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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of nuclear medicine&PET center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

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Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions

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Neural Regeneration Research 2025年第7期20卷 2116-2128页

作者： Yuxue Mu Ning Zhang Dongyu Wei Guoqing Yang Lilingxuan Yao Xinyue Xu Yang Li Junhui Xue Zuoming Zhang Tao Chen Aerospace Clinical medical center School of Aerospace MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Aviation medicine Xijing HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Emergency medicine Wuhan No.1 HospitalWuhanHubei ProvinceChina Third Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina Fourth Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina

A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain ***,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under *** 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic *** investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail *** results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly *** addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated *** findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

关键词： glial fibrous acidic protein gliosis Müller cells nerve growth factor neural differentiation neurodegeneration proteomic retinal degeneration retinal outer nuclear layer simulated weightlessness

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Companion diagnostics for the targeted therapy of gastric cancer

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World Journal of Gastroenterology 2015年第39期21卷 10948-10955页

作者： Changhoon Yoo Young Soo Park departments of Oncology Asan Medical Center University of Ulsan College of Medicine Department of Pathology Asan Medical Center University of Ulsan College of Medicine

Gastric cancer is the fourth most common type ofcancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer.

关键词： Companion diagnostics gastric cancer human epiderm

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric medical Research center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and nuclear medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Early treadmill exercise increases macrophage migration inhibitory factor expression after cerebral ischemia/reperfusion

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Neural Regeneration Research 2019年第7期14卷 1230-1236页

作者： Min Cheol Chang Chae Ri Park Seung Hwa Rhie Woo Hyun Shim Dae Yul Kim Department of Rehabilitation medicine College of MedicineYeungnam University asan Institute for Life Sciences Asan Medical CenterUniversity of Ulsan College of Medicine Department of Rehabilitation medicine Asan Medical CenterUniversity of Ulsan College of Medicine Department of Radiology Asan Medical CenterUniversity of Ulsan College of Medicine

The neuroprotective function of macrophage migration inhibitory factor(MIF) in ischemic stroke was rarely *** study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stroke and to determine whether these effects are associated with the expression levels of MIF and brain-derived neurotrophic factor(BDNF) in the ischemic area.A total of 40 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group [middle cerebral artery occlusion(MCAO)-Ex,n = 10),ischemia and sedentary group(MCAO-St,n = 10),sham-surgery and exercise group(Sham-Ex,n= 10),or sham-surgery and sedentary group(Sham-St,n = 10).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 minutes,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without *** in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 minutes once a day for 5 consecutive *** reperfusion,the hanging time tested by the wire hang test was longer and the relative fractional anisotropy determined by MRI was higher in the peri-infarct region of the MCAO-Ex group compared with the MCAO-St *** expression levels of MIF and BDNF in the peri-infarct region were upregulated in the MCAO-Ex *** MIF and BDNF levels were positively correlated with relative fractional anisotropy changes in the peri-infarct *** was no significant difference in the levels of MIF and BDNF in the peri-infarct region between the Sham-Ex and Sham-St *** study demonstrated that early exercise(initiated 48 hours after the MCAO) could improve motor and neuronal recovery after ischemic ***,the increased levels of MIF and BDNF in the peri-infarct region(penumbra) may be one of the mechanisms of enhanced neurological function *** experiments were approved by the Institutional Animal Care and Use Committee in asan medical center in South Korea(2016-12-126).

关键词： ischemic stroke early exercise macrophage migration inhibitory factor brain-derived neurotrophic factor motor recovery neural regeneration

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Clinical significance of MET gene amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum combination chemotherapy

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Chinese Journal of Cancer Research 2019年第4期31卷 620-631页

作者： Seyoung Seo Min-Hee Ryu Baek-Yeol Ryoo Yangsoon Park Young Soo Park Young-Soon Na Chae-Won Lee Ju-Kyung Lee Yoon-Koo Kang departments of Oncology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Department of Pathology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea asan Institute for Life Science Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea

Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative ***: MET amplification was assessed using fluorescence in situ hybridization(FISH) in 50 patients and quantitative polymerase chain reaction(qPCR) in 326 patients;259 patients treated with first-line fluoropyrimidine and platinum were included for survival ***: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5(κ=0.778, P5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of ≥2(33.3% vs. 10.5% P=0.007), peritoneal metastasis(76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels(28.6% vs. 7.3%, P=0.006). The median overall survival(OS) and progression-free survival(PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio(HR)=0.68, 95% confidence interval(95% CI): 0.35-1.32,P=0.254 for PFS;HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS].Conclusions: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.

关键词： MET amplification advanced gastric cancer prognosis quantitative real-time polymerase chain reaction

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Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of Basic medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for Clinical medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

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Intra-abdominal desmoid tumors mimicking gastrointestinal stromal tumors——8 cases: A case report

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World Journal of Gastroenterology 2019年第16期25卷 2010-2018页

作者： Jwa Hoon Kim Min-Hee Ryu Young Soo Park Hyun Jin Kim Hyojung Park Yoon-Koo Kang Department of Oncology Asan Medical CenterUniversity of Ulsan College of Medicine Department of Pathology Asan Medical Center University of Ulsan College of Medicine Department of Radiology Asan Medical Center University of Ulsan College of Medicine

BACKGROUND Intra-abdominal desmoid tumors(DTs) can mimic recurrence or progression of gastrointestinal stromal tumors(GISTs). Differential diagnosis is important to avoid unnecessary or inappropriate *** SUMMARY All 8 patients experienced surgical resection of GIST, and median time to diagnosis of DT was 1.8 years after surgical resection. All sites of DT were in the peritoneum around the surgical sites of GIST. The following clinical suspicion coupled with radiological findings contributed to the suspicion of intraabdominal DTs:(1) Occurrence of a new single lesion in the peritoneum around the surgical sites of GIST;(2) uncontrolled lesion with imatinib while other lesions being controlled with imatinib;(3) well-defined ovoid shaped lesion with delayed or mild enhancement and absence of necrosis, hemorrhage, and cystic change on computed tomography; and(4) a lesion showing mild or no hypermetabolic activity on 18 fluorodeoxyglucose-positron emission tomography,contrary to initially hyperactive lesion of GIST. All DTs were surgically removed except for one unresectable DT and only one DT recurred at another site of peritoneum, which was also surgically *** Intra-abdominal DT should be a differential diagnosis for a new single lesion in patients with GIST.

关键词： Desmoid tumor Gastrointestinal stromal tumor Radiology Surgicalresection Imatinib mesylate Case report

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Interleukin-2 gene-encoded stromal cells inhibit the growth of metastatic cholangiocarcinomas

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World Journal of Gastroenterology 2006年第12期12卷 1889-1894页

作者： Myung-HwanKim Sang Soo Lee Sung Koo Lee Seung-Gyu Lee Chul-Won Suh Gyung-Yub Gong Jung-Sun Park Young-Hoon Kim Sang-Hee Kim Department of Gastroenterology University of Ulsan College of MedicineAsan Medical CenterSeoulKorea Department of Surgery University of Ulsan College of MedicineAsan Medical CenterSeoulKorea Department of Oncology University of Ulsan College of MedicineAsan Medical CenterSeoul Korea Department of Pathology University of Ulsan College of MedicineAsan Medical CenterSeoulKorea asan Institute for Life Sciences.Seoul Korea

AIM： To demonstrate bone marrow stromal cells （BMSCs） can be used as an attractive target for genetic modification in the treatment of malignant diseases. METHODS： Using a hamster model of biliary cancer, we investigated the therapeutic effects of interleukin-2 （IL-2） gene-modified BHSCs. Syrian golden hamsters were injected via the femoral vein with 5×10^5 cells of the KIGB-5 biliary cancer cell line （n=20）. One week later, the hamsters were injected intraperitoneally with BMSCs containing Ad/hIL-2 and Ad/△E1, unmodified BHSCs, or RPHI only （control） and observed for 12 wk （n=5/each group）. RESULTS： All hamsters treated with BMSCs containing Ad/hIL-2 survived with no evidence of the disease during this period. In contrast, hamsters in the other three groups showed disseminated metastases involving the lungs as eady as 4 wk.CONCLUSION： Ad/IL-2 therapy is effective in the treatment of biliary cancer.

关键词： Bone marrow stromal cell Adenovirus/hIL-2 Biliary cancer

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Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation

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Neural Regeneration Research 2020年第8期15卷 1483-1489页

作者： Su Hwan Bae Mi Ran Yoo Ye Yeong Kim In Kyung Hong Mi Hee Kim Seung Hak Lee Dae Yul Kim Department of Rehabilitation medicine Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea asan Institute for Life Sciences Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system *** studies suggested that MIF protects neurons in ischemic ***,few studies are reported on the role of MIF in neurological recovery after ischemic *** purpose of this study is to identify the molecular mechanism of neuroprotection mediated by *** neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL MIF recombinant(30 ng/mL)or ISO-1(MIF antagonist;50μM)was administered to human neuroblastoma *** cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with MIF,OGD/R with *** viability was analyzed using WST-1 *** levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic ***-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 *** blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R *** levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R *** administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R *** results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells

关键词： apoptosis brain-derived neurotrophic factor hypoxia in vitro ischemic stroke macrophage migration inhibitory factor nerve regeneration neuroprotective effect reperfusion

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