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Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects 针对辐照肠道的间充质干细胞衍生细胞外囊泡发挥治疗作用
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-26 DOI: 10.7150/thno.97623
Ningning He, Mingxin Dong, Yuxiao Sun, Mengmeng Yang, Yan Wang, Liqing Du, Kaihua Ji, Jinhan Wang, Manman Zhang, Yeqing Gu, Xinran Lu, Yang Liu, Qin Wang, Zongjin Li, Huijuan Song, Chang Xu, Qiang Liu
{"title":"Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects","authors":"Ningning He, Mingxin Dong, Yuxiao Sun, Mengmeng Yang, Yan Wang, Liqing Du, Kaihua Ji, Jinhan Wang, Manman Zhang, Yeqing Gu, Xinran Lu, Yang Liu, Qin Wang, Zongjin Li, Huijuan Song, Chang Xu, Qiang Liu","doi":"10.7150/thno.97623","DOIUrl":"https://doi.org/10.7150/thno.97623","url":null,"abstract":"<b>Background:</b> Radiation-induced intestinal injuries are common in patients with pelvic or abdominal cancer. However, these injuries are currently not managed effectively. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been extensively used in regenerative medicine. However, the results of MSC-EVs in the repair of radiation-induced intestinal damage have been unsatisfactory. We here investigated the nanotherapeutic functions of MSC-EVs in radiation-induced intestinal injury./n<b>Methods:</b> We visualized the biodistribution and trend of MSC-EVs through <i>in vivo</i> imaging. A radiation-induced intestinal injury model was constructed, and the therapeutic effect of MSC-EVs was explored through <i>in vivo</i> and <i>in vitro</i> experiments. Immunofluorescence and qRT-PCR assays were conducted to explore the underlying mechanisms./n<b>Results:</b> MSC-EVs exhibited a dose-dependent tendency to target radiation-injured intestines while providing spatiotemporal information for the early diagnosis of the injury by quantifying the amount of MSC-EVs in the injured intestines through molecular imaging. Meanwhile, MSC-EVs displayed superior nanotherapeutic functions by alleviating apoptosis, improving angiogenesis, and ameliorating the intestinal inflammatory environment. Moreover, MSC-EVs-derived miRNA-455-5p negatively regulated SOCS3 expression, and the activated downstream Stat3 signaling pathway was involved in the therapeutic efficacy of MSC-EVs in radiation-induced intestinal injuries./n<b>Conclusion:</b> MSC-EVs can dose-dependently target radiation-injured intestinal tissues, allow a spatiotemporal diagnosis in different degrees of damage to help guide personalized therapy, offer data for designing EV-based theranostic strategies for promoting recovery from radiation-induced intestinal injury, and provide cell-free treatment for radiation therapy.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
βAR-mTOR-lipin1 pathway mediates PKA-RIIβ deficiency-induced adipose browning βAR-mTOR-lipin1通路介导PKA-RIIβ缺乏诱导的脂肪褐变
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-26 DOI: 10.7150/thno.97046
Bingwei Wang, Zhiping Hu, Long Cui, Miao Zhao, Zhijie Su, Yong Jiang, Jiarui Liu, Yun Zhao, Yujia Hou, Xiaoning Yang, Chenyu Zhang, Bingbing Guo, Daotong Li, Liang Zhao, Shengmin Zheng, Yiguo Zhao, Weipeng Yang, Dunfang Wang, Siwang Yu, Shigong Zhu, Yi Yan, Geheng Yuan, Kailong Li, Wenqiang Zhang, Lihua Qin, Weiguang Zhang, Feng Sun, Jianyuan Luo, Ruimao Zheng
{"title":"βAR-mTOR-lipin1 pathway mediates PKA-RIIβ deficiency-induced adipose browning","authors":"Bingwei Wang, Zhiping Hu, Long Cui, Miao Zhao, Zhijie Su, Yong Jiang, Jiarui Liu, Yun Zhao, Yujia Hou, Xiaoning Yang, Chenyu Zhang, Bingbing Guo, Daotong Li, Liang Zhao, Shengmin Zheng, Yiguo Zhao, Weipeng Yang, Dunfang Wang, Siwang Yu, Shigong Zhu, Yi Yan, Geheng Yuan, Kailong Li, Wenqiang Zhang, Lihua Qin, Weiguang Zhang, Feng Sun, Jianyuan Luo, Ruimao Zheng","doi":"10.7150/thno.97046","DOIUrl":"https://doi.org/10.7150/thno.97046","url":null,"abstract":"<b>Background:</b> Enhancing white adipose tissue (WAT) browning combats obesity. The RIIβ subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIβ gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored./n<b>Methods:</b> This study investigates the mechanisms underlying WAT browning in RIIβ-KO mice. Genetic approaches such as β3-adrenergic receptors (β3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 <i>in vitro</i>, while AAV-shRNAs were used for the same purpose <i>in vivo</i>./n<b>Results:</b> We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIβ-KO mice. The WAT browning can be dampened by β<sub>3</sub>ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIβ-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, β<sub>3</sub>AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, <i>in vivo</i> knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity./n<b>Conclusions:</b> The β<sub>3</sub>AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Nanomedicines as Guardians of the Heart: Unleashing the Power of Antioxidants to Alleviate Myocardial Ischemic Injury 守护心脏的纳米药物:释放抗氧化剂的力量,缓解心肌缺血损伤
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-26 DOI: 10.7150/thno.99961
Dongjian Han, Fuhang Wang, Deliang Shen
{"title":"Nanomedicines as Guardians of the Heart: Unleashing the Power of Antioxidants to Alleviate Myocardial Ischemic Injury","authors":"Dongjian Han, Fuhang Wang, Deliang Shen","doi":"10.7150/thno.99961","DOIUrl":"https://doi.org/10.7150/thno.99961","url":null,"abstract":"Ischemic heart disease (IHD) is increasingly recognized as a significant cardiovascular disease with a growing global incidence. Interventions targeting the oxidative microenvironment have long been pivotal in therapeutic strategies. However, many antioxidant drugs face limitations due to pharmacokinetic and delivery challenges, such as short half-life, poor stability, low bioavailability, and significant side effects. Fortunately, nanotherapies exhibit considerable potential in addressing IHD. Nanomedicines offer advantages such as passive/active targeting, prolonged circulation time, enhanced bioavailability, and diverse carrier options. This comprehensive review explores the advancements in nanomedicines for mitigating IHD through oxidative stress regulation, providing an extensive overview for researchers in the field of antioxidant nanomedicines. By inspiring further research, this study aims to accelerate the development of novel therapies for myocardial injury.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Nanotechnology based gas delivery system: a “green” strategy for cancer diagnosis and treatment 基于纳米技术的气体输送系统:癌症诊断和治疗的 "绿色 "战略
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-26 DOI: 10.7150/thno.98884
Meixu Chen, Tianyue Xu, Linlin Song, Ting Sun, Zihan Xu, Yujie Zhao, Peixin Du, Ling Xiong, Zhankun Yang, Jing Jing, Hubing Shi
{"title":"Nanotechnology based gas delivery system: a “green” strategy for cancer diagnosis and treatment","authors":"Meixu Chen, Tianyue Xu, Linlin Song, Ting Sun, Zihan Xu, Yujie Zhao, Peixin Du, Ling Xiong, Zhankun Yang, Jing Jing, Hubing Shi","doi":"10.7150/thno.98884","DOIUrl":"https://doi.org/10.7150/thno.98884","url":null,"abstract":"Gas therapy, a burgeoning clinical treatment modality, has garnered widespread attention to treat a variety of pathologies in recent years. The advent of nanoscale gas drug therapy represents a novel therapeutic strategy, particularly demonstrating immense potential in the realm of oncology. This comprehensive review navigates the landscape of gases endowed with anti-cancer properties, including hydrogen (H<sub>2</sub>), carbon monoxide (CO), carbon dioxide (CO<sub>2</sub>), nitric oxide (NO), oxygen (O<sub>2</sub>), sulfur dioxide (SO<sub>2</sub>), hydrogen sulfide (H<sub>2</sub>S), ozone (O<sub>3</sub>), and heavier gases. The selection of optimal delivery vectors is also scrutinized in this review to ensure the efficacy of gaseous agents. The paper highlights the importance of engineering stimulus-responsive delivery systems that enable precise and targeted gas release, thereby augmenting the therapeutic efficiency of gas therapy. Additionally, the review examines the synergistic potential of integrating gas therapy with conventional treatments such as starvation therapy, ultrasound (US) therapy, chemotherapy, radiotherapy (RT), and photodynamic therapy (PDT). It also discusses the burgeoning role of advanced multimodal and US imaging in enhancing the precision of gas therapy applications. The insights presented are pivotal in the strategic development of nanomedicine platforms designed for the site-specific delivery of therapeutic gases, heralding a new era in cancer therapeutics.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane 线粒体编码的肽 MOTS-c 通过促进 TRIM72 向膜的转位参与质膜修复
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-19 DOI: 10.7150/thno.100321
Hong Jia, Lyu-Chen Zhou, Yong-Feng Chen, Wei Zhang, Wei Qi, Peng Wang, Xiao Huang, Jian-Wei Guo, Wai-Fang Hou, Ran-Ran Zhang, Jing-Jun Zhou, Da-Wei Zhang
{"title":"Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane","authors":"Hong Jia, Lyu-Chen Zhou, Yong-Feng Chen, Wei Zhang, Wei Qi, Peng Wang, Xiao Huang, Jian-Wei Guo, Wai-Fang Hou, Ran-Ran Zhang, Jing-Jun Zhou, Da-Wei Zhang","doi":"10.7150/thno.100321","DOIUrl":"https://doi.org/10.7150/thno.100321","url":null,"abstract":"<b>Rationale:</b> An impairment of plasma membrane repair has been implicated in various diseases such as muscular dystrophy and ischemia/reperfusion injury. MOTS-c, a short peptide encoded by mitochondria, has been shown to pass through the plasma membrane into the bloodstream. This study determined whether this biological behavior was involved in membrane repair and its underlying mechanism./n<b>Methods and Results:</b> In human participants, the level of MOTS-c was positively correlated with the abundance of mitochondria, and the membrane repair molecule TRIM72. In contrast to high-intensity eccentric exercise, moderate-intensity exercise improved sarcolemma integrity and physical performance, accompanied by an increase of mitochondria beneath the damaged sarcolemma and secretion of MOTS-c. Furthermore, moderate-intensity exercise increased the interaction between MOTS-c and TRIM72, and MOTS-c facilitated the trafficking of TRIM72 to the sarcolemma. <i>In vitro</i> studies demonstrated that MOTS-c attenuated membrane damage induced by hypotonic solution, which could be blocked by siRNA-TRIM72, but not AMPK inhibitor. Co-immunoprecipitation study showed that MOTS-c interacted with TRIM72 C-terminus, but not N-terminus. The dynamic membrane repair assay revealed that MOTS-c boosted the trafficking of TRIM72 to the injured membrane. However, MOTS-c itself had negligible effects on membrane repair, which was recapitulated in TRIM72<sup>-/-</sup> mice. Unexpectedly, MOTS-c still increased the fusion of vesicles with the membrane in TRIM72<sup>-/-</sup> mice, and dot blot analysis revealed an interaction between MOTS-c and phosphatidylinositol (4,5) bisphosphate [PtdIns (4,5) P<sub>2</sub>]. Finally, MOTS-c blunted ischemia/reperfusion-induced membrane disruption, and preserved heart function./n<b>Conclusions:</b> MOTS-c/TRIM72-mediated membrane integrity improvement participates in mitochondria-triggered membrane repair. An interaction between MOTS-c and plasma lipid contributes to the fusion of vesicles with membrane. Our data provide a novel therapeutic strategy for rescuing organ function by facilitating membrane repair with MOTS-c.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
EBV-associated epithelial cancers cells promote vasculogenic mimicry formation via a secretory cross-talk with the immune microenvironment EBV相关上皮癌细胞通过与免疫微环境的分泌性交叉对话促进血管生成模拟的形成
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-19 DOI: 10.7150/thno.100171
Tong Xiang, Fengze Sun, Tingting Liu, Jingjing Zhao, Jieying Yang, Dijun Ouyang, Hao Chen, Qian Zhu, Qijing Wang, Yongqiang Li, Jia He, Chaopin Yang, Xinyi Yang, Yuanyuan Chen, Yan Tang, Desheng Weng, Qiuzhong Pan, Qi Yang, Jianchuan Xia
{"title":"EBV-associated epithelial cancers cells promote vasculogenic mimicry formation via a secretory cross-talk with the immune microenvironment","authors":"Tong Xiang, Fengze Sun, Tingting Liu, Jingjing Zhao, Jieying Yang, Dijun Ouyang, Hao Chen, Qian Zhu, Qijing Wang, Yongqiang Li, Jia He, Chaopin Yang, Xinyi Yang, Yuanyuan Chen, Yan Tang, Desheng Weng, Qiuzhong Pan, Qi Yang, Jianchuan Xia","doi":"10.7150/thno.100171","DOIUrl":"https://doi.org/10.7150/thno.100171","url":null,"abstract":"<b>Background:</b> Vasculogenic mimicry (VM) induced by Epstein-Barr virus (EBV) infection plays an important role in resistance to anti-vascular endothelial growth factor (VEGF) therapy in EBV-associated epithelial cancers; however, the interaction between VM and the immune microenvironment has not been systematically investigated./n<b>Methods:</b> IHC and multiplex IHC analysis the relationships among tumour-associated macrophage (TAM), VM and EBV infection in EBV-associated epithelial cancer biopsies. <i>In vitro</i> and <i>in vivo</i> evidence using CRISPR-Cas9 system engineered EBV-infected epithelial cancer cells and mouse models support functional role and mechanism for M2c-like macrophages in the VM formation. The prediction of VM in the effectiveness of anti-angiogenic agent was analysed using clinical datasets./n<b>Results:</b> EBV-associated epithelial cancer biopsies revealed that infiltration of the TAM surrounding the VM is closely associated with EBV infection. AKT/mTOR/HIF-1α pathway in EBV-infected epithelial cancer cells control the secretion of CCL5 and CSF-1, enabling the recruitment of monocytes and their differentiation into M2c macrophages which promote VM formation by MMP9. Combination of anti-angiogenesis agents and HIF-1α inhibitor caused marked decreases in CD31-positive micro-vessels, VM, and M2c-like macrophages. VM scores can be used as biomarkers to predict the efficacy of anti-angiogenic agent therapy in EBV-associated epithelial cancers./n<b>Conclusions:</b> Our findings define a secretory cross-talk between tumour cells and the immune microenvironment in EBV-associated epithelial cancer, revealing an unexpected role of EBV in epithelial cancer cells, controlling VM formation via M2c-like macrophages./n/n\u0000","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
IL-33/ST2 induces macrophage-dependent ROS production and TRPA1 activation that mediate pain-like responses by skin incision in mice IL-33/ST2 可诱导巨噬细胞依赖性 ROS 生成和 TRPA1 激活,从而介导小鼠皮肤切口疼痛样反应
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-19 DOI: 10.7150/thno.97856
Ruoyao Xu, Yushuang Pan, Kaige Zheng, Muyan Chen, Chengyu Yin, Qimiao Hu, Jie Wang, Qing Yu, Peiyi Li, Yan Tai, Junfan Fang, Boyu Liu, Jianqiao Fang, Guihua Tian, Boyi Liu
{"title":"IL-33/ST2 induces macrophage-dependent ROS production and TRPA1 activation that mediate pain-like responses by skin incision in mice","authors":"Ruoyao Xu, Yushuang Pan, Kaige Zheng, Muyan Chen, Chengyu Yin, Qimiao Hu, Jie Wang, Qing Yu, Peiyi Li, Yan Tai, Junfan Fang, Boyu Liu, Jianqiao Fang, Guihua Tian, Boyi Liu","doi":"10.7150/thno.97856","DOIUrl":"https://doi.org/10.7150/thno.97856","url":null,"abstract":"<b>Background:</b> Insufficiently managed incisional (INC) pain severely affects patients' life quality and rehabilitation after a major operation. However, mechanisms underlying INC pain still remain poorly understood./n<b>Methods:</b> A mouse model of INC pain was established by skin plus deep muscle incision. Biochemistry assay, <i>in vivo</i> reactive oxygen species (ROS) imaging, Ca<sup>2+</sup> imaging combined with retrograde labelling, neuron tracing and nocifensive behavior test, etc. were utilized for mechanism investigation./n<b>Results:</b> We found pro-nociceptive cytokine interleukin -33 (IL-33) ranked among top up-regulated cytokines in incised tissues of INC pain model mice. IL-33 was predominantly expressed in keratinocytes around the incisional area. Neutralization of IL-33 or its receptor suppression of tumorigenicity 2 protein (ST2) or genetic deletion of <i>St2</i> gene (<i>St2</i><sup>-/-</sup>) remarkably ameliorated mechanical allodynia and improved gait impairments of model mice. IL-33 contributes to INC pain by recruiting macrophages, which subsequently release ROS in incised tissues via ST2-dependent mechanism. Transfer of excessive macrophages enhanced oxidative injury and reproduced mechanical allodynia in <i>St2</i><sup>-/-</sup> mice upon tissue incision. Overproduced ROS subsequently activated functionally up-regulated transient receptor potential ankyrin subtype-1 (TRPA1) channel innervating the incisional site to produce mechanical allodynia. Neither deleting <i>St2</i> nor attenuating ROS affected wound healing of model mice./n<b>Conclusions:</b> Our work uncovered a previously unrecognized contribution of IL-33/ST2 signaling in mediating mechanical allodynia and gait impairment of a mouse model of INC pain. Targeting IL-33/ST2 signaling could be a novel therapeutic approach for INC pain management.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
SEMA6B induces macrophage-mediated inflammation and hepatocyte apoptosis in hepatitis B virus-related acute-on-chronic liver failure SEMA6B 在乙型肝炎病毒相关急慢性肝衰竭中诱导巨噬细胞介导的炎症和肝细胞凋亡
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-19 DOI: 10.7150/thno.97007
Hui Yang, Qun Cai, Jiaojiao Xin, Xi Liang, Hozeifa Mohamed Hassan, Jiaxian Chen, Lulu He, Suwan Sun, Beibei Guo, Shiwen Ma, Bingqi Li, Xiaofei Zeng, Meiqian Hu, Peng Li, Jinjin Luo, Wen Hu, Heng Yao, Xingping Zhou, Yuheng Kong, Qiuzhi Wang, Xin Chen, Jing Jiang, Dongyan Shi, Jun Li
{"title":"SEMA6B induces macrophage-mediated inflammation and hepatocyte apoptosis in hepatitis B virus-related acute-on-chronic liver failure","authors":"Hui Yang, Qun Cai, Jiaojiao Xin, Xi Liang, Hozeifa Mohamed Hassan, Jiaxian Chen, Lulu He, Suwan Sun, Beibei Guo, Shiwen Ma, Bingqi Li, Xiaofei Zeng, Meiqian Hu, Peng Li, Jinjin Luo, Wen Hu, Heng Yao, Xingping Zhou, Yuheng Kong, Qiuzhi Wang, Xin Chen, Jing Jiang, Dongyan Shi, Jun Li","doi":"10.7150/thno.97007","DOIUrl":"https://doi.org/10.7150/thno.97007","url":null,"abstract":"<b>Rationale:</b> Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) have a high short-term mortality rate. Semaphorin-6B (SEMA6B) plays a crucial role in the pathogenesis of HBV-ACLF, but its molecular basis remains unclear. This study aimed to elucidate the mechanisms of SEMA6B in HBV-ACLF progression./n<b>Methods:</b> A total of 321 subjects with HBV-ACLF, liver cirrhosis (LC), chronic hepatitis B (CHB), and normal controls (NC) from a prospective multicenter cohort were studied. 84 subjects (HBV-ACLF, n = 50; LC, n = 10; CHB, n = 10; NC, n = 14) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs) to clarify the mechanisms of SEMA6B in HBV-ACLF. These mechanisms were validated through in vitro studies with hepatocytes and macrophages, as well as in vivo using SEMA6B knockout mice and mice treated with synthetic SEMA6B siRNA./n<b>Results:</b> Transcriptome analysis of PBMCs showed that SEMA6B was among the most differentially expressed genes when comparing patients with HBV-ACLF to those with LC, CHB, or NC. ROC analysis demonstrated the reliable diagnostic value of SEMA6B for HBV-ACLF in both the sequencing cohort and an external validation cohort (AUROC = 0.9788 and 0.9026, respectively). SEMA6B levels were significantly higher in the HBV-ACLF patients, especially in non-survivors, with high expression mainly observed in macrophages and hepatocytes in liver tissue. Genes significantly associated with highly expressed SEMA6B were enriched in inflammation and apoptosis pathways in HBV-ACLF non-survivors. Overexpression of SEMA6B in macrophages activated systemic inflammatory responses, while its overexpression in hepatocytes inhibited proliferation through G0/G1 cell cycle arrest and induced apoptosis. Knocking out SEMA6B rescued mice with liver failure by improving liver functions, reducing inflammatory responses, and decreasing hepatocyte apoptosis. Transcriptome analysis of liver tissue showed that SEMA6B knockout significantly ameliorated the liver failure signature, significantly downregulating inflammation-related pathways. Importantly, therapeutic delivery of synthetic SEMA6B siRNA also improved liver function, and reduced both inflammation and hepatocyte apoptosis in mice with liver failure./n<b>Conclusion:</b> SEMA6B, a potential diagnostic biomarker for HBV-ACLF, exacerbates liver failure through macrophage-mediated systemic inflammation and hepatocyte apoptosis. These findings highlight SEMA6B as a promising early treatment target for HBV-ACLF patients.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Intranasal delivery of imaging agents to the brain 通过鼻腔向大脑输送成像剂
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-19 DOI: 10.7150/thno.98473
Abdallah Almahmoud, Harendra S Parekh, Brett M Paterson, Karnaker Reddy Tupally, Viktor Vegh
{"title":"Intranasal delivery of imaging agents to the brain","authors":"Abdallah Almahmoud, Harendra S Parekh, Brett M Paterson, Karnaker Reddy Tupally, Viktor Vegh","doi":"10.7150/thno.98473","DOIUrl":"https://doi.org/10.7150/thno.98473","url":null,"abstract":"The potential of intranasal administered imaging agents to altogether bypass the blood-brain barrier offers a promising non-invasive approach for delivery directly to the brain. This review provides a comprehensive analysis of the advancements and challenges of delivering neuroimaging agents to the brain by way of the intranasal route, focusing on the various imaging modalities and their applications in central nervous system diagnostics and therapeutics. The various imaging modalities provide distinct insights into the pharmacokinetics, biodistribution, and specific interactions of imaging agents within the brain, facilitated by the use of tailored tracers and contrast agents./n<b>Methods:</b> A comprehensive literature search spanned PubMed, Scopus, Embase, and Web of Science, covering publications from 1989 to 2024 inclusive. Starting with advancements in tracer development, we going to explore the rationale for integration of imaging techniques, and the critical role novel formulations such as nanoparticles, nano- and micro-emulsions in enhancing imaging agent delivery and visualisation./n<b>Results:</b> The review highlights the use of innovative formulations in improving intranasal administration of neuroimaging agents, showcasing their ability to navigate the complex anatomical and physiological barriers of the nose-to-brain pathway. Various imaging techniques, MRI, PET, SPECT, CT, FUS and OI, were evaluated for their effectiveness in tracking these agents. The findings indicate significant improvements in brain targeting efficiency, rapid uptake, and sustained brain presence using innovative formulations./n<b>Conclusion:</b> Future directions involve the development of optimised tracers tailored for intranasal administration, the potential of multimodal imaging approaches, and the implications of these advancements for diagnosing and treating neurological disorders.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Processed microalgae: green gold for tissue regeneration and repair 加工微藻:组织再生和修复的绿色黄金
IF 12.4 1区 医学
Theranostics Pub Date : 2024-08-19 DOI: 10.7150/thno.99181
Sen Liu, Ling Shi, Hailong Luo, Kaiyuan Chen, Meichen Song, Yingjun Wu, Fengzhi Liu, Meng Li, Jie Gao, Yan Wu
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