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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

AI empowers exploration of protein universe

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Science China(Life Sciences) 2025年第2期68卷 588-589页

作者： Wuke Wang Xingxu Huang Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospitaland Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China

Deaminases which perform the function of converting cytosine to thymine are ubiquitous in nature with over 120,000 known variants,each exhibiting significant ***,gene editing technologies have remarkably revealed that these deaminases share similar ***,the mining of novel proteins has been conducted through sequence alignment and the categorization of conserved regions to identify functional modules within protein sequences.

关键词： functions powers alignment

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu Zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of Medical Engineering and translational medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems

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Neural Regeneration Research 2025年第9期20卷 2591-2593页

作者： Alena Salasova Anders Nykjær Danish Research Institute of translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular medicine and Centre of Excellence PROMEMODepartment of BiomedicineAarhus UniversityAarhusDenmark

The formation of the mammalian nervous system and its maturation into sensory,motor,cognitive,and behavioral circuits is a complex process that begins during early embryogenesis and lasts until young *** neurodevelopm... 详细信息

关键词： progr jointly CS2

Graph based recurrent network for context specific synthetic lethality prediction

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Science China(Life Sciences) 2025年第2期68卷 527-540页

作者： Yuyang Jiang Jing Wang Yixin Zhang ZhiWei Cao Qinglong Zhang Jinsong Su Song He Xiaochen Bo Academy of Medical Engineering and translational medicine Tianjin UniversityTianjin 300072China Department of Bioinformatics Institute of Health Service and Transfusion MedicineBeijing 100850China School of medicine Tsinghua UniversityBeijing 100084China School of Informatics Xiamen UniversityXiamen 361005China

The concept of synthetic lethality(SL)has been successfully used for targeted *** further explore SL for cancer therapy,identifying more SL interactions with therapeutic potential are ***,graph neural network-based deep learning methods have been proposed for SL prediction,which reduce the SL search space of wet-lab based ***,these methods ignore that most SL interactions depend strongly on genetic context,which limits the application of the predicted *** this study,we proposed a graph recurrent network-based model for specific context-dependent SL prediction(SLGRN).In particular,we introduced a Graph Recurrent Network-based encoder to acquire a context-specific,low-dimensional feature representation for each node,facilitating the prediction of novel *** leveraged gate recurrent unit(GRU)and it incorporated a context-dependent-level state to effectively integrate information from all *** a result,SLGRN outperforms the state-of-the-arts models for SL *** subsequently validate novel SL interactions under different contexts based on combination therapy or patient survival *** in vitro experiments and retrospective clinical analysis,we emphasize the potential clinical significance of this context-specific SL prediction model.

关键词： synthetic lethality graph recurrent network context-specific graph combination therapy

Decellularized amniotic membrane promotes the anti-inflammatory response of macrophages via PI3K/AKT/HIF-1α pathway

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Chinese Chemical Letters 2025年第1期36卷 403-407页

作者： Xiongbo Song Jinwen Xiao Juan Wu Li Sun Long Chen Department of Orthopedics Guizhou Provincial People’s HospitalGuiyang 550000China The Lab of Tissue Engineering and translational medicine College of MedicineGuizhou UniversityGuiyang 550000China Wuhan Kangchuang Biotechnology Wuhan 430074China

Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative *** biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of *** findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential *** application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate *** investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene *** study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.

关键词： Macrophage Decellularized amniotic membrane Anti-inflammatory response Hypoxia inducible factor-1α Epidermal growth factor

Rectal neuroendocrine tumors: Can we predict their behavior?

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World Journal of Gastroenterology 2025年第5期31卷 129-132页

作者： Elisabetta Dell'Unto Francesco Panzuto Gianluca Esposito Department of Medical-Surgical Sciences and translational medicine Sapienza University of RomeRome 00189LazioItaly

Rectal neuroendocrine tumors(r-NETs)are the second most common type of neuroendocrine tumor in the gastrointestinal tract,with an increase in incidence in the last *** are low-grade tumors and,given their low risk of meta-stasis,current guidelines recommend endoscopic resection for small *** GATIS predicting score,proposed by Zeng et al,represents an innovative model designed to predict individualized survival outcomes for patients with r-NETs,analyzing the relationship between clinicopathological features and patient *** authors identified tumor grade,T stage,tumor size,age,and progno-stic nutritional index as key prognostic factors,demonstrating that the GATIS Score provides a more accurate prognosis assessment compared to the World Health Organization classification or the tumor-node-metastasis staging ***,further larger prospective studies are necessary,and the scientific community's efforts in this context should be directed toward developing interna-tional multicentric prospective studies,with the ultimate aim of accurately de-fining and understanding the behavior of these conditions.

关键词： Rectal neuroendocrine tumors Prognostic factors GATIS prognostic score Carcinoids Survival outcomes

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration Research 2025年第2期20卷 481-482页

作者： Khaled Alok Timothy G.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA translational Brain Research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological *** pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been *** objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

Treating incurable non-communicable diseases by targeting iron metabolism and ferroptosis

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Science China Life Sciences 2025年

作者： Ruoxuan Ni Jianwei Jiang Fudi Wang Junxia Min The First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine The Second Affiliated Hospital School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine

Both iron metabolism and ferroptosis (an iron-dependent form of programmed cell death) have been connected to the development and progression of many currently incurable non-communicable diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis,Huntington’s disease, metabolic dysfunction-associated steatohepatitis, heart failure, and both treatment-relapsed and refractory cancers,such as pancreatic ductal adenocarcinoma and triple-negative breast cancer. Thus, understanding the relationship between iron and these diseases can pave the way for the development of novel therapeutic strategies. Here, we summarize the latest evidence supporting the pathological roles of dysregulated iron metabolism and ferroptosis in a wide range of preclinical animal models of these currently incurable non-communicable diseases. We also summarize the feasibility of targeting iron metabolism and ferroptosis for the prevention and treatment of iron-and ferroptosis-related diseases that currently have limited treatment options. In addition, we provide our perspectives on the challenges and promises regarding the translational potential of targeting dysregulated iron metabolism and ferroptosis to treat diseases,highlighting the future roadmap for developing iron-and ferroptosis-targeted therapeutics.

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