Theranostics最新文献

{"title":"Multiple crosslinked, self-healing, and shape-adaptable hydrogel laden with pain-relieving chitosan@borneol nanoparticles for infected burn wound healing.","authors":"Zexing Deng, Yi Guo, Xuefeng Wang, Jiajie Song, Guan Yang, Litong Shen, Yuheng Wang, Xin Zhao, Baolin Guo, Wen Wang","doi":"10.7150/thno.102569","DOIUrl":"10.7150/thno.102569","url":null,"abstract":"<p><p><i>Rationale:</i> Next-generation wound dressings with multiple biological functions hold promise for addressing the complications and pain associated with burn wounds. <i>Methods:</i> A hydrogel wound dressing loaded with a pain-relieving drug was developed for treating infected burn wounds. Polyvinyl alcohol chemically grafted with gallic acid (PVA-GA), sodium alginate chemically grafted with 3-aminobenzeneboronic acid (SA-PBA), Zn²⁺, and chitosan-coated borneol nanoparticles with anti-inflammatory and pain-relieving activities were combined to afford a nanoparticle-loaded hydrogel with a PVA-GA/Zn²⁺/SA-PBA network crosslinked via multiple physicochemical interactions. <i>Results:</i> The developed hydrogel demonstrated adhesiveness, self-healing, shape adaptability, injectability, degradability, conformity to complicated wound surfaces, and other desirable biological functions, including a pH-responsive drug release behavior and antibacterial, antioxidant, anti-inflammatory, and proangiogenic activities. In a murine scald wound model, the hydrogel effectively prevented infection by <i>Staphylococcus aureus</i> and downregulated pain perception (measured using mouse grimace scale scores and hind paw lifting and licking times), thereby accelerating wound healing. <i>Conclusion:</i> This study provides broad prospects for the development of new hydrogel systems that can substantially improve the dynamic management of infected burn wounds.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 4","pages":"1439-1455"},"PeriodicalIF":12.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012109","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":"Loss of DDX24 inhibits lung cancer progression by stimulating IKBKG splicing-mediated autophagy.","authors":"Siwen Sun, Xiaomeng Jing, Guangquan Tong, Chaoqun Chen, Shuaijun Xie, Chong Wang, Dan Chen, Jinyao Zhao, Yangfan Qi, Wenjing Zhang, Congcong Liu, Ge Zhang, Jinrui Zhang, Bing Sun, Yang Wang, Yuesheng Lv","doi":"10.7150/thno.102425","DOIUrl":"10.7150/thno.102425","url":null,"abstract":"<p><p><b>Rationale:</b> Lung cancer remains a major global health burden with limited therapeutic options. Alternative splicing, a critical post-transcriptional process, contributes to lung cancer progression through autophagy, although the underlying mechanisms remain largely unexplored. This study aims to elucidate the role of DDX24 as a splicing factor that contributes to lung cancer progression via autophagy. <b>Methods:</b> To establish the link between DDX24 and lung cancer progression, we performed colony formation assays, growth curve analyses, and xenograft tumor models in nude mice. Mass spectrometry and RNA sequencing were employed to investigate the involvement of DDX24 in alternative splicing, with a specific focus on the splicing of IKBKG. The mechanisms by which DDX24 regulates autophagy were further explored using co-immunoprecipitation and luciferase reporter assays. <b>Results:</b> The splicing factor DDX24 is significantly elevated in lung cancer tissues. Loss of DDX24 suppresses lung cancer growth by promoting autophagy. We identified DDX24 as a splicing factor that plays critical roles in the regulation of alternative splicing. Mechanistically, DDX24 regulates the alternative splicing of autophagy-related genes, including IKBKG. We demonstrate that DDX24 directly binds to IKBKG pre-mRNA, whereas DDX24 ablation stimulates the generation of the long splicing isoform of IKBKG, thereby promoting autophagy through activating of the NF-kB signaling pathway and the transcription of the BECN1 gene. Functional rescue experiments confirm that the long IKBKG isoform-mediated autophagy confers the anti-tumor effects of DDX24 depletion. In addition, IKBKG-L is positively associated with improved survival in lung cancer patients. <b>Conclusions:</b> This study uncovers a novel regulatory axis involving DDX24, IKBKG splicing, and autophagy in lung cancer. Our findings suggest that targeting DDX24 may represent a promising therapeutic strategy for lung cancer treatment, offering new insights into the molecular underpinnings of this disease.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 5","pages":"1879-1895"},"PeriodicalIF":12.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081071","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":"Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy.","authors":"Xinyue Shao, Xiaoling Zhao, Binghao Wang, Jiahui Fan, Jinping Wang, Hailong An","doi":"10.7150/thno.103636","DOIUrl":"10.7150/thno.103636","url":null,"abstract":"<p><p>In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in the field of cancer therapy. By precisely targeting the TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, and abnormally expressed proteins, etc., these Nano-DDS enable effective delivery of therapeutic agents and reversal of MDR. This scientific research community is increasing its investment in the development of diversified systems and exploring their anti-drug resistance potential. Therefore, it is particularly important to conduct a comprehensive review of the research progress of TME-targeted Nano-DDS in recent years. After a brief introduction of TME and tumor MDR, the design principle and structure of liposomes, polymer micelles and inorganic nanocarriers are focused on, and their characteristics as TME-targeted nanocarriers are described. It also demonstrates how these systems break through the cancer MDR treatment through various targeting mechanisms, discusses their synthetic innovation, research results and resistance overcoming mechanisms. The review was concluded with deliberations on the key challenges and future outlooks of targeting TME Nano-DDS in cancer therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 5","pages":"1689-1714"},"PeriodicalIF":12.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081085","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":"Metabolism of hepatic stellate cells in chronic liver diseases: emerging molecular and therapeutic interventions.","authors":"Mengyao Yan, Yimin Cui, Qian Xiang","doi":"10.7150/thno.106597","DOIUrl":"10.7150/thno.106597","url":null,"abstract":"<p><p>Chronic liver diseases, primarily metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic and metabolic dysfunction-associated alcoholic liver disease (MetALD), and viral hepatitis, can lead to liver fibrosis, cirrhosis, and cancer. Hepatic stellate cell (HSC) activation plays a central role in the development of myofibroblasts and fibrogenesis in chronic liver diseases. However, HSC activation is influenced by the complex microenvironments within the liver, which are largely shaped by the interactions between HSCs and various other cell types. Changes in HSC phenotypes and metabolic mechanisms involve glucose, lipid, and cholesterol metabolism, oxidative stress, activation of the unfolded protein response (UPR), autophagy, ferroptosis, senescence, and nuclear receptors. Clinical interventions targeting these pathways have shown promising results in addressing liver inflammation and fibrosis, as well as in modulating glucose and lipid metabolism and metabolic stress responses. Therefore, a comprehensive understanding of HSC phenotypes and metabolic mechanisms presents opportunities for novel therapeutic approaches aimed at halting or even reversing chronic liver diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 5","pages":"1715-1740"},"PeriodicalIF":12.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081073","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":"Ultrasound-activated erythrocyte membrane-camouflaged Pt (II) layered double hydroxide enhances PD-1 inhibitor efficacy in triple-negative breast cancer through cGAS-STING pathway-mediated immunogenic cell death.","authors":"Yanjie Wu, Zhiyu Zhao, Mengli Ma, Weijin Zhang, Wei Liu, Xiaochen Liang, Ting Zhao, Yi Luo, Yunjie Wang, Mengqi Li, Tingting Li, Cong Liu, Xian Luo, Shengyu Wang, Wanyun Li, Wei Zeng, Hong Wang, Wengang Li, Ting Wu, Zhihai Ke, Fanghong Luo","doi":"10.7150/thno.102284","DOIUrl":"10.7150/thno.102284","url":null,"abstract":"<p><p><b>Rationale:</b> Immunogenic cell death (ICD) offers a promising avenue for the treatment of triple-negative breast cancer (TNBC). However, optimizing immune responses remains a formidable challenge. This study presents the design of RBCm@Pt-CoNi layered double hydroxide (RmPLH), an innovative sonosensitizer for sonodynamic therapy (SDT), aimed at enhancing the efficacy of programmed cell death protein 1 (PD-1) inhibitors by inducing robust ICD responses. <b>Methods:</b> Pt-CoNi layered double hydroxide (LDH) nanocages were synthesized using a two-step method, followed by functionalization with red blood cell membranes to prepare RmPLH. The <i>in vitro</i> assessments included evaluations of cell toxicity, cellular uptake, and sonodynamic effects of RmPLH. Key mechanisms-such as oxidative stress, DNA damage, pyroptosis, cGAS/STING pathway activation, and inhibition of cellular migration and invasion-were explored under varying treatment conditions in 4T1 cells. Tumor-bearing mice were employed to evaluate tumor-targeting capabilities and the synergistic tumor-suppressive effects of RmPLH combined with PD-1 inhibitors. Comprehensive safety evaluations, including blood tests, biochemical analyses, and histopathological examinations, were also conducted. <b>Results:</b> The synthesized Pt-CoNi LDH exhibited a uniform rhombic dodecahedral nanocage morphology with an average particle size of approximately 231 nm. Encapsulation with red blood cell membranes conferred prolonged systemic circulation, enhanced tumor targeting, and reduced immune clearance for RmPLH. Upon ultrasound (US) stimulation, the LDH released substantial levels of reactive oxygen species (ROS) and platinum ions. The ROS effectively induced endoplasmic reticulum stress and ferroptosis, while platinum ions facilitated DNA crosslinking, triggering significant DNA damage. ROS-induced pyroptosis released inflammatory mediators and damage-associated molecular patterns (DAMPs), which activated the cGAS/STING pathway and reinforced ICD. Combining RmPLH with PD-1 inhibitors significantly enhanced therapeutic efficacy against TNBC. Furthermore, safety assessments confirmed the excellent biocompatibility and biosafety of RmPLH<b>.</b> <b>Conclusion:</b> The integration of RmPLH with PD-1 inhibitors substantially amplifies ICD, fostering robust antigen-specific T cell immunity and offering a promising therapeutic strategy for TNBC. This study represents a pioneering application of Pt (II)-based LDH nanocages in oncology, laying a foundation for future innovations in tumor immunotherapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 4","pages":"1456-1477"},"PeriodicalIF":12.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012148","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":"Glutamatergic pathways from medial prefrontal cortex to paraventricular nucleus of thalamus contribute to the methamphetamine-induced conditioned place preference without affecting wakefulness.","authors":"Xiang Li, Xing Xu, Quying Feng, Ning Zhou, Yuhong He, Ying Liu, Haoqing Tai, Hee Young Kim, Yu Fan, Xiaowei Guan","doi":"10.7150/thno.100688","DOIUrl":"10.7150/thno.100688","url":null,"abstract":"<p><p>Methamphetamine (METH) is a commonly abused psychostimulant with a high addictive nature. The paraventricular nucleus of thalamus (PVT), a key nucleus for arousal, has attracted much attention in the reward process of substance use. However, at which stage dose the PVT encode the reward process? How to reduce the side-effects of modulating PVT on wakefulness during the treatment of substance use? These issues remain unclear. The goal of the current study is to explore the role of the PVT and the glutamatergic projections from medial prefrontal cortex (mPFC) to PVT in the reward process of METH. <b>Methods:</b> Here, the conditioned place preference (CPP) was used to assess the reward process of METH in male mice, combined with methods of c-Fos mapping, virus-based neural tracing, patch-clamp recording, EEG-EMG recordings, optogenetics and designer receptor exclusively activated by designer drugs (<i>DREADDs</i>). <b>Results:</b> The glutamatergic neurons in PVT (PVT^Glu) were triggered during METH CPP-Test, rather than by METH CPP-Training. Suppressing either PVT^Glu or glutamatergic projection from mPFC to PVT efficiently disrupted the acquisition of METH CPP in male mice, mainly mediated by the GluN2A subunit of NMDA receptor. Further, inhibition of PVT^Glu affected the rhythm of EEG-EMG, whereas inhibition of glutamatergic projection from mPFC to PVT did not. <b>Conclusion:</b> PVT^Glu is involved in the reward process of METH at the retrieval stage of METH-conditioned context, rather than at the stage of encoding association between METH and context. The glutamatergic projections from mPFC to PVT, especially the GluN2A molecule, may be a promising therapeutic target for reducing METH reward, as there are no significant side effects on wakefulness.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 5","pages":"1822-1841"},"PeriodicalIF":12.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080988","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":"Cardiomyocyte S1PR1 promotes cardiac regeneration via AKT/mTORC1 signaling pathway.","authors":"Xiuxiang Liu, Jinnan Yue, Caixia Zhou, Yunhao Duan, Xiaoli Chen, Jie Liu, Shougang Zhuang, Yu Luo, Jinjin Wu, Yuzhen Zhang, Lin Zhang","doi":"10.7150/thno.103797","DOIUrl":"10.7150/thno.103797","url":null,"abstract":"<p><p><b>Aims:</b> Lower vertebrates and some neonatal mammals are known to possess the ability to regenerate cardiomyocyte and fully recover after heart injuries within a limited period. Understanding the molecular mechanisms of heart regeneration and exploring new ways to enhance cardiac regeneration hold significant promise for therapeutic intervention of heart failure. Sphingosine 1-phospahte receptor 1 (S1PR1) is highly expressed in cardiomyocytes and plays a crucial role in heart development and pathological cardiac remodeling. However, the effect of cardiomyocyte-expressing S1PR1 on heart regeneration has not yet been elucidated. This study aims to investigate the role of cardiomyocyte S1PR1 in cardiac regeneration following heart injuries. <b>Methods and Results:</b> We generated cardiomyocyte (CM)-specific <i>S1pr1</i> knock-out mice and demonstrated that CM-specific <i>S1pr1</i> loss-of-function severely reduced cardiomyocyte proliferation and inhibited heart regeneration following apex resection in neonatal mice. Conversely, AAV9-mediated CM-specific <i>S1pr1</i> gain-of-function significantly enhanced cardiac regeneration. We identified that S1PR1 activated the AKT/mTORC1/CYCLIN D1 and BCL2 signaling pathways to promote cardiomyocyte proliferation and inhibit apoptosis. Moreover, CM-targeted gene delivery system via AAV9 to overexpress S1PR1 significantly increased cardiomyocyte proliferation and improved cardiac functions following myocardial infarction in adult mice, suggesting a potential method to enhance cardiac regeneration and improve cardiac function in the injured heart. <b>Conclusions:</b> This study demonstrates that CM-S1PR1 plays an essential role in cardiomyocyte proliferation and heart regeneration. This research provides a potential strategy by CM-targeted S1PR1 overexpression as a new therapeutic intervention for heart failure.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 4","pages":"1524-1551"},"PeriodicalIF":12.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012054","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":"A H2S-activated NIR-II imaging probe for precise diagnosis and pathological evaluation of colorectal tumor.","authors":"Yu Ji, Qinxian Huang, Qian Jia, Haohao Yan, Yajing Chi, Yuanyuan Jia, Chaoqiang Qiao, Yanbin Feng, Zuo Yang, Ruili Zhang, Zhongliang Wang","doi":"10.7150/thno.103999","DOIUrl":"10.7150/thno.103999","url":null,"abstract":"<p><p><b>Rationale:</b> The quick and accurate detection of colorectal cancer (CRC) is essential for improving the treatment efficacy and patient survival, which nevertheless remains challenging due to low specificity and sensitivity of current CRC diagnostic approaches. Therefore, providing a robust solution for real-time and accurate tumor delineation is highly desirable. <b>Methods:</b> We report a novel polyacrylic acid-mediated strategy to develop the endogenous hydrogen sulfide (H₂S)-activated NIR-II probe DCNP@PB for specific visualization of CRC and image-guided tumor surgery. The stability, biocompatibility, H₂S-responsiveness, and NIR-II imaging capability were evaluated <i>in vitro</i> and <i>in vivo</i>. Human CRC tissues were used to evaluated the performance of the DCNP@PB. <b>Results:</b> By exploiting the effective inner filter effect (IFE) and fluorescence resonance energy transfer (FRET) between DCNPs and PB, luminescence of DCNP@PB can be rapidly switched ON in response to H₂S in colorectal tumor, affording high tumor-to-background ratio (TBR). Notably, H₂S-responsive range of DCNP@PB well matches the H₂S concentration at tumor site, thereby minimizing nonspecific activation by other sulfur-containing substances in a complicated biological environment. Such accurate H₂S responsiveness not only benefits the differentiation between tumor and normal tissues in the mouse model, but also clearly delineates the cancerous boundaries in human tissues specimens. <b>Conclusion:</b> This work presents not only a promising example of H₂S-activated NIR-II optical probe that could be intravenously injected for <i>in vivo</i> applications to afford reliable information and quick feedback, but also an effective strategy to design the activatable imaging probes for precise tumor diagnosis and intraoperative decision support.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 1","pages":"189-201"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915715","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":"Ultra-small quercetin-based nanotherapeutics ameliorate acute liver failure by combatting inflammation/cellular senescence cycle.","authors":"Yali Feng, Xiaoli Zhang, Juan Li, Shan Fu, Weicheng Xu, Jinfeng Liu, Yuan Yang, Tianyan Chen, Yingren Zhao, Dongmin Li, Mingzhen Zhang, Yingli He","doi":"10.7150/thno.103746","DOIUrl":"https://doi.org/10.7150/thno.103746","url":null,"abstract":"<p><p><b>Background:</b> Acute liver failure (ALF) is marked by a substantial generation of reactive oxygen species (ROS), which can induce both cellular senescence and a pronounced inflammatory response. Senescent cells secrete factors collectively termed the senescence-associated secretory phenotype (SASP), which exacerbate inflammation, while inflammation can reciprocally promote cellular senescence. Quercetin (Que), recognized for its ROS-scavenging capabilities, holds the potential for anti-inflammatory and anti-senescent effects. However, its extremely low aqueous solubility constrains its clinical efficacy in treating inflammation. <b>Methods:</b> We employed a simple and stable coordination method to synthesize ultra-small quercetin-Fe nanoparticles (QFN) by complexing quercetin with iron ions. The ROS-scavenging, anti-inflammatory, and anti-senescent effects of QFN were evaluated <i>in vitro</i>. A lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF mice model was used to investigate the therapeutic effects of QFN <i>in vivo</i>, and transcriptomic analysis was conducted to elucidate the mechanisms underlying QFN-mediated hepatoprotection. <b>Results:</b> Our findings demonstrate that QFN possesses remarkable water solubility and highly efficient ROS-scavenging properties. <i>In vitro</i>, QFN effectively inhibits macrophage-mediated inflammation and mitigates hepatocyte senescence. <i>In vivo</i>, QFN significantly attenuates LPS/D-GalN-induced ALF by protecting against macrophage inflammation and cellular senescence, thereby disrupting the self-perpetuating cycle of inflammation and aging. Moreover, its potent ROS scavenging capacity not only suppresses cellular apoptosis but also facilitates liver regeneration. Transcriptomic analyses further reveal that QFN exerts its protective effects through the modulation of key pathways involved in cellular senescence and inflammation. <b>Conclusions:</b> In summary, our study characterizes QFN as a potent ROS-scavenging modulator that exhibits both anti-inflammatory and anti-senescent properties, effectively disrupting the detrimental feedback loop between inflammation and cellular senescence. QFN holds considerable potential as a therapeutic agent for the treatment of ALF and other pathologies associated with inflammation and aging.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"1035-1056"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955416","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":"S100A proteins show a spatial distribution of inflammation associated with the glioblastoma microenvironment architecture.","authors":"Blanca Cómitre-Mariano, Berta Segura-Collar, Gabriel Vellila-Alonso, Rubén Contreras, Aurelio Henandez-Lain, Manuel Valiente, Juan M Sepulveda, Stephen Garrett Marcus, Guillermo García-Posadas, Luis Jiménez-Roldán, Ángel Perez-Nuñez, Ricardo Gargini","doi":"10.7150/thno.100638","DOIUrl":"10.7150/thno.100638","url":null,"abstract":"<p><p><b>Background:</b> Glioblastoma IDH wild type (GBM IDH wt) has a poor prognosis and a strongly associated with inflammatory processes. Inflammatory molecules generate positive feedback with tumor cells fueling tumor growth as well as recruitment of immune cells that promote aggressiveness. Although the role of many inflammatory molecules is well known, there are many macromolecules, such as the S100A proteins, whose role is only now beginning to be established. <b>Methods:</b> Using RNA-seq, bioinformatics tools and a cohort of glioma patients to validate the results, we have analysed the inflammatory processes involved in glioma. Transcriptional profiles were also used to define biological processes of relevance to specific S100A proteins. Finally, we characterized the relevant immune populations with an IHC analysis and transcriptional profiling. <b>Results:</b> We have noted an increased expression of S100A in GBM IDH wt compared to gliomas IDH mutants. This allowed us to analyse the involvement of different members of the family, such as S100A9, A11 and A13 as possible regulators of inflammatory processes in the GBM-IDH wt microenvironment. Thus, we observed that S100A9 is located in hypoxic areas linked to the function of neutrophils, S100A11 is found in vascular areas associated with the function of perivascular pericytes and macrophages, and finally, S100A13 which is related to the dysfunction of microglia. <b>Conclusion:</b> Our findings define different functions for S100A9, A11 and A13 proteins that are associated with the architecture of the glioblastoma microenvironment and define its progression. Moreover, these alterations can be reversed by the RAGE inhibitor, Azeliragon which is in a phase I/II clinical trial NCT05635734.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 2","pages":"726-744"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915561","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}