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Science China Chemistry 2025年第1期68卷 1-2页

作者： Qihang Ding Mengrong He Meijia Gu department of Chemistry Korea University department of ultrasound medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) School of Pharmaceutical Sciences Wuhan University

Malignant neoplasms consistently pose a significant threat to global public health [1,2]. In recent years, immunotherapy has demonstrated remarkable clinical success; however, its efficacy is limited by the scarcity of immune cell infiltration within tumor microenvironments. Cell pyroptosis, a gasdermin-mediated process characterized by cellular swelling,rupture, and the release of intracellular contents such as IL-1β, IL-18, ATP, HMGB1, plays a crucial role in this context[3,4].

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Tumor inflammation-specific self-amplifying fluorescent molecular probes induce an anti-tumor immune response

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Science China Chemistry 2025年第1期68卷 273-287页

作者： Shuguang Yang Lijun Hu Hong Xiao Zecong Xiao Xintao Shuai PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-sen University department of ultrasound The Fifth Affiliated Hospital Sun Yat-sen University department of Medical ultrasound The Third Affiliated Hospital of Sun Yat-sen University Nanomedicine Research Center The Third Affiliated Hospital of Sun Yat-sen University

Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy. Nonetheless, the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes. Herein, we reported a self-amplifying fluorescent molecular probe, Bis-HTPICG, for photodynamic therapy(PDT) and subsequent PDT-induced immunoreaction. The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO), a crucial enzyme secreted by neutrophils at inflammation sites. Upon exposure to laser irradiation, Bis-HTP-ICG showed a high PDT efficacy, inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion. The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis, instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG, neutrophils and ***, PDT efficiently incites immunogenic cell death(ICD) in tumor cells, initiating an anti-tumor immune response including dendritic cells(DCs) maturation, T cell proliferation and reprogramming of tumor-associated neutrophils(TANs). This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.

关键词： fluorescent molecular probes self-amplifying myeloperoxidase photodynamic therapy

Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

STIL enhances the development of lung adenocarcinoma by regulating the glycolysis pathway

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Oncology Research 2025年第1期33卷 123-132页

作者： LEI WANG XIANJIN XIE department of Respiratory medicine Jen Ching Memorial HospitalSuzhou215300China department of Respiratory medicine Shandong Provincial Third HospitalJinan250010China

Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and *** set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose ***:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse *** enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of *** E2F1 reversed the promotion effect of the STIL overexpression on cell viability and ***,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD ***:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic *** comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.

关键词： SCL/TAL1 interrupting locus(STIL) Lung adenocarcinoma E2 promoter binding factor 1 Glycolysis

The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

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

Phosphodiesterase 9 localization in cytoplasm and nucleus:the gateway to selective targeting in neuroprotection?

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Neural Regeneration Research 2025年第6期20卷 1701-1702页

作者： Giovanni Ribaudo Matteo Giannangeli Margrate Anyanwu Alessandra Gianoncelli department of Molecular and Translational medicine University of BresciaBresciaItaly

The umbrella term"neurodege ne rative disorders"(NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous *** diseases affect more than 50million people *** disorders are characterized by sundry factors and pathophysiological mechanisms that a re challenging to be fully *** of these rely on cell signaling pathways to preserve homeostasis,involving second messengers such as cyclic adenosine monophosphate (cAMP)and cyclic guanosine 3',5'-monophosphate(cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon *** kinases A and G (PKA and PKG),phosphodiesterases (PDEs),and scaffold proteins are among them.

关键词： gateway homeostasis preserve

Therapeutic potential of stem cells in subarachnoid hemorrhage

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Neural Regeneration Research 2025年第4期20卷 936-945页

作者： Hideki Kanamaru Hidenori Suzuki department of Neurosurgery Mie University Graduate School of MedicineTsuJapan

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and *** the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm *** may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient *** complications such as brain volume loss and chronic hydrocephalus can further impact *** the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective *** cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable *** review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

关键词： delayed cerebral ischemia early brain injury matricellular protein neurogenesis stem cell therapy subarachnoid hemorrhage

Neurocircuit regeneration by extracellular matrix reprogramming

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Neural Regeneration Research 2025年第8期20卷 2300-2301页

作者： Shengzhang Su Ian N.Levasseur Kimberly M.Alonge department of Medicinal Chemistry University of WashingtonSeattleWAUSA department of Chemistry University of WashingtonSeattleWAUSA department of medicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

关键词： matrix programming

Comparing role of ATP between acute pain in neuromyelitis optica spectrum disorder and peripheral neuropathic pain

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Neural Regeneration Research 2025年第1期20卷 184-185页

作者： Teruyuki Ishikura Tatsusada Okuno department of Molecular Neuroscience Graduate School of MedicineOsaka UniversityOsakaJapan department of Neurology Osaka University Graduate School of MedicineOsaka UniversityOsakaJapan

In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.

关键词： pain acute pathology