Theranostics最新文献

{"title":"Exosome-like nanoparticles derived from fruits, vegetables, and herbs: innovative strategies of therapeutic and drug delivery.","authors":"Bo Zhao, Hangjuan Lin, Xinchi Jiang, Wanshu Li, Yuli Gao, Minghui Li, Yanan Yu, Ninggang Chen, Jianqing Gao","doi":"10.7150/thno.97096","DOIUrl":"10.7150/thno.97096","url":null,"abstract":"<p><p>Over the past ten years, significant advancements have been made in exploring plant-derived exosome-like nanoparticles (PELNs) for disease therapeutics and drug delivery. PELNs, as inherent nanoscale particles comprised of proteins, lipids, nucleic acids, and secondary metabolites, exhibit the capacity for cellular uptake by human cells. This intercellular interaction transcends biological boundaries, effectively influencing biological functions in animals. PELNs have outstanding biocompatibility, low immunogenicity, enhanced safety, and environmentally friendly sustainability. This article summarized the preparation methods and characteristics of PELNs. It provided a systematic review of the varied roles of PELNs derived from fruits, vegetables, and herbs in disease therapeutics and drug delivery. The challenges in their production and application were discussed, and future prospects in this rapidly evolving field were explored.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141151","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":"Reconstituting gut microbiota-colonocyte interactions reverses diet-induced cognitive deficits: The beneficial of <i>eucommiae cortex</i> polysaccharides.","authors":"Mengli Wang, Penghao Sun, Xuejun Chai, Yong-Xin Liu, Luqi Li, Wei Zheng, Shulin Chen, Xiaoyan Zhu, Shanting Zhao","doi":"10.7150/thno.99468","DOIUrl":"10.7150/thno.99468","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Rationale:&lt;/b&gt; Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of &lt;i&gt;Eucommiae cortex&lt;/i&gt; polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. &lt;b&gt;Methods:&lt;/b&gt; Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with &lt;i&gt;Escherichia coli&lt;/i&gt; (&lt;i&gt;E. coli&lt;/i&gt;) from HFD mice confirmed that inhibition of &lt;i&gt;Proteobacteria&lt;/i&gt; by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of &lt;i&gt;Proteobacteria&lt;/i&gt; in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. &lt;b&gt;Results:&lt;/b&gt; Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum &lt;i&gt;Proteobacteria&lt;/i&gt; and cognitive performance in mice. Further, introducing &lt;i&gt;E. coli&lt;/i&gt; from HFD-fed mice into standard diet-fed mice underscored the integral role of &lt;i&gt;Proteobacteria&lt;/i&gt; proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of &lt;i&gt;Proteobacteria&lt;/i&gt; and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of &lt;i&gt;Proteobacteria&lt;/i&gt;. &lt;b&gt;Conclusions:&lt;/b&gt; Our study elucidates that colonocyte metabolic disturbances, which promote &lt;i&gt;Proteobacteria&lt;/i&gt; overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulator","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141165","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":"Erratum: Porphyrin-grafted Lipid Microbubbles for the Enhanced Efficacy of Photodynamic Therapy in Prostate Cancer through Ultrasound-controlled <i>In Situ</i> Accumulation: Erratum.","authors":"Yujia You, Xiaolong Liang, Tinghui Yin, Min Chen, Chen Qiu, Chuang Gao, Xiaoyou Wang, Yongjiang Mao, Enze Qu, Zhifei Dai, Rongqin Zheng","doi":"10.7150/thno.100601","DOIUrl":"https://doi.org/10.7150/thno.100601","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/thno.22469.].</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902937","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":"Cypher/ZASP drives cardiomyocyte maturation via actin-mediated MRTFA-SRF signalling.","authors":"Jialan Lyu, Zhicheng Pan, Ruobing Li, Hailong Yu, Yuesheng Zhang, Dongfei Wang, Xiang Yin, Yan He, Liding Zhao, Siyuan Chen, Shan Zhang, Hongqiang Cheng, Xiaogang Guo","doi":"10.7150/thno.98734","DOIUrl":"10.7150/thno.98734","url":null,"abstract":"<p><p><b>Rationale:</b> Cardiomyocytes (CMs) undergo dramatic structural and functional changes in postnatal maturation; however, the regulatory mechanisms remain greatly unclear. Cypher/Z-band alternatively spliced PDZ-motif protein (ZASP) is an essential sarcomere component maintaining Z-disc stability. Deletion of mouse Cypher and mutation in human ZASP result in dilated cardiomyopathy (DCM). Whether Cypher/ZASP participates in CM maturation and thereby affects cardiac function has not been answered. <b>Methods:</b> Immunofluorescence, transmission electron microscopy, real-time quantitative PCR, and Western blot were utilized to identify the role of Cypher in CM maturation. Subsequently, RNA sequencing and bioinformatics analysis predicted serum response factor (SRF) as the key regulator. Rescue experiments were conducted using adenovirus or adeno-associated viruses encoding SRF, both <i>in vitro</i> and <i>in vivo</i>. The molecular mechanisms were elucidated through G-actin/F-actin fractionation, nuclear-cytoplasmic extraction, actin disassembly assays, and co-sedimentation assays. <b>Results:</b> Cypher deletion led to impaired sarcomere isoform switch and morphological abnormalities in mitochondria, transverse-tubules, and intercalated discs. RNA-sequencing analysis revealed significant dysregulation of crucial genes related to sarcomere assembly, mitochondrial metabolism, and electrophysiology in the absence of Cypher. Furthermore, SRF was predicted as key transcription factor mediating the transcriptional differences. Subsequent rescue experiments showed that SRF re-expression during the critical postnatal period effectively rectified CM maturation defects and notably improved cardiac function in Cypher-depleted mice. Mechanistically, Cypher deficiency resulted in the destabilization of F-actin and a notable increase in G-actin levels, thereby impeding the nuclear localisation of myocardin-related transcription factor A (MRTFA) and subsequently initiating SRF transcription. <b>Conclusion:</b> Cypher/ZASP plays a crucial role in CM maturation through actin-mediated MRTFA-SRF signalling. The linkage between CM maturation abnormalities and the late-onset of DCM is suggested, providing further insights into the pathogenesis of DCM and potential treatment strategies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902935","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":"Endosome-microautophagy targeting chimera (eMIATAC) for targeted proteins degradation and enhance CAR-T cell anti-tumor therapy.","authors":"Kunjian Lei, Jingying Li, Zewei Tu, Chuandong Gong, Junzhe Liu, Min Luo, Wenqian Ai, Lei Wu, Yishuang Li, Zhihong Zhou, Zhihao Chen, Shigang Lv, Minhua Ye, Miaojing Wu, Xiaoyan Long, Xingen Zhu, Kai Huang","doi":"10.7150/thno.98574","DOIUrl":"10.7150/thno.98574","url":null,"abstract":"<p><p><b>Rationale:</b> Since oncogene expression products often exhibit upregulation or abnormally activated activity, developing a technique to regulate abnormal protein levels represent a viable approach for treating tumors and protein abnormality-related diseases. <b>Methods:</b> We first screened out eMIATAC components with high targeted degradation efficiency and explored the mechanism by which eMIATAC induced target protein degradation, and verified the degradation efficiency of the target protein by protein imprinting and flow cytometry. Next, we recombined eMIATAC with some controllable elements to verify the regulatable degradation performance of the target protein. Subsequently, we constructed eMIATAC that can express targeted degradation of AKT1 and verified its effect on GBM cell development in vitro and in vivo. Finally, we concatenated eMIATAC with CAR sequences to construct CAR-T cells with low BATF protein levels and verified the changes in their anti-tumor efficacy. <b>Results:</b> we developed a system based on the endosome-microautophagy-lysosome pathway for degrading endogenous proteins: endosome-MicroAutophagy TArgeting Chimera (eMIATAC), dependent on Vps4A instead of lysosomal-associated membrane protein 2A (LAMP2A) to bind to the chaperone Hsc70 and the protein of interest (POI). The complex was then transported to the lysosome by late endosomes, where degradation occurred similarly to microautophagy. The eMIATACs demonstrated accuracy, efficiency, reversibility, and controllability in degrading the target protein EGFP. Moreover, eMIATAC exhibited excellent performance in knocking down POI when targeting endogenous proteins in vivo and in vitro. <b>Conclusions:</b> The eMIATACs could not only directly knock down abnormal proteins for glioma treatment but also enhance the therapeutic effect of CAR-T cell therapy for tumors by knocking down T cell exhaustion-related proteins. The newly developed eMIATAC system holds promise as a novel tool for protein knockdown strategies. By enabling direct control over endogenous protein levels, eMIATAC has the potential to revolutionize treatment for cancer and genetic diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902936","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":"ISG15 accelerates acute kidney injury and the subsequent AKI-to-CKD transition by promoting TGFβR1 ISGylation.","authors":"Na Cui, Chengyu Liu, Xiang Tang, Liangliang Song, Zixuan Xiao, Chen Wang, Yancai Wu, Yihao Zhou, Chentai Peng, Yuxia Liu, Ling Zheng, Xinran Liu, Kun Huang, Hong Chen","doi":"10.7150/thno.95796","DOIUrl":"10.7150/thno.95796","url":null,"abstract":"<p><p><b>Rationale:</b> Acute kidney injury (AKI) has substantial rates of mortality and morbidity, coupled with an absence of efficacious treatment options. AKI commonly transits into chronic kidney disease (CKD) and ultimately culminates in end-stage renal failure. The interferon-stimulated gene 15 (ISG15) level was upregulated in the kidneys of mice injured by ischemia-reperfusion injury (IRI), cisplatin, or unilateral ureteral obstruction (UUO), however, its role in AKI development and subsequent AKI-to-CKD transition remains unknown. <b>Methods:</b> <i>Isg15</i> knockout (<i>Isg15</i> KO) mice challenged with bilateral or unilateral IRI, cisplatin, or UUO were used to investigate its role in AKI. We established cellular models with overexpression or knockout of ISG15 and subjected them to hypoxia-reoxygenation, cisplatin, or transforming growth factor- β1 (TGF-β1) stimulation. Renal RNA-seq data obtained from AKI models sourced from public databases and our studies, were utilized to examine the expression profiles of ISG15 and its associated genes. Additionally, published single cell RNA-seq data from human kidney allograft biopsies and mouse IRI model were analyzed to investigate the expression patterns of ISG15 and the type I TGF-β receptor (TGFβR1). Western blotting, qPCR, co-immunoprecipitation, and immunohistochemical staining assays were performed to validate our findings. <b>Results:</b> Alleviated pathological injury and renal function were observed in <i>Isg15</i> KO mice with IRI-, cisplatin-, or UUO-induced AKI and the following AKI-to-CKD transition. In hypoxia-reoxygenation, cisplatin or TGF-β1 treated HK-2 cells, knockout ISG15 reduced stimulus-induced cell fibrosis, while overexpression of ISG15 with modification capacity exacerbated cell fibrosis. Immunoprecipitation assays demonstrated that ISG15 promoted ISGylation of TGFβR1, and inhibited its ubiquitination. Moreover, knockout of TGFβR1 blocked ISG15's fibrosis-exacerbating effect in HK-2 cells, while overexpression of TGFβR1 abolished the renal protective effect of ISG15 knockout during IRI-induced kidney injury. <b>Conclusions:</b> ISG15 plays an important role in the development of AKI and subsequent AKI-to-CKD transition by promoting TGFβR1 ISGylation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902939","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":"Transcranial blood-brain barrier opening in Alzheimer's disease patients using a portable focused ultrasound system with real-time 2-D cavitation mapping.","authors":"Sua Bae, Keyu Liu, Antonios N Pouliopoulos, Robin Ji, Sergio Jiménez-Gambín, Omid Yousefian, Alina R Kline-Schoder, Alec J Batts, Fotios N Tsitsos, Danae Kokossis, Akiva Mintz, Lawrence S Honig, Elisa E Konofagou","doi":"10.7150/thno.94206","DOIUrl":"10.7150/thno.94206","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;&lt;i&gt;Background&lt;/i&gt;&lt;/b&gt; : Focused ultrasound (FUS) in combination with microbubbles has recently shown great promise in facilitating blood-brain barrier (BBB) opening for drug delivery and immunotherapy in Alzheimer's disease (AD). However, it is currently limited to systems integrated within the MRI suites or requiring post-surgical implants, thus restricting its widespread clinical adoption. In this pilot study, we investigate the clinical safety and feasibility of a portable, non-invasive neuronavigation-guided FUS (NgFUS) system with integrated real-time 2-D microbubble cavitation mapping. &lt;b&gt;&lt;i&gt;Methods&lt;/i&gt;&lt;/b&gt; : A phase 1 clinical study with mild to moderate AD patients (N = 6) underwent a single session of microbubble-mediated NgFUS to induce transient BBB opening (BBBO). Microbubble activity under FUS was monitored with real-time 2-D cavitation maps and dosing to ensure the efficacy and safety of the NgFUS treatment. Post-operative MRI was used for BBB opening and closure confirmation as well as safety assessment. Changes in AD biomarker levels in both blood serum and extracellular vesicles (EVs) were evaluated, while changes in amyloid-beta (Aβ) load in the brain were assessed through &lt;sup&gt;18&lt;/sup&gt;F-florbetapir PET. &lt;b&gt;&lt;i&gt;Results&lt;/i&gt;&lt;/b&gt; : BBBO was achieved in 5 out of 6 subjects with an average volume of 983 ± 626 mm&lt;sup&gt;3&lt;/sup&gt; following FUS at the right frontal lobe both in white and gray matter regions. The outpatient treatment was completed within 34.8 ± 10.7 min. Cavitation dose significantly correlated with the BBBO volume (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; &gt; 0.9, &lt;i&gt;N&lt;/i&gt; = 4), demonstrating the portable NgFUS system's capability of predicting opening volumes. The cavitation maps co-localized closely with the BBBO location, representing the first report of real-time transcranial 2-D cavitation mapping in the human brain. Larger opening volumes correlated with increased levels of AD biomarkers, including Aβ42 (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.74), Tau (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.95), and P-Tau181 (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 0.86), assayed in serum-derived EVs sampled 3 days after FUS (&lt;i&gt;N&lt;/i&gt; = 5). From PET scans, subjects showed a lower Aβ load increase in the treated frontal lobe region compared to the contralateral region. Reduction in asymmetry standardized uptake value ratios (SUVR) correlated with the cavitation dose (&lt;i&gt;R&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; &gt; 0.9, &lt;i&gt;N&lt;/i&gt; = 3). Clinical changes in the mini-mental state examination over 6 months were within the expected range of cognitive decline with no additional changes observed as a result of FUS. &lt;b&gt;&lt;i&gt;Conclusion&lt;/i&gt;&lt;/b&gt; : We showed the safety and feasibility of this cost-effective and time-efficient portable NgFUS treatment for BBBO in AD patients with the first demonstration of real-time 2-D cavitation mapping. The cavitation dose correlated with BBBO volume, a slowed increase in pathology, and serum detection of AD proteins. Our study highlights the potential for accessible FUS treatment in AD, with ","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902985","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":"Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis.","authors":"Yajie Cai, Shuo Li, Yang Yang, Shuni Duan, Guifang Fan, Jinzhao Bai, Qi Zheng, Yiqing Gu, Xiaojiaoyang Li, Runping Liu","doi":"10.7150/thno.96184","DOIUrl":"10.7150/thno.96184","url":null,"abstract":"<p><p><b>Rationale:</b> The treatment of ulcerative colitis (UC) presents an ongoing clinical challenge. Emerging research has implicated that the cGAS-STING pathway promotes the progression of UC, but conflicting results have hindered the development of STING as a therapeutic target. In the current study, we aim to comprehensively elucidate the origins, downstream signaling and pathogenic roles of myeloid STING in colitis and colitis-associated carcinoma (CAC). <b>Methods:</b> <i>Tmem173</i> ^fl/fl <i>Lyz2-Cre</i> ^ert2 mice were constructed for inducible myeloid-specific deletion of STING. RNA-sequencing, flow cytometry, and multiplex immunohistochemistry were employed to investigate immune responses in DSS-induced colitis or AOM/DSS-induced carcinogenesis. Colonic organoids, primary bone marrow derived macrophages and dendritic cells, and splenic T cells were used for <i>in vitro</i> studies. <b>Results:</b> We observed that myeloid STING knockout in adult mice inhibited macrophage maturation, reduced DC cell activation, and suppressed pro-inflammatory Th1 and Th17 cells, thereby protecting against both acute and chronic colitis and CAC. However, myeloid STING deletion in neonatal or tumor-present mice exhibited impaired immune tolerance and anti-tumor immunity. Furthermore, we found that TFAM-associated mtDNA released from damaged colonic organoids, rather than bacterial products, activates STING in dendritic cells in an extracellular vesicle-independent yet endocytosis-dependent manner. Both IRF3 and NF-κB are required for STING-mediated expression of IL-12 family cytokines, promoting Th1 and Th17 differentiation and contributing to excessive inflammation in colitis. <b>Conclusions:</b> Detection of the TFAM-mtDNA complex from damaged intestinal epithelium by myeloid STING exacerbates colitis through IL-12 cytokines, providing new evidence to support the development of STING as a therapeutic target for UC and CAC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902938","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":"Nucleic acid-based nanotherapeutics for treating sepsis and associated organ injuries.","authors":"Huang-Ping Yu, Fu-Chao Liu, Yu-Kuo Chung, Ahmed Alalaiwe, Calvin T Sung, Jia-You Fang","doi":"10.7150/thno.98487","DOIUrl":"10.7150/thno.98487","url":null,"abstract":"<p><p>In recent years, gene therapy has been made possible with the success of nucleic acid drugs against sepsis and its related organ dysfunction. Therapeutics based on nucleic acids such as small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs), and plasmid DNAs (pDNAs) guarantee to treat previously undruggable diseases. The advantage of nucleic acid-based therapy against sepsis lies in the development of nanocarriers, achieving targeted and controlled gene delivery for improved efficacy with minimal adverse effects. Entrapment into nanocarriers also ameliorates the poor cellular uptake of naked nucleic acids. In this study, we discuss the current state of the art in nanoparticles for nucleic acid delivery to treat hyperinflammation and apoptosis associated with sepsis. The optimized design of the nanoparticles through physicochemical property modification and ligand conjugation can target specific organs-such as lung, heart, kidney, and liver-to mitigate multiple sepsis-associated organ injuries. This review highlights the nanomaterials designed for fabricating the anti-sepsis nanosystems, their physicochemical characterization, the mechanisms of nucleic acid-based therapy in working against sepsis, and the potential for promoting the therapeutic efficiency of the nucleic acids. The current investigations associated with nanoparticulate nucleic acid application in sepsis management are summarized in this paper. Noteworthily, the potential application of nanotherapeutic nucleic acids allows for a novel strategy to treat sepsis. Further clinical studies are required to confirm the findings in cell- and animal-based experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for commercialization. It is expected that numerous anti-sepsis possibilities will be investigated for nucleic acid-based nanotherapeutics in the future.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902979","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":"Remote actuation and on-demand activation of biomaterials pre-incorporated with physical cues for bone repair.","authors":"Xueping Kong, Tianyi Zheng, Zhaoyi Wang, Tong Zhou, Jiezhong Shi, Ying Wang, Ben Zhang","doi":"10.7150/thno.97610","DOIUrl":"10.7150/thno.97610","url":null,"abstract":"<p><p>The high incidence of bone defect-related diseases caused by trauma, infection, and tumor resection has greatly stimulated research in the field of bone regeneration. Generally, bone healing is a long and complicated process wherein manipulating the biological activity of interventional scaffolds to support long-term bone regeneration is significant for treating bone-related diseases. It has been reported that some physical cues can act as growth factor substitutes to promote osteogenesis through continuous activation of endogenous signaling pathways. This review focuses on the latest progress in bone repair by remote actuation and on-demand activation of biomaterials pre-incorporated with physical cues (heat, electricity, and magnetism). As an alternative method to treat bone defects, physical cues show many advantages, including effectiveness, noninvasiveness, and remote manipulation. First, we introduce the impact of different physical cues on bone repair and potential internal regulatory mechanisms. Subsequently, biomaterials that mediate various physical cues in bone repair and their respective characteristics are summarized. Additionally, challenges are discussed, aiming to provide new insights and suggestions for developing intelligent biomaterials to treat bone defects and promote clinical translation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902983","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}