Pub Date : 2025-09-27DOI: 10.1016/j.bmt.2025.100112
Jing Chen , Xu Zhu , Jun Huo , Shang Wu , Ting Zhou , Chunyu Cheng , Hao Dong , Yan Li , Xianchi Dong , Yuxin Chen
CD4+ T cells play a pivotal role in adaptive immunity, recognizing peptide antigens presented by MHC II molecules during infections and tumor development. Identifying immunodominant MHC II epitopess is essential for understanding CD4+ T cell responses; however, current methods such as mass spectrometry, suffer from low sensitivity and throughput, while computational algorithms show variable accuracy. To overcome these challenges, we developed EliteMHCII, a high-throughput immunopeptidome profiling platform that identifies antigen-derived MHC II epitopes and measures peptide binding affinity across 24 globally common MHC II alleles. Using EliteMHCII, we assessed the immunodominant epitopes of the SARS-CoV-2 RBD protein. Validation in vaccinated individuals and humanized mouse models revealed a strong correlation between high-affinity peptides and robust CD4+ T cell responses, while low-affinity peptides failed to elicit responses. Therefore, our immunopeptidome profiling platform, EliteMHCII, serves as a rapid, high throughput, feasible platform for CD4+ T cell epitope discovery at a global populational level in the context of infectious diseases and cancer immunotherapy.
{"title":"A high-throughput immunopeptidome platform for MHC II alleles to characterize antigen-specific CD4+ T cells","authors":"Jing Chen , Xu Zhu , Jun Huo , Shang Wu , Ting Zhou , Chunyu Cheng , Hao Dong , Yan Li , Xianchi Dong , Yuxin Chen","doi":"10.1016/j.bmt.2025.100112","DOIUrl":"10.1016/j.bmt.2025.100112","url":null,"abstract":"<div><div>CD4<sup>+</sup> T cells play a pivotal role in adaptive immunity, recognizing peptide antigens presented by MHC II molecules during infections and tumor development. Identifying immunodominant MHC II epitopess is essential for understanding CD4<sup>+</sup> T cell responses; however, current methods such as mass spectrometry, suffer from low sensitivity and throughput, while computational algorithms show variable accuracy. To overcome these challenges, we developed EliteMHCII, a high-throughput immunopeptidome profiling platform that identifies antigen-derived MHC II epitopes and measures peptide binding affinity across 24 globally common MHC II alleles. Using EliteMHCII, we assessed the immunodominant epitopes of the SARS-CoV-2 RBD protein. Validation in vaccinated individuals and humanized mouse models revealed a strong correlation between high-affinity peptides and robust CD4<sup>+</sup> T cell responses, while low-affinity peptides failed to elicit responses. Therefore, our immunopeptidome profiling platform, EliteMHCII, serves as a rapid, high throughput, feasible platform for CD4<sup>+</sup> T cell epitope discovery at a global populational level in the context of infectious diseases and cancer immunotherapy.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100112"},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The emergence of cultivated meat has attracted much attention as a revolutionary product for meat. Biomaterial scaffolds are the key component and have been extensively studied in cultivated meat production, enabling cell adhesion, proliferation, and directed differentiation. However, the structural and mechanical biomimicry of edible scaffolds is hard to be achieved, hindering the large-scale production of cultivated meats. In this paper, we comprehensively summarize the construction of cultivated meat from cell-laden biomimetic scaffolds and its future research directions. We describe the cellular components of cultivated meat composition and their culture medium components. To tailor more edible scaffolds for high-efficient production of cultivated meats, advanced techniques including 3D bioprinting, electrostatic spinning, and tissue molding techniques have been developed. We then discuss recent research advances in scaffolding materials that maintain the three-dimensional (3D) morphology of cultivated meats and bioreactors. Next, we discussed the conditions and problems that should be solved for the industrial production of cultivated meat. Finally, we outline current challenges in the development of cultivated meat and a prospective outlook for the future of cultivated meat. We anticipate that the continued development of cultivated meat will lead to significant advances in the food and medical fields.
{"title":"Engineering biomimetic scaffolds for cultivated meats","authors":"Lanlan Zhang , Yixuan Shang , Jingjing Gan , Zhuhao Wu , Yuanjin Zhao","doi":"10.1016/j.bmt.2025.100113","DOIUrl":"10.1016/j.bmt.2025.100113","url":null,"abstract":"<div><div>The emergence of cultivated meat has attracted much attention as a revolutionary product for meat. Biomaterial scaffolds are the key component and have been extensively studied in cultivated meat production, enabling cell adhesion, proliferation, and directed differentiation. However, the structural and mechanical biomimicry of edible scaffolds is hard to be achieved, hindering the large-scale production of cultivated meats. In this paper, we comprehensively summarize the construction of cultivated meat from cell-laden biomimetic scaffolds and its future research directions. We describe the cellular components of cultivated meat composition and their culture medium components. To tailor more edible scaffolds for high-efficient production of cultivated meats, advanced techniques including 3D bioprinting, electrostatic spinning, and tissue molding techniques have been developed. We then discuss recent research advances in scaffolding materials that maintain the three-dimensional (3D) morphology of cultivated meats and bioreactors. Next, we discussed the conditions and problems that should be solved for the industrial production of cultivated meat. Finally, we outline current challenges in the development of cultivated meat and a prospective outlook for the future of cultivated meat. We anticipate that the continued development of cultivated meat will lead to significant advances in the food and medical fields.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100113"},"PeriodicalIF":0.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-09DOI: 10.1016/j.bmt.2025.100102
Rong Lu , Kaibo Tang , Run Pan , Shangxuan Shi , Xiao'ao Xue , Tingfang Hwang , Yang Song , Weijun Tang , Yue Yu , He Wang , Yao Lu , Ting Lin
Background
Osteoarthritis (OA) is a degenerative joint disorder influenced by genetic, molecular, and environmental factors. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, necroptosis, ferroptosis, and autophagy, are linked to cartilage degradation, but their role in OA pathogenesis remains unclear.
Methods
Based on a large-scale GWAS database, this study employs a two-sample Mendelian randomization (MR) framework, integrating genomic data from 14 genes related to PCD at three levels (DNA methylation, gene expression, and protein abundance) to reveal causal relationships between these genes and OA. The MR analysis utilizes QTLs (mQTL, eQTL, and pQTL) as instrumental variables and employs five regression models (MR-Egger regression, Random-Effects Inverse Variance Weighted, Weighted Median, Weighted Mode, and Simple Mode) to assess causal effects. Furthermore, the reliability of causal inference is strengthened through FDR multiple testing correction, Steiger test, and colocalization analysis. Multi-omics evidence is integrated to identify key PCD genes causally related to OA. Finally, enrichment analysis, PPI analysis, and OA-related transcriptome analysis are used to explore the biological mechanisms of these key PCD genes.
Findings
Through MR analysis, we ultimately identified 103 PCD-related CpG sites, 170 PCD-related gene expressions, and 53 PCD-related protein levels that have significant causal relationships with OA. Multi-omics integration pinpointed 2 Tier 1 genes (CASP10, CASP3) and 14 Tier 2 genes (e.g., FGR, GAPDH). Validation across three cohorts confirmed causal associations for CASP10, GAPDH, PARK7, and others. Enrichment analysis implicated these genes in critical biological processes, such as neuronal apoptosis, protease binding, and the MAPK signaling pathway. Protein-protein interaction (PPI) network analysis identified CASP3 (Degree = 9) and CASP10 (Degree = 4) as central hubs, suggesting they may play a central role in the pathophysiological mechanisms of OA and could serve as potential therapeutic targets for OA. Transcriptome analysis confirmed MR findings. Tier 1 gene CASP3 was significantly upregulated in OA patients (log2FC = 1.30, adjusted P < 0.05), and CASP10 showed non-significant upregulation. Tier 2 genes (GAPDH, CD14, CHMP2B, GM2A, ITGAM) also showed significant changes (P < 0.05) consistent with MR results.
Interpretation
This study provides a multi-omic framework for understanding the role of PCD in OA, providing insights into potential PCD-targeted therapies.
{"title":"The biological association between programmed cell death function and osteoarthritis using multi-omic Mendelian Randomization","authors":"Rong Lu , Kaibo Tang , Run Pan , Shangxuan Shi , Xiao'ao Xue , Tingfang Hwang , Yang Song , Weijun Tang , Yue Yu , He Wang , Yao Lu , Ting Lin","doi":"10.1016/j.bmt.2025.100102","DOIUrl":"10.1016/j.bmt.2025.100102","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is a degenerative joint disorder influenced by genetic, molecular, and environmental factors. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, necroptosis, ferroptosis, and autophagy, are linked to cartilage degradation, but their role in OA pathogenesis remains unclear.</div></div><div><h3>Methods</h3><div>Based on a large-scale GWAS database, this study employs a two-sample Mendelian randomization (MR) framework, integrating genomic data from 14 genes related to PCD at three levels (DNA methylation, gene expression, and protein abundance) to reveal causal relationships between these genes and OA. The MR analysis utilizes QTLs (mQTL, eQTL, and pQTL) as instrumental variables and employs five regression models (MR-Egger regression, Random-Effects Inverse Variance Weighted, Weighted Median, Weighted Mode, and Simple Mode) to assess causal effects. Furthermore, the reliability of causal inference is strengthened through FDR multiple testing correction, Steiger test, and colocalization analysis. Multi-omics evidence is integrated to identify key PCD genes causally related to OA. Finally, enrichment analysis, PPI analysis, and OA-related transcriptome analysis are used to explore the biological mechanisms of these key PCD genes.</div></div><div><h3>Findings</h3><div>Through MR analysis, we ultimately identified 103 PCD-related CpG sites, 170 PCD-related gene expressions, and 53 PCD-related protein levels that have significant causal relationships with OA. Multi-omics integration pinpointed 2 Tier 1 genes (<em>CASP10</em>, <em>CASP3</em>) and 14 Tier 2 genes (e.g., <em>FGR</em>, <em>GAPDH</em>). Validation across three cohorts confirmed causal associations for <em>CASP10</em>, <em>GAPDH</em>, <em>PARK7</em>, and others. Enrichment analysis implicated these genes in critical biological processes, such as neuronal apoptosis, protease binding, and the MAPK signaling pathway. Protein-protein interaction (PPI) network analysis identified CASP3 (Degree = 9) and CASP10 (Degree = 4) as central hubs, suggesting they may play a central role in the pathophysiological mechanisms of OA and could serve as potential therapeutic targets for OA. Transcriptome analysis confirmed MR findings. Tier 1 gene <em>CASP3</em> was significantly upregulated in OA patients (log2FC = 1.30, adjusted <em>P</em> < 0.05), and <em>CASP10</em> showed non-significant upregulation. Tier 2 genes (<em>GAPDH</em>, <em>CD14</em>, <em>CHMP2B</em>, <em>GM2A</em>, <em>ITGAM</em>) also showed significant changes (<em>P</em> < 0.05) consistent with MR results.</div></div><div><h3>Interpretation</h3><div>This study provides a multi-omic framework for understanding the role of PCD in OA, providing insights into potential PCD-targeted therapies.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.bmt.2025.100101
Hongyi Chen , Rui Cheng , Se Hun Chung , Arsalan Marghoub , Hui Zhong , Guohao Fang , Stavroula Balabani , Lucy Di-Silvio , Jie Huang
Direct ink writing (DIW) is a room-temperature extrusion-based 3D printing technique that enables the fabrication of dense, customizable implants from viscous inks with precise spatial control. In this study, we present an engineering design framework for DIW-printed PCL/Laponite composites by tuning ink formulations and printing orientations to systematically investigate and control the complex interplay between shape fidelity, mechanical performance, and cellular response. Our findings show that printing at 0° orientation enhances filament-aligned surface topographies, which guide osteoblast attachment and significantly promote cell proliferation and mineralization. In contrast to previous studies using fused deposition modeling (FDM), we observe that printing at 90° orientation (perpendicular to the tensile load direction) results in higher mechanical performance due to improved filament bonding. Increasing Laponite loading (up to 30 %) improves shape retention by increasing ink viscosity, raises Young's modulus by up to 110 %, and enhances surface bioactivity by introducing hydrophilic and bioactive cues. This study provides a tunable strategy for engineering bioactive and surface-active implants for the clinical need for non-load-bearing orthopaedic applications where structural integrity, surface-mediated osteointegration, and customized geometry are clinically essential.
{"title":"Direct ink writing of bioactive PCL/laponite bone Implants: Engineering the interplay of design, process, structure, and function","authors":"Hongyi Chen , Rui Cheng , Se Hun Chung , Arsalan Marghoub , Hui Zhong , Guohao Fang , Stavroula Balabani , Lucy Di-Silvio , Jie Huang","doi":"10.1016/j.bmt.2025.100101","DOIUrl":"10.1016/j.bmt.2025.100101","url":null,"abstract":"<div><div>Direct ink writing (DIW) is a room-temperature extrusion-based 3D printing technique that enables the fabrication of dense, customizable implants from viscous inks with precise spatial control. In this study, we present an engineering design framework for DIW-printed PCL/Laponite composites by tuning ink formulations and printing orientations to systematically investigate and control the complex interplay between shape fidelity, mechanical performance, and cellular response. Our findings show that printing at 0° orientation enhances filament-aligned surface topographies, which guide osteoblast attachment and significantly promote cell proliferation and mineralization. In contrast to previous studies using fused deposition modeling (FDM), we observe that printing at 90° orientation (perpendicular to the tensile load direction) results in higher mechanical performance due to improved filament bonding. Increasing Laponite loading (up to 30 %) improves shape retention by increasing ink viscosity, raises Young's modulus by up to 110 %, and enhances surface bioactivity by introducing hydrophilic and bioactive cues. This study provides a tunable strategy for engineering bioactive and surface-active implants for the clinical need for non-load-bearing orthopaedic applications where structural integrity, surface-mediated osteointegration, and customized geometry are clinically essential.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"11 ","pages":"Article 100101"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cervical cancer is one of the leading causes of cancer-related deaths among women worldwide, imposing a particularly heavy burden in low- and middle-income countries. In recent years, advanced artificial intelligence (AI)-based technologies, including convolutional neural networks (CNNs) for image analysis and natural language processing (NLP) of electronic health records (EHRs), have substantially improved detection performance, individualized risk prediction, and the design of tailored treatment regimens. By leveraging expert visual recognition and synthesizing multimodal clinical data, these approaches offer the potential for more accurate screening and faster diagnosis. However, routine adoption hinges on resolving issues of data heterogeneity, algorithm interpretability, and ethical deployment. In this review, we summarize the latest AI breakthroughs in cervical cancer management, emphasize their promise for enhancing early intervention and personalized therapy, and call for rigorous validation to ensure safe, equitable integration into practice.
{"title":"Advanced AI-based technologies for early detection and personalized management of cervical cancer","authors":"Yuheng Zhang , Yazhang Xu , Chenxin Wang , Zengjie Zhang , Kailiang Zhou , Yueliang Zhu , Xiaohua Yu","doi":"10.1016/j.bmt.2025.100100","DOIUrl":"10.1016/j.bmt.2025.100100","url":null,"abstract":"<div><div>Cervical cancer is one of the leading causes of cancer-related deaths among women worldwide, imposing a particularly heavy burden in low- and middle-income countries. In recent years, advanced artificial intelligence (AI)-based technologies, including convolutional neural networks (CNNs) for image analysis and natural language processing (NLP) of electronic health records (EHRs), have substantially improved detection performance, individualized risk prediction, and the design of tailored treatment regimens. By leveraging expert visual recognition and synthesizing multimodal clinical data, these approaches offer the potential for more accurate screening and faster diagnosis. However, routine adoption hinges on resolving issues of data heterogeneity, algorithm interpretability, and ethical deployment. In this review, we summarize the latest AI breakthroughs in cervical cancer management, emphasize their promise for enhancing early intervention and personalized therapy, and call for rigorous validation to ensure safe, equitable integration into practice.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"11 ","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-31DOI: 10.1016/j.bmt.2025.100098
Yi Wu , Zhipeng Zhao , Shouchang Jiao , Tianhang Song , Cong Du , Binbin Fan , Yaokun Pang , Hua Yuan , Hanlin Ou
Organic room temperature phosphorescent (RTP) materials, characterized by their prolonged luminescence lifetime and superior biocompatibility, exhibit significant potential for applications in bioimaging. Through the application of time resolved techniques, the interference caused by tissue autofluorescence can be substantially minimized, enabling high signal-to-background ratio imaging. Furthermore, these materials serve as promising candidates for temperature sensing probes and photodynamic therapy agents. Although research on RTP materials has expanded rapidly in recent years, a comprehensive review covering organometallic and pure organic phosphorescent materials for bioimaging remains limited. This paper systematically summarizes recent advancements in both organometallic and pure organic phosphorescent materials used in bioimaging and critically discusses the challenges they encounter, aiming to provide valuable insights for future developments in this field.
{"title":"Recent advances in organic phosphorescent materials for bioimaging","authors":"Yi Wu , Zhipeng Zhao , Shouchang Jiao , Tianhang Song , Cong Du , Binbin Fan , Yaokun Pang , Hua Yuan , Hanlin Ou","doi":"10.1016/j.bmt.2025.100098","DOIUrl":"10.1016/j.bmt.2025.100098","url":null,"abstract":"<div><div>Organic room temperature phosphorescent (RTP) materials, characterized by their prolonged luminescence lifetime and superior biocompatibility, exhibit significant potential for applications in bioimaging. Through the application of time resolved techniques, the interference caused by tissue autofluorescence can be substantially minimized, enabling high signal-to-background ratio imaging. Furthermore, these materials serve as promising candidates for temperature sensing probes and photodynamic therapy agents. Although research on RTP materials has expanded rapidly in recent years, a comprehensive review covering organometallic and pure organic phosphorescent materials for bioimaging remains limited. This paper systematically summarizes recent advancements in both organometallic and pure organic phosphorescent materials used in bioimaging and critically discusses the challenges they encounter, aiming to provide valuable insights for future developments in this field.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"11 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-24DOI: 10.1016/j.bmt.2025.100088
Shuxin Zhong , Dingrui Nie , Xueting Peng , Kangjie Qiu , Jinyi Liu , Zhangshuai Dai , Xianfeng Zha , Songnan Sui , Weini Li , Weizhang Wang , Cunte Chen , Yangqiu Li , Chengwu Zeng
BCR-ABL positive (BCR-ABL+) leukemia is driven by constitutive activation of tyrosine kinase activity, with tyrosine kinase inhibitors (TKIs) serving as the standard treatment. However, resistance to TKIs remains a significant clinical challenge. In this study, we demonstrate that HSPA8 is highly expressed in BCR-ABL+ leukemia cells, and elevated HSPA8 expression correlates with poor prognosis in BCR-ABL+ B-acute lymphoblastic leukemia (B-ALL). Inhibition of HSPA8 using Apoptozole (Az) or VER15508 (VER) reduced the viability of BCR-ABL+ leukemia cells, induced cell death, and suppressed colony formation. Through proteomic analysis, we identified GPX4, a key regulator of ferroptosis, as a major target of HSPA8 inhibition. Notably, co-treatment with HSPA8 inhibitors and GPX4 inhibitors (RSL3), or TKIs, synergistically downregulated GPX4 expression and induced ferroptosis in BCR-ABL+ leukemia cells, including those resistant to TKIs. In vivo, combination therapy with Az and RSL3 significantly prolonged survival in a BCR-ABL+ leukemia mouse model. Overall, our findings provide compelling evidence that targeting HSPA8, in combination with GPX4 inhibition or TKIs, can effectively induce ferroptosis, overcome drug resistance, and offer a novel therapeutic strategy for these malignancies.
BCR-ABL阳性（BCR-ABL+）白血病是由酪氨酸激酶活性的组成性激活驱动的，酪氨酸激酶抑制剂（TKIs）作为标准治疗。然而，对TKIs的耐药性仍然是一个重大的临床挑战。在本研究中，我们证实HSPA8在BCR-ABL+白血病细胞中高表达，并且HSPA8表达升高与BCR-ABL+ b -急性淋巴细胞白血病（B-ALL）的预后不良相关。凋亡唑（Az）或VER15508 （VER）抑制HSPA8降低BCR-ABL+白血病细胞的活力，诱导细胞死亡，抑制集落形成。通过蛋白质组学分析，我们确定了铁ptosis的关键调节因子GPX4是HSPA8抑制的主要靶点。值得注意的是，与HSPA8抑制剂和GPX4抑制剂（RSL3）或TKIs共同治疗，协同下调GPX4表达并诱导BCR-ABL+白血病细胞（包括对TKIs耐药的细胞）铁下垂。在体内，Az和RSL3联合治疗可显著延长BCR-ABL+白血病小鼠模型的生存期。总之，我们的研究结果提供了令人信服的证据，表明靶向HSPA8，结合GPX4抑制或TKIs，可以有效地诱导铁下垂，克服耐药性，并为这些恶性肿瘤提供了一种新的治疗策略。
{"title":"Targeting HSPA8 to repress GPX4 and induce ferroptosis in BCR-ABL positive leukemia","authors":"Shuxin Zhong , Dingrui Nie , Xueting Peng , Kangjie Qiu , Jinyi Liu , Zhangshuai Dai , Xianfeng Zha , Songnan Sui , Weini Li , Weizhang Wang , Cunte Chen , Yangqiu Li , Chengwu Zeng","doi":"10.1016/j.bmt.2025.100088","DOIUrl":"10.1016/j.bmt.2025.100088","url":null,"abstract":"<div><div>BCR-ABL positive (BCR-ABL+) leukemia is driven by constitutive activation of tyrosine kinase activity, with tyrosine kinase inhibitors (TKIs) serving as the standard treatment. However, resistance to TKIs remains a significant clinical challenge. In this study, we demonstrate that HSPA8 is highly expressed in BCR-ABL+ leukemia cells, and elevated HSPA8 expression correlates with poor prognosis in BCR-ABL+ B-acute lymphoblastic leukemia (B-ALL). Inhibition of HSPA8 using Apoptozole (Az) or VER15508 (VER) reduced the viability of BCR-ABL+ leukemia cells, induced cell death, and suppressed colony formation. Through proteomic analysis, we identified GPX4, a key regulator of ferroptosis, as a major target of HSPA8 inhibition. Notably, co-treatment with HSPA8 inhibitors and GPX4 inhibitors (RSL3), or TKIs, synergistically downregulated GPX4 expression and induced ferroptosis in BCR-ABL+ leukemia cells, including those resistant to TKIs. In vivo, combination therapy with Az and RSL3 significantly prolonged survival in a BCR-ABL+ leukemia mouse model. Overall, our findings provide compelling evidence that targeting HSPA8, in combination with GPX4 inhibition or TKIs, can effectively induce ferroptosis, overcome drug resistance, and offer a novel therapeutic strategy for these malignancies.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"11 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) remain a major global health challenge due to their progressive nature and lack of curative treatments. Traditional animal models and 2D cell cultures fail to recapitulate the complex microenvironment and human-specific pathophysiology of these disorders. In response, advanced 3D in vitro models incorporating functional biomaterials have emerged as promising platforms for replicating disease mechanisms, enabling personalized medicine, and accelerating therapeutic discovery. This review highlights recent progress in the design and application of bioinspired and engineered biomaterials, including natural, synthetic, and hybrid scaffolds, which mimic the extracellular matrix and guide neural cell behavior. Hydrogels, stimuli-responsive polymers, and conductive nanocomposites are increasingly used in scaffold fabrication and 3D bioprinting. Integration with patient-derived induced pluripotent stem cells (iPSCs) and microfluidic platforms enables the creation of physiologically relevant models that replicate key pathological features. We discuss the importance of quantitative materials characterization including porosity, stiffness, swelling, degradation, and wettability in ensuring scaffold reproducibility and translational relevance. Despite challenges like vascularization and culture stability, innovations are addressing these barriers. Advanced biomaterials enable precise cell placement and structure. High-precision bioprinting and microfluidics support perfusable vessels. AI-driven data integration enhances scalability, optimizes conditions, analyzes large datasets, and improves reproducibility by minimizing batch variability in 3D in vitro models. Recent advances in bioelectric and electrochemical biomaterials including piezoelectric PLLA membranes, wirelessly self-powered Zn/Ag2O scaffolds, 3D-printed carbon nanoelectrodes, and conductive POSS-PCL/graphene nanocomposites offer promising multifunctional platforms for 3D neurodegenerative disease models.
{"title":"Advanced 3D biomaterials and bioprinting strategies for in vitro modeling of neurodegenerative diseases","authors":"Meenaloshini Gopalakrishnan , Deepshikaa Kannan , Karthikeyan Elumalai , Karthik Karunakar , Sujaritha Jayaraj , Mahalakshmi Devaraji , Nandhini Jayaprakash","doi":"10.1016/j.bmt.2025.100089","DOIUrl":"10.1016/j.bmt.2025.100089","url":null,"abstract":"<div><div>Neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) remain a major global health challenge due to their progressive nature and lack of curative treatments. Traditional animal models and 2D cell cultures fail to recapitulate the complex microenvironment and human-specific pathophysiology of these disorders. In response, advanced 3D in vitro models incorporating functional biomaterials have emerged as promising platforms for replicating disease mechanisms, enabling personalized medicine, and accelerating therapeutic discovery. This review highlights recent progress in the design and application of bioinspired and engineered biomaterials, including natural, synthetic, and hybrid scaffolds, which mimic the extracellular matrix and guide neural cell behavior. Hydrogels, stimuli-responsive polymers, and conductive nanocomposites are increasingly used in scaffold fabrication and 3D bioprinting. Integration with patient-derived induced pluripotent stem cells (iPSCs) and microfluidic platforms enables the creation of physiologically relevant models that replicate key pathological features. We discuss the importance of quantitative materials characterization including porosity, stiffness, swelling, degradation, and wettability in ensuring scaffold reproducibility and translational relevance. Despite challenges like vascularization and culture stability, innovations are addressing these barriers. Advanced biomaterials enable precise cell placement and structure. High-precision bioprinting and microfluidics support perfusable vessels. AI-driven data integration enhances scalability, optimizes conditions, analyzes large datasets, and improves reproducibility by minimizing batch variability in 3D in vitro models. Recent advances in bioelectric and electrochemical biomaterials including piezoelectric PLLA membranes, wirelessly self-powered Zn/Ag<sub>2</sub>O scaffolds, 3D-printed carbon nanoelectrodes, and conductive POSS-PCL/graphene nanocomposites offer promising multifunctional platforms for 3D neurodegenerative disease models.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"11 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144272579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aortic valve calcification (AVC) represents a progressive, age-associated disorder characterized by substantial mortality, yet effective early diagnostic markers for AVC complicated by periodontitis, a common inflammatory condition linked to systemic inflammation, remain elusive. Our investigation sought to uncover immune-specific molecular indicators for AVC in patients with periodontitis using bioinformatics and machine learning.
Methods
Gene expression data for AVC (utilizing datasets GSE153555, GSE148219, GSE51472) and periodontitis (from dataset GSE16134) underwent analysis. We identified differentially expressed genes (DEGs) and determined the overlapped genes between AVC and periodontitis. The study included functional enrichment, protein-protein interaction (PPI) network construction, and immune infiltration analyses. To screen potential target genes, four machine learning models were developed (SVM, RF, XGB, GLM), with validation performed using an external dataset and clinical specimens via qRT-PCR.
Results
A total of 30 intersecting genes between AVC and periodontitis were identified. Four key genes—CXCL12, HCST, ITGA4, and GZMK—were selected through machine learning. The nomogram model combining these genes demonstrated high diagnostic accuracy, with an AUC of 0.985 in the training set and AUC values of 0.8, 0.72, 0.88, and 0.76 for HCST, ITGA4, CXCL12, and GZMK, respectively, in the external validation using the GSE51472 dataset. qRT-PCR validation in clinical samples confirmed that these genes were significantly upregulated in AVC patients with periodontitis. These genes were also correlated with immune cell infiltration, suggesting their potential role in AVC pathogenesis.
Conclusion
These findings provide new clinical molecular diagnostics, treatment related molecular markers for AVC in patients with periodontitis and may facilitate further basic research into biological functions.
{"title":"Integrated bioinformatics analysis and machine learning approach for the identification of immune-related genes in the diagnosis of aortic valve calcification with periodontitis","authors":"Duolikun Mutailifu, Abudousaimi Aini, Abudunaibi Maimaitiaili","doi":"10.1016/j.bmt.2025.100087","DOIUrl":"10.1016/j.bmt.2025.100087","url":null,"abstract":"<div><h3>Background</h3><div>Aortic valve calcification (AVC) represents a progressive, age-associated disorder characterized by substantial mortality, yet effective early diagnostic markers for AVC complicated by periodontitis, a common inflammatory condition linked to systemic inflammation, remain elusive. Our investigation sought to uncover immune-specific molecular indicators for AVC in patients with periodontitis using bioinformatics and machine learning.</div></div><div><h3>Methods</h3><div>Gene expression data for AVC (utilizing datasets GSE153555, GSE148219, GSE51472) and periodontitis (from dataset GSE16134) underwent analysis. We identified differentially expressed genes (DEGs) and determined the overlapped genes between AVC and periodontitis. The study included functional enrichment, protein-protein interaction (PPI) network construction, and immune infiltration analyses. To screen potential target genes, four machine learning models were developed (SVM, RF, XGB, GLM), with validation performed using an external dataset and clinical specimens via qRT-PCR.</div></div><div><h3>Results</h3><div>A total of 30 intersecting genes between AVC and periodontitis were identified. Four key genes—CXCL12, HCST, ITGA4, and GZMK—were selected through machine learning. The nomogram model combining these genes demonstrated high diagnostic accuracy, with an AUC of 0.985 in the training set and AUC values of 0.8, 0.72, 0.88, and 0.76 for HCST, ITGA4, CXCL12, and GZMK, respectively, in the external validation using the GSE51472 dataset. qRT-PCR validation in clinical samples confirmed that these genes were significantly upregulated in AVC patients with periodontitis. These genes were also correlated with immune cell infiltration, suggesting their potential role in AVC pathogenesis.</div></div><div><h3>Conclusion</h3><div>These findings provide new clinical molecular diagnostics, treatment related molecular markers for AVC in patients with periodontitis and may facilitate further basic research into biological functions.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"10 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01DOI: 10.1016/j.bmt.2025.100085
Mujibur Khan , Jannatul Ferdaus , Khaleda Akter , Hossain Ahmed , Mahrima Parvin , Sawaiz Kashif , Ali S. Arbab
The advent of nanotechnology has significantly advanced cancer treatment by introducing innovative approaches to targeted drug delivery and enhanced therapeutic efficiency. Nano drugs and nanocarriers, owing to their nanoscale dimensions, extensive surface area, and ability to modulate biodistribution, have proven effective in localizing tumor sites and enabling sustained drug release. These properties result in greater cytotoxicity and minimize systemic side effects compared to conventional therapies. Moreover, nanoparticles can be functionalized with molecular targeting agents, such as peptides, and combined with imaging dyes to improve the precision and monitoring of in-vivo treatments. A promising development in this domain is the utilization of biological carriers, particularly exosomes. These extracellular vesicles (30–150 nm in size) are secreted by various cells and possess a unique capacity to influence the tumor microenvironment through intercellular interactions and direct fusion with cell membranes. This review examines recent advancements in cancer drug delivery, with an emphasis on the design and processing of nano drugs and evaluates the potential of engineered exosomes as a transformative modality in cancer therapeutics.
{"title":"A comprehensive review of cancer drug nanoparticles synthesis, processing technology and its effect in drug delivery","authors":"Mujibur Khan , Jannatul Ferdaus , Khaleda Akter , Hossain Ahmed , Mahrima Parvin , Sawaiz Kashif , Ali S. Arbab","doi":"10.1016/j.bmt.2025.100085","DOIUrl":"10.1016/j.bmt.2025.100085","url":null,"abstract":"<div><div>The advent of nanotechnology has significantly advanced cancer treatment by introducing innovative approaches to targeted drug delivery and enhanced therapeutic efficiency. Nano drugs and nanocarriers, owing to their nanoscale dimensions, extensive surface area, and ability to modulate biodistribution, have proven effective in localizing tumor sites and enabling sustained drug release. These properties result in greater cytotoxicity and minimize systemic side effects compared to conventional therapies. Moreover, nanoparticles can be functionalized with molecular targeting agents, such as peptides, and combined with imaging dyes to improve the precision and monitoring of in-vivo treatments. A promising development in this domain is the utilization of biological carriers, particularly exosomes. These extracellular vesicles (30–150 nm in size) are secreted by various cells and possess a unique capacity to influence the tumor microenvironment through intercellular interactions and direct fusion with cell membranes. This review examines recent advancements in cancer drug delivery, with an emphasis on the design and processing of nano drugs and evaluates the potential of engineered exosomes as a transformative modality in cancer therapeutics.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"10 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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