Abstract Postmenopausal osteoporosis, marked by diminished bone regenerative capacity and elevated fracture risk, urgently requires innovative osteoanabolic strategies. Plant‐derived extracellular vesicle (PDEV)‐like particles (EVLPs) have emerged as promising therapeutic candidates due to their bioactive cargo and cross‐kingdom regulatory potential. Building on the traditional use of Dipsaci Radix (DR) in bone repair, this study investigates DR‐derived EVLPs (DREVLPs) as novel bone‐forming nanotherapeutics. We successfully isolated and characterized DREVLPs, demonstrating their remarkable osteogenic capacity through bone morphogenetic protein 2 (BMP2) pathway activation. In bone marrow mesenchymal stem cells (BMSCs), DREVLPs significantly upregulated RUNX2 and collagen I while triggering the BMP2/Smads signaling phosphorylation cascade. Oral administration in ovariectomized mice revealed precise skeletal targeting with DREVLPs preferentially accumulating in femurs and BMSCs. Treatment substantially preserved trabecular architecture, increasing bone volume fraction compared with untreated controls. Molecular analyses confirmed pathway activation through elevated BMP2, p‐Smad1/5/9, and osteogenic markers in bone tissue—effects comparable to clinical bisphosphonates but through anabolic rather than anti‐resorptive mechanisms. These findings establish plant EVLPs as a new category of bone‐forming agents, with DREVLPs representing a translatable oral nanotherapy that addresses the critical unmet need for safe anabolic treatments in postmenopausal osteoporosis through targeted activation of endogenous BMP2 signaling.
{"title":"Plant‐derived extracellular vesicle‐like particles as novel osteoanabolic agents: Activating bone morphogenetic protein 2/Smads signaling axis for bone regeneration in postmenopausal osteoporosis","authors":"Qing Zhao, Yue Cao, Zhengting Wu, Yingqi Cao, Qi You, Yuanyuan Xia, Xuejun Tan, Dongxiao Li, Tianxin Qiu, Xiuping Cai, Zhaodi Guo, Lei Zheng, Kewei Zhao","doi":"10.1002/inmd.70086","DOIUrl":"https://doi.org/10.1002/inmd.70086","url":null,"abstract":"Abstract Postmenopausal osteoporosis, marked by diminished bone regenerative capacity and elevated fracture risk, urgently requires innovative osteoanabolic strategies. Plant‐derived extracellular vesicle (PDEV)‐like particles (EVLPs) have emerged as promising therapeutic candidates due to their bioactive cargo and cross‐kingdom regulatory potential. Building on the traditional use of Dipsaci Radix (DR) in bone repair, this study investigates DR‐derived EVLPs (DREVLPs) as novel bone‐forming nanotherapeutics. We successfully isolated and characterized DREVLPs, demonstrating their remarkable osteogenic capacity through bone morphogenetic protein 2 (BMP2) pathway activation. In bone marrow mesenchymal stem cells (BMSCs), DREVLPs significantly upregulated RUNX2 and collagen I while triggering the BMP2/Smads signaling phosphorylation cascade. Oral administration in ovariectomized mice revealed precise skeletal targeting with DREVLPs preferentially accumulating in femurs and BMSCs. Treatment substantially preserved trabecular architecture, increasing bone volume fraction compared with untreated controls. Molecular analyses confirmed pathway activation through elevated BMP2, p‐Smad1/5/9, and osteogenic markers in bone tissue—effects comparable to clinical bisphosphonates but through anabolic rather than anti‐resorptive mechanisms. These findings establish plant EVLPs as a new category of bone‐forming agents, with DREVLPs representing a translatable oral nanotherapy that addresses the critical unmet need for safe anabolic treatments in postmenopausal osteoporosis through targeted activation of endogenous BMP2 signaling.","PeriodicalId":511595,"journal":{"name":"Interdisciplinary Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/inmd.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147910189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongxia Ruan, Mengyuan Lyu, Hongli Lai, Lu Niu, Zhenzhen Zhao, Tangyuheng Liu, Shuting Lei, B. Ying
Tuberculosis (TB) is a fatal infectious disease that continues to pose a serious public health threat. The emergence of drug‐resistant TB has further worsened the burden of the disease. The interaction between the host and the pathogen involves multiple modes of cell death, which play a role in determining immune outcomes. Several studies have established a strong correlation between cell death and TB progression. This review explores the molecular mechanisms of various cell death modes in Mycobacterium tuberculosis (Mtb) infection and how Mtb's virulence effectors regulate these pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis. Furthermore, therapeutic strategies targeting cell death pathways have shown promising results in TB treatment. Importantly, this review highlights the significant potential of mitochondria in mediating communication between different cell death modes and influencing the final outcomes. Overall, this work provides a comprehensive summary of the role of cell death in host immune responses and immune evasion by Mtb. It also offers valuable insights into the pathogenesis of TB and immune evasion strategies employed by Mtb and contributes to the development of more effective anti‐TB therapies.
{"title":"Host‐pathogen dialogues in different cell death modes during Mycobacterium tuberculosis infection","authors":"Hongxia Ruan, Mengyuan Lyu, Hongli Lai, Lu Niu, Zhenzhen Zhao, Tangyuheng Liu, Shuting Lei, B. Ying","doi":"10.1002/inmd.20230044","DOIUrl":"https://doi.org/10.1002/inmd.20230044","url":null,"abstract":"Tuberculosis (TB) is a fatal infectious disease that continues to pose a serious public health threat. The emergence of drug‐resistant TB has further worsened the burden of the disease. The interaction between the host and the pathogen involves multiple modes of cell death, which play a role in determining immune outcomes. Several studies have established a strong correlation between cell death and TB progression. This review explores the molecular mechanisms of various cell death modes in Mycobacterium tuberculosis (Mtb) infection and how Mtb's virulence effectors regulate these pathways, including apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis. Furthermore, therapeutic strategies targeting cell death pathways have shown promising results in TB treatment. Importantly, this review highlights the significant potential of mitochondria in mediating communication between different cell death modes and influencing the final outcomes. Overall, this work provides a comprehensive summary of the role of cell death in host immune responses and immune evasion by Mtb. It also offers valuable insights into the pathogenesis of TB and immune evasion strategies employed by Mtb and contributes to the development of more effective anti‐TB therapies.","PeriodicalId":511595,"journal":{"name":"Interdisciplinary Medicine","volume":"20 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139796973","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}
A significant number of nucleic acid therapies have been approved, highlighting the vast potential of nucleic acid therapeutics. Although numerous delivery strategies have been investigated, and progress has been made in nucleic acid delivery systems, the oral delivery route still presents a significant obstacle. Recently, a novel and promising force in oral nucleic acid delivery has emerged, namely Decoctosomes and Bencaosomes, obtained from the decoction of natural herbs, which refers to boiled Chinese herbal medicines. The active components of Decoctosomes include small molecules, peptides, and small RNAs (sRNAs). sRNAs were the first targets of extensive research. Additionally, Bencaosomes have been proven effective in several disease mouse models as artificially enhanced decoctosome products. This perspective summarizes the development and possible future directions of Decoctosomes and Bencaosomes, two varieties of nanoparticles that may open the door to new possibilities in nucleic acid therapy.
{"title":"Nanoparticles derived from herbal preparations May represent a novel nucleic acid therapy","authors":"Tingle Feng, Waqas Ahmed, Talha Ahmed, Lukui Chen","doi":"10.1002/inmd.20230029","DOIUrl":"https://doi.org/10.1002/inmd.20230029","url":null,"abstract":"A significant number of nucleic acid therapies have been approved, highlighting the vast potential of nucleic acid therapeutics. Although numerous delivery strategies have been investigated, and progress has been made in nucleic acid delivery systems, the oral delivery route still presents a significant obstacle. Recently, a novel and promising force in oral nucleic acid delivery has emerged, namely Decoctosomes and Bencaosomes, obtained from the decoction of natural herbs, which refers to boiled Chinese herbal medicines. The active components of Decoctosomes include small molecules, peptides, and small RNAs (sRNAs). sRNAs were the first targets of extensive research. Additionally, Bencaosomes have been proven effective in several disease mouse models as artificially enhanced decoctosome products. This perspective summarizes the development and possible future directions of Decoctosomes and Bencaosomes, two varieties of nanoparticles that may open the door to new possibilities in nucleic acid therapy.","PeriodicalId":511595,"journal":{"name":"Interdisciplinary Medicine","volume":"41 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139868895","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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