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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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The potential mechanism and clinical application value of remote ischemic conditioning in stroke

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Neural Regeneration Research 2025年第6期20卷 1613-1627页

作者： Yajun Zhu Xiaoguo Li Xingwei Lei Liuyang Tang Daochen Wen Bo Zeng Xiaofeng Zhang Zichao Huang Zongduo Guo The first affiliated hospital of Chongqing Medical university ChongqingChina

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

关键词： Akt apoptosis autophagy cerebral perfusion cerebral vascular stenosis clinical transformation hemorrhagic stroke ischemic stroke neuroinflammation neuroprotection Notch1 PI3K remote ischemic conditioning stroke

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Complete response of gallbladder cancer treated with gemcitabine and cisplatin chemotherapy combined with durvalumab:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 226-232页

作者： Kai Chen Xu Feng Yuan Shi Xin-Lin Li Zheng-Rong Shi Xiang Lan Department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced ***,the efficacy of this treatment for GBC remains *** SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative *** three cycles of therapy,a partial response was *** one year of combined therapy,a clinical complete response was successfully *** maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the *** patient experienced tolerable toxicities of reversible grade 2 nausea and *** adverse events were observed in the patient throughout the entirety of the *** The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse *** research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.

关键词： Gallbladder cancer Chemotherapy Immunotherapy Durvalumab Complete response Case report

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Computed tomography enterography-based radiomics for assessing mucosal healing in patients with small bowel Crohn's disease

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World Journal of Gastroenterology 2025年第3期31卷 62-72页

作者： Hao Ding Yuan-Yuan Fang Wen-Jie Fan Chen-Yu Zhang Shao-Fei Wang Jing Hu Wei Han Qiao Mei Department of Gastroenterology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022Anhui ProvinceChina Department of Radiation Oncology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022Anhui ProvinceChina Department of Gastroenterology Suzhou First People's HospitalSuzhou 234099Anhui ProvinceChina

BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD ***,it poses a significant challenge due to its limited accessibility through conventional endoscopic *** To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD *** Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic *** demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic *** diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),*** Of the 73 patients enrolled,25 patients achieved *** radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by *** These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.

关键词： Crohn’s disease Computed tomography enterography Mucosal healing Nomogram Radiomics

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Unraveling the therapeutic potential of Calculus Bovis in liver cancer:A novel step for targeted cancer treatment

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World Journal of Gastroenterology 2025年第3期31卷 127-129页

作者： Xing-Yu Chen Xiang Lan Department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

Hepatocellular carcinoma is one of the leading causes of cancer-related deaths globally,and effective treatments are urgently *** present study aimed to investigate the inhibitory effect of Calculus Bovis(CB)on liver cancer and the underlying *** inhibited M2 tumor-associated macrophage polarization and modulated the Wnt/β-catenin signaling pathway,thereby suppressing the proliferation of liver cancer *** inhibitory effect on liver cancer growth was confirmed by both in vivo and in vitro experiments(detailed by Huang et al).The present study provides a theoretical basis for the application of CB for the treatment of liver cancer,providing new avenues for liver cancer treatment.

关键词： Calculus Bovis Liver cancer M2 tumor-associated macrophage polarization Wnt/β-catenin Pathway Tumor microenvironment

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Transarterial chemoembolization combined with lenvatinib and sintilimab vs lenvatinib alone in intermediate-advanced hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 52-61页

作者： Fei-Da Wu Hai-Feng Zhou Wei Yang Di Zhu Bi-Fei Wu Hai-Bin Shi Sheng Liu Wei-Zhong Zhou Department of Interventional Radiology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor *** chemoembolization(TACE)is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia,thereby promoting *** studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might im-prove ***,a tyrosine kinase inhibitor,has demonstrated superior outcomes compared to sorafenib,while immune checkpoint inhibitors such as sintilimab show potential when combined with ***,the efficacy and safety of TACE combined with lenvatinib and sintilimab(TACE+SL)compared to TACE with lenvatinib alone(TACE+L)in patients with intermediate-ad-vanced HCC has not yet been *** To evaluate the efficacy and safety of TACE+SL therapy in comparison to TACE+L therapy in patients with intermediate-advanced *** A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September *** characteristics were compared,and propensity score matching was *** survival(OS),progression-free survival(PFS),and objective response rate(ORR)were evaluated between the two groups,and adverse events were *** The study included 57 patients,with 30 in the TACE+SL group and 27 in the TACE+L *** TACE+SL group demonstrated significantly improved median PFS and OS compared to the TACE+L group(PFS:14.1 months vs 9.6 months,P=0.016;OS:22.4 months vs 14.1 months,P=0.039),along with a higher ORR(70.0%vs 55.6%).After propensity score matching,30 patients were included,with the TACE+SL group again showing longer median PFS and a trend toward improved OS(PFS:14.6 months vs 9.2 months,P=0.012;OS:23.9 months vs 16.3 months,P=0.063),and a higher ORR(73.3%vs 53.3%).No severe adverse events were *** TACE+SL demonstrat

关键词： Hepatocellular carcinoma Transarterial chemoembolization Sintilimab Lenvatinib Immunotherapy Programmed cell death 1 Prognosis

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Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

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World Journal of Gastroenterology 2025年第3期31卷 134-137页

作者： Qi-Rong Jiang Da-Wu Zeng Department of Hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Infectious Diseases The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350004Fujian ProvinceChina

In this article,we provide commentary on the recent article by Zhao et *** focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and *** comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy *** gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome ***,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated *** these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal *** conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

关键词： Hepatitis B virus Cirrhosis Portal hypertension Hepatic encephalopathy Transjugular intrahepatic portosystemic shunt Gut microbiota

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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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