Biomedical Technology最新文献

{"title":"Integrated strategy of collagen fiber arrangement-inspired magnetic nanochain-doped ordered biphasic scaffold and gradient magnetic field stimulation for osteochondral regeneration","authors":"Junwei Xu ,&nbsp;Yi Cui ,&nbsp;Xuemei Sun ,&nbsp;Zhiheng Chen ,&nbsp;Kun Li ,&nbsp;Meili Liu ,&nbsp;Ping Li","doi":"10.1016/j.bmt.2026.100134","DOIUrl":"10.1016/j.bmt.2026.100134","url":null,"abstract":"<div><h3>Background</h3><div>Osteochondral defects pose significant clinical challenges owing to the complex anisotropic collagen alignment of osteochondral tissue and its limited self-healing capacity. Although mechanically biomimetic scaffolds have been widely applied in osteochondral repair, existing scaffolds exhibit limited structural and functional biomimicry, resulting in osteochondral repair efficacy that requires further improvement.</div></div><div><h3>Technology</h3><div>Bioinspired by the unique collagen fiber alignment of natural osteochondral tissue, this study developed a technology of magnetically guided ordered biphasic scaffold combined with gradient magnetic field stimulation. Via alkaline dissolution and thermal crosslinking, Fe₃O₄ nanochains (NCs) were horizontally oriented in the agarose-based cartilage phase and vertically oriented in the poly(ethylene glycol) diacrylate/agarose-based subchondral bone phase. This scaffold system synergized with a 3–15 mT gradient magnetic field (MF) to enable the integrated repair of osteochondral defects.</div></div><div><h3>Results</h3><div>We adjusted the scaffold's magnetism by modulating the content of Fe₃O₄ NCs, and further investigated the impacts of the magnetic ordered scaffolds and external MF on the differentiation of bone marrow mesenchymal stem cells. Results showed that the cartilage-phase scaffold (0.025 % w/v NCs, 0.27 emu/g) upregulated type II collagen (chondrogenesis), while the subchondral bone-phase scaffold (1.0 % w/v NCs, 1.20 emu/g) boosted osteogenic differentiation. Specifically, 3 mT static MF enhanced chondrogenesis via ECM-receptor signaling, while 15 mT static MF stimulated osteogenesis by activating PI3K/Akt pathway. Animal studies demonstrated that the magnetic biphasic hierarchical scaffold combined with 3–15 mT gradient MF significantly improved osteochondral repair, including nearly double the new subchondral bone volume fraction, a smoother cartilage surface, and collagen fiber alignment that more closely resembled natural osteochondral tissue. This work highlights the potential of the magnetic ordered scaffold-gradient MF technology in osteochondral repair, and is further poised for synergistic development with 3D bioprinting, intelligent manufacturing, and single-cell sequencing, injecting new impetus into the clinical translation of magnetic tissue engineering.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"13 ","pages":"Article 100134"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173671","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}

{"title":"Barcode screening reveals the key role of gold nanoparticle morphology in tumor targeting","authors":"Chaojin Li ,&nbsp;Feng Gong ,&nbsp;Xiaodong Liu ,&nbsp;Ang Li","doi":"10.1016/j.bmt.2026.100135","DOIUrl":"10.1016/j.bmt.2026.100135","url":null,"abstract":"<div><div>Currently, nanoparticles (NPs) still face challenges in achieving efficient tumor targeted delivery, especially in balancing in vivo distribution and cellular uptake efficiency. A recent study published in Advanced Functional Materials utilized DNA barcoding combined with high-throughput in vivo screening to systematically evaluate the targeting of gold NPs of different shapes and sizes in tumors. The results showed that large-sized triangular gold NPs exhibited the highest cellular uptake efficiency in vitro, and achieved significant tumor enrichment and excellent siRNA delivery in vivo through surface modification of RGD peptides. Further photothermal experiments showed that triangular particles can rapidly raise the temperature to 57 °C in the tumor area, achieving effective tumor ablation. This study indicates that large triangular gold NPs possess advantages in cellular uptake, in vivo enrichment ability, and photothermal therapy potential, providing a new strategy for precise tumor targeted therapy. The study highlights that nanoparticle morphology plays a dominant role in governing in vivo tumor accumulation and therapeutic outcomes.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"13 ","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173763","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}

{"title":"Integrated tardigrade-based biomimetic strategy and stem cell expansion and differentiation for a novel radioprotection approach","authors":"Biao Zhang ,&nbsp;Jun-Nian Zhou ,&nbsp;Quan Zeng ,&nbsp;Zhi-Rui Liu,&nbsp;Yu-Ting Gao,&nbsp;Fu-Dong Chen,&nbsp;Tao Fan,&nbsp;Ya-Li Jia,&nbsp;Jia-Fei Xi,&nbsp;Xue-Tao Pei,&nbsp;Wen Yue","doi":"10.1016/j.bmt.2025.100132","DOIUrl":"10.1016/j.bmt.2025.100132","url":null,"abstract":"<div><h3>Background</h3><div>Tardigrades have attracted widespread research attention due to their extraordinary radiotolerance, of which the damage suppressor protein (DSUP) is regarded as a key molecule responsible for their robust DNA repair capability. How to translate these findings into safe and efficacious radioprotection strategies for humans remains an ongoing research challenge.</div></div><div><h3>Technology</h3><div>Given that ionizing radiation (IR)-induced hematopoietic failure caused by depletion of bone marrow hematopoietic stem/progenitor cells (HSPCs) is a major cause of mortality, we propose using gene editing and stem cell technologies to precisely knock in DSUP gene into isolated murine HSPCs, thereby generating HSPCs with enhanced radiotolerance. In this study, we first obtained DSUP-modified mouse HSPCs by isolating, culturing, and transfecting mouse HSPCs using lentivirus transfection, as well as DSUP-modified human HSPCs via three stages of hematopoietic induction and differentiation from DSUP-modified human pluripotent stem cells (PSCs).</div></div><div><h3>Results</h3><div>The radioprotection capacity of <em>DSUP</em>-modified stem cells was confirmed by a series of <em>in vitro</em> assays. Given the differentiation potential of myeloid progenitor cells (MPCs) and without requirement for human leukocyte antigen matching during hematopoietic stem cell transplant, we then obtained <em>DSUP</em>-modified mouse MPCs by differentiated from the expanded mouse HSPCs in polyvinyl alcohol (PVA) culture system for more than 30 days. <em>DSUP</em>-modified MPCs can also maintain lower radiation-induced apoptosis and DNA damage. Pre-infusion of <em>DSUP</em>-modified MPCs improves irradiated-mice survival rate by 30 % without long-term side effects. While not residing in bone marrow or spleen, these cells alleviated hematopoietic failure by restoring peripheral red blood cells and platelets and accelerated hematopoietic recovery. Mechanistically, DSUP forms phase separation structures that can recruit DNA repair proteins to double-strand breaks, promoting homologous recombination repair. Taken together, our results demonstrated <em>DSUP</em>-modified MPCs offer a promising stem cell-based radioprotection technology, highlighting a novel biomimetic approach for radioprotection.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"13 ","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079319","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}

{"title":"Biocompatible screw-based biomechanical alignment technique for improving surgical effect in adolescent flexible flatfoot","authors":"Xiaofan Wang ,&nbsp;Qing Lin ,&nbsp;Lifeng Qiu ,&nbsp;Yang Liu ,&nbsp;Siyan Guan ,&nbsp;Zhizhi Luo ,&nbsp;Yang Wang ,&nbsp;Shuncai Hu ,&nbsp;Feng Lin","doi":"10.1016/j.bmt.2026.100136","DOIUrl":"10.1016/j.bmt.2026.100136","url":null,"abstract":"<div><h3>Background</h3><div>The surgical management of adolescent flexible flatfoot with accessory navicular injury remains controversial.</div></div><div><h3>Technology</h3><div>We developed a minimally invasive technique combining biocompatible screw–based hindfoot biomechanical alignment correction with Kidner surgery. A biocompatible screw was implanted in the tarsal sinus to stabilize the subtalar joint and maintain normal anatomical relationships of the talocalcaneal and talonavicular joints, thereby correcting hindfoot alignment.</div></div><div><h3>Results</h3><div>Postoperatively, the hindfoot valgus angle improved significantly from 11.3° ± 3.3° to 3.0° ± 1.6° (<em>P</em> &lt; 0.001), and the Meary angle decreased from 19.8° ± 9.4° to 4.6° ± 4.1° (<em>P</em> &lt; 0.001), indicating effective reconstruction of hindfoot and midfoot alignment. Functional outcomes also improved markedly: AOFAS scores rose from 71.6 ± 12.8 preoperatively to 93.7 ± 8.1 postoperatively (<em>P</em> &lt; 0.001), and VAS pain scores dropped from 6.1 ± 3.1 to 2.6 ± 1.1 (<em>P</em> &lt; 0.001). No serious complications were observed during follow-up, and the biocompatible screws demonstrated excellent stability and biocompatibility.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that this combined approach effectively corrects pathological biomechanics, achieves anatomical realignment, and significantly enhances functional recovery while alleviating pain. It represents a safe, feasible, and promising strategy for treating adolescent flexible flatfoot with accessory navicular injury, offering a novel pathway toward precise, minimally invasive care.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"13 ","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147385178","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}

{"title":"Decellularized extracellular matrix: Advanced bioplatforms for functional tissue restoration via innovative decellularization techniques","authors":"Zhe Wang ,&nbsp;Xiang Lin ,&nbsp;Yunpeng Shi ,&nbsp;Hong Yan ,&nbsp;Yixuan Shang ,&nbsp;Haozhen Ren","doi":"10.1016/j.bmt.2025.100131","DOIUrl":"10.1016/j.bmt.2025.100131","url":null,"abstract":"<div><h3>Background</h3><div>In recent years, tissue engineering has experienced rapid development, with bioscaffolds emerging as a focal point of research due to their favorable bioactivity, biocompatibility, and capacity to provide mechanical support for cellular growth. The bioscaffolds have great potential in tissue regeneration. However, conventional natural scaffolds and polymer scaffolds pose risks of immunogenicity, while also face challenges in mimicking the <em>in vivo</em> microenvironment and the biochemical and mechanical properties of natural organs/tissues, which collectively limit their repair capability. The development of decellularized extracellular matrix (dECM) technology offers a viable solution to these challenges, demonstrating considerable potential for advancing organ and tissue regeneration.</div></div><div><h3>Technology</h3><div>This reviews the classification of dECM, outlines various current methods for its preparation, and comprehensively examines its latest advances in tissue repair and regenerative medicine, including applications in skin, bone, nerve, heart, lung, liver, and kidney tissues.</div></div><div><h3>Results</h3><div>This review systematically examines recent advances in dECM production and regenerative medicine applications. We classify dECM subtypes, detail contemporary decellularization protocols, and highlight their biomedical utility. Superior biocompatibility substantially mitigates post-transplant immune rejection risk, underscoring strong clinical translation potential for tissue engineering.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"13 ","pages":"Article 100131"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915116","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}

{"title":"Progress of computational biomechanical modelling for calcaneal fracture fixation","authors":"Duo Wai-Chi Wong ,&nbsp;James Chung-Wai Cheung ,&nbsp;Lucci Lugee Liyeung ,&nbsp;Esther Man-Wai Chow ,&nbsp;Winson Chiu-Chun Lee ,&nbsp;Wenxin Niu ,&nbsp;Ming Ni","doi":"10.1016/j.bmt.2026.100133","DOIUrl":"10.1016/j.bmt.2026.100133","url":null,"abstract":"<div><h3>Background</h3><div>Calcaneal fractures are among the most disabling and costly orthopaedic injuries, frequently requiring surgical fixation via open reduction and internal fixation (ORIF) or minimally invasive fixation (MIF). Finite element (FE) analysis is an increasingly critical <em>in silico</em> tool for optimizing implant designs and comparing fixation constructs, yet the technical modelling strategies and limitations specific to calcaneal fracture biomechanics have not been systematically mapped.</div></div><div><h3>Technology</h3><div>The FE modelling pipeline comprises sequential technical domains: (1) medical image-based geometry reconstruction and mesh generation; (2) material assignment (elastic modulus, Poisson's ratio, constitutive laws for bone, cartilage, and ligaments); (3) virtual fracture creation (gap width specification, Sanders classification implementation); (4) implant insertion (plate/screw/nail geometry, contact definition); (5) boundary conditions (standing/gait loading protocols, constraint schemes, muscle force incorporation); (6) solver configuration (static/quasi-static analysis); and (7) outcome extraction (von Mises stress, displacement, construct stiffness, micromotion metrics, etc.). This systematic scoping review followed JBI methodology and PRISMA-ScR guidelines to identify FE studies from PubMed, Web of Science, Scopus, and IEEE Xplore. Methodological quality was evaluated using the MQSSFE instrument for computational orthopaedic models.</div></div><div><h3>Results</h3><div>Twenty-three studies were included, predominantly using single-subject CT models with artificially created Sanders type II–III intra-articular fractures. Most employed calcaneus-only geometries, linear elastic isotropic bone properties, tetrahedral meshes, and quasi-static stance loading. Locking plates, hybrid plate–screw constructs, screw-only MIF, and intramedullary nails were compared via stress distribution and construct stiffness. Several studies introduced topology-optimized plates and micromotion-based fracture gap metrics, demonstrating that MIF with supplementary percutaneous screws can achieve biomechanical stability comparable to ORIF. However, verification (mesh convergence) and validation procedures were inconsistently reported, dynamic loading and multi-patient cohorts were rare, and interfragmentary strain–based healing criteria were largely absent. This delineation of the current technical design space highlights priorities for more physiologically realistic and methodologically robust <em>in silico</em> studies.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"13 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147385335","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}

{"title":"Prodrug nanoassembly technology for colorectal cancer therapy","authors":"Qing Wang ,&nbsp;Shiyi Zuo ,&nbsp;Xixuan Yang ,&nbsp;Yaqi Li ,&nbsp;Cuiyun Liu ,&nbsp;Yaqiao Li ,&nbsp;Shuo Wang ,&nbsp;Wenjing Wang ,&nbsp;Danping Wang ,&nbsp;Jiayu Guo ,&nbsp;Jin Sun ,&nbsp;Zhonggui He ,&nbsp;Zhenbao Li ,&nbsp;Bingjun Sun","doi":"10.1016/j.bmt.2025.100114","DOIUrl":"10.1016/j.bmt.2025.100114","url":null,"abstract":"<div><div>The clinical efficacy of Irinotecan is constrained by individual variability in its enzymatic conversion to the active metabolite, SN38. While direct administration of SN38 bypasses this enzymatic process and demonstrates potent anti-tumor activity, its clinical application remains hindered by poor physicochemical properties and off-target toxicity. These challenges highlight the necessity for efficient drug delivery strategies. Prodrug nanoassemblies combine the advantages of nano drug delivery technology and prodrug strategy, offering an effective approach to address these limitations. The modification module in prodrug design plays a critical role in imparting prodrugs self-assembly ability. Monomethyl branched-chain fatty acids (mmBCFAs), known for their biocompatibility and metabolite safety, show great potential as a worthy option. In this study, we designed and synthesized SN38-SS-BAc₁₈ by incorporating 16-methylheptanoic acid (BAc₁₈) as the modification module, and a disulfide bond as the responsive module for tumor-specific activation. The resulting SN38-SS-BAc₁₈ significantly improved the undesirable physicochemical properties of SN38 and exhibited enhanced self-assembly performance. Due to its prolonged circulation time, high tumor accumulation, and specific release profiles, the prodrug nanoassemblies (SN38-SS-BAc₁₈ NPs) exhibited superior anti-tumor efficacy and biosafety. This study addressed multiple therapeutic limitations of SN38 and Irinotecan, providing valuable insights for the rational design of efficient prodrug nanoassemblies for colorectal cancer treatment.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424718","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}

{"title":"Targeting Fcgr1 to repress FAPy-adenine-induced osteoporosis in osteosarcoma receiving chemotherapy","authors":"Wei Xu ,&nbsp;Liwen Song ,&nbsp;Qifeng Yu ,&nbsp;Shichao Tong ,&nbsp;Yi Wang ,&nbsp;Yifan Li ,&nbsp;Jin Qiu ,&nbsp;Zhikun Li","doi":"10.1016/j.bmt.2025.100118","DOIUrl":"10.1016/j.bmt.2025.100118","url":null,"abstract":"<div><div>Chemotherapy-induced bone loss in patients with osteosarcoma (OS) has attracted increasing attention worldwide. Previous studies have revealed the interactions between OS cells and osteoclasts via secretion of various cytokines. However, the specific impacts of chemically injured OS cells on osteoclast functions remain unknown. Untargeted metabolomics is a high-throughput analytical technique used to screen potential biomarkers and identify unknown metabolites in various biological samples. In this study, cisplatin (CDDP)-injured OS cell supernatant promoted the osteoclast differentiation of bone marrow macrophages (BMMs). Untargeted metabolomic analysis revealed the metabolic profile of injured OS cells, and FAPy-adenine (FA), which was upregulated by approximately 2000-fold, was identified in the supernatant. FA promoted the osteoclast differentiation of BMMs in a dose-dependent manner. RNA sequencing revealed increased Fc gamma receptor 1 (Fcgr1) expression levels in FA-treated BMMs. Fcgr1 overexpression promoted the osteoclast differentiation of BMMs and Cathepsin K expression, whereas its knockdown inhibited the pro-osteoclast differentiation effect of FA. Furthermore, FA accelerated osteoporosis progression in ovariectomy model rats. Upregulation of Fcgr1 levels promoted bone loss, whereas its silencing inhibited the bone loss induced by FA in ovariectomy model rats. Collectively, these findings suggest that FA released from CDDP-injured OS cells contributes to osteoporosis progression by upregulating Fcgr1 levels, providing new insights into chemotherapy-induced bone loss in patients with OS.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528855","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}

{"title":"Integrative cell subtype-to-drug discovery technology for angiomyolipomas ​treatment","authors":"Junxian Cao ,&nbsp;Xiao Chang ,&nbsp;Shiwen Deng ,&nbsp;Hongjun Yang ,&nbsp;Gang Guo ,&nbsp;Peng Chen","doi":"10.1016/j.bmt.2025.100117","DOIUrl":"10.1016/j.bmt.2025.100117","url":null,"abstract":"<div><div>Tuberous sclerosis complex mutation renal angiomyolipomas (TSC-RAML) are benign tumors driven by abnormal growth of mesenchymal-derived cells. Although mTOR inhibitors are clinically used, drug resistance and incomplete tumour shrinkage highlight the need for new treatment approaches. Here, we developed a new strategy combining single-cell transcriptomics, network pharmacology, and functional experiments to identify targeted therapies for TSC-RAMLs. Single-cell RNA sequencing of tumour tissues from 4 TSC-RAML patients uncovered a distinct mesenchymal subpopulation (TSC-RAML-Cells) with upregulated pathways in adipogenesis and mTOR signalling. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA) on TSC-RAML-Cells, we identified three disease-associated modules containing hub genes critical for tumour survival. Cross-referencing these modules with the Connectivity Map (CMAP) drug database prioritized AS-605240 as a potential therapeutic candidate. Protein-protein interaction (PPI) network analysis further revealed PI3KCA as a central target, and molecular dynamics simulations confirmed stable binding between AS-605240 and PI3KCA, with a binding free energy of −7.8 ​kcal/mol, supporting its mechanism of action. In vitro experiments using patient-derived TSC-RAML cells showed that AS-605240 suppressed cell growth in a dose-dependent manner (IC50 ​= ​7.8 ​μM) and increased apoptosis rates through inhibition of the PI3K/AKT pathway. This work not only proposes AS-605240 as a promising therapy for TSC-RAMLs but also provides a scalable “cell subtype-to-drug\" discovery framework. By integrating single-cell omics and computational drug repurposing, this approach accelerates precision medicine development for rare diseases.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100117"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473559","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}

{"title":"The biological association between programmed cell death function and osteoarthritis using multi-omic Mendelian Randomization","authors":"Rong Lu ,&nbsp;Kaibo Tang ,&nbsp;Run Pan ,&nbsp;Shangxuan Shi ,&nbsp;Xiao'ao Xue ,&nbsp;Tingfang Hwang ,&nbsp;Yang Song ,&nbsp;Weijun Tang ,&nbsp;Yue Yu ,&nbsp;He Wang ,&nbsp;Yao Lu ,&nbsp;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> ​&lt; ​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> ​&lt; ​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":"2025-12-01","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}