Theranostics最新文献

{"title":"Poly (I:C)-induced inflammation requires the activation of toll-like receptor 3/Ca²⁺/CaMKII/pannexin 1-dependent signaling.","authors":"Magdiel Salgado, Vania Sepúlveda-Arriagada, Macarena Konar-Nié, María A García-Robles, Juan C Sáez","doi":"10.7150/thno.100687","DOIUrl":"10.7150/thno.100687","url":null,"abstract":"<p><p>Pannexin1 (Panx1) is a glycoprotein, ubiquitously expressed throughout vertebrate tissues. In the cell membrane, it forms non-selective hemichannels (Panx1 HCs) that allow the release of ATP. This extracellular ATP triggers purinergic signaling relevant to the immune responses to pathogens, including viruses. While the activity of Panx1 HCs is known to be elevated by some viruses, the underlying molecular mechanism remains elusive. <b>Methods</b>: In this study, we used Poly(I:C), a double-stranded RNA analog that constitutes a hallmark of viral infections. Peritoneal macrophages were obtained from wild-type and Panx1 knock-out mice. The mRNA levels of proinflammatory cytokines were quantified by RT-qPCR. We also evaluated hemichannel activity through dye uptake assays, whereas Ca²⁺ signals were studied using Fura-2 and GcamP6. Panx1-P2X₇R interaction was studied by proximity ligation assays. <b>Results:</b> Panx1 expression and activity were crucial for the proinflammatory response induced by Poly(I:C) in RAW264.7 cells and peritoneal macrophages. In HeLa cells transfected with mPanx1 (HeLa-mPanx1) and RAW264.7 cells, Poly (I:C) increased Panx1 HC activity in a concentration-dependent manner, which was inhibited by ¹⁰Panx1, a peptide that selectively blocks Panx1 HCs. Furthermore, the Poly(I:C)-induced rise in Panx1 HC activity correlated with a rapid increase in intracellular Ca²⁺ signal, dependent on TLR3 and P2X₇R activity. Interestingly, lasting exposure to Poly (I:C) promoted the interaction and internalization of the Panx1-P2X₇R complex, which depended on CaMKII, Panx1 HC, and P2X₇R activities. The Poly (I:C)-induced increase in Panx1 HC activity was entirely prevented by Ca²⁺ chelation with BAPTA-AM, CaMKII blockage with KN-62, or PKA activation with db-cAMP. These findings were consistent with data from Panx1 mutants that either avoid or mimic phosphorylation at kinase target sites. Supporting this finding, we demonstrated that CaMKII activity is essential for the inflammatory response triggered by Poly (I:C) in macrophages. <b>Conclusion</b>: A TLR3/Ca²⁺/CaMKII/Panx1 HC pathway is crucial in orchestrating the cellular response to viral patterns and presents a potential novel target for preventing infections and alleviating the harmful effects associated with RNA-based viral infections.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2470-2486"},"PeriodicalIF":12.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483981","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":"Nsun2 controls cardiac homeostasis and hypertrophic response by regulating PRKACA expression.","authors":"Dongdong Jian, Xiaolei Cheng, Datun Qi, Shixing Wang, Chenqiu Wang, Yingchao Shi, Zhen Li, Shouyi Jin, Zhen Jia, Peng Teng, Zhen Pei, Xiaoping Gu, Liguo Jian, Wengong Wang, Xia Yi, Junyue Xing, Hao Tang","doi":"10.7150/thno.104441","DOIUrl":"10.7150/thno.104441","url":null,"abstract":"<p><p><b>Rationale:</b> Internal modifications of mammalian RNA have been suggested to be essential for the maintenance of cardiac homeostasis. However, the role of RNA cytosine methylation (m5C) in the heart remains largely unknown. <b>Methods:</b> Bulk and single cell RNA sequencing data and tissues from the human hearts were exploited for analyzing the expression of RNA m5C modifying proteins. Neonatal rat and adult mouse cardiomyocytes were isolated to assess the impact of Nsun2 on cellular hypertrophic response. Cre/LoxP-mediated gene knockout and recombinant adeno-associated virus serotype 9 (rAAV9) were employed respectively to achieve cardiac-specific interference of the expression of related genes in mice that were subjected to heart stresses from aging, aortic constriction, and angiotensin II stimulation. RNA m5C immunoprecipitation sequencing (m5C-RIP-seq), RNA pull-down, polysome profiling, reporter gene analysis, and IonOptix measurement were conducted to elucidate the involved regulatory mechanisms. <b>Results:</b> Nsun2 expression was significantly elevated in human, rat, and mouse hypertrophic myocardial cells. Knockout of Nsun2 (αMHC-Cre^ERT2, Nsun2 flox^+/+) abolished the hypertrophic response of mice to diverse stresses, while accelerating the progression of heart failure. Mechanistically, Nsun2 specifically methylates PKA catalytic subunit alpha (PRKACA) mRNA, which substantially promotes PRKACA translation in a YBX1-dependent manner. Nsun2 ablation markedly attenuated the activation of PKA signaling, as evidenced by the reduced PKA activity and protein phosphorylation levels of PKA substrates, impaired myocyte contraction and relaxation, and disturbed calcium transients. Overexpressing Nsun2 and PRKACA-3'UTR transcripts in the myocardia sensitized and desensitized heart hypertrophic responses, respectively, whereas co-administration of the PKA inhibitor H-89 or overexpressing PRKACA-3'UTR transcript lacking Nsun2 methylating regions failed to produce corresponding responses, reiterating the significance of Nsun2-PRKACA regulation in the cardiac hypertrophic program. <b>Conclusion:</b> These observations reveal the importance of Nsun2-PRKACA regulation in cardiac homeostasis, which provides novel insights into heart function modulation and sheds light on future treatments for hypertrophic remodeling associated heart diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2393-2412"},"PeriodicalIF":12.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483848","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":"Renal tubular epithelial-derived follistatin-like 1 protects against UUO-induced renal fibrosis in mice via inhibiting NF-κB-mediated epithelial inflammation.","authors":"Zhuan Niu, Jiasen Guo, Xingzu Liu, Mo Chen, Yueyue Jin, Maolin Yao, Xiaoxu Li, Qianqian Che, Shuzi Li, Chenjie Zhang, Kunyue Shangguan, Dekun Wang, Chuan'ai Chen, Wenli Yu, Xiaoyue Tan, Wen Ning, Lian Li","doi":"10.7150/thno.100969","DOIUrl":"10.7150/thno.100969","url":null,"abstract":"<p><p><b>Rationale:</b> Renal fibrosis is commonly recognized as the ultimate pathway for most chronic kidney diseases (CKD). Renal tubular epithelial inflammation drives the initiation and progression of renal fibrosis. Follistatin-like 1 (FSTL1) is a small matricellular protein, whose expression pattern, function and underlying mechanism in regulating renal inflammation and fibrosis remains largely unknown. <b>Methods:</b> We utilized two <i>Fstl1</i>-deficient genetic mouse models: heterozygous <i>Fstl1^+/-</i> mice and whole-body <i>Fstl1</i> conditional knockout mice, and a mouse model with FSTL1 overexpression via adenoviral vector infection. These mice were subjected to unilateral ureteral obstruction (UUO). We used an <i>Fstl1</i> lineage tracing mouse to investigate the expression and location of induced FSTL1 in the obstructed kidney. We investigated the effect of FSTL1 on TNF-α induced epithelial inflammation and the NF-κB pathway by overexpression or knockdown of FSTL1 in human kidney epithelial cells (HK2). <b>Results:</b> We observed increased expression of FSTL1 in kidneys from patients with CKD, and UUO mouse model of renal injury and fibrosis. Deletion of <i>Fstl1</i> in mice aggravated UUO-induced inflammatory kidney injury and subsequent fibrosis. Conversely, overexpression of FSTL1 by adenoviral vector infection in mice mitigated expression of proinflammatory cytokines and the fibrotic phenotype. Mechanistically, we identified that increased FSTL1 was mostly derived from the tubular epithelium of the obstructed mouse kidney. FSTL1 inhibited human renal epithelial cell inflammatory responses, as assessed by reducing the NF-κB pathway, release of IL-1β and IL-6, expression of intercellular adhesion molecule 1 (ICAM-1), and monocyte adhesion to kidney epithelial cells. <b>Conclusions:</b> These findings suggest that FSTL1 plays a protective role against kidney fibrosis by inhibiting renal epithelial inflammation via the NF-κB pathway in epithelium, thereby offering a potential novel strategy for treating progressive CKD.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2413-2427"},"PeriodicalIF":12.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483982","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":"The sentinel against brain injury post-subarachnoid hemorrhage: efferocytosis of erythrocytes by leptomeningeal lymphatic endothelial cells.","authors":"Hong-Ji Deng, Yun-Huo Xu, Kun Wu, Yun-Cong Li, Yong-Jin Zhang, Han-Fu Yu, Chong Li, Dan Xu, Fei Wang","doi":"10.7150/thno.103701","DOIUrl":"10.7150/thno.103701","url":null,"abstract":"<p><p><b>Rationale:</b> The clearance of extravasated erythrocytes represents the most reasonable strategy against brain injury post-subarachnoid hemorrhage (SAH). There is little knowledge about the autologous clearance of extravasated erythrocytes post-SAH. The leptomeningeal lymphatic endothelial cells (LLECs) have been less studied functionally, which were firstly harvested and cultured <i>in vitro</i> by our group previously and are probably related to the clearance of extravasated erythrocytes post-SAH for they closely surround subarachnoid space. <b>Methods:</b> We established a SAH animal model, employed primary LLECs <i>in vitro</i>, mimicked the conditions of the SAH <i>in vitro</i>, performed RNA sequencing, and transfected LLECs with adenovirus and adeno-associated virus both <i>in vivo</i> and <i>in vitro</i> to reveal the molecular mechanisms of efferocytosis of erythrocytes by LLECs and its neuroprotection post-SAH. <b>Results:</b> Firstly, we demonstrated the eryptosis-initiated degradation of extravasated erythrocytes <i>in vitro</i>. Furthermore, we found LLECs preferentially adhered and engulfed apoptotic erythrocytes <i>in vivo</i> and <i>in vitro</i> while sparing from intact erythrocytes, suggesting their novel capacity in the efferocytosis of erythrocytes. Additionally, the efferocytosis of erythrocytes by LLECs plays a role on neuroprotection via improving neurological functions, maintaining neurostructural integrity, and alleviating neuropathological consequences post-SAH. During efferocytosis, phosphatidylserine (PS) and phosphatidylserine receptor (PSR) mediated the recognition of apoptotic erythrocytes by LLECs. We also confirmed that NHL repeat-containing 2 (NHLRC2) positively regulated the efferocytosis of erythrocytes by LLECs to serve as a central regulator in it mediated neuroprotection post-SAH. <b>Conclusions:</b> This study elucidated the efferocytosis of erythrocytes by LLECs and subsequently neuroprotection post-SAH. These findings highlight a prompt, efficient, and regulable pathway for the autologous clearance of extravasated erythrocytes that performs as a sentinel against brain injury post-SAH.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2487-2509"},"PeriodicalIF":12.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483985","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":"Targeted delivery of Grem1 and IL-10 separately by mesenchymal stem cells effectively mitigates SETD2-deficient inflammatory bowel disease.","authors":"Rebiguli Aji, Yue Xu, Ziyi Wang, Wenxin Feng, Liming Gui, Hanyu Rao, Wei Zhang, Ningyuan Liu, Wei-Qiang Gao, Li Li","doi":"10.7150/thno.105876","DOIUrl":"10.7150/thno.105876","url":null,"abstract":"<p><p><b>Rationale:</b> Inflammatory bowel disease (IBD) is a relapsing and idiopathic disorder. The low therapeutic efficacy of IBD urgently prompts us to seek new treatment methods. <b>Methods and Results:</b> In this study, we report an adipose-derived mesenchymal stem cell (AT-MSC)-based treatment strategy in which AT-MSCs specifically deliver BMP inhibitor Grem1 and anti-inflammatory factor IL-10 to inflammatory colon tissues in SETD2 deficient dextran sulfate sodium (DSS)-induced colitis mouse models. Targeted delivery of Grem1 reduced colitis by promoting intestinal stem cell regeneration and enhancing mucosal regenerative capacity. Furthermore, targeted delivery of IL-10 reduced colitis by reducing inflammatory cytokines. <b>Conclusion:</b> Our AT-MSCs based therapeutic strategy effectively mitigated IBD. This study has deepened our understanding of IBD therapy and provided a theoretical foundation for its clinical treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2215-2228"},"PeriodicalIF":12.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483984","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":"USP14 modulates stem-like properties, tumorigenicity, and radiotherapy resistance in glioblastoma stem cells through stabilization of MST4-phosphorylated ALKBH5.","authors":"Xiao Zhou, Qiaoxi Xia, Botao Wang, Junjun Li, Bing Liu, Sisi Wang, Min Huang, Ronghui Zhong, Shi-Yuan Cheng, Xuan Wang, Xiaobing Jiang, Tianzhi Huang","doi":"10.7150/thno.103629","DOIUrl":"10.7150/thno.103629","url":null,"abstract":"<p><p><b>Rationale</b>: Glioblastoma (GBM) is the most aggressive type of primary brain cancer and contains self-renewing GBM stem cells (GSCs) that contribute to tumor growth and therapeutic resistance. However, molecular determinants governing therapeutic resistance of GSCs are poorly understood. <b>Methods</b>: We performed genome-wide analysis of deubiquitylating enzymes (DUBs) in patient-derived GSCs and used gene-specific shRNAs to identify an important DUB gene contributing to GSC survival and radioresistance. Subsequently, we employed mass spectrometry and immunoprecipitation to show the interaction between USP14 and ALKBH5, and identified the upstream kinase MST4, which is essential for the deubiquitylation and stabilization of ALKBH5. Additionally, we performed integrated transcriptome and m⁶A-seq analyses to uncover the key downstream pathways of ALKBH5 that influence GSC radioresistance. <b>Results</b>: Our study demonstrates the essential role of the deubiquitinase USP14 in maintaining the stemness, tumorigenic potential, and radioresistance of GSCs. USP14 stabilizes the m⁶A demethylase ALKBH5 by preventing its K48-linked ubiquitination and degradation through HECW2. The phosphorylation of ALKBH5 at serine 64 and 69 by MST4 increases its interaction with USP14, promoting ALKBH5 deubiquitylation. Furthermore, ALKBH5 directly interacts with the USP14 transcript in a manner dependent on YTHDF2, establishing a positive feedback loop that sustains the overexpression of both proteins in GSCs. The MST4-USP14-ALKBH5 signaling pathway is crucial for enhancing stem cell-like traits, facilitating homologous recombination repair of DNA double-strand breaks, and promoting radioresistance and tumorigenicity in GSCs. This signaling cascade is further stimulated in GSCs following exposure to ionizing radiation (IR). Inhibiting USP14 with the small molecule IU1 disrupts ALKBH5 deubiquitylation and increases the effectiveness of IR therapy on GSC-derived brain tumor xenografts. <b>Conclusion:</b> Our results identify the MST4-USP14-ALKBH5 signaling pathway as a promising therapeutic target for treating GBM.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2293-2314"},"PeriodicalIF":12.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484004","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":"3D bioprintable Mg²⁺-incorporated hydrogels tailored for regeneration of volumetric muscle loss.","authors":"Moon Sung Kang, Jeong Min Kim, Hyo Jung Jo, Hye Jin Heo, Yun Hak Kim, Kyung Min Park, Dong-Wook Han","doi":"10.7150/thno.103677","DOIUrl":"10.7150/thno.103677","url":null,"abstract":"<p><p><b>Rationale:</b> Current therapeutic approaches for volumetric muscle loss (VML) face challenges owing to limited graft availability and insufficient bioactivity. Three-dimensional (3D) bioprinting has become an alternative technology for fabricating native tissue-mimetic grafts, allowing for tailored structures and complex designs. <b>Methods:</b> We developed an Mg²⁺-incorporated bioink composed of thiolated gelatin (GtnSH) and maleimide-conjugated gelatin (GtnMI) decorated with magnesium peroxide (MgO₂), referred to as a GtnSH/GtnMI/MgO₂ bioink. We designed <i>in situ</i> crosslinking between GtnSH and GtnMI to prepare cytocompatible bioink for 3D bioprinting of muscle mimetics. <b>Results:</b> The incorporated MgO₂ particles provided oxygen supplementation and myogenic cues. <i>In vitro</i> assays demonstrated that C2C12 myoblasts encapsulated in the GtnSH/GtnMI/MgO₂ bioink exhibited high viability, intrinsic proliferation rate, and increased expression of key myogenic markers. <i>In vivo</i> transplantation of the 3D bioprinted GtnSH/GtnMI/MgO₂ constructs facilitated muscle mass restoration and M2 macrophage polarization. Additionally, they downregulate the activities of CD4⁺ and CD8⁺ lymphocytes, inducing a transition from the initial inflammatory to the restoration phase. <b>Conclusion:</b> The GtnSH/GtnMI/MgO₂ bioink is a potential therapeutic strategy for enhancing myogenesis and skeletal muscle tissue regeneration.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2185-2200"},"PeriodicalIF":12.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483524","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":"Collagen-targeted PET imaging for progressive experimental lung fibrosis quantification and monitoring of efficacy of anti-fibrotic therapies.","authors":"Alexandre Magno Maneschy Dias, Olivier Burgy, Mathieu Moreau, Victor Goncalves, Lenny Pommerolle, Romain Douhard, Alan Courteau, Alex Helbling, Mélanie Guillemin, John Simonet, Alexandra Oudot, Carmen Garrido, Philippe Bonniaud, Françoise Goirand, Bertrand Collin, Pierre-Simon Bellaye","doi":"10.7150/thno.106367","DOIUrl":"10.7150/thno.106367","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by an excessive collagen deposition ultimately leading to tissue stiffening and functional decline. Beyond IPF, other progressive pulmonary fibrosis are often associated with connective tissue diseases and may develop in ∼18-32% of patients. Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression without curing it. The current lack of biomarker to accurately assess and predict disease progression and therapy efficacy for IPF remains a major clinical concern. <b>Methods:</b> In our study, collagen deposition was monitored in bleomycin-induced lung fibrosis in mice by <i>in vivo</i> molecular imaging using a collagen-targeted radiopharmaceutical, [⁶⁸Ga]Ga-NODAGA-collagelin. Fibrosis progression was also monitored using computed tomography, the gold standard technique to detect lung fibrosis in patients. <b>Results:</b> We demonstrated that the bleomycin-induced increase in collagen lung content can be accurately quantified by [⁶⁸Ga]Ga-NODAGA-collagelin PET imaging in correlation with disease stage and severity. The lung uptake of [⁶⁸Ga]Ga-NODAGA-collagelin was mainly found in fibrotic areas of lungs in bleomycin-receiving mice. Most interestingly, [⁶⁸Ga]Ga-NODAGA-collagelin PET imaging allowed the <i>in vivo</i> non-invasive monitoring of nintedanib efficacy as well as the anti-fibrotic effect of the JAK inhibitor, tofacitinib. <b>Conclusion:</b> Thus, collagen-targeted PET imaging appears as a promising non-invasive tool for staging, monitoring and prediction of disease progression and therapy efficacy towards personalized medicine in IPF.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2092-2103"},"PeriodicalIF":12.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483634","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":"Neural mechanism of trigeminal nerve stimulation recovering defensive arousal responses in traumatic brain injury.","authors":"Qian Zhang, Haiyun Ma, Lifang Huo, Shaoling Wang, Qian Yang, Zhimin Ye, Jie Cao, Shaoling Wu, Chao Ma, Congping Shang","doi":"10.7150/thno.106323","DOIUrl":"10.7150/thno.106323","url":null,"abstract":"<p><p>The arousal state is defined as the degree to which an individual is aware of themselves and their surroundings, and is a crucial component of consciousness. Trigeminal nerve stimulation (TNS), a non-invasive clinical neuromodulation technique, has shown potential in aiding the functional recovery of patients with impaired consciousness. Understanding the specific neuronal subpopulations and circuits through which TNS improves arousal states is essential for advancing its clinical application. <b>Methods:</b> A mouse model of traumatic brain injury (TBI) was established using a weight-drop technique to induce neurological dysfunction, and the arousal state was assessed through visual and auditory defensive responses. Techniques such as viral tracing, chemogenetics, patch-clamp recordings, calcium signaling, and neurotransmitter probes were employed to investigate the relevant subpopulations of trigeminal ganglion (TG) neurons and the underlying mechanisms in the central nervous system. <b>Results:</b> Neuronal subgroups involved in TNS therapy at the key peripheral nucleus, the TG, were identified. Two distinct types of neurons were found to contribute differently: The Tac1+TG-locus coeruleus (LC)-superior colliculus (SC) pathway elevated noradrenaline levels in the SC, enhancing receptive field sensitivity recovery in TBI mice; the Piezo2+TG-paraventricular hypothalamic nucleus (PVN)-substantia nigra pars compacta (SNc)-dorsal striatum (DS) pathway initiated dopamine (DA) release in the DS, ameliorating motor disorders in TBI mice. <b>Conclusion:</b> These pathways contribute to the improvement of defensive arousal responses from different perspectives. The findings from this study imply that TNS effectively restores defensive arousal responses to visual and auditory threats in mice suffering from TBI, offering insights that may facilitate the implementation of TNS therapy in clinical settings.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2315-2337"},"PeriodicalIF":12.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483841","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":"Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.","authors":"Hong Wang, Fei Zhou, Wenqing Qin, Yun Yang, Xiaojiaoyang Li, Runping Liu","doi":"10.7150/thno.105276","DOIUrl":"10.7150/thno.105276","url":null,"abstract":"<p><p>Cancer remains a major challenge to global public health, with rising incidence and high mortality rates. The tumor microenvironment (TME) is a complex system of immune cells, fibroblasts, extracellular matrix (ECM), and blood vessels that form a space conducive to cancer cell proliferation. Myeloid-derived suppressor cells (MDSCs) are abundant in tumors, and they drive immunosuppression through metabolic reprogramming in the TME. This review describes how metabolic pathways such as glucose metabolism, lipid metabolism, amino acid metabolism, and adenosine metabolism have a significant impact on the function of MDSCs by regulating their immunosuppressive activity and promoting their survival and expansion in tumors. The review also explores key metabolic targets in MDSCs and strategies to modulate MDSC metabolism to improve the tumor immune microenvironment and enhance anti-tumor immune responses. Understanding these pathways can provide insight into potential therapeutic targets for modulating MDSC activity and improving outcomes of cancer immunotherapies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 6","pages":"2159-2184"},"PeriodicalIF":12.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483932","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}