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MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

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Neural Regeneration Research 2025年第5期20卷 1431-1444页

作者： Yuehua Cui Xiaokuang Ma Jing Wei Chang Chen Neha Shakir Hitesch Guirram Zhiyu Dai Trent Anderson Deveroux Ferguson Shenfeng Qiu Basic Medical Sciences University of Arizona College of Medicine-PhoenixPhoenixAZUSA Department of medicine University of Arizona College of Medicine-PhoenixPhoenixAZUSA

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse *** have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine *** investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing *** found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection *** findings are further corroborated by increased synaptic activity and transient generation of immature silent *** MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and *** data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult *** findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

关键词： aging circuit connectivity cortical circuits molecular mechanisms neural regeneration neurodegeneration synapses

Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying Tan Li Zhang Wen-Tao Jiang School of medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of molecular Diagnosis and Treatment of Liver Cancer Tianjin First Center HospitalTianjin 300192China Department of Liver Transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

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Neural Regeneration Research 2025年第11期20卷 3233-3244页

作者： Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang Department of molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon Center for Regenerative Science and medicine University of Texas Southwestern Medical CenterDallasTXUSA Peter O’Donnell Jr.Brain Institute University of Texas Southwestern Medical CenterDallasTXUSA

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following *** targeting this pathway is beneficial to brain injury remains *** this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral *** inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology ***,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin *** findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

关键词： adeno-associated virus Citron homology Citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury

MINIMIZING EXCITATION LIGHT LEAKAGE AND MAXIMIZING MEASUREMENT SENSITIVITY FOR molecular IMAGING WITH NEAR-INFRARED FLUORESCENCE

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Journal of Innovative Optical Health Sciences 2011年第3期4卷 301-307页

作者： BANGHE ZHU EVA M.SEVICK-MURACA Center for molecular Imaging The Brown Foundation Institute of molecular medicine The University of Texas Health Science Center at Houston Houston TX 77030USA

Near-infraredfluorescence(NIRF)imaging involves the separation of weakfluorescence signals from backscattered excitation *** measurement sensitivity of current NIRF imaging systems is limited by the excitation light leakage through *** this contribution,the authors demonstrate that the excitation light leakage can be suppressed upon using appropriatefilter combination and *** excitation light leakage and measurement sensitivity were assessed and compared in this study by computing the transmission ratios of excitation to emission light collected and the signal-to-noise ratios in well-controlled phantom studies with differentfilter combinations and *** appropriatefilter combinations and permutations,we observe as much as two orders of magnitude reduction in the transmission ratio and higher signal-to-noise ratio.

关键词： molecular imaging fluorescence opticalfilter excitation light leakage noise floor

Traditional Chinese medicine Treatment, Gua Sha, can Induce Subtle molecular Changes in Gene Expression

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Biomedical and Environmental Sciences 2023年第5期36卷 441-451页

作者： QI Fei CAI Ye CHEN Jun Jie CHEN Chun Li HAN Xue Er XIA Qiu KAPRANOV Philipp Institute of Genomics School of MedicineHuaqiao UniversityXiamen 361021FujianChina Traditional Chinese medicine Hospital of Huian Quanzhou 36200FujianChina

Objective Here, we explored molecular changes that could potentially mediate healing effects of Gua Sha — a method employed by the Chinese traditional medicine with proven track records of safe and efficient applications dating back to ancient times as well as support from randomized controlled trials performed by modern medical studies — yet remaining almost entirely unexplored by the modern-day high-throughput methods of the-omics *** We investigated transcriptome changes occurring shortly after Gua Sha treatment in the whole blood of healthy volunteers using bulk RNA-seq analysis. We applied various analytical tools to identify genes with consistent expression changes in multiple individuals in response to Gua Sha and their *** We found that while the changes were very subtle and individual-specific, we could identify consistent upregulation of three histone genes. Further analysis of the potential regulatory networks of these histone genes revealed the enrichment of functions involved in the immune response and *** The significance of these results in the context of potential effects of Gua Sha and the next steps in exploring the molecular mechanisms of action of this technique are discussed.

关键词： Gua Sha Transcriptomics Histone Long non-coding RNAs Chinese traditional medicine Immune system Inflammation

Dip2a regulates stress susceptibility in the basolateral amygdala

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Neural Regeneration Research 2025年第6期20卷 1735-1748页

作者： Jing Li Zixuan He Weitai Chai Meng Tian Huali Yu Xiaoxiao He Xiaojuan Zhu Key Laboratory of molecular Epigenetics Ministry of Education Institute of Genetics and CytologyNortheast Normal UniversityChangchunJilin ProvinceChina

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

关键词： 5-hydroxytryptamine acute restraint stress basolateral amygdala CaMKII neurons DIP2A metabolomics neurotransmitters principal component analysis stress susceptibility tryptophan

Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： María Belén Cieri Alberto Javier Ramos Laboratorio de Neuropatología molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

Exosomes as promising frontier approaches in future cancer therapy

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 28-33页

作者： Fatt-Yang Chew Chin-Hung Tsai Kuang-Hsi Chang Yu-Kang Chang Ruey-Hwang Chou Yi-Jui Liu Department of Medical Imaging China Medical University HospitalTaichung 404TaiwanChina Department of Radiology School of MedicineChina Medical UniversityTaichung 404TaiwanChina Department of Cancer Center Tungs’Taichung MetroHarbor HospitalTaichung 435TaiwanChina Department of Chest medicine Tungs’Taichung MetroHarbor HospitalTaichung 435TaiwanChina Department of Post-Baccalaureate medicine College of MedicineNational Chung Hsing UniversityTaichung 402TaiwanChina Department of Medical Research Tungs’Taichung MetroHarbor HospitalTaichung 435TaiwanChina Center for General Education China Medical UniversityTaichung 404TaiwanChina General Education Center Jen-Teh Junior College of MedicineNursing and ManagementMiaoli 356TaiwanChina Department of Nursing Jen-Teh Junior College of MedicineNursing and ManagementMiaoli 356TaiwanChina Graduate Institute of Biomedical Sciences China Medical UniversityTaichung 404TaiwanChina Center for molecular medicine China Medical University HospitalTaichung 404TaiwanChina Department of Medical Laboratory and Biotechnology Asia UniversityTaichung 413TaiwanChina Department of Automatic Control Engineering Feng Chia UniversityTaichung 407TaiwanChina

In this editorial,we will discuss the article by Tang et al published in the recent issue of the World Journal of Gastrointestinal *** explored an innovative approach to enhancing gemcitabine(GEM)delivery and efficacy using human bone marrow mesenchymal stem cells(HU-BMSCs)-derived *** manufacture of GEM-loaded HU-BMSCs-derived exosomes(Exo-GEM)has been *** Tang et al’s study demonstrated that Exo-GEM exhibits enhanced cytotoxicity and apoptosis-inducing effects compared to free GEM,highlighting the potential of exosome-based drug delivery systems as a more effective and targeted approach to chemotherapy in pancreatic *** in vivo studies are required to confirm the safety and effectiveness of Exo-GEM before it can be considered for clinical use.

关键词： Mesenchymal stem cells Exosomes Gemcitabine Pancreatic cancer Apoptosis

Melanin-based nanoparticles in biomedical applications:From molecular imaging to treatment of diseases

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Chinese Chemical Letters 2019年第3期30卷 533-540页

作者： Xinyu Wang Jie Sheng Min Yang Key Laboratory of Nuclear medicine Ministry of Health Jiangsu Key Laboratory of Molecular Nuclear Medicine Jiangsu Institute of Nuclear Medicine The First Clinical Medical College Nanjing Medical University

Melanin nanoparticles(MNPs) is a kind of natural nanomaterial, not only retain the inherent characteristics of melanin(metal ion chelation, photothermal conversion property, etc.) but also can exhibit more excellent properties, such as high dispersion stability, good biocompatibility and biodegradability. Furthermore, these performances can be enhanced to target the specific sites and treat diseases by the surface modification or combination with functional substance. All these advantages of MNPs made it an ideal platform for developing biomedical applications. In this paper, the MNPs preparation methods were summarized first. Biomedical applications of MNPs were also reviewed,including molecular imaging(magnetic resonance, positron emission tomography, and photoacoustic imaging) and treatment of diseases(drug delivery, photothermal therapy, antioxidant therapy, and iron overload therapy). Further development and prospects of MNPs for practice in biology or medicine were also discussed.

关键词： Melanin Nanoparticles Imaging Drug delivery Biomedical application