Theranostics最新文献

{"title":"C-X-C motif chemokine receptor 4-directed PET signal in the arterial tree is not consistently linked to calcified plaque burden and cardiovascular risk.","authors":"Aleksander Kosmala, Natalie Hasenauer, Sebastian E Serfling, Kerstin Michalski, Matthias Fröhlich, Niklas Dreher, Philipp E Hartrampf, Takahiro Higuchi, Andreas K Buck, Alexander Weich, Theresa Reiter, Rudolf A Werner","doi":"10.7150/thno.102910","DOIUrl":"https://doi.org/10.7150/thno.102910","url":null,"abstract":"<p><p><b>Purpose:</b> To establish the extent, distribution and frequency of in-vivo vessel wall [⁶⁸Ga]Ga-PentixaFor uptake and to determine its relationship with calcified atherosclerotic plaque burden (CAP) and cardiovascular risk factors (CVRF). <b>Methods:</b> 65 oncological patients undergoing [⁶⁸Ga]Ga-PentixaFor PET/CT were assessed. Radiotracer uptake (target-to-background ratio [TBR]) and CAP burden (including number of CAP sites, calcification circumference and thickness) in seven major vessel segments per patient were determined. We then investigated associations of vessel wall uptake with CAP burden, cardiovascular risk (CVRF and European Society of Cardiology [ESC] SCORE2/SCORE2-OP risk chart) and image noise (determined by coefficient of variation [CoV] from unaffected liver parenchyma). <b>Results:</b> We identified 1292 sites of high focal [⁶⁸Ga]Ga-PentixaFor uptake (PentixaFor+ sites) in the vessel wall in 65/65 (100%) patients, with concomitant calcification in 385/1292 (29.8%) sites. There were no significant associations between vessel wall uptake and CAP burden (number of PentixaFor+ sites: r ≤ 0.18, <i>P</i> ≥ 0.14; PentixaFor+ TBR: r ≤ 0.08, <i>P</i> ≥ 0.54). The number of PentixaFor+ sites showed a moderate correlation with cardiovascular risk (ESC SCORE2/SCORE2-OP, r = 0.30; number of CVRF, r = 0.26; <i>P</i> = 0.04, respectively), but failed to reach significance for PentixaFor+ TBR (r ≤ 0.18, <i>P</i> ≥ 0.22). In univariable regression analysis, body mass index (odds ratio [OR] 1.08, 95%-confidence interval [CI] 1.02-1.14) and CoV (OR, 1.07; CI, 1.05-1.10) were linked to TBR and the number of PentixaFor+ sites (<i>P</i> < 0.01, respectively), while injected activity was only associated with the latter imaging parameter (OR, 0.99; CI, 0.98-1.00; <i>P</i> = 0.04). In multivariable regression, injected activity (OR, 1.00; CI, 0.99-1.00) and CoV (OR, 1.06; CI, 1.06-1.07) remained significantly associated with the number of PentixaFor+ sites (<i>P</i> < 0.01, respectively). CoV, however, was the only parameter significantly linked to PentixaFor+ TBR on multivariable analysis (OR, 1.02; CI, 1.01-1.03; <i>P</i> < 0.01). <b>Conclusion:</b> On a visual and quantitative level, high focal [⁶⁸Ga]Ga-PentixaFor uptake in the arterial tree was not consistently linked to vessel wall calcification or cardiovascular risk. Image noise, however, may account for a substantial portion of apparent vessel wall uptake.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"804-814"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering nanosystems for regulating reproductive health in women.","authors":"Qinrui Fu, Lejun Fu","doi":"10.7150/thno.102626","DOIUrl":"10.7150/thno.102626","url":null,"abstract":"<p><p>Reproductive health-related diseases have a significant impact on the well-being of millions of women worldwide, severely compromising their quality of life. Women encounter unique challenges in terms of reproductive health, including gynecological diseases and malignant neoplasms prior to pregnancy, as well as complications during pregnancy that greatly undermine their physical and mental health. Despite recent advancements in the field of female reproduction, substantial challenges still persist. To address these challenges, nanotechnology-based diagnostic and therapeutic strategies have emerged to provide intelligent detection and treatment for pathologies related to women's reproductive health. Although some progress has been made with nanotherapeutics in this domain, its application is still nascent due to the delicate and intricate nature of the female reproductive system. This review comprehensively presents the latest advancements in nanomedicine for regulating woman's reproductive health. Firstly, based on the time period of onset, nanomedicine applications are categorized into four subcategories: 1) preconception diseases such as polycystic ovary syndrome, endometriosis, and gynecologic malignancy treatment; 2) pregastrulation period diseases including placenta accreta spectrum disorders and ectopic pregnancy; 3) mid-term pregnancy diseases like preeclampsia; and 4) late pregnancy diseases such as deep vein thrombosis during pregnancy. The systematic introduction covers the progress made by nanomedicine in various disease areas. Finally, this article discusses the challenges faced by these nanomedicines from research to clinical translation while also highlighting future directions.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 2","pages":"439-459"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the clinical assessment of glomerular podocyte pathology in kidney biopsies via super-resolution microscopy and angiopoietin-like 4 staining.","authors":"Xiaojing Liu, Suxia Wang, Gang Liu, Yan Wang, Shunlai Shang, Guming Zou, Shimin Jiang, Xuliang Wang, Li Yang, Wenge Li","doi":"10.7150/thno.101498","DOIUrl":"https://doi.org/10.7150/thno.101498","url":null,"abstract":"<p><p><b>Rationale:</b> The tertiary structure of normal podocytes prevents protein from leaking into the urine. However, observing the complexity of podocytes is challenging because of the scale differences in their three-dimensional structure and the close proximity between neighboring cells in space. In this study, we explored podocyte-secreted angiopoietin-like 4 (ANGPTL4) as a potential morphological marker via super-resolution microscopy (SRM). <b>Methods and Results:</b> Specimens from patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), along with normal controls, were analyzed via immunofluorescence and immunohistochemistry to determine the expression and localization of ANGPTL4, confirming its extensive presence in podocytes across both healthy and diseased conditions. Immunoelectron microscopy revealed that ANGPTL4 is distributed throughout the podocyte cell body, primary processes, and foot processes. Compared with conventional podocyte markers such as nephrin and synaptopodin, ANGPTL4 excels in depicting the three-dimensional structure of podocytes via SRM imaging. We then refined a protocol using tyramide signal amplification staining and confocal microscopy to uniformly enhance podocyte fluorescence, facilitating the clinical assessment of biopsies. In patients diagnosed with MCD and FSGS, measurements of slit diaphragm density, primary process width, and foot process width were taken after further co-staining with nephrin to identify patterns of podocyte morphological alterations. Distinctive patterns of foot process effacement were identified in MCD and FSGS patients, with FSGS patients showing more pronounced podocyte injury. <b>Conclusions:</b> ANGPTL4 serves as a reliable morphological marker for podocyte analysis, offering enhanced visualization of their three-dimensional structure and facilitating the identification of distinct pathological changes in nephrotic syndrome patients.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"784-803"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring of cancer ferroptosis with [¹⁸F]hGTS13, a system xc- specific radiotracer.","authors":"Abraham Moses, Rim Malek, Mustafa Tansel Kendirli, Pierre Cheung, Madeleine Landry, Marco Herrera-Barrera, Abbas Khojasteh, Monica Granucci, Syed A Bukhari, Jody E Hooper, Melanie Hayden-Gephart, Scott J Dixon, Lawrence D Recht, Corinne Beinat","doi":"10.7150/thno.101882","DOIUrl":"https://doi.org/10.7150/thno.101882","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, characterized by resistance to conventional therapies and poor survival. Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic target for GBM treatment. However, there are currently no non-invasive imaging techniques to monitor the engagement of pro-ferroptotic compounds with their respective targets, or to monitor the efficacy of ferroptosis-based therapies. System xc-, an important player in cellular redox homeostasis, plays a critical role in ferroptosis by mediating the exchange of cystine for glutamate, thus regulating the availability of cysteine, a crucial precursor for glutathione synthesis, and influencing the cellular antioxidant defense system. We have recently reported the development and validation of [¹⁸F]hGTS13, a radiopharmaceutical specific for system xc-. <b>Methods:</b> In the current work, we characterized the sensitivity of various cell lines to pro-ferroptotic compounds and evaluated the ability of [¹⁸F]hGTS13 to distinguish between sensitive and resistant cell lines and monitor changes in response to ferroptosis-inducing investigational compounds. We then associated changes in [¹⁸F]hGTS13 uptake with cellular glutathione content. Furthermore, we evaluated [¹⁸F]hGTS13 uptake in a rat model of glioma, both before and after treatment with imidazole ketone erastin (IKE), a pro-ferroptotic inhibitor of system xc- activity. <b>Results:</b> Treatment with erastin2, a system xc- inhibitor, significantly decreased [¹⁸F]hGTS13 uptake and cellular glutathione content <i>in vitro</i>. Dynamic PET/CT imaging of C6 glioma-bearing rats with [¹⁸F]hGTS13 revealed high and sustained uptake within the intracranial glioma and this uptake was decreased upon pre-treatment with IKE. <b>Conclusion:</b> In summary, [¹⁸F]hGTS13 represents a promising tool to distinguish cell types that demonstrate sensitivity or resistance to ferroptosis-inducing therapies that target system xc-, and monitor the engagement of these drugs.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"836-849"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical molecular imaging technology and its application in precise surgical navigation of liver cancer.","authors":"Pan He, Haitian Tang, Yating Zheng, Xiao Xu, Xuqi Peng, Tao Jiang, Yongfu Xiong, Yang Zhang, Yu Zhang, Gang Liu","doi":"10.7150/thno.102671","DOIUrl":"10.7150/thno.102671","url":null,"abstract":"<p><p>Recent innovations in medical imaging technology have placed molecular imaging techniques at the forefront of diagnostic advancements. The current research trajectory in this field aims to integrate personalized molecular data of patients and diseases with traditional anatomical imaging data, enabling more precise, non-invasive, or minimally invasive diagnostic options for clinical medicine. This article provides an in-depth exploration of the basic principles and system components of optical molecular imaging technology. It also examines commonly used targeting mechanisms of optical probes, focusing especially on indocyanine green-the FDA-approved optical dye widely used in clinical settings-and its specific applications in diagnosing and treating liver cancer. Finally, this review highlights the advantages, limitations, and future challenges facing optical molecular imaging technology, offering a comprehensive overview of recent advances, clinical applications, and potential impacts on liver cancer treatment strategies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"1017-1034"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention of radiotherapy-induced pro-tumorigenic microenvironment by SFK inhibitors.","authors":"Yong June Choi, Myung Jun Kim, Young Joo Lee, Munkyung Choi, Wan Seob Shim, Miso Park, Yong-Chul Kim, Keon Wook Kang","doi":"10.7150/thno.100970","DOIUrl":"https://doi.org/10.7150/thno.100970","url":null,"abstract":"<p><p><b>Background:</b> Radiotherapy is a widely employed technique for eradication of tumor using high-energy beams, and has been applied to approximately 50% of all solid tumor patients. However, its non-specific, cell-killing property leads to inevitable damage to surrounding normal tissues. Recent findings suggest that radiotherapy-induced tissue damage contributes to the formation of a pro-tumorigenic microenvironment. <b>Methods:</b> Here, we utilized two mouse strains and two organ-targeted radiotherapy models to uncover the mechanisms underlying the development of the radiotherapy-induced microenvironment. <b>Results:</b> Radiotherapy-induced tissue damage stimulates infiltration of monocyte-derived macrophages and their differentiation into M2 macrophages, ultimately leading to fibrosis and the formation of a pro-tumorigenic microenvironment. Notably, SRC family kinases (SFKs) emerged as crucial factors in the formation of the radiotherapy-induced pro-tumorigenic microenvironment. SFKs activation in epithelial cells and fibroblasts was triggered by direct exposure to irradiation or M2 macrophage cytokines. Remarkably, the administration of SFK-targeted inhibitors reversed myofibroblast activation, effectively ameliorating fibrosis and the pro-tumorigenic microenvironment in radiated tissues. Further, combined administration of radiotherapy and SFK-targeted inhibitors significantly enhanced the survival of tumor-bearing mice. <b>Conclusions:</b> Reshaping the tissue microenvironment by targeting SFKs is a potential strategy for preventing metastasis and recurrence following radiotherapy. The finding that clinically imperceptible damage can trigger a pro-tumorigenic microenvironment suggests the need for combining SFK-targeted inhibitors with radiotherapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"875-893"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia into <i>de novo</i> large cerebral infarction.","authors":"Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim","doi":"10.7150/thno.104132","DOIUrl":"10.7150/thno.104132","url":null,"abstract":"<p><p><b>Rationale:</b> It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia in mice, yet leads to various outcomes (asymptomatic-to-death) in humans. We hypothesized that inhibition of nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction. <b>Methods:</b> Using 900 mice, we i) investigated stroke-related effects of UCAO with/without intraperitoneal administration of the NOS inhibitor (NOSi) N_ω-nitro-L-arginine methyl ester (L-NAME, 400 mg/kg); ii) examined the rescue effect of the NO-donor, molsidomine (200 mg/kg at 30 minutes); and iii) tested the impact of antiplatelet medications. To corroborate preclinical findings, we conducted clinical studies. <b>Results:</b> UCAO alone induced infarction rarely (~2%) or occasionally (~14%) in C57BL/6 and BALB/c mice, respectively. However, L-NAME+UCAO induced large-arterial infarction in ~75% of C57BL/6 and BALB/c mice. Six-hour laser-speckle imaging detected spreading ischemia in ~40% of C57BL/6 and BALB/c mice with infarction (vs. none without) by 24-hours. In agreement with vasoconstriction/microthrombus formation shown by intravital-microscopy, molsidomine and the endothelial-NOS-activating antiplatelet cilostazol attenuated/prevented progression to infarction. Moreover, UCAO without L-NAME caused infarction in ~22% C57BL/6 and ~31% ApoE knock-out mice with hyperglycemia/hyperlipidemia, which associated with ~60% greater levels of symmetric dimethylarginine (SDMA, an endogenous NOSi). Further, increased levels of glucose and cholesterol associated with significantly larger infarct volumes in 438 UCAO-stroke patients. Lastly, Mendelian randomization identified a causative role of NOS inhibition (elevated SDMA concentration) in ischemic stroke risk (OR = 1.24; 95% CI, 1.11-1.38; <i>P</i> = 7.69×10^-5). <b>Conclusion:</b> NOS activity determines the fate of hypoperfused brain following acute UCAO, where SDMA could be a potential risk predictor.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 2","pages":"585-604"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in GelMA bioactive hydrogels: Strategies for infection control and bone tissue regeneration.","authors":"Lei Huang, Ziyao Guo, Xiaoxia Yang, Yinchun Zhang, Yiyun Liang, Xiaxue Chen, Xiaoling Qiu, Xuan Chen","doi":"10.7150/thno.103725","DOIUrl":"10.7150/thno.103725","url":null,"abstract":"<p><p>Infectious bone defects present a significant clinical challenge, characterized by infection, inflammation, and subsequent bone tissue destruction. Traditional treatments, including antibiotic therapy, surgical debridement, and bone grafting, often fail to address these defects effectively. However, recent advancements in biomaterials research have introduced innovative solutions for managing infectious bone defects. GelMA, a three-dimensional network of hydrophilic polymers that can absorb and retain substantial amounts of water, has attracted considerable attention in the fields of materials science and biomedical engineering. Its distinctive properties, such as biocompatibility, responsiveness to stimuli, and customisable mechanical characteristics make GelMA an exemplary scaffold material for bone tissue engineering. This review aims to thoroughly explore the current literature on antibacterial and osteogenic strategies using GelMA hydrogels for the restoration of infected bones. It discusses their fabrication methods, biocompatibility, antibacterial effectiveness, and bioactivity. We conclude by discussing the existing challenges and future research directions in this field, with the hope of inspiring further innovations in the synthesis, modification, and application of GelMA-based hydrogels for infection control and bone tissue regeneration.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 2","pages":"460-493"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet membrane decorated exosomes enhance targeting efficacy and therapeutic index to alleviate arterial restenosis.","authors":"Shan Lu, Ruihan Wang, Minghao Cai, Chen Yuan, Bin Gao, Daqiao Guo, Yisheng Xu, Weiguo Fu, Xiaohua Yu, Yi Si","doi":"10.7150/thno.103747","DOIUrl":"10.7150/thno.103747","url":null,"abstract":"<p><p><b>Rationale:</b> Postinterventional restenosis is a major challenge in the treatment of peripheral vascular disease. Current anti-restenosis drugs inhibit neointima hyperplasia but simultaneously impair endothelial repair due to indiscrminative cytotoxity. Stem cell-derived exosomes provide multifaceted therapeutic effects by delivering functional miRNAs to endothelial cells, macrophages, and vascular smooth muscle cells (VSMCs). However, their clinical application is severly limited by poor targeting and low tissue uptake in injured vessel. <b>Methods:</b> To address this challenge, we constructed platelet-mimetic exosomes (PM-EXOs) by fusing mesenchymal stem cell (MSC)-derived exosomes with platelet membrane in order to harness the natural ability of platelets to target vascular injury, evade clearance by the mononuclear phagocyte system, and penetrate into the intima by hitchhiking on inflammatory monocytes. <b>Results:</b> PM-EXOs demonstrated enhanced cellular uptake by endothelial cells and macrophages, exerting proangiogenic and immunomodulatory effects via the delivery of functional miRNAs <i>in vitro</i>. The intravenously administrated PM-EXOs exhibited extended circulation time and a 4-fold enhancement in targeting injured arteries compared to unmodified exosomes. In mouse and rat carotid artery injury models, PM-EXOs were shown to promote endothelial repair on the denuded arterial wall, lower the M1/M2 ratio of infiltrated macrophages, and eventually inhibit phenotypic switch of vascular smooth muscle cells and reduce the formation of neointima without causing systemic toxicity. <b>Conclusions:</b> This biomimetic strategy may be leveraged to boost the therapeutic index of exosomes and realize the multifaceted treatment of arterial restenosis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 2","pages":"408-427"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat acclimation defense against exertional heat stroke by improving the function of preoptic TRPV1 neurons.","authors":"Jing Li, Ziqing Zhou, You Wu, Jianshuai Zhao, Haokai Duan, Yuliang Peng, Xiaoke Wang, Zhongmin Fan, Lu Yin, Mengyun Li, Fuhong Liu, Yongheng Yang, Lixia Du, Jin Li, Haixing Zhong, Wugang Hou, Fanglin Zhang, Hongwei Ma, Xijing Zhang","doi":"10.7150/thno.101422","DOIUrl":"10.7150/thno.101422","url":null,"abstract":"<p><p><b>Rationale:</b> Record-breaking heatwaves caused by greenhouse effects lead to multiple hyperthermia disorders, the most serious of which is exertional heat stroke (EHS) with the mortality reaching 60 %. Repeat exercise with heat exposure, termed heat acclimation (HA), protects against EHS by fine-tuning feedback control of body temperature (Tb), the mechanism of which is opaque. This study aimed to explore the molecular and neural circuit mechanisms of the HA training against EHS. <b>Methods:</b> Male C57BL/6 mice (6-8 weeks) and male TRPV1-Cre mice (6-8 weeks) were used in our experiments. The EHS model with or without HA training were established for this study. RNA sequencing, qPCR, immunoblot, immunofluorescent assays, calcium imaging, optogenetic/ chemical genetic intervention, virus tracing, patch clamp, and other methods were employed to investigate the molecular mechanism and neural circuit by which HA training improves the function of the medial preoptic area (mPOA) neurons. Furthermore, a novel exosome-based strategy targeting the central nervous system to deliver irisin, a protective peptide generated by HA, was established to protect against EHS. <b>Results:</b> HA-related neurons in the mPOA expressing transient receptor potential vanilloid-1 (TRPV1) were identified as a population whose activation reduces Tb; inversely, dysfunction of these neurons contributes to hyperthermia and EHS. mPOA^TRPV1 neurons facilitate vasodilation and reduce adipose tissue thermogenesis, which is associated with their inhibitory projection to the raphe pallidus nucleus (RPa) and dorsal medial hypothalamus (DMH) neurons, respectively. Furthermore, HA improves the function of preoptic heat-sensitive neurons by enhancing TRPV1 expression, and <i>Trpv1</i> ablation reverses the HA-induced heat tolerance. A central nervous system-targeted exosome strategy to deliver irisin, a protective peptide generated by HA, can promote preoptic TRPV1 expression and exert similar protective effects against EHS. <b>Conclusions:</b> Preoptic TRPV1 neurons could be enhanced by HA, actively contributing to heat defense through the mPOA\"DMH/RPa circuit during EHS, which results in the suppression of adipose tissue thermogenesis and facilitation of vasodilatation. A delivery strategy of exosomes engineered with RVG-Lamp2b-Irisin significantly improves the function of mPOA^TRPV1 neurons, providing a promising preventive strategy for EHS in the future.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 4","pages":"1376-1398"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}