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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong department of Spine surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)Key Laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Quality Control of minimally invasive Spine surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial Center for Engineering and Technology Research of minimally invasive Spine surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Search for microglia-specific peptides:advances in the discovery toolbox

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Neural Regeneration Research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle M.Koss department of surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;M1 and M2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

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HNRNPC as a pan-cancer biomarker and therapeutic target involved in tumor progression and immune regulation

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Oncology Research 2025年第1期33卷 83-102页

作者： YUEZHOU ZHANG ZHAO ZHANG JINXIN DONG CHANGAN LIU department of Hepatobiliary surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing400016China department of Hepatobiliary surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China

Background:Aberrant expression of RNA-binding proteins(RBPs)has been linked to a variety of diseases,including hematological disorders,cardiovascular diseases,and multiple types of *** nuclear ribonucleoprotein C(HNRNPC),a member belonging to the heterogeneous nuclear ribonucleoprotein(hnRNP)family,plays a pivotal role in nucleic acid *** studies have underscored the significance of HNRNPC in tumorigenesis;however,its specific role in malignant tumor progression remains inadequately ***:We leveraged publicly available databases,including The Cancer Genome Atlas(TCGA),to explore the potential involvement of HNRNPC across various ***,we performed experimental validation studies focused on liver ***:Our analysis revealed that HNRNPC is overexpressed in a wide range of common malignancies,including liver and lung cancers,and is strongly linked to unfavorable ***,HNRNPC was observed to be closely linked to tumor *** immune checkpoint analysis and immune cell infiltration assessment,HNRNPC emerged as a potential target for modulating tumor ***,silencing of HNRNPC markedly inhibited the proliferation,metastasis,and infiltration of liver cancer ***:In summary,our findings highlight HNRNPC as a prognostic marker in various cancers,including liver cancer,and suggest its involvement in shaping the tumor immune *** insights offer potential avenues for improving clinical outcomes in tumors with elevated HNRNPC expression,particularly through immunotherapeutic strategies.

关键词： Heterogeneous nuclear ribonucleoprotein C(HNRNPC) Pan-cancer analysis Tumor immunity Prognostic biomarker Immunotherapeutic target Hepatocellular carcinoma

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lncRNA SNHG4 enhanced gastric cancer progression by modulating miR-409-3p/CREB1 axis

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Oncology Research 2025年第1期33卷 185-198页

作者： ZHOUYANG CHENG YUCHEN HUA YANG CAO JUN QIN department of General surgery Affiliated Hospital of Nantong UniversityNantong226001China department of surgery Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong226001China department of Operation Affiliated Hospital of Nantong UniversityNantong226001China

Objective:Gastric cancer(GC)is a globally common cancer characterized by high incidence and mortality *** in the molecular understanding of GC provide promising targets for GC diagnosis and *** non-coding RNAs(lncRNAs)and their downstream regulators are regarded to be implicated in the progression of multiple types of *** have shown that the lncRNA small nucleolar RNA host gene 4(SNHG4)serves as a tumor promoter in various malignancies,while its function in GC has yet to be ***,our study aimed to explore the role and underlying mechanism of SNHG4 in ***:We used qRT-PCR to analyze SNHG4 expression in GC tissues and ***-Meier analysis was used to assess the correlation between SNHG4 expression and the survival rate of GC *** function experiments such as CCK-8,BrdU,colony formation,flow cytometry analysis,and transwell were performed to explore the effects of SNHG4 on GC cell proliferation,apoptosis,cell cycle,migration,and *** also established xenograft mouse models to explore the effect of SNHG4 on GC tumor ***,dual luciferase reporter assay was used to verify the interaction between SNHG4 and miR-409-3p and between miR-409-3p and cAMP responsive element binding protein 1(CREB1).Results:The results indicated that SNHG4 was overexpressed in GC tissues and cell lines,and was linked with poor survival rate of GC ***4 promoted GC cell proliferation,migration,and invasion while inhibiting cell apoptosis and cell cycle arrest in *** in vivo experiment indicated that SNHG4 facilitated GC tumor ***,SNHG4 was demonstrated to bind to ***,CREB1 was directly targeted by *** assays demonstrated that miR-409-3p deficiency reversed the suppressive impact of SNHG4 knockdown on GC cell ***,miR-409-3p was also revealed to inhibit GC cell proliferation,migration,and invasion by targeting CREB1

关键词： Gastric cancer Small nucleolar RNA host gene 4(SNHG4) MicroRNA-409-3p(miR-409-3p) cAMP responsive element binding protein 1(CREB1)

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Large-for-size syndrome prophylaxis in infant liver recipients with low body mass

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World Journal of Transplantation 2025年第1期15卷 72-85页

作者： Konstantin Semash Timur Dzhanbekov department of mini-invasive surgery National Children's Medical CenterTashkent 100171ToshkentUzbekistan

Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in ***,the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains *** review explores historical developments,various approaches to measuring the required functional liver mass,and techniques to prevent complications associated with large-for-size grafts in infants.

关键词： Pediatric liver transplantation Large-for-size syndrome Preoperative evaluation of donor and recipient Liver volumetry Monosegmental transplantation Left lateral sector graft Reduced size liver graft Abdominal wall reconstruction Liver transplantation Liver resection

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Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin Chen Jinghong Xu Bin Jiang Lei Li Yawei Li Yuliang Dai Bing Wang department of Spine surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

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Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

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Neural Regeneration Research 2025年第7期20卷 1883-1899页

作者： Mingyu Zhang Chunyu Xiang Renrui Niu Xiaodong He Wenqi Luo Wanguo Liu Rui Gu department of Orthopedic surgery China-Japan Union Hospital of Jilin UniversityChangchunJilin ProvinceChina

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely ***,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic *** are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and ***,they can potentially treat traumatic and nontraumatic central nervous system *** this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics ***,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain *** studies related to liposomes are still in the laboratory stage and have not yet entered clinical ***,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and ***,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

关键词： Alzheimer's disease amyotrophic lateral sclerosis brain tumors central nervous system Huntington's disease liposome drug delivery neurological disorders Parkinson's disease spinal cord injury traumatic brain injury

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Ceramide induces apoptosis in human lung adenocarcinoma A549 cells through mitogen-activated protein kinases

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Acta Pharmacologica Sinica 2007年第3期28卷 439-445页

作者： Nobuo MURATA Tatsuo YAMAKAWA department of surgery Mini-invasive surgery CenterTeikyo University Mizonokuchi HospitalKawasaki 213-8507Japan

Aim:To provide experimental data for further research on the signal transductionof apoptosis in lung adenocarcinoma cells,we examined the effects of exogenousC2-ceramide administration on several members of the mitogen-activated proteinkinase(MAPK)superfamily and caspase-3 in A549 ***:Cell viabilityand apoptosis were analyzed by cell counting kit-8 assay and flow *** MAPK and caspase-3 proteins were detected by Western ***:C2-ceramide selectively altered the phosphorylation state &members ofthe MAPK superfamily,causing hyperphosphorylation ofmitogen-activated pro-tein kinase kinase(MEK)1/2 and the p38 MAPK,but not affecting the phosphory-lation ofextracellular signal-regulated kinase 1/2 and the c-Jun N-terminal ***-203580(a p38 MAPK inhibitor)and p38 siRNA,but not U0126(a MEKinhibitor),partially rescued cell death induced by C2-ceramide.C2-ceramide promoted theactivation of ***:Exogenous C2-ceramide induced apoptosisin human lung adenocarcinoma A549 *** activation of MAPK and caspase-3were involved in the mechanisms ofC2-ceramide-induced apoptosis in A549 cells.

关键词： ceramide apoptosis mitogen-activated protein kinases A549 cells

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Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期68卷 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu department of Hepatobiliary and Pancreatic surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ Transplantation Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital department of Hepatobiliary and Pancreatic surgery The First Affiliated HospitalZhejiang University School of Medicine department of Urology The Second Affiliated HospitalZhejiang University School of Medicine department of Hepatobiliary and Pancreatic surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie Lin Weihong Xu department of Spinal surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and Research Center Peking University People’s HospitalBeijingChina department of Orthopedic surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

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