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Prediction of fibril formation by early-stage amyloid peptide aggregation

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Journal of Pharmaceutical Analysis 2020年第2期10卷 194-199页

作者： Jiaojiao Hu Huiyong Sun Haiping Hao Qiuling Zheng Department of Pharmaceutical Analysis School of PharmacyChina Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China Key Laboratoryof Drug Metabolism and Pharmacokinetics China Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityTongjiaxiang#24NanjingJiangsu210009China

Amyloid fibrils are found in systemic amyloidosis diseases such as Alzheimer's disease,Parkinson's disease,and type II diabetes.Currently,these diseases are diagnosed by observation of fibrils or plaques,which is an ineffective method for early diagnosis and treatment of disease.The goal of this study was to develop a simple and quick method to predict the possibility and speed of fibril formation before its occurrence.Oligomers generated from seven representative peptide segments were first isolated and detected by ion-mobility mass spectrometry(IM-MS).Then,their assemblies were disrupted using formic acid(FA).Interestingly,oligomers that showed small ion intensity changes upon FA addition had rapid fibril formation.By contrast,oligomers that had large ion intensity changes generated fibrils slowly.Two control peptides(aggregation/no fibrils and no aggregation/no fibrils)did not show changes in their ion intensities,which confirmed the ability of this method to predict amyloid formation.In summary,the developed method correlated MS intensity ratio changes of peptide oligomers on FA addition with their amyloid propensities.This method will be useful for monitoring peptide/protein aggregation behavior and essential for their mechanism studies.

关键词： Mass spectrometry Amyloid fibril early-stage oligomer Peptide aggregation

Record of early-stage Rodingitization from the Purang Ophiolite Complex,Western Tibet

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Journal of Earth Science 2019年第6期30卷 1108-1124页

作者： Songjie Wang Xu-Ping Li Wenyong Duan Fanmei Kong Zeli Wang Shandong Key Laboratory of Depositional Mineralization and Sedimentary Minerals Shandong University of Science and Technology

Rodingitization,commonly coupled with serpentinization of ultramafic rocks,bears significant information for fluid-rock interactions and element transfer from sea-floor to subduction zone environments.Numerous outcrops of rodingites are exposed along the Yarlung Zangbo suture zone(YZSZ)of southern Tibet,providing us an excellent opportunity to probe the petrogenetic processes,and unravel their implications for regional tectonic evolution.Several studies have been performed on rodingites from the eastern to central portions of the YZSZ,whereas limited work has ever been conducted on rodingitized rocks from the western segment of the YZSZ,precluding a comprehensive understanding of this lithological type.In this paper,we present detailed studies of petrology,mineral,whole-rock geochemistry and phase equilibrium modeling on a suite of newly recognized rodingites within the Purang ophiolite massif in the southwestern part of the YZSZ.The rodingites have a major metasomatic mineral association of chlorite,clinozoisite,amphibole and minor amounts of plagioclase,representing products of an early-stage rodingitization.They generally present compositions of low SiO2(48.89 wt.%–53.57 wt.%),Fe2O3^T(3.77 wt.%–5.56 wt.%),Na2O(1.31 wt.%–1.93 wt.%),Al2O3(4.78 wt.%–8.84 wt.%),moderate CaO(9.69 wt.%–11.23 wt.%),and high MgO(24.11 wt.%–26.08 wt.%)concentrations with extremely high Mg^# values[Mg^#=100×Mg/(Mg+Fe^2+)molar]of 89–92.Bulk-rock recalculation reveals that the rodingites have a protolith of mantle-derived olivine gabbro or gabbronorite.They have low rare earth element compositions(∑REE=2.4 ppm–6.5 ppm)and are characterized by flat LREE and slightly enriched HREE patterns with positive Eu anomalies;they also exhibit positive anomalies in Sr,U and Pb and negative anomalies in high-field strength elements,including Nb,P and Ti,suggesting for a subduction-zone imprinting.Phase equilibrium modeling shows that the rodingitization did take place at P<2 kbar and T=~350–400℃,consistent with low greenschist facies conditions.Taking

关键词： Purang ophiolite complex early-stage rodingitization geochemistry phase equilibrium modeling western Tibet

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma

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World Journal of Gastroenterology 2014年第47期20卷 17883-17893页

作者： Xue Xu Lin Feng Yu Liu Wei-Xun Zhou Ying-Cai Ma Gui-Jun Fei Ning An Yuan Li Xi Wu Fang Yao Shu-Jun Cheng Xing-Hua Lu Department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical College Graduate School of Peking Union Medical College and Chinese Academy of Medical Science State Key Laboratory of Molecular Oncology Cancer Institute HospitalPeking Union Medical CollegeChinese Academy of Medical Sciences Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical College Department of Gastroenterology Qinghai Provincial People’s Hospital

AIM:To investigate the differentiated whole genome expression profiling of gastric high-and low-grade intraepithelial neoplasia and early-stage adenocarcinoma.METHODS:Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013.Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia(LGIN),20 high-grade intraepithelial neoplasia(HGIN),19 early-stage adenocarcinoma(EGC),and 19 chronic gastritis tissue samples using Agilent 4×44K Whole Human Genome microarrays.Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm.A gene ontology(GO)enrichment analysis was performed using the Gene Spring software GX 12.6.The differentially expressed gene was verified using a real-time TaqManPCR assay with independent tissue samples,including 26 LGIN,15 HGIN,14 EGC,and 20 chronic gastritis.The expression of G0S2 were further validated by immunohistochemical staining(IHC)in 24 LGIN,40 HGIN,30 EGC and 61 chronic gastritis specimens.RESULTS:The gene expression patterns of LGIN and HGIN tissues were distinct.There were 2521 significantly differentially expressed transcripts in HGIN,with951 upregulated and 1570 downregulated.A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism,defense response,and nuclear factorκB(NF-κB)cascade.While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues,only 38 transcripts were upregulated in EGC.A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC.It is worth noting that,compared with LGIN,289 transcriptswere expressed at higher levels both in HGIN and EGC.A characteristic gene,G0/G1 switch 2(G0S2)was one of the 289 transcripts and related to metabolism,the immune response,and the

关键词： Gastric early-stage adenocarcinoma Highand low-gra

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

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World Journal of Gastroenterology 2016年第33期22卷 7431-7439页

作者： Atsuo Shida Norio Mitsumori Hiroshi Nimura Yuta Takano Taizou Iwasaki Muneharu Fujisaki Naoto Takahashi Katsuhiko Yanaga Department of Surgery Jikei University School of Medicine

Accurate prediction of lymph node(LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer(EGC). However,consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search,we identified several independent variables associated with LN metastasis in EGC,which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand,even if we use these promising parameters,we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN(SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review,we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition,we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

关键词： early-stage gastric cancer Sentinel node navigation surgery Prediction of lymph node metastasis

Postoperative UFT-/Tegafur-based Chemotherapy Versus Postoperative Radiotherapy for early-stage Non-small Cell Lung Cancer:A Systematic Review and Network Meta-analysis

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Journal of Oncology Research 2019年第2期1卷 11-18页

作者： Lixin Yu Mi Song Shuaifei Ji School of basic medicine Air Force Medical UniversityXi’anChina Graduate school general hospital of PLABeijingChina

Background:Both of UFT-/Tegafur-based postoperative chemotherapy and postoperative radiotherapy have made large progress in treatment of early-stage non-small cell lung cancer.While it is unclear that,whether UFT-/Tegafur-based postoperative chemotherapy is superior to postoperative radiotherapy for early-stage non-small cell lung cancer with no direct evidence.Methods:Electronic databases(Pubmed,embase,cochrane library and clinicaltrials.gov)were searched to obtain relevant studies.This systematic review and meta-analysis is reported in accordance with the Preferred Items for Systematic Reviews and Meta-analysis(PRISMA)Statement and was registered at International Prospective Register of Systematic Reviews(number CRD42018095979).Sensitive analysis was conducted by excluding overweight studies.Funnel plot and egger’s test were performed to conduct publication bias.Results:Twenty-one randomized control trials were included.Our results suggested UFT-/Tegafur-based postoperative chemotherapy could improve overall survival over postoperative radiotherapy[HR=0.69(0.59-0.80),p=0.000].But subgroup analysis about stage showed there was no significant difference between them,no matter of stage I,II and III.As to chemotherapy regime,both UFT-/Tegafur+platinum+vinca alkaloid[HR=0.68(0.56-0.82),p=0.000]and UFT-/Tegafur only[HR=0.66(0.54-0.79),p=0.000]were superior to radiotherapy.Subgroup analysis about radiotherapy delivery method and dose showed,significant improvement of chemotherapy over radiotherapy for Cobalt-60 only[HR=0.54(0.39-0.75),p=0.000],Cobalt-60 and linac[HR=0.69(0.59-0.81),p=0.000]and≥45 Gy[HR=0.64(0.54-0.75),p=0.000],but not for linac only[HR=0.78(0.60-1.03),p=0.081]and≥45 Gy[HR=0.86(0.67-1.11),p=0.241].Conclusion:UFT-/Tegafur-based postoperative chemotherapy was superior to postoperative radiotherapy for improving overall survival of early-stage non-small cell lung cancer,but it is not always so under certain circumstance,such as RT delivery method and radiation dose.Of course,it is imperative to further ex

关键词： Chemotherapy Radiotherapy Postoperative early-stage non-small cell lung cancer Meta-analysis

Detection of the <i>PIK3CA</i>Mutation in Circulating Tumor DNA as a Possible Predictive Indicator for Poor Prognosis of early-stage Breast Cancer

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Journal of Cancer Therapy 2018年第1期9卷 42-54页

作者： Ayaka Sato Masahiko Tanabe Yumi Tsuboi Masako Ikemura Keiichiro Tada Yasuyuki Seto Yoshinori Murakami Division of Molecular Pathology Institute of Medical Science The University of Tokyo Tokyo Japan Department of Breast and Endocrine Surgery Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Pathology Graduate School of Medicine The University of Tokyo Tokyo Japan

Objectives: Circulating tumor DNA (ctDNA) is shown to provide the real-time genomic information of metastatic breast cancer. This study elucidates the clinico-pathological significance of ctDNA in early-stage breast cancer using the PIK3CA mutation as an indicator. Materials and Methods: Twenty-seven primary breast cancers without metastasis were surgically resected and pathologically diagnosed at the University of Tokyo Hospital, Japan. Genomic DNA of primary tumor was extracted from formalin-fixed and paraffin-embedded specimens. ctDNA was extracted from fresh-frozen plasma from patients. The PIK3CA mutations at E542K, E545K and H1047R were examined by Sanger sequencing or droplet digital PCR in 27 tumors and pre- and post-surgery plasma. Results: The PIK3CA mutations were detected in 13 (48%) of 27 primary tumors. These mutations did not significantly correlate with specific clinico-pathological characteristics of tumors. When ctDNA was examined, 4 (33%) of 12 cases carrying the mutated PIK3CA showed the identical mutation in pre-surgery plasma and 2 (50%) of them showed the identical mutations in post-surgery plasma. Interestingly, in these 2 cases in pathological stages IIIA and IA, fractional abundance of the mutated PIK3CA alleles to the total alleles in pre-surgery ctDNA was around 1% or more and was higher than that of the other two cases without PIK3CA mutations in post-surgery ctDNA. Conclusions: The PIK3CA mutation in ctDNA is detectable even in a subset of early-stage breast cancer. Furthermore, fractional abundance of the mutated PIK3CA in pre-surgery ctDNA could provide a possible predictive indicator for tumor burden and for choosing the appropriate adjuvant treatment of breast cancer.

关键词： early-stage Breast Cancer PIK3CA Circulating Tumor DNA Plasma Droplet Digital PCR

Comparison of Stereotactic Body Radiotherapy Delivery Techniques for early-stage Lung Cancer Using Lung Toxicity Modeling

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology 2018年第1期7卷 1-14页

作者： Chunhui Han Timothy E. Schultheiss Jeffrey Y. C. Wong Department of Radiation Oncology City of Hope National Medical Center Duarte CA USA

Purpose: Lung toxicity is a primary side effect in stereotactic radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). We aimed to use a set of radiobiological models to evaluate and compare modern IMRT delivery techniques with three-dimensional conformal techniques for SBRT treatment of NSCLC in terms of lung toxicity, and aimed to compare the results from different radiobiologcal models. Methods: Ten early-stage NSCLC patients treated with SBRT were retrospectively selected. Five treatment plans were generated to deliver 50 Gy in five fractions to the planning target volume for each case: a helical tomotherapy (HT) plan, two three-dimensional cofnromal radiotherapy (3D-CRT) plans using 6-MV and 10-MV photon beams respectively, and two volumetric modulated arc therapy (VMAT) plans using one and two arc fields respectively. The lung RDV was calculated with three parallel functional sub-unit (FSU) models and two normal tissue complication probability (NTCP) models. Results: Both the HT and VMAT plans showed significantly higher contralateral mean lung dose and lower ipsilateral mean lung dose compared to the 3D-CRT plans. There was no statistically significant difference in terms of lung toxicities between the IMRT and 3D-CRT techniques using either the FSU models or the NTCP models. Based on both the FSU and the NTCP models, there was strong correlation between lung toxicity and the mean lung dose in SBRT treatment plans. Conclusions: Based on both the NTCP and parallel FSU models, both IMRT and traditional 3D-CRT delivery techniques could achieve comparable lung sparing inn SBRT treatment of early-stage lung cancer. However, the validity of the radiobiological model results should be checked by clinical data.

关键词： early-stage Lung Cancer SBRT Stereotactic Body Radiotherapy Lung Toxicity

Effect of Shenfu injection on microcirculation effect index in early-and middle-stage of cardiogenic shock rats

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中国药理学与毒理学杂志 2017年第10期31卷 990-990页

作者： Li JIANG Lan-bin YU Xiao-Jun YAN Yu CHEN Rong YAO Guo-liang XU Research Center for Differentiation and Development of TCM Basic Theory Jiangxi University of Traditional Chinese Medicine Nanchang 330004 China Jiangxi Provincial Key laboratory of TCM etiopathogenisis Nanchang 330004 China

OBJECTIVE Shenfu injection(SFI)is an effective treatment of cardiogenic shock,the pathology of the central link was microcirculation disturbance.However,whether the microcirculation status of the early-and mid-stage of cardiogenic shock has any difference is unclear.This study aimed to observe the effect of SFI on the microcirculatory disturbance in mesentery for early-and mid-stage of cardiogenic shock rat.METHODS The early-and mid-stage model of cardiogenic shock was established by ligating the ending or root of left anterior descending coronary arteries(LADCA).The rats were randomly divided into 9 groups,ie control group,early-stage model group,mid-stage model group,3 early medicated groups and 3 mid medicated groups(the dosage was 1,3.33,10 mL·kg^(-1) SFI for cardiogenic shock rats of early-and mid-stage,respectively).Parameters in mesenteric microcirculation,such as velocity of RBCs in venules,diameters of venules,the count of leukocyte adhesion and vascular permeability which calculated by FITC-dextran leakage were observed through an GeneandiM2 inverted intravital microscope and high-speed video camera system.RESULTS The cardiogenic shock induced by ligating the LADCA resulted in a number of responses in microcirculation,including a significant increase in the counts of adhesive leukocytes,narrowing of the vascular diameter,decrease in the velocity of RBCs and dextran efflux.All of the above parameters for early-stage cardiogenic shock rats were attenuated by the treatment with SFI,especially the dosage of 10 mL·kg^(-1).While SFI had no apparent time-effect on the vascular diameter and vascular permeability in mesentery for mid-stage cardiogenic shock rats.CONCLUSION The microcirculation status of the early-and mid-stage of cardiogenic shock rats were quite different.The efficacy of early treatment with SFI was more obvious than the mid administration,which could provide experimental and theoretical basis for the patients with cardiogenic shock in an earlier time.

关键词： Shenfu injection microcirculatory early-stage mid-stage cardiogenic shock

Hepatocellular carcinoma extracellular vesicle ECG score as a diagnostic tool close to the ideal

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Hepatobiliary Surgery and Nutrition 2023年第6期12卷 930-932页

作者： Artur Słomka Tudor Mocan Arnulf G.Willms Veronika Lukacs-Kornek Miroslaw T.Kornek Department of Pathophysiology Nicolaus Copernicus University in ToruńLudwik Rydygier Collegium MedicumBydgoszczPoland UBBMed Department Babes-Bolyai UniversityCluj-NapocaRomania Department of Gastroenterology “Prof.Dr.Octavian Fodor”Regional Institute of Gastroenterology and HepatologyCluj-NapocaRomania Department of General and Visceral Surgery German Armed Forces HospitalHamburgGermany Institute of Molecular Medicine and Experimental Immunology University Hospital of the Rheinische Friedrich-Wilhelms-UniversityBonnGermany Department of Internal Medicine I University Hospital of the Rheinische Friedrich-Wilhelms-UniversityBonnGermany

Introduction In recent decades,numerous indicators for early detection and monitoring of hepatocellular carcinoma(HCC)have been suggested and published in reputable journals.These markers have gained recognition and endorsement from prominent international associations such as the European Association for the Study of the Liver(EASL),the Asian Pacific Association for the Study of the Liver(APASL),as well as national professional organizations like the American Association for the Study of Liver Diseases(AASLD),among others.

关键词： Extracellular vesicles(EVs) hepatocellular carcinoma(HCC) early-stage biomarker