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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun Department of Neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 1-9页

作者： Hui Wan Yu-Xin Zhang Guan-Yue Shan Jun-Ya Cheng Duan-Rui Qiao Yi-Ying Liu Wen-Na Shi Hai-Jun Li Institute of Translational Medicine The First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina Department of Bioengineering Pharmacy School of Jilin UniversityChangchun 130061Jilin ProvinceChina Institute of Liver Diseases Institute of Translational MedicineThe First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina

In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal *** pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV *** infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic *** addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral *** loss of immune cell function caused by HBV infection ultimately leads to ***-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.

关键词： Hepatitis B virus Hepatocellular carcinoma Hepatitis B virus-DNA Immune tolerance Antiviral therapy

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Exosomes:the next-generation therapeutic platform for ischemic stroke

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Neural Regeneration Research 2025年第5期20卷 1221-1235页

作者： Wenjing Yin Hongyin Ma Yang Qu Jiaxin Ren Yingying Sun Zhen-Ni Guo Yi Yang Stroke Center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina Neuroscience Research Center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional ***,there is an urgent need to develop new methods for the treatment of this *** are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological *** have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain *** physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic *** rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages *** in technology have also driven clinical translational research on *** this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction ***,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified *** optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic ***,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

关键词： blood–brain barrier electroacupuncture engineering exercise exosomes ischemic stroke mesenchymal stem cells microglia neuroprotection stents

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Bowel preparation before colonoscopy: Consequences, mechanisms, and treatment of intestinal dysbiosis

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World Journal of Gastroenterology 2025年第2期31卷 13-26页

作者： Ze-Long Zheng Qing-Fan Zheng Li-Qiang Wang Yi Liu Department of Gastroenterology(Endoscopy Center) China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina

The term“gut microbiota”primarily refers to the ecological community of various microorganisms in the gut,which constitutes the largest microbial community in the human *** adequate bowel preparation can improve the results of colonoscopy,it may interfere with the gut *** preparation for colonoscopy can lead to transient changes in the gut microbiota,potentially affecting an individual’s health,especially in vulnerable populations,such as patients with inflammatory bowel ***,measures such as oral pro-biotics may ameliorate these adverse *** focused on the bowel prepa-ration-induced changes in the gut microbiota and host health status,hypothesized the factors influencing these changes,and attempted to identify measures that may reduce dysbiosis,thereby providing more information for individualized bowel preparation for colonoscopy in the future.

关键词： Bowel preparation Colonoscopy Microbiota Inflammatory bowel disease Probiotics

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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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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

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Biomass Fraction of Phosphate-Accumulating Organisms Grown in Anoxic and Aerobic Stages under Optimum Nitrate Concentration

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Journal of Donghua university(English Edition) 2014年第3期31卷 278-286页

作者：王晓玲李娜谢添张芳董利鹏殷宝用 Key Laboratory of Songliao Aquatic Environment Ministry of EducationJilin Jianzhu University School of Municipal and Environmental Engineering Jilin Jianzhu University

The effects of nitrate concentration on the capability of phosphorus uptake in the main anoxic stage were ***, the biomass fractions — heterotrophs, phosphateaccumulating organisms( PAOs),and nitrifying organisms in a pilot-scale enhanced biological phosphorus removal( EBPR) system— were both experimentally and theoretically evaluated( from the mass balance calculations of organic matter, nitrogen and phosphorus),under optimum nitrate concentration in the main anoxic stage,in which the influent chemical oxygen demand( COD)concentration was stabilized at( 290 ± 10) mg·L- 1and the influent total phosphorus( TP) concentration was stabilized at( 7. 0 ± 0. 5)mg · L- 1. In long term operations,the process exhibited high performance in removing organic matter, nitrogen, and phosphorus. Approximately 46. 41% of organic matter,57. 21% of nitrogen,and 48. 14% of phosphorus were removed from the influent in the form of carbon dioxide,nitrogen gas,and polyphosphate,respectively. XH( heterotrophs),XPAO( PAOs),and XAUT( autotrophs) were regarded as the major organisms responsible for biomass production. The yield fractions of XHgrowth in the first anoxic,the second anoxic,and the aerobic stages were 10. 24%,19. 11%,and 19. 71%,respectively; the yield fractions of XPAO growth in the second anoxic and the aerobic stages were 24. 34% and19. 86%,respectively; the yield fraction of XAUTgrowth in the aerobic stage was 6. 74%. These results showed that XHand XPAOformed the major community. Moreover,a higher amount of XPAOgrowth on stored poly-hydroxyalkanoates( PHAs) under the anoxic condition was seen in this EBPR system for municipal wastewater treatment.

关键词： biomass anoxic phosphorus uptake heterotrophs phosphate-accumulating organisms nitrifying organisms

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Control for Modified university of Cape Town Process Using Oxidation-Reduction Potential in the Second Anoxic Zone

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Journal of Donghua university(English Edition) 2013年第3期30卷 215-221页

作者：王晓玲林英姿李娜张芳谢添董利鹏 Key Laboratory of Songliao Aquatic Environment Ministry of EducationJilin Jianzhu University School of Municipal and Environmental Engineering Jilin Jianzhu University

The aim of this work is to evaluate the feasibility of applying the technology of oxidation-reduction potential （ORP） control on the municipal wastewater treatment system for nitrogen and phosphorus removal. Meanwhile the relation between the optimal ORP （ ORPopt ） and influent C/N ratio was evaluated, in which the influent chemical oxygen demand （ COD ） concentration was stabilized at （290 ± 10 ） mg/L, the influent total phosphorus （TP） concentration was stabilized at （7.0 ± 0.5 ） mg/L. The results indicated that：（1） the ORP in the second anoxic zone had effect on nitrogen and phosphorus removal capability, and the average percentages of phosphorus uptake in ANO2 zone （ ηa ） increased with increasing ORP, i. e. , increasing from 12. 0% at - 143 mV to 22.0%,30.0%,37.0%, and45.0% at -123, -111, -105 and -95 mV, respectively; （2） the ORPopt as function of influent C/N ratio could be calculated by the equation： y ffi 252. 73e〈 -x/3.39） _ 131.01 ; the maximum percentage of phosphorus uptake in ANO2 as function of the ORPopt could be calculated by the equation： y ffi -0.49e（x/15.58）＋ 1. 51. The ORPopt was the important process control parameter that must be optimized for operation of enhanced biological phosphorus removal （ EBPR ） system. Moreover, ORP sensor is very simple, and the industrial applications of this strategy is practical.

关键词： modified university of Cape Town (MUCT) process nitrate oxidation-reduction potential (ORP) phosphorus uptake

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High-pressure-induced phase transition in cinchomeronic acid polycrystalline form-I

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Chinese Physics B 2019年第1期28卷 490-496页

作者： Ting-Ting Yan Dong-Yang Xi Jun-Hai Wang Xu-Feng Fan Ye Wan Li-Xiu Zhang Kai Wang School of Science Shenyang jianzhu university School of Materials Science and Engineering Shenyang jianzhu university Analysis and Detection Technology Research Center Shenyang jianzhu university State Key Laboratory of Superhard Materials jilin university

Diamond anvil cells combined with Raman spectroscopy and angle-dispersive x-ray diffraction(ADXRD) were used to investigate the compression behavior of cinchomeronic acid(C_7H_5NO_4, CA), a hydrogen-bonded polymorphs. The compression of form-I at approximately 6.5 GPa caused an irreversible phase transition that produced the new polymorph form-III. Lattice and internal modes in the Raman spectra were analyzed to determine the modifications in the local environment of CA form-I molecules. The form-III was indexed and refined to a low-symmetry triclinic structure with space group P1. The mechanism for the phase transition involved the reconstructions in the hydrogen-bonded networks in CA form-I.

关键词： phase transformations pressure vibrational spectroscopy x-ray diffraction

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