao, Ming Zhang, Shouye Hu, Zhi Yang
{"title":"Extracellular vesicles from glucocorticoids‐preconditioned synovial mesenchymal stem cells exert antiarthritic effects by downregulating the mRNA m6A modification of NLRP3 in macrophages through miR‐212‐5p","authors":"Xiaolong Shao, Ming Zhang, Shouye Hu, Zhi Yang","doi":"10.1002/btm2.70042","DOIUrl":"https://doi.org/10.1002/btm2.70042","url":null,"abstract":"Osteoarthritis (OA) is a prevalent chronic degenerative joint disease with no known treatment for reversing its progression. However, recent studies have shown promising results for nano‐sized extracellular vesicles derived from preconditioned synovial mesenchymal stem cells (SMSCs) in treating various diseases, including OA. Glucocorticoids (GCs) possess potent anti‐inflammatory properties, but their long‐term use is limited due to potential adverse reactions. Building on previous research, this study aimed to investigate the therapeutic potential of extracellular vesicles secreted from GCs‐pretreated SMSCs (GCs‐EVs) in exerting antiarthritic effects. The results demonstrated that GCs‐EVs effectively inhibited cartilage degeneration and osteophyte formation in the OA mouse model by suppressing the release of inflammatory cytokines from synovial macrophages. This effect was attributed to the high expression of miR‐212‐5p in GCs‐EVs, which specifically inhibited the expression of methyltransferase‐like 3 (Mettl3). Consequently, the mRNA N6‐methyladenosine (m<jats:sup>6</jats:sup>A) level of nod‐like receptor pyrin domain 3 inflammasome (NLRP3) in macrophages was reduced, leading to decreased NLRP3 inflammasome activity and increased antiarthritic effects. Furthermore, in the co‐culture system, GCs‐EVs enhanced chondrocyte proliferation and migration while inhibiting chondrocyte apoptosis by suppressing the secretion of inflammatory factors by macrophages.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"19 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optogenetic modulation of peripheral nociceptive neurons with biocompatible optoelectronic implants 生物相容性光电植入物对外周伤害性神经元的光遗传学调控
IF 5.7 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-06-26 DOI: 10.1002/btm2.70034
Paul Chu Sin Chung, Valentina Paggi, Marie Pertin, Guylène Kirschmann, Elena A. Konnova, Frédéric Michoud, Ivan Furfaro, Bernard L. Schneider, Stéphanie P. Lacour, Isabelle Decosterd
{"title":"Optogenetic modulation of peripheral nociceptive neurons with biocompatible optoelectronic implants","authors":"Paul Chu Sin Chung,&nbsp;Valentina Paggi,&nbsp;Marie Pertin,&nbsp;Guylène Kirschmann,&nbsp;Elena A. Konnova,&nbsp;Frédéric Michoud,&nbsp;Ivan Furfaro,&nbsp;Bernard L. Schneider,&nbsp;Stéphanie P. Lacour,&nbsp;Isabelle Decosterd","doi":"10.1002/btm2.70034","DOIUrl":"10.1002/btm2.70034","url":null,"abstract":"<p>Hyperexcitability of peripheral sensory neurons plays a critical role in the development and maintenance of chronic pain. Pharmacological analgesics used in clinics reduce neuronal activity. They often come with non-negligible side effects. Optogenetic approaches can modulate neuronal activity and are attracting growing interest for therapeutic uses, but the delivery of light in different parts of the body requires the development of specific optoelectronic interfaces. We designed and produced a microfabricated optoelectronic implant to deliver yellow light (559 nm) onto the sciatic nerve. We have surgically implanted the device in transgenic mice expressing the yellow light-sensitive inhibitory archaerhodopsin (ArchT) in nociceptive neurons. Yellow light induced a significant reduction in the responses of the nociceptive neurons and curbed the behavioral responses to noxious mechanical and thermal stimuli. Remarkably, the yellow light-related inhibition did not alter the behavioral responses evoked by innocuous mechanical stimulation or by intense inflammation. The optoelectronic implants showed reliable and reproducible opto-electrical performance. For stimulation parameters used in vivo (3.3 V, 60–80 mW/mm<sup>2</sup>, 20 s train pulses, 1 Hz, 80% duty-cycle, and an inter-train interval of 1 s), limited temperature increase was measured in an environment mimicking neural tissue surrounded by muscle and fat. Similarly, the basal sensitivity of the implanted mice remains comparable to non-implanted mice, suggesting a safe integration of the soft electronic device. Our study confirmed that optoelectronic implants tailored to the sciatic nerve can provide specific light spectra and intensities at adequate levels for the optogenetic actuator to trigger significant electrophysiological and behavioral responses in pain perception.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dissecting contributions of pulmonary arterial remodeling to right ventricular afterload in pulmonary hypertension 肺动脉重构对肺动脉高压右心室后负荷的解剖贡献
IF 5.7 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-06-26 DOI: 10.1002/btm2.70035
Sunder Neelakantan, Emilio A. Mendiola, Byron Zambrano, Alexander Vang, Kyle J. Myers, Peng Zhang, Gaurav Choudhary, Reza Avazmohammadi
{"title":"Dissecting contributions of pulmonary arterial remodeling to right ventricular afterload in pulmonary hypertension","authors":"Sunder Neelakantan,&nbsp;Emilio A. Mendiola,&nbsp;Byron Zambrano,&nbsp;Alexander Vang,&nbsp;Kyle J. Myers,&nbsp;Peng Zhang,&nbsp;Gaurav Choudhary,&nbsp;Reza Avazmohammadi","doi":"10.1002/btm2.70035","DOIUrl":"10.1002/btm2.70035","url":null,"abstract":"<p>Pulmonary hypertension (PH) is defined as an elevation in the right ventricular (RV) afterload, characterized by increased hemodynamic pressure in the main pulmonary artery (PA). Elevations in RV afterload increase RV wall stress, resulting in RV remodeling and potentially RV failure. From a biomechanical standpoint, the primary drivers for RV afterload elevations include increases in pulmonary vascular resistance (PVR) in the distal vasculature and decreases in vessel compliance in the proximal arteries. However, the individual contributions of the various vascular remodeling events toward the progression of PA pressure elevations and altered vascular hemodynamics remain elusive. In this study, we used a subject-specific one-dimensional (1D) fluid–structure interaction (FSI) model to investigate the alteration of pulmonary hemodynamics in PH and to quantify the contributions of decreased compliance and increased resistance toward increased main pulmonary artery (MPA) pressure. We used a combination of subject-specific hemodynamic measurements, ex-vivo mechanical testing and histological analysis of arterial tissue specimens, and ex-vivo x-ray micro-tomography imaging to develop the 1D FSI model and dissect the contribution of PA remodeling events toward alterations in the MPA pressure waveform. Both the amplitude and pulsatility of the MPA pressure waveform were analyzed. Our results indicated that increased distal resistance has the greatest effect on the increase in maximum MPA pressure, while decreased vessel compliance caused significant elevations in the characteristic impedance. The method presented in this study will serve as an essential step toward understanding the complex interplay between PA remodeling events that lead to the most adverse effect on RV function.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next-generation bioreactors 多轴旋转载荷损害椎间盘过渡区:使用新一代生物反应器的离体研究
IF 5.7 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-06-08 DOI: 10.1002/btm2.70033
Amra Šećerović, Aapo Ristaniemi, Francesco Crivelli, Sarah Heub, Mauro Alini, Gilles Weder, Diane Ledroit, Stephen J. Ferguson, Sibylle Grad
{"title":"Multiaxial rotational loading compromises the transition zone of the intervertebral disc: Ex vivo study using next-generation bioreactors","authors":"Amra Šećerović,&nbsp;Aapo Ristaniemi,&nbsp;Francesco Crivelli,&nbsp;Sarah Heub,&nbsp;Mauro Alini,&nbsp;Gilles Weder,&nbsp;Diane Ledroit,&nbsp;Stephen J. Ferguson,&nbsp;Sibylle Grad","doi":"10.1002/btm2.70033","DOIUrl":"10.1002/btm2.70033","url":null,"abstract":"<p>Bioreactors have become indispensable tools in spine research, enabling long-term intervertebral disc culture under controlled biological and mechanical conditions. Conventional systems are often limited to uniaxial loading, restricting their ability to replicate the complex, multidirectional biomechanics of the spine. To overcome this limitation, we developed a next-generation bioreactor capable of simulating multiaxial motions while preserving the disc's biological environment. In this study, we investigated the effects of complex loading patterns on early disc degeneration by subjecting bovine whole-organ discs to combined extension, lateral bending, and torsion at 0.3 Hz for 2 h daily over 14 days. To assess the impact of loading magnitude and the specific contribution of torsion, discs were exposed to either low- or high-angle rotations, with or without torsional loading at higher angles. Histological analysis revealed a marked loss of glycosaminoglycans (GAG) and collagen type II within the inner annulus fibrosus and transitional nucleus pulposus (NP), encompassing the transition zone (TZ), as well as GAG depletion in the central NP. Matrix degradation was observed across all loading conditions, with the most severe breakdown occurring under high-angle extension, bending, and torsion. All loading regimes induced cell death in the TZ and central NP, although torsion-free loading better maintained cell viability. These findings highlight the TZ, alongside the commonly affected NP, as a critical early site of degeneration. The study further underscores the importance of incorporating multiaxial loading in disc degeneration models and provides new insights into the biomechanical mechanisms underlying disc pathology.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microfluidic approaches for liquid biopsy in glioblastoma: Insights into diagnostic and follow‐up strategies 胶质母细胞瘤液体活检的微流体方法:诊断和随访策略的见解
IF 7.4 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-05-22 DOI: 10.1002/btm2.70032
Clara Bayona, Teodora Ranđelović, Claudia Olaizola‐Rodrigo, Ignacio Ochoa
{"title":"Microfluidic approaches for liquid biopsy in glioblastoma: Insights into diagnostic and follow‐up strategies","authors":"Clara Bayona, Teodora Ranđelović, Claudia Olaizola‐Rodrigo, Ignacio Ochoa","doi":"10.1002/btm2.70032","DOIUrl":"https://doi.org/10.1002/btm2.70032","url":null,"abstract":"Glioblastoma (GBM) is a highly malignant brain tumor with a poor survival prognosis of 12–15 months despite current therapeutic strategies. Diagnosing GBM is challenging, often requiring invasive techniques such as tissue biopsy and imaging methods that can provide inconclusive results. In this regard, liquid biopsy represents a promising alternative, providing tumor‐derived information from less invasive sources such as blood or cerebrospinal fluid. However, the typically low concentrations of these biomarkers pose challenges for traditional detection techniques, limiting their sensitivity and specificity. Recent advances in microfluidics offer a potential solution by enhancing the isolation and detection of tumor‐derived cells and molecules, thus improving their detectability. This review discusses the latest progress in microfluidic‐based liquid biopsy systems for glioblastoma, laying the basis for future diagnostic practices that are less invasive and more accurate. As these technologies evolve, they hold the potential to transform GBM diagnosis and monitoring, ultimately improving patient outcomes.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"76 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial and photosynthetic therapy: A crucial strategy for remodeling cellular metabolic function 线粒体和光合疗法:重塑细胞代谢功能的关键策略
IF 5.7 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-05-19 DOI: 10.1002/btm2.70027
Muhammad Samee Mubarik, Zizhen Zhao, Mehdi Khoshnamvand, De-Sheng Pei, Ailing Fu
{"title":"Mitochondrial and photosynthetic therapy: A crucial strategy for remodeling cellular metabolic function","authors":"Muhammad Samee Mubarik,&nbsp;Zizhen Zhao,&nbsp;Mehdi Khoshnamvand,&nbsp;De-Sheng Pei,&nbsp;Ailing Fu","doi":"10.1002/btm2.70027","DOIUrl":"10.1002/btm2.70027","url":null,"abstract":"<p>Extranuclear organelle transplantation, an emerging field in cell biology and bioengineering, presents innovative therapeutic possibilities by transferring organelles such as mitochondria between cells or across species. In living organisms, mitochondria and chloroplasts are closely related to converting substances and energy within cells. Transplantation therapy of mitochondria seeks to rebuild cell metabolic function in diseased or damaged cells and has broad application potential in treating metabolic diseases. The therapies provide a distinctive technology for cellular restoration by targeting energy generation at the organelle level, which will offer new energy resources for animal cells. At present, mitochondrial transplantation therapy has been applied as a novel approach to rescue patients in clinical settings, and chloroplast-based transplantation endows animal cells to utilize light energy (photosynthetic animal cells). In this review, we discuss the exciting development and application prospects of mitochondrial and photosynthetic therapy in biomedicine. The technology of extranuclear transplantation would exert innovative and profound impacts on biological therapy.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergizing photodynamic therapy and ethanol ablation: Light-activatable sustained-exposure ethanol injection technology for enhanced tumor ablation 协同光动力治疗和乙醇消融:光激活持续暴露乙醇注射技术增强肿瘤消融
IF 5.7 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-05-15 DOI: 10.1002/btm2.70028
Chen-Hua Ma, Jeffrey Yang, John A. Quinlan, Kathryn McNaughton, Michele L. Kaluzienski, Tessa Hauser, Matthew F. Starost, Jenna L. Mueller, Huang-Chiao Huang
{"title":"Synergizing photodynamic therapy and ethanol ablation: Light-activatable sustained-exposure ethanol injection technology for enhanced tumor ablation","authors":"Chen-Hua Ma,&nbsp;Jeffrey Yang,&nbsp;John A. Quinlan,&nbsp;Kathryn McNaughton,&nbsp;Michele L. Kaluzienski,&nbsp;Tessa Hauser,&nbsp;Matthew F. Starost,&nbsp;Jenna L. Mueller,&nbsp;Huang-Chiao Huang","doi":"10.1002/btm2.70028","DOIUrl":"10.1002/btm2.70028","url":null,"abstract":"<p>Chemical ablative therapies offer effective alternatives for tumor treatment, particularly when surgical resection or heat-based ablation therapies are unsuitable due to the tumor's stage, location, or extent. Photodynamic therapy (PDT), which involves delivering light-activated, tumor-killing photosensitizers, and percutaneous ethanol injection (PEI), which involves the direct injection of pure ethanol into tumor nodules, are two non-heat-based chemical ablative methods that have been proven safe with low adverse effects for unresectable tumors. We have investigated combining these two treatments using a new formulation known as BPD-EC-EtOH. This formulation includes three components: (1) benzoporphyrin derivative, a commonly used photosensitizer for PDT; (2) ethyl cellulose (EC), an FDA-approved polymer that forms a gel in the water phase and enhances drug retention; and (3) pure ethanol for PEI application. Here, we demonstrated the localization of BPD and confirmed that it retains its photochemical properties within the EC-EtOH gel in tissue-mimicking phantoms and in swine liver tissues. We also characterized EC's ability to act as a light-scattering agent, which effectively extends light propagation distance in both in vitro models and ex vivo porcine liver tissues, potentially overcoming the limitations of light penetration in pigmented organs. We then investigated the therapeutic effects of BPD-EC-EtOH using two well-established subcutaneous animal models of hepatocellular carcinoma and pancreatic ductal adenocarcinoma, both in single- and multi-cycle combination treatments, showing tumor-killing effects. These findings highlight the potential of BPD-EC-EtOH as a novel therapeutic approach, effective with either single or multi-cycle treatment sessions.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolic and proteomic signatures differentiate inflammatory phenotypes from cancer and predict treatment response in patient sera 代谢和蛋白质组学特征区分炎症表型和癌症,并预测患者血清中的治疗反应
IF 5.7 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-05-15 DOI: 10.1002/btm2.70029
Gabriel Cutshaw, Elena V. Demidova, Philip Czyzewicz III, Elizabeth Quam, Nicole Lorang, AL Warith AL Siyabi, Surinder Batra, Sanjeevani Arora, Rizia Bardhan
{"title":"Metabolic and proteomic signatures differentiate inflammatory phenotypes from cancer and predict treatment response in patient sera","authors":"Gabriel Cutshaw,&nbsp;Elena V. Demidova,&nbsp;Philip Czyzewicz III,&nbsp;Elizabeth Quam,&nbsp;Nicole Lorang,&nbsp;AL Warith AL Siyabi,&nbsp;Surinder Batra,&nbsp;Sanjeevani Arora,&nbsp;Rizia Bardhan","doi":"10.1002/btm2.70029","DOIUrl":"10.1002/btm2.70029","url":null,"abstract":"<p>Tumors shift their metabolic needs to enable uncontrolled proliferation. Therefore, metabolic assessment of cancer patient sera provides a significant opportunity to noninvasively monitor disease progression and enable mechanistic understanding of the pathways that lead to response. Here, we show Raman spectroscopy (RS), a highly sensitive and label-free analytical tool, is effective in metabolic profiling across diverse cancer types in patient sera from both pancreatic ductal adenocarcinoma (PDAC) and locally advanced rectal cancer (LARC). We also combine metabolic data with proteomic signatures to predict treatment response. Our data show RS peaks successfully differentiate PDAC patients from healthy controls. Peaks associated with sugars, tyrosine, and DNA/RNA distinguish PDAC patients from chronic pancreatitis, an inflammatory condition that is notoriously difficult to discern from PDAC via current clinical approaches. Furthermore, our study is expanded to investigate response to chemoradiation therapy in LARC patient sera where at pre-treatment multiple metabolites including glycine, carotenoids, and sugars are jointly correlated to the neoadjuvant rectal (NAR) score indicative of poor prognosis. Via classical univariate AUC–ROC analysis, several RS peaks were found to have an AUC&gt;0.7, highlighting the potential of RS in identifying key metabolites for differentiating complete and poor responders of treatment. Gene set enrichment analysis revealed enrichment of metabolic, immune, and DDR-related pathways associated with CRT response. Notably, RS-derived metabolites were significantly correlated with multiple immune signaling proteins and DDR markers, suggesting these distinct analytes converge to reflect systemic changes within the tumor microenvironment. By integrating metabolic, proteomic, and DDR data, we identified pre-treatment activation of galactose and glycerolipid metabolism, and post-treatment engagement of cell cycle and p53 signaling pathways. Our findings show that RS, when integrated with complementary protein marker analysis, holds the potential to bridge the translational divide enabling a clinically relevant approach for both diagnosis and predicting response in patient samples.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Self‐assembly of verteporfin dimers into folate receptor‐targeted lipid nanoparticles for photodynamic therapy of ovarian cancer 维替泊芬二聚体自组装成叶酸受体靶向脂质纳米颗粒用于卵巢癌光动力治疗
IF 7.4 2区 医学
Bioengineering & Translational Medicine Pub Date : 2025-05-14 DOI: 10.1002/btm2.70031
Carla Arnau del Valle, Payal Srivastava, Kathryn McNaughton, Huang‐Chiao Huang
{"title":"Self‐assembly of verteporfin dimers into folate receptor‐targeted lipid nanoparticles for photodynamic therapy of ovarian cancer","authors":"Carla Arnau del Valle, Payal Srivastava, Kathryn McNaughton, Huang‐Chiao Huang","doi":"10.1002/btm2.70031","DOIUrl":"https://doi.org/10.1002/btm2.70031","url":null,"abstract":"Photodynamic therapy (PDT) is a minimally invasive treatment that involves the administration of a light‐activatable drug followed by light activation of the lesion to produce reactive oxygen species that kill cancer cells. Visudyne®, a liposomal formulation of benzoporphyrin derivative (BPD) photosensitizer, is clinically approved for PDT of ocular diseases and is now being tested for PDT and imaging of pancreatic, brain, and other cancers. While Visudyne® improves the pharmacokinetics of BPD, it lacks treatment selectivity. To reduce PDT‐associated side effects such as skin and bowel toxicity while enhancing therapeutic outcomes, developing cancer‐targeted BPD nanotechnology is essential. Many cancers are characterized by overexpression of folate receptor (FR) and present high levels of glutathione (GSH). Here, we report the synthesis of a dimeric‐BPD (dBPD) activatable by red light for PDT and imaging of cancer cells. Self‐assembled lipid nanoparticles (NPs) are developed by the aggregation of dBPD and further functionalized with FA (FA‐dBPD‐NPs) and with drug release capability via cleavage of the disulfide linkers through GSH. The FA‐dBPD‐NPs present high drug payload, GSH‐triggered release effect, FRs overexpressing cell targeting, endoplasmic reticulum accumulation, and effective PDT in ovarian cancer cells.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"14 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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