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Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

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Neural Regeneration Research 2025年第5期20卷 1416-1430页

作者： Mou Gao Qin Dong Dan Zou Zhijun Yang Lili Guo Ruxiang Xu department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina department of Neurosurgery Chinese PLA General HospitalBeijingChina department of Neurology Fu Xing HospitalCapital Medical UniversityBeijingChina

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and *** previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological ***,the mechanism of CXCR4 upregulation in induced neural stem cells remains *** this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 ***,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial *** agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury ***,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head *** conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neura

关键词： Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell microglia neuroinflammation

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Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome:Focusing on inflammation and molecular mechanisms

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Animal Models and Experimental Medicine 2025年第1期8卷 5-19页

作者： Mohammad Yasin Zamanian Hamidreza Zafari Maria K.Osminina Alla A.Skakodub Raed Fanoukh Aboqader Al-Aouadi Maryam Golmohammadi Nikta Nikbakht Iman Fatemi department of Physiology School of MedicineHamadan University of Medical SciencesHamadanIran department of Pharmacology and Toxicology School of PharmacyHamadan University of Medical SciencesHamadanIran department of Orthopedic Surgery Joint Reconstruction Research CenterImam Khomeini Hospital ComplexSchool of MedicineTehran University of Medical SciencesTehranIran Pediatric department I.M.Sechenov First Moscow State Medical University of the Ministry of Health of Russia(Sechenov University)MoscowRussian Federation department of Pediatric Preventive Dentistry E.V.Borovsky I.M.Sechenov First Moscow State Medical University of the Ministry of Health of Russia(Sechenov University)MoscowRussian Federation department of Medicine College of MedicineAl-Ayen Iraqi UniversityThi-QarIraq School of Medicine Shahid Beheshti University of Medical SciencesTehranIran department of Physical Medicine and Rehabilitation School of PharmacyHamadan University of Medical SciencesHamadanIran Research Center of Tropical and Infectious Diseases Kerman University of Medical SciencesKermanIran

Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global *** therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse ***(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive *** delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing *** study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of *** from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free *** liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher *** anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of ***,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory *** findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

关键词： dexamethasone inflammation liposome rheumatoid arthritis TNF-α

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Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz Węgrzyn department of Molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

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DNA walker induced “signal on” fluorescence aptasensor strategy for rapid and sensitive detection of extracellular vesicles in gastric cancer

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Chinese Chemical Letters 2025年第2期36卷 328-331页

作者： Gaojian Yang Zhiyang Li Rabia Usman Zhu Chen Yuan Liu Song Li Hui Chen Yan Deng Yile Fang Nongyue He State Key Laboratory of Digital medical Engineering School of Biological Science and Medical Engineering Southeast University department of Clinical Laboratory the Affiliated Drum Tower Hospital of Nanjing University Medical School Hunan Key Laboratory of Biomedical Nanomaterials and Devices Hunan University of Technology Institute of Cytology and Genetics School of Basic Medical Sciences Hengyang Medical School University of South China Institute for Future Sciences University of South China

The extracellular vesicles show great potential as a noninvasive biomarker for the early detection of cancer. Hence, there is an urgent requirement to create biosensors that are time-saving, simple, and easily scalable in order to accomplish rapid, sensitive, and quantitative detection of extracellular vesicles. In this study, we present a self-propelled DNA walker powered by endonuclease *** CI, which enables the development of a “signal on” sensing platform for the rapid and highly sensitive detection of extracellular vesicles. The DNA motor employed tracks made of streptavidin magnetic beads, which consisted of substrate strands labeled with fluorescein and motor strands locked by aptamers. The aptamer recognition of the target protein on extracellular vesicles unlocked the motor strand, initiating the DNA motor process. After replacing the optimal buffer solution containing the endonuclease *** I, the motor strands autonomously moved along the streptavidin magnetic beads track, continuously releasing fluorescent molecules and producing detectable fluorescence signals. Under optimal conditions, the detection range was from 2×10～4particles/mL to 2×10～9particles/mL, with a detection limit of 2.9×10～3particles/mL,demonstrating excellent selectivity. This method has demonstrated good selectivity in different tumorderived extracellular vesicles and performs well in complex biological samples. The ability to effectively analyze surface proteins of extracellular vesicles in a short period of time gives our DNA walker a tremendous potential for developing simple and cost-effective clinical diagnostic devices.

关键词： Aptamer Detection Extracellular vesicles Nt.BbvCI Streptavidin magnetic beads

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A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

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Neural Regeneration Research 2025年第7期20卷 2084-2094页

作者： Tong Li Quhan Cheng Jingai Zhang Boxin Liu Yu Shi Haoxue Wang Lijie Huang Su Zhang Ruixin Zhang Song Wang Guangxu Lu Peifu Tang Zhongyang Liu Kai Wang department of Orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijingChina department of Training and Sports Medicine Characteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina medical School of Chinese PLA BeijingChina Key Laboratory of Bioactive Materials for the Ministry of Education College of Life SciencesNankai UniversityTianjinChina department of Orthopedics Tianjin HospitalTianjinChina department of Rehabilitation Medicine Er Quan Hospital of PAPWuxiJiangsu ProvinceChina

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor *** an alternative,nerve guidance conduits may be *** ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve *** designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align ***,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber *** presence of aligned fibers on the inner surface can promote the extension of nerve cells along the *** helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide *** novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

关键词： aligned fibers anti-kinking helical fibers nerve guidance conduit nerve regeneration peripheral nerve injury topological guidance

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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina department of Neurology The First Hospital of Tsinghua UniversityBeijingChina department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

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Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

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Neural Regeneration Research 2025年第9期20卷 2437-2453页

作者： Siyi Xu Junqiu Jia Rui Mao Xiang Cao Yun Xu department of Neurology Nanjing Drum Tower HospitalClinical College of Jiangsu UniversityNanjingJiangsu ProvinceChina department of Neurology Nanjing Drum Tower HospitalChinese Academy of Medical Science&Peking Union Medical CollegeNanjingJiangsu ProvinceChina department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical Diseases Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina Nanjing Neurology medical Center NanjingJiangsu ProvinceChina

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health *** optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent *** are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell ***,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these *** evidence has highlighted the significant role of mitophagy in acute central nervous system *** this review,we provide a comprehensive overview of the process,classification,and related mechanisms of *** also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate *** the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

关键词： autophagy intracerebral hemorrhage ischemic stroke mitochondria mitochondrial biogenesis mitochondrial quality control mitophagy spinal cord injury subarachnoid hemorrhage traumatic brain injury

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Small bites,big impact:The importance of evening snacks in patients with advanced chronic liver disease

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World Journal of Hepatology 2025年第1期17卷 1-4页

作者： Federica Perazza Federico Ravaioli department of medical and Surgical Sciences University of BolognaBologna 40138Italy

People with advanced chronic liver disease(ACLD)have an enhanced risk of malnutrition,which has multifactorial etiology and is mainly linked to a reduced energy and protein intake;malnutrition is critical for patients with cirrhosis since it is often associated with sarcopenia,a skeletal muscle depletion with a loss of muscle mass and ***-evening snacks have been extensively studied,and guidelines are recommended to counteract the effects of prolonged fasting at night in patients with ***,it has not been fully explored whether late evening snacking is clarified as a milestone to address the nutritional needs of people with ACLD or whether it has a potential role in improving body *** this randomised control trial,Yu et al demonstrated that long-term nocturnal snacks have the potential to significantly improve body composition by body fat mass,visceral fat area and body cell mass in patients with *** the improvement in skeletal muscle mass was minor,the promising results in other compositions provide hope for future research and patient care.

关键词： Nutrition Cirrhosis Advanced chronic liver disease Malnutrition Sarco-penia Skeletal muscle mass

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Global hotspots and trends on environmental exposure and cardiovascular disease from 1999 to 2022

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World Journal of Cardiology 2025年第1期17卷 92-109页

作者： Xin-Jie Zhang Qing Tan Zheng-Yu Xu Song Wen Shu-Bo Chen department of Graduate Chengde Medical UniversityShijiazhuang 067000Hebei ProvinceChina department of Surgical Urology Hebei Province Xingtai People’s HospitalXingtai 054031Hebei ProvinceChina department of Rheumatology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510260Guangdong ProvinceChina department of Orthopedics Tianjin Medical University General HospitalTianjin 300052China department of Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080Guangdong ProvinceChina

BACKGROUND The increasing risk of cardiovascular disease(CVD)associated with worsening environmental exposure is a critical health concern garnering global research *** To systematically assess the scope and characteristics of research on the relationship between environmental exposure and *** A thorough examination of publications on the relationship between environmental exposure and CVD from 1999 to 2022 was carried out by extensively screening the literature using the Web of Science Core *** language of the selected publications was standardized to ***,different academic tools such as CiteSpace,VOSviewer,HistCite,Python,Matplotlib,and Bibliometrix were utilized to examine the research trends in this *** The study’s findings indicated a steady increase in scientific publications among the 1640 analyzed documents,peaking in 2022 with 197 *** United States emerged as the leading nation regarding high-quality publications and international *** University was identified as the most prolific institution.“Environmental research”was the most frequently contributing journal,and Muenzel T was recognized as the top *** research hotspots are primarily concentrated on themes such as“cardiovascular disease”,“exposure”,“risk”,“mortality”,and“air pollution”.CONCLUSION This study highlights increasing research on the link between environmental exposure and CVD,identifying key exposures and diseases while emphasizing the need for further investigation into underlying mechanisms.

关键词： Bibliometrics Environmental exposure Cardiovascular disease CiteSpace VOSviewer Web of Science

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RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus

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Science China(Life Sciences) 2025年第2期68卷 441-453页

作者： Xue Pang Lin Gu Qiu-Ying Han Jia-Qing Xing Ming Zhao Shao-Yi Huang Jun-Xi Yi Jie Pan Hao Hong Wen Xue Xue-Qing Zhou Zhi-Hui Su Xin-Ran Zhang Li-Ming Sun Shao-Zhen Jiang Dan Luo Ling Chen Zheng-Jie Wang Yu Yu Tian Xia Xue-Min Zhang Ai-Ling Li Tao Zhou Hong Cai Tao Li Nanhu Laboratory National Center of Biomedical AnalysisBeijing 100039China School of Basic medical Sciences Fudan UniversityShanghai 200032China department of Basic medical Sciences School of MedicineTsinghua UniversityBeijing 100084China

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid(CSF)flow by beating their motile cilia *** ependymal denudation or ciliary dysfunction causes ***,we report that the deficiency of regulator of Gprotein signaling 22(RGS22)results in severe congenital hydrocephalus in both mice and ***,RGS22 is specifically expressed in ependymal cells within the *** conditional knock-out mice,we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce ***,we show that Rgs22 deficiency leads to the ependymal denudation and impaired *** phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor(LPAR)signaling under Rgs22^(-/-)condition,as the LPAR blockade effectively alleviates hydrocephalus in Rgs22^(-/-)***,our findings unveil a previously unrecognized role of RGS22 in the central nervous system,and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.

关键词： RGS22 hydrocephalus ependymal cells

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