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CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

Neural Regeneration Research 2025年第8期20卷 2420-2432页

作者： Lin Yin Yalan Xu Jie Mu Yu Leng Lei Ma Yu Zheng Ruizhi Li Yin Wang Peifeng Li Hai Zhu Dong Wang Jing Li Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina School of Basic Medicine Qingdao UniversityQingdaoShandong ProvinceChina college of Life Sciences and School of PharmacyMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina department of Urology Qingdao Municipal Hospital Affiliated to Qingdao UniversityQingdaoShandong ProvinceChina

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding *** of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully *** has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic ***,the function of CNKSR2 in the cytoplasm remains to be *** this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of *** a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the *** also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker *** colocalization analysis confirmed the centrosomal localization of *** we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal *** manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and ***,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum *** findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

关键词： autism spectrum disorder centrosome CNKSR2 intellectual disability interactome mass spectrometry microtubule neurodevelopmental disease protein complexes protein-protein interactions

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Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

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Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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Improving postoperative outcomes in patients with pancreatic cancer:Inflammatory and nutritional biomarkers

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World Journal of Clinical Oncology 2025年第1期16卷 59-64页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305Taiwan Division of cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561Taiwan Division of cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328Taiwan

This editorial assesses the prognostic value of preoperative inflammatory and nutritional biomarkers in patients undergoing surgical resection for pancreatic *** et al evaluated the ability of seven biomarkers to predict postoperative recovery and long-term *** biomarkers were albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,nutritional risk index,and geriatric nutritional risk *** PNI was found to be a strong predictor of both overall and recurrence-free survival,underscoring its clinical relevance in managing patients with pancreatic cancer.

关键词： Pancreatic cancer Prognostic nutritional index Systemic immune-inflammation index Postoperative recovery Prognosis

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Radiomics and molecular analysis:Bridging the gap for predicting hepatocellular carcinoma prognosis

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World Journal of Clinical Cases 2025年第4期13卷 56-60页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng department of medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305TaiwanChina Division of cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561TaiwanChina Division of cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002TaiwanChina department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404333TaiwanChina

This editorial examines a recent study that used radiomics based on computed tomography(CT)to predict the expression of the fibroblast-related gene enhancer of zeste homolog 2(EZH2)and its correlation with the survival of patients with hepatocellular carcinoma(HCC).By integrating radiomics with molecular analysis,the study presented a strategy for accurately predicting the expression of EZH2 from CT *** findings demonstrated a strong link between the radiomics model,EZH2 expression,and patient *** noninvasive approach provides valuable insights into the therapeutic management of HCC.

关键词： Hepatocellular carcinoma Computed tomography Radiomics Enhancer of zeste homologue 2 expression Non-invasive imaging

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Transoesophageal emergency ventricular pacing with esophageal balloon electrode catheter

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Journal of Geriatric cardiology 2008年第3期5卷 142-145页

作者： Fangsheng Zheng Rongqiang Yan Hairong Zhao Luxia Mao department of cardiology, affiliated hospital of qingdao university medical college, qingdao Shandong 266003, China department of cardiology Affiliated Hospital of Qingdao University Medical College

Objective To evaluate the safety and possibility of transesophageal emergency ventricular pacing with esophageal balloonelectrode *** Sixty four patients with critical bradyarrhythmias were divided randomly to receive either transesophagealventricular pacing with esophageal balloon electrode catheter(*** group,n=32),or transesophageai ventricular pacing withnormal esophageal electrode catheter(normal catheter group,n=32).Pulse width(ms),current output(mA),and the success rate werecompared between the 2 *** Success rate in the balloon catheter group was 87.5%,which was significantly higher thanthat in the nodal catheter group(18.7%,X2=27.7,P＜0.01).The success rate oftransesophageal ventricular pacing with esophagealballoon electrode catheter was 87.5%.The average current output(mA)was significantly lower in the balloon catheter group than thatin the normal catheter group (24.5+2.5 mA VS 53±3.4mA,P＜0.05).Conclusions Esophageal balloon electrode catheter pacing couldbecome an available teclmiqBe for transesophageal emergency ventricular pacing.

关键词： ventriculax pacing balloon elcctrode catheter emergency.

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Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2025年第1期 103-115页

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Basic MedicineJilin University State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Veterinary MedicineJilin University college of Mathematics Jilin University Bioinformatic Lab School of MathematicsShandong University department of cardiology China-Japan Union HospitalJilin University

The coronavirus disease 2019（COVID-19） outbreak caused by the severe acute respiratory syndrome coronavirus-2（SARS-CoV-2） developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality（CAC）, and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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Is heart rate reduction more important than target dose in chronic heart failure therapy with a beta-blocker?

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Journal of Geriatric cardiology 2011年第4期8卷 260-262页

作者： Yong-Fang Guo Yi An department of cardiology The Affiliated Hospital of Medical College of Qingdao UniversityQingdao 266000Shandong ProvinceChina

1 Introduction Beta-adrenoceptor blocking agents(beta-blockers)are now well established as cornerstone therapy in patients with systolic chronic heart failure(CHF).[1]Clinical data have overwhelmingly proven the beneficial effects of beta-blocker therapy in terms of improving patient prognosis,decreasing requirements for hospitalization,and postponing disease progression.[2-4]However,it remains unclear what the optimal efficacious and safe dose for an individual patient with CHF is,and whether this can simply be inferred from the target dose for each beta-blocking agent as used in the major clinical trials.

关键词： heart rate beta-blockers chronic heart failure

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Human β-NGF gene transferred to cat corneal endothelial cells

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International Journal of Ophthalmology(English edition) 2016年第7期9卷 937-942页

作者： Wen-Juan Luo Min Liu Gui-Qiu Zhao Chuan-Fu Wang Li-Ting Hu Xiang-Ping Liu department of Ophthalmology the Affiliated Hospital of Medical College Qingdao University Central Laboratory of the affiliated hospital of medical college Qingdao University

AIM： To transfect the cat corneal endothelial cells （CECs） with recombinant human β-nerve growth factor gene adeno-associated virus （AAV-β-NGF） and to observe the effect of the expressed β-NGF protein on the proliferation activity of cat CECs. METHODS： The endothelium of cat cornea was torn under the microscope and rapidly cultivated in Dulbecco＇s modified Eagle＇s medium （DMEM） to form single layer CECs and the passage 2 endothelial cells were used in this experiment. The recombinant human AAV-β-NGF was constructed. The recombinant human AAV-β-NGF was transferred into cat CECs directly. Three groups were as following： normal CEC control group, CEC-AAV control group and recombinant CEC- AAV-β-NGF group. Forty-eight hours after transfection, the total RNA was extracted from the CEC by Trizol. The expression of the β-NGF target gene detected by fluorescence quantitative polymerase chain reaction; proliferation activity of the transfected CEC detected at 48h by MTT assay; the percentage of G1 cells among CECs after transfect was detected by flow cytometry method （FCM）; cell morphology was observed under inverted phase contrast microscope. RESULTS： The torn endothelium culture technique rapidly cultivated single layer cat corneal endothelial cells. The self-designed primers for the target gene and reference gene were efficient and special confirmed through electrophoresis analysis and DNA sequencing. Forty-eight hours after transfect, the human β-NGF gene mRNA detected by fluorescence quantitative polymerase chain reaction showed that there was no significant difference between normal CEC control group and CEC-AAV control group （P〉0.05）; there was significant difference between two control groups and recombinant CEC-AAV-β-NGF group （P〈0.05）. MTT assay showed that transfect of recombinant AAV-β-NGF promoted the proliferation activity of cat CEC, while there was no significant difference between normal CEC control group and CEC-AAV control group （P〉0.05）. FCM result show

关键词： nerve growth factor corneal endothelialcell transfect proliferation

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ACL reconstruction with BPTB autograft and irradiated fresh frozen allograft

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2009年第4期10卷 306-316页

作者： Kang SUN Shao-qi TIAN Ji-hua ZHANG Chang-suo XIA Cai-long ZHANG Teng-bo YU department of Orthopaedics affiliated hospital of medical college Qingdao University Qingdao 266003 China Healthy Physical Examination Center Affiliated Hospital of Medical College Qingdao University Qingdao 266003 China

Objective： To analyze the clinical outcomes of arthroscopic anterior cruciate ligament （ACL） reconstruction with irradiated bone-patellar tendon-bone （BPTB） allograft compared with non-irradiated allograft and autograft. Methods： All BPTB allografts were obtained from a single tissue bank and the irradiated allografts were sterilized with 2.5 mrad of irradiation prior to distribution. A total of 68 patients undergoing arthroscopic ACL reconstruction were prospectively randomized consecutively into one of the two groups （autograft and irradiated allograft groups）. The same surgical technique was used in all operations done by the same senior surgeon. Before surgery and at the average of 31 months of follow-up （ranging from 24 to 47 months）, patients were evaluated by the same observer according to objective and subjective clinical evaluations. Results： Of these patients, 65 （autograft 33, irradiated allograft 32） were available for full evaluation. When the irradiated allografl group was compared to the autograft group at the 31 -month follow-up by the Lachman test, the anterior drawer test （ADT）, the pivot shift test, and KT-2000 arthrometer test, statistically significant differences were found. Most importantly, 87.8% of patients in the autograft group and just only 31.3% in the irradiated allograft group had a side-to-side difference of less than 3 mm according to KT-2000. The failure rate of the ACL reconstruction with irradiated allograft （34.4%） was higher than that with autograft （6.1%）. The anterior and rotational stabilities decreased significantly in the irradiated allograft group. According to the overall International Knee Documentation Committee （1KDC）, functional and subjective evaluations, and activity level testing, no statistically significant differences were found between the two groups. Besides, patients in the irradiated allograft group had a shorter operation time and a longer duration of postoperative fever. When the patients had a fever, the

关键词： Anterior cruciate ligament (ACE) reconstruction Patellar tendon Autograft Allograft Irradiation Prospectiverandomized study

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Expression of gastrointestinal nesfatin-1 and gastric emptying in ventromedial hypothalamic nucleus- and ventrolateral hypothalamic nucleus-lesioned rats

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World Journal of Gastroenterology 2014年第22期20卷 6897-6905页

作者： Zi-Bin Tian Run-Jun Deng Gui-Rong Sun Liang-Zhou Wei Xin-Juan Kong Xue-Li Ding Xue Jing Cui-Ping Zhang Yin-Lin Ge department of Gastroenterology Affiliated Hospital of Medical College of Qingdao University Clinical Laboratory Affiliated Hospital of Medical College of Qingdao University department of Biochemistry and Molecular Biology Medical College of Qingdao University

AIM: To determine the expression levels of gastrointestinal nesfatin-1 in ventromedial hypothalamic nucleus (VMH)-lesioned (obese) and ventrolateral hypothalamic nucleus (VLH)-lesioned (lean) rats that exhibit an imba... 详细信息

关键词： Nucleobindin Nesfatin-1 Gastrointestinal tract Gastric emptying Ventromedial hypothalamic nucleus Hyperphagia Obesity Anorexia

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