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Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas

World Journal of Gastroenterology 2010年第10期16卷 1201-1208页

作者： Yoshimitsu Akiyama Department of Molecular Oncology Graduate School of Medicine and DentistryTokyo Medicaland Dental University

AIM:To understand the implication of GATA-4 and GATA-5 methylation in gastric ***: Methylation status of GATA-4 and GATA-5 CpG islands in human gastric mucosa samples, including normal gastric biopsies from 45 outpatients, gastric dysplasia [low-grade gastric intraepithelial neoplasia (GIN), n = 30; indefinite, n = 77], and 80 paired spo- radic gastric carcinomas (SGC) as well as the adjacent non-neoplastic gastric tissues was analyzed by methylation specific polymerase chain reaction (MSP) and confirmed by denatured high performance liquid chromatography (DHPLC). Immunohistochemical staining was used to detect protein expression. The correlation between GATA-4 and GATA-5 methylation and clinicopathological characteristics of patients including Helicobacter pylori (H. pylori) infection was ***:GATA-4 and GATA-5 methylation was frequently observed in SGCs (53.8% and 61.3%, respectively) and their corresponding normal tissues (41.3% and 46.3%) by MSP. The result of MSP was consistent with that of DHPLC. Loss of both GATA-4 and GATA-5 proteins was associated with their methylation in SGCs (P = 0.01). Moreover, a high frequency of GATA-4 and GATA-5 methylation was found in both gastric low-grade GIN (57.1% and 69.0%) and indefinite for dysplasia (42.9% and 46.7%), respectively. However, GATA-4 and GATA-5 methylation was detected only in 4/32 (12.5%) and 3/39 (7.7%) of normal gastric biopsies. GATA-4 methylation in both normal gastric mucosa and low-grade GIN was also significantly associated with H. pylori infection (P=0.023 and 0.027, two-sides).CONCLUSION: Epigenetic inactivation of GATA-4 (and GATA-5) by methylation of CpG islands is an early freuent event during gastric carcinogenesis and is significantly correlated with H. pylori infection.

关键词： Dysplasia Gastric carcinoma GATA-4 GATA-5 Helicobacter pylori Methylation

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Effects of electroacupuncture on the functionality of NG2-expressing cells in perilesional brain tissue of mice following ischemic stroke

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Neural Regeneration Research 2022年第7期17卷 1556-1565页

作者： Hong Ju Lee Da Hee Jung Nam Kwen Kim Hwa Kyoung Shin Byung Tae Choi Department of Korean Medical Science School of Korean MedicinePusan National UniversityYangsanRepublic of Korea graduate Training program of Korean medicine for Healthy Aging Pusan National UniversityYangsanRepublic of Korea Department of Korean Ophthalmology Otolaryngology and DermatologySchool of Korean MedicinePusan National UniversityYangsanRepublic of Korea

Neural/glial antigen 2(NG2)-expressing cells has multipotent stem cell activity under cerebral *** study examined the effects of electroacupuncture(EA)therapy(2 Hz,1 or 3 mA,20 minutes)at the Sishencong acupoint on motor function after ischemic insult in the brain by investigating the rehabilitative potential of NG2-derived cells in a mouse model of ischemic *** stimulation alleviated motor deficits caused by ischemic stroke,and 1 mA EA stimulation was more efficacious than 3 mA EA stimulation or positive control treatment with edaravone,a free radical *** properties of NG2-expressing cells were altered with 1 mA EA stimulation,enhancing their survival in perilesional brain tissue via reduction of tumor necrosis factor alpha *** stimulation robustly activated signaling pathways related to proliferation and survival of NG2-expressing cells and increased the expression of neurotrophic factors such as brain-derived neurotrophic factor,tumor growth factor beta,and neurotrophin *** the perilesional striatum,EA stimulation greatly increased the number of NG2-expressing cells double-positive for oligodendrocyte,endothelial cell,and microglia/macrophage markers(CC1,CD31,and CD68).EA therapy also greatly activated brain-derived neurotrophic factor/tropomyosin receptor kinase B and glycogen synthase kinase 3 beta *** results indicate that EA therapy may prevent functional loss at the perilesional site by enhancing survival and differentiation of NG2-expressing cells via the activation of brain-derived neurotrophic factor-induced signaling,subsequently ameliorating motor *** animal experiments were approved by the Animal Ethics Committee of Pusan National University(approval ***2019-2199 and PNU2019-2884)on April 8,2019 and June 19,2019.

关键词： brain-derived neurotrophic factor differentiation electroacupuncture motor function neural/glial antigen 2 perilesional striatum stroke survival

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Study of the safety of oral Triphala aqueous extract on healthy volunteers

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Journal of Integrative medicine 2020年第1期18卷 35-40页

作者： Pratya Phetkate Tanawan Kummalue Prasob-orn Rinthong Somboon Kietinun Kusuma Sriyakul graduate program in Integrative medicine Chulabhorn International College of MedicineThammasat UniversityPathum Thani 12120Thailand Department of Clinical Pathology Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Pharmaceutical Chemistry and Natural Products Research Unit Faculty of PharmacyMahasarakham UniversityMaha Sarakham 44150Thailand

Background:Triphala extract is a well known medicinal herbal formula which is usually prescribed by Thai traditional doctors to adjust the physiological functions of the *** studies have reported that Triphala has antioxidant,anti-inflammatory,antihypercholesterolemia and anticancer *** this herbal recipe is commonly used in Thailand,its human safety,especially in the oral form,has not been *** therefore conducted a clinical trial(Phase I).Objective:This study evaluated the safety of administering the aqueous extract of Triphala to healthy volunteers at 2500 mg/***,setting,participants and interventions:An open-label,single-arm trial was conducted at Chulabhorn International College of medicine,Thammasat University,Pathum Thani,Thailand,between July 2017 and July *** study enrolled 10 male and 10 female healthy volunteers;all were given Triphala(water extract;five capsules of 500 mg each)orally,once a day,at bedtime,for four consecutive *** outcome measures:Signs and symptoms,physical examinations,hematology and blood chemistry were assessed at the beginning of the trial and every week thereafter,for four consecutive *** finishing the trial,on day 28,all volunteers were invited to a follow-up session on day 35 to evaluate the safety of the herbal recipe using the same ***:At the oral dose of 2500 mg/d,Triphala had no serious adverse effects in healthy ***,it was found to have significantly improved the volunteers’high-density lipoprotein cholesterol(HDL-C)levels on day 35 and also reduced their blood sugar levels on days 14 and ***:We conclude that aqueous extract of Triphala is safe for healthy volunteers and that it elevates HDL-C levels and lowers blood *** clinical study should investigate its effects on HDL-C and blood sugar levels among the dyslipidemic and prediabetic *** registration:This trial was registered in the Thai Clinical Trial Regis

关键词： Triphala Clinical trial Safety Healthy volunteers

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Prognostic angiogenic markers(endoglin, VEGF, CD31) and tumor cell proliferation(Ki67) for gastrointestinal stromal tumors

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World Journal of Gastroenterology 2015年第22期21卷 6924-6930页

作者： Rodrigo Panno Basilio-de-Oliveira Vera Lucia Nunes Pannain Pathology Post-graduate program Federal University of Rio de Janeiro Department of Pathology and Clinical Support Federal University of Rio de Janeiro State Department of Pathology Pathology Post-Graduate Program Federal University of Rio de Janeiro

AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor(VEGF)], proliferative index(Ki67), and prognosis of patients with gastrointestinal stromal tumors(GIST).METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin(CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density(IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF,Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5%positive cells. The prognosis was classified as good(patient alive without recurrence) or poor(patient with recurrence/death).RESULTS: The distribution of tumor sites among the54 analyzed samples was as follows: 27(50%) in the stomach, 20(37.1%) in the small intestine, 6(11.1%)in the colon, and 1(1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm(median: 8cm); in 12 cases(22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases(77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis(P 1.2%) and CD31(> 2.5%) in the receiver-operating characteristic curve were related to a poorer *** with a better prognosis showed significantly null/weak staining for VEGF(P < 0.001). Ki-67 expression of≥ 5% was strongly correlated with a worse prognosis(P< 0.001). In the multivariate analysis, C

关键词： Angiogenesis Immunohistochemistry,CD105 CD31 Gastrointestinal stromal tumors Vascularendothelial growth factor Ki-67

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Targeting multiple signaling pathways:the new approach to acute myeloid leukemia therapy

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Signal Transduction and Targeted Therapy 2021年第1期6卷 41-69页

作者： Jenna LCarter Katie Hege Jay Yang Hasini AKalpage Yongwei Su Holly Edwards Maik Hüttemann Jeffrey WTaub Yubin Ge Cancer Biology graduate program Wayne State University School of MedicineDetroitMIUSA MD/PhD program Wayne State University School of MedicineDetroitMIUSA Department of Oncology Wayne State University School of MedicineDetroitMIUSA Molecular Therapeutics program Barbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitMIUSA Center for Molecular medicine and Genetics Wayne State University School of MedicineDetroitMIUSA National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and EngineeringThe Ministry of EducationSchool of Life SciencesJilin UniversityChangchunChina Division of Pediatric Hematology/Oncology Children’s Hospital of MichiganDetroitMIUSA Department of Pediatrics Wayne State University School of MedicineDetroitMIUSA

Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in *** this,very little improvement in survival rates has been achieved over the past few *** is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 *** the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and *** we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc *** has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML *** addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival *** also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC *** comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.

关键词： myeloid approach approval

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Analysis of spatial distribution characteristics and driving factors of ethnicminority villages in China using geospatial technology and statistical models

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Journal of Mountain Science 2024年第8期21卷 2770-2789页

作者： SHAO Dandan ZOH Kyungjin Interdisciplinary program in Landscape Architecture Graduate School of Environmental StudiesSeoul National UniversitySeoul 08826Korea graduate School of Environmental Studies Seoul National UniversitySeoul 08826Korea

This study aims to reveal the spatial structural characteristics of 1,652 Ethnic-Minority Villages(EMV)in China and to analyze the mechanisms driving their spatial *** are a special type of settlement space that preserve a large number of historical traces of the ethnic culture of ancient *** are important carriers of China’s excellent traditional culture and are key to the implementation of rural revitalization *** this study,1652 EMV in China were selected as the research *** Nearest Neighbor Index,kernel density,and spatial autocorrelation index were employed to reveal the spatial structural characteristics of minority *** network models,spatial lag models,and geographical detectors were used to analyze the formation mechanism of spatial heterogeneity in *** results indicate that:(1)EMV exhibit significant spatial differentiation characterized by“single-core with multiple surrounding sub-centers,”“polarization between east and west,”“decreasing quantity from southwest to east coast to northeast to northwest,”and“large dispersion with small agglomeration.”(2)EMV are mainly distributed in areas rich in intangible cultural heritage,with high vegetation coverage and low altitude,far from central cities,and having limited arable land and an underdeveloped economy and transportation,particularly in shaded or riverbank areas.(3)Distance from the nearest river(X3),distance from central cities(X8),national intangible cultural heritage(X9),and NDVI(X10)were the main driving factors affecting the spatial distribution of EMV,whereas elevation(X1)and GDP(X5)had the weakest *** EMV are a relatively unique territorial spatial unit,the identification of their spatial heterogeneity characteristics not only deepens the research content of settlement geography,but also involves the assessment,protection,and development of Minority Villages,which is of great significance for the inheritance and utilization of excellent

关键词： Ethnic-Minority Villages Spatial structure Settlement geography Neural network model Spatial econometric model GeoDetector

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Cdx2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus

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World Journal of Gastroenterology 2013年第4期19卷 536-541页

作者： Kenji Makita Riko Kitazawa Shuho Semba Koto Fujiishi Miku Nakagawa Ryuma Haraguchi Sohei Kitazawa Division of Molecular Pathology Ehime University Graduate School of MedicineToon 791-0295Japan Division of Pathology Kobe University Graduate School of MedicineKobe 650-0017Japan

AIM:To examine how the expression of caudal type homebox transcription factor 2(Cdx2) is regulated in the development of malignancy in Barrett's ***:Cdx2,mucin(MUC) series(MUC2,MUC5AC and MUC6),p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by *** clusters of cells from(1) MUC2 and Cdx2-positive intestinal metaplastic mucosa;(2) MUC5AC and MUC6-positive,and MUC2 and Cdx2-negative high-grade dysplasia(HD),or intramucosal adenocarcinoma(IMC);and(3) MUC5AC,MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma(PDA) were analyzed by methylationspecific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 ***:Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin,MUC series and Cdx2,but negative for p53.A portion of the low-grade to HD was positive for E-cadherin,MUC5AC,MUC6 and p53,but negative for MUC2 and *** definite IMC area was strongly positive for MUC5AC,MUC6 and p53,but negative for MUC2 and *** of the Cdx2 promoter was not observed in intestinal metaplasia,while hypermethylation of part of its promoter was observed in hot dipped and *** of a large fraction of the Cdx2 promoter was observed in ***:Cdx2 expression is restored irrespective of the methylation status of its *** positive immunohistochemical results can be a molecular mark for gene silencing memory.

关键词： Barrett ’s esophagus Caudal type homebox transcription factor 2 Intestinal metaplasia Promoter hypermethylation

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An improved flexible tolerance method for solving nonlinear constrained optimization problems:Application in mass integration

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Chinese Journal of Chemical Engineering 2017年第5期25卷 617-631页

作者： Alice Medeiros Lima Wu Hong Kwong Antonio José Goncalves Cruz Chemical Engineering graduate program Federal University of Sao Carlos Department of Chemical Engineering Department of Chemical Engineering Federal University of Sao Carlos

This paper proposes the use of the flexible tolerance method(FTM) modified with adaptive Nelder–Mead parameters and barrier to solve constrained optimization problems. The problems used to analyze the performance of the methods were taken from G-Suite functions, and the methods with the best performance were applied in mass integration problems. Four methods were proposed:(1) flexible tolerance method(FTM) using adaptive parameters(FTMA),(2) flexible tolerance method with scaling(FTMS) and with adaptive parameters(FTMAS),(3) FTMS including the barrier modification(MFTMS) and(4) MFTMS hybridized with PSO(MFTMS-PSO). The success rates of these methods were 100%(MFTMS), 85%(MFTMS-PSO), 40%(FTMAS) and 30%(FTMA).Numerical experiments indicated that the MFTMS could efficiently and reliably improve the accuracy of global optima. In mass integration, the method was able, from current process situation, to reach the optimum process configuration that includes integration issues, which was not possible using FTM in its standard formulation. The hybridization of FTMS with PSO(without barrier), FTMS-PSO, was also able to solve mass integration problems efficiently.

关键词： Flexible tolerance method Adaptive parameters Scaling Constrained optimization Barrier PSO Mass integration

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Targeted tumor coating with antigenic, CTL-recognizable peptides via Annexin A5 chimeric constructs following chemotherapy redirects adaptive CD8+ T cell immunity for tumor clearance

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Cellular & Molecular Immunology 2021年第6期18卷 1578-1580页

作者： Tae Heung Kang Andrew Yang Yachea Tsai Louise Ferrall Chien-Fu Hung Institute of Biomedical Science and Technology Konkuk UniversitySeoulSouth Korea Genetics and Genomics graduate program Baylor College of MedicineHoustonTXUSA Medical Scientist Training program Baylor College of MedicineHoustonTXUSA Department of Pathology Johns Hopkins UniversityBaltimoreMDUSA Department of Oncology Johns Hopkins UniversityBaltimoreMDUSA

A common drawback of many cancer immunotherapies,including immune checkpoint blockade,is their reliance on the expression of immunogenic tumor antigens by cancer cells for immune recognition and clearance,which limits their efficacy against cancers with weak antigenicity.1 To overcome this obstacle,we and others have explored strategies to harness the immune responses against nontumor antigens and redirect those immune responses to target tumor cells.2,3,4,5 In particular,we have pioneered a therapeutic strategy fusing tumor-targeting proteins with known antigenic peptide epitopes not naturally expressed by tumor cells,which are flanked by peptide sequences that can be recognized and cleaved by proteases overexpressed in most cancers.2,3 This strategy facilitates the targeted delivery of immunogenic peptides into tumor foci,the release of immunogenic peptides into the tumor microenvironment(TME)via tumor protease cleavage,and subsequent loading of these peptides onto major histocompatibility complex class 1(MHC-I)on the tumor cell surface,allowing the recognition of coated tumor cells by the respective peptide-specific cytotoxic CD8+T lymphocytes(CTLs)for elimination.

关键词： immunity overcome coating

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Decreased prevalence of celiac disease among Brazilian elderly

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World Journal of Gastroenterology 2013年第12期19卷 1930-1935页

作者： Lucas Malta Almeida Luiz Claudio Castro Rosa Harumi Uenishi Fernanda Coutinho de Almeida Patricia Maria Fritsch Lenora Gandolfi Riccardo Pratesi Yanna Karla de Medeiros Nóbrega graduate program in Medical Sciences University of Brasilia School of Medicin Doctoral fellow of Coordenao de Aperfeioamento de Pessoal de Nível Superior graduate program in Health Sciences University of Brasilia School of Health Sciences Research Center for Celiac disease University of Brasilia School of Medicine Department of Pharmaceutical Sciences University of Brasilia School of Health Sciences Research Center for Celiac Disease University of Brasilia School of Medicine

AIM: To evaluate the prevalence of celiac disease in a group of Brazilian individuals over 60 years of age and compare it with the previously known prevalence in a pediatric group living in the same geographical ***: The research protocol was approved by the Ethics Committee of the University of Brasilia School of medicine, Brasilia, Brazil. Blood samples from 946 individuals (295 male and 651 female) aged 60 years or older were collected between May 2010 and July 2011. The study subjects' mean and median ages were 68.1 and 67 years, respectively, ranging from 60 to 92 years. That age distribution closely corresponded to the age distribution of the Brazilian population according to the Brazilian 2010 census. The participants were consecutive and unselected outpatients undergoing blood tests at the University of Brasilia Hospital's Clinical Pathology Laboratory. All sera were tested for immunoglobulin A anti-transglutaminase antibodies (IgA-tTG) by enzymelinked immunosorbent assay, and those that were positive were further tested for immunoglobulin A antiendomysium antibodies (IgA-EMA). Human leukocyte antigen (HLA) genotyping was performed for all individuals who exhibited positive serologic results for IgA-tTG and/or ***: Out of the 946 studied patients, only one previously diagnosed case of biopsy-proven celiac disease was detected. For the remaining subjects, nine serum samples tested positive for IgA-tTG antibodies; however, none of them tested positive for IgA-EMA antibodies. The HLA genotyping of those nine subjects revealed that one was carrying DQA1*0501 and two were carrying DQB1*0201 alleles. These data showed that, among those 946 elderly individuals, the prevalence of celiac disease (CD) was 0.1% (95%CI: 0.00-0.59). The prevalence of CD for the elderly group was compared with that observed for the group of 2034 children younger than 15 years (age range, 1-14 years; mean age, 8 years) who took part in our previous CD prevalence screen

关键词： Celiac disease Gluten-sensitive enteropathy Epidemiology Elderly Mortality

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