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Journal of Molecular Cell Biology 2022年第1期14卷 47-55页

作者： Qiansen Zhang Jie Fu shaoying Zhang Peipei Guo shĳie Liu Juwen shen Jiangtao Guo huaiyu Yang shanghai Key Laboratory of Regulatory Biology Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Biophysics and Department of Pathology of Sir Run Run shaw hospital Zhejiang University School of MedicineHangzhou 310058China

Two-pore domain potassium (K2P) channels gate primarily within the selectivity filter, termed ‘C-type’ gating. Due to the lack of structural insights into the nonconductive (closed) state, ‘C-type’ gating mechanisms remain elusive. here, molecular dynamics (md) simulations on TREK-1, a K2P channel, revealed that M4 helix movements induce filter closing in a novel ‘deeper-down’ structure that represents a ‘C-type’ closed state. The ‘down’ structure does not represent the closed state as previously proposed and instead acts as an intermediate state in gating. The study identified the allosteric ‘seesaw’ mechanism of M4 helix movements in modulating filter closing. Finally, guided by this recognition of K2P gating mechanisms, md simulations revealed that gain-of-function mutations and small-molecule activators activate TREK-1 by perturbing state transitions from open to closed states. Together, we reveal a ‘C-type’ closed state and provide mechanical insights into gating procedures and allosteric regulations for K2P channels.

关键词： K2P state selectivity filter C-type gating

Toward dental caries: Exploring nanoparticle-based platforms and calcium phosphate compounds for dental restorative materials

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Bioactive Materials 2019年第1期4卷 43-55页

作者： Abdulrahman A.Balhaddad Anmar A.Kansara Denise hidan Michael D.Weir hockin h.K.Xu mary Anne S.Melo Ph.D.Program in Biomedical Sciences University of Maryland School of DentistryBaltimoreMD21201USA Division of Biomaterials&Tissue Engineering Department of Advanced Oral Sciences and TherapeuticsUniversity of Maryland School of DentistryBaltimoreMD21201USA Department of Restorative Dental Sciences Imam Abdulrahman Bin Faisal UniversityCollege of DentistryDammamSaudi Arabia Department of Restorative Dentistry Umm Al-Qura UniversityCollege of DentistryMakkahSaudi Arabia Division of Operative Dentistry Dept.of General DentistryUniversity of Maryland School of DentistryBaltimoreMD21201USA

Millions of people worldwide suffer from a toothache due to tooth cavity,and often permanent tooth *** caries,also known as tooth decay,is a biofilm-dependent infectious disease that damages teeth by minerals loss and presents a high incidence of clinical restorative polymeric fillings(tooth colored fillings).Until now,restorative polymeric fillings present no *** complexity of oral biofilms contributes to the difficulty in developing effective novel dental *** has been explored in the development of bioactive dental materials to reduce or modulate the activities of caries-related ***-structured platforms based on calcium phosphate and metallic particles have advanced to impart an anti-caries potential to restorative *** bioactivity of these platforms induces prevention of mineral loss of the hard tooth structure and antibacterial activities against caries-related *** has been suggested that this bioactivity could minimize the incidence of caries around restorations(CARS)and increase the longevity of such filling *** last few years witnessed growing numbers of studies on the preparation evaluations of these novel ***,the caries disease process and the role of pathogenic caries-related biofilm,the increasing incidence of CARS,and the recent efforts employed for incorporation of bioactive nanoparticles in restorative polymer materials as useful strategies for prevention and management of caries-related-bacteria are *** highlight the status of the most advanced and widely explored interaction of nanoparticle-based platforms and calcium phosphate compounds with an eye toward translating the potential of these approaches to the dental clinical reality.

关键词： Dental materials Bioactive Nanoparticles Dental caries

The Contribution of Linear Growth Components to hypertension in Secondary School Adolescents in an Urban Setting in Cameroon

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Journal of Biosciences and Medicines 2022年第12期10卷 151-166页

作者： Loveline Lum Niba Lifoter Kenneth Navti Afahnwi Alvine Takem mary Bi Suh Atanga Department of Public health The University of Bamenda Bambili Cameroon Nutrition and health Research Group (NhRG) Bamenda Cameroon Department of Biochemistry The University of Bamenda Bambili Cameroon Department of Nursing and Midwifery The University of Bamenda Bambili Cameroon

Background: Components of height have been found to be positively associated with blood pressure (BP) both in developed and developing nations. however, amongst Cameroon secondary school adolescents, the relationship between heights, sh and sh.h.with BP has rarely been studied. The purpose of this study was to determine the proportion of secondary school adolescents with elevated BP and high BP and to evaluate the relationship between the different components of linear growth with BP. Methods: An institution-based cross-sectional study involving 602 adolescents (399 girls and 203 boys, mean age 14.9 ± 2.3 years) attending some public and private secondary schools in the Bamenda municipality of the North West Region of Cameroon. Anthropometric and BP measurements were carried out following standard procedures. Pearson correlation and linear regression were used to determine the relationship between the various components of height (height, sh, sh.h. with BP amongst the children. Results: The overall prevalence of elevated BP and hypertension amongst the study participants was 21.9% and 15.6% respectively (with 8.3% and 7.3% of the hypertensive children in Stage I and Stage II respectively). however, there were no significant gender differences in the prevalence of elevated BP and high BP (p = 0.497). Girls had a significantly (p Conclusion: This study has demonstrated that height was positively associated with SBP amongst children and adolescents. Thus, height can be used in predicting adolescents with a high risk of developing high BP in our setting.

关键词： Linear Growth Components hypertension Secondary School Adolescents Cameroon

东莨菪碱透皮贴剂：可替代昂丹司琼和氟哌利多用于预防手术后呕吐症状的新制剂

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麻醉与镇痛 2008年第1期4卷 64-69页

作者： Patti F. White, PhD, md Jun Tang, md Dajun Song, md, PhD Jayne E. Coleman, md Ronald h. Wender, md Babatunde Ogunnaike, md Alexander Sloninsky, md Rajani Kapu, md mary sh.h. md Tom Webb, md 潘明(译) 王多友(校) Department of Anesthesiology and Pain Management University of Texas Southwestern Medical Center at Dallas Dallas Texas Department of Anesthesiology Cedars Sinai Medical Center in Los Angeles Los Angeles California 不详

背景鉴于对使用氟哌利多的争议和5-hT3受体拮抗剂的高昂价格，人们期望出现一种效价合理、可常规用于预防呕吐的药物来替代它们。我们设计了两个平行、随机、双盲、空白和安慰剂对照研究来比较东莨菪碱透皮贴剂（TDS）1．5mg和静脉注射... 详细信息

背景鉴于对使用氟哌利多的争议和5-hT3受体拮抗剂的高昂价格，人们期望出现一种效价合理、可常规用于预防呕吐的药物来替代它们。我们设计了两个平行、随机、双盲、空白和安慰剂对照研究来比较东莨菪碱透皮贴剂（TDS）1．5mg和静脉注射昂丹司琼4mg及氟哌利多1．25mg作为多模式给药方案的一部分，对手术后呕吐“高危”人群早期和晚期的止吐效果及其副作用。方法150例患者参与本研究，其中包括腹腔镜手术（n=80）和整形外科手术（n=70）。患者入手术室前60分钟接受一枚有效的TDS贴剂（含东莨菪碱1．5mg）或一个外表相同的空白贴片。所有患者均接受标准全身麻醉。第2次给药是在手术接近结束时给予患者静脉注射2ml生理盐水（TDS贴剂的两组）、氟哌利多1．25mg或昂丹司琼4mg（空白贴片组）。记录患者手术后恶心、呕吐／干呕的发生率、是否需要止吐药物治疗、用药后的完全有效率（即用药后既无迁延性恶心亦无反复发生呕吐，无需使用止吐药物进行治疗）。此外，对手术后72小时之内的视觉紊乱、口干、昏睡和烦躁不安等不良反应进行记录。结果手术后72小时内，TDS贴剂组、氟哌利多组和昂丹司琼组患者呕吐和需要止吐药物治疗的患者差异无显著性。各治疗组中完全有效率为41％-51％，各组间差异无显著性。TDS组口干的发生率显著高于氟哌利多组和昂丹司琼组（21％vs3％）。结论TDS贴剂作为手术前给药用于预防手术后早期和晚期恶心、呕吐与氟哌利多1．25mg或昂丹司琼4mg效果相同，但是TDS贴剂更易引起口干。

关键词：手术后呕吐透皮贴剂氟哌利多呕吐症状昂丹司琼东莨菪碱预防 5-hT3受体拮抗剂

Guanidine derivative inhibits C. albicans biofilm growth on denture liner without promote loss of materials’ resistance

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Bioactive Materials 2020年第2期5卷 228-232页

作者： Isadora Martini Garcia Stéfani Becker Rodrigues Maria Eduarda Rodrigues Gama Vicente Castelo Branco Leitune mary Anne Melo Fabrício Mezzomo Collares Dental Materials Laboratory Postgraduate Program in DentistrySchool of DentistryFederal University of Rio Grande Do SulRua Ramiro Barcelos2492Rio Branco90035-003Porto AlegreRSBrazil Ph.D.Program in Biomedical Sciences University of Maryland School of DentistryBaltimoreMD21201USA Operative Dentistry Division General Dentistry Department University of Maryland School of DentistryBaltimoreMD21201USA

To reduce the burden of denture stomatitis and oral candidiasis,an aqueous solution containing polyhexamethylene guanidine hydrochloride(PhMGh)was investigated as an antifungal disinfectant against the leading cause of these oral conditions,Candida *** solutions formulated with concentrations ranging from 0.125 to 0.50 wt%enabled increasing disinfection at the initial 5min-contact with 72h-mature candida biofilms formed on denture liner *** 10 min-contact,the solution at lower concentration has reached total fungal *** results also indicated that the denture liners preserved their mechanical property after the maximum contact time with the solution at the highest tested *** PhMGh aqueous solutions at 0.125 wt%could be applied to promote interim denture liner disinfection without promoting the loss of materials’mechanical property.

关键词： Dental materials Guanidine Antifungal agents Candidiasis Denture liner

雌激素替代疗法治疗轻到中度Alzheimer病：随机对照试验

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美国医学会杂志（中文版） 2000年第6期19卷 282-290页

作者： Ruth A. Mulnard, RN, DNSc Anthony Gamst, PhD Michael Grundman, md,MPh Ronald Thomas, PhD Leon J. Thal, md Alzheimer病协作组 Carl W. Cotman, PhD Claudia Kawas, md Christopher h. van Dyck, md mary Sano, PhD Rachelle Doody, md, PhD Elizabeth Koss, PhD Eric Pfeiffer, md shelia Jin, md, MPh

背景：几项小型临床试验提示雌激素替代疗法可能有助于女性Alzheimer病（AD）患者的治疗。　　目的：确定雌激素替代疗法能否改善轻到中度女性AD患者总体功能、认知或日常生活能力。　　设计：Alzheimer病协作组于1995年10月至1999年1... 详细信息

背景：几项小型临床试验提示雌激素替代疗法可能有助于女性Alzheimer病（AD）患者的治疗。　　目的：确定雌激素替代疗法能否改善轻到中度女性AD患者总体功能、认知或日常生活能力。　　设计：Alzheimer病协作组于1995年10月至1999年1月进行的一项随机、双盲、安慰剂对照临床试验。　　参加单位：美国32个研究中心。　　受试对象：总共120例轻到中度女性AD患者。细微精神状态检查评分介于12～28分间，既往已行子宫切除术。　　干预：受试者随机服用雌激素0.625 mg/d（n=42）、1.25 mg/d（n=39）或者剂型相同的安慰剂（n=39）。1例患者于随机后接受药物治疗前退出试验；97例完成试验。　　主要结果评定：主要结果评定指标为临床整体印象的改变（CGIC），分值为7分，采用意向治疗(intent-to-treat)分析。次要指标包括其他总评估以及情绪、特殊认知功能（记忆、注意力和语言）、运动功能和日常生活能力；于随访 2、6、12和15个月时，对雌激素组与安慰剂组进行比较。　　结果：雌激素组与安慰剂组CGIC评分为5.1比5.0 (P=0.43)；雌激素组80%的患者恶化，而安慰剂组74%恶化(P=0.48)。除临床痴呆评分提示雌激素组恶化外(雌激素组与安慰剂组相比治疗后平均变化为0.5比0.2，P=0.01)，两组次要结果指标无显著差异。　　结论：雌激素替代治疗1年不能延缓轻、中度女性AD患者病情的进展，整体功能、认知和功能预后亦无改善。研究结果不支持雌激素对这种疾病有治疗作用的结论。雌激素对AD的潜在预防作用尚需进一步研究。

关键词：早老性痴呆雌激素替代疗法

Genome-wide antagonism between 5-hydroxymethylcytosine and DNA methylation in the adult mouse brain

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Frontiers in Biology 2014年第1期9卷 66-74页

作者： Junjie U. GUO Keith E. SZULWACh Yijing SU Yujing LI Bing YAO Zihui XU Joo heon sh1N Bing XIE Yuan GAO Guo-li MING Peng JIN hongjun SONG Institute for Cell Engineering Johns Hopkins University School of Medicine Baltimore MD 21205 USA The Solomon h. Snyder Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 USA Department of Neurology Johns Hopkins University School of Medicine Baltimore MD 21205 USA. Department of human Genetics Emory University School of Medicine 615 Michael Street Atlanta GA 30322 USA Lieber Institute for Brain Development Johns Hopkins University School of Medicine Baltimore MD 21205 USA

Mounting evidence points to critical roles for DNA modifications, including 5-methylcytosine （5mC） and its oxidized forms, in the development, plasticity and disorders of the mammalian nervous system. The novel DNA base 5- hydroxymethylcytosine （5hmC） is known to be capable of initiating passive or active DNA demethylation, but whether and how extensively 5hmC functions in shaping the post-mitotic neuronal DNA methylome is unclear. here we report the genome-wide distribution of 5hmC in dentate granule neurons from adult mouse hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene bodies, especially in exons, and correlates with gene expression. Direct genome-wide comparison of 5hmC distribution between embryonic stem cells and neurons reveals extensive differences, reflecting the functional disparity between these two cell types. Importantly, integrative analysis of 5hmC, overall DNA methylation and gene expression profiles of dentate granule neurons in vivo reveals the genome-wide antagonism between these two states of cytosine modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome by promoting active DNA demethylation.

关键词： dentate granule neuron active DNA demethylation TET methylome

雌孕激素联合疗法与静脉血栓形成风险之间的关系

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美国医学会杂志（中文版） 2006年第1期25卷 43-43页

作者： mary Cushman, md, MSc Lewis h, Kuller, md Ross Prentice, PhD 顾佳（译）

背景：绝经后激素特代疗法能增加静脉中血栓形成的危险。目前，尚不清楚影响血栓形成的其他因素是否会进一步增加其危险性。目的：妇女健康启动项目之雌孕激素联合疗法临床试验（Women’s health Initiative Estrogen Plus Progestin）... 详细信息

背景：绝经后激素特代疗法能增加静脉中血栓形成的危险。目前，尚不清楚影响血栓形成的其他因素是否会进一步增加其危险性。目的：妇女健康启动项目之雌孕激素联合疗法临床试验（Women’s health Initiative Estrogen Plus Progestin）观察了静脉血栓的发病率以及存在其他血栓形成危险因素时激素替代疗法与静脉血栓形成之间的关系，现报道其最终数据资料。设计、地点及参试者：16608名50一79岁绝经后妇女纳入本随机、双盲、对照试验，她们于1993～1998年在美国40所临床中心接受了随访，为期5．6年。采用窠式病例对照研究，在基线时测定的147例女性血栓患者及513例对照者基因变异情况，这些基因变异均与血栓形成有关。干预：参试者随机分配0．625mg／d妊马雌酮（conjugated equine estrogen）＋2．5mg／d安宫黄体酮（medroxyprogesterone acetate）或安慰剂。主要观察指标：经证实的中央型深静脉血栓和肺栓塞。结果：167例联合应用雌孕激素者（3．5／1000人-年）及76例服用安慰剂者（1．7／1000人-年）出现静脉血栓；风险比（hazard ratio，hR）为2．06（95％可信区间[confidence interval，CT]，1．57—2．70）。激素替代疗法的危险性随患者年龄的增加而增加：与50-59岁服用安慰剂的妇女相比，60～69岁妇女的hR为4．28（95％CI，2．38～7．72），70—79岁妇女的hR为7．46（95％CI，4．32～14．38）。与服用安慰剂组体重正常的妇女相比，超重及肥胖妇女联合应用雌孕激素后相关危险性增加：hR分别为3．80（95％CI，2．08～6．94）和5．61（95％CI，3．12—10．11）。与安慰剂组未出现基因突变的妇女相比，凝血因子V基因的Leiden位点发生突变使激素诱发血栓形成的危险升高6．69倍（95％CI，3．09—14．49）。其他基因变异（凝血酶原基因20210A、甲基四氢叶酸还原酶基因C677T、凝血因子XⅢ基因Val34Leu、纤溶酶原激活剂抑制物1基因4G／5G、凝血因子VhR2）并不影响激素替代疗法与静脉血栓形成之间的父系。结论：雌孕激系联合疗法使患者发生静脉血栓的危险增加一倍。患者年龄较大、超重、肥胖、凝血因子V基因的Leiden位点发生突变均能增加雌孕激素联合疗法的危险。

关键词：静脉血栓形成雌孕激素联合疗法风险比凝血因子V基因纤溶酶原激活剂抑制物激素替代疗法甲基四氢叶酸还原酶 interval Val34Leu

Application of single and combination therapy of clarithromycin and tamoxifen to suppress breast cancer cell proliferation and metabolism

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中华乳腺病杂志（电子版） 2012年第1期6卷 26-31页

作者： Wings T.Y.Loo Louis W.C.Chow Adrian Y.S Yip mary N.B.Cheung UNIMED Medical Institute Organization for Oncology and Translational Research Hong Kong Organization for Oncology and Translational Research School of Chinese Medicine Li Ka Shing Faculty of MedicineUniversity of Hong Kong Clinical Trial Center Li Ka Shing Faculty of MedicineUniversity of Hong Kong

Objective This study compares the anti-tumor effects of single and combination use of clarithromycin and tamoxifen on estrogen receptor (ER) positive breast cancer cell lines,BT-483 and MCF-7 as well as triple negative cell line,MBA-md-231,which acts as a negative *** effect of solid breast tumor inhibition by clarithromycin is also *** BT-483,MCF-7 and MBA-md-231 were cultured in 6-well plates in a 37 ℃ humidified incubator without CO2 for 24 h prior to the addition of the test *** test groups were clarithromycin (Group 1),tamoxifen (Group 2),clarithromycin and tamoxifen (Group 3),and control (Group 4).Group 3 was prepared in 1 to 1 ratio at a concentration of 1.5 mmol/L clarithromycin and 25 μmol/L *** the other hand,1 mm3 solid breast tumors were submerged into various groups as above for 24 *** the harvest day,the proliferation of cancer cells and solid breast tumor samples were measured by WST-1 proliferation reagent while ATP bioluminescence assay was employed to measure the metabolic rate of the three cell *** The proliferation of BT-483 and MCF-7 was suppressed most by combination use of clarithromycin and tamoxifen with statistical *** two drugs did not have an inhibitory effect on the hormonal negative cancer *** solid breast tumor samples,all the test groups showed reduced metabolic rate as compared with the control group (Phromycin are effective in suppressing cell proliferation and metabolism rate of breast cancer cells while single use of clarithromycin effectively inhibits the proliferation of solid breast tumor.

关键词：摘要编辑部编辑工作读者

human hematopoietic cells express two forms of thecytokine receptor common γ-chain (γc)

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Cell Research 1997年第2期7卷 195-205页

作者： shI YU FANG mary hILL ANTON NOVAK ZhIQING ChEN RUO XIANG WANG ChOONGChIN LIEW GORDON B. MILLS (Oncology Research, The Toronto hospital, 200 ElizabcthSt., Toronto, Ontario, Canada MSG 2C4Department of Immunology, holland Laboratoryof American Red Cr Oncology Research The Toronto Hospital Toronto Canada Department of Immunology Holland Laboratory of American Red Cross Rockville USA Department of Genetics Research Institute The Hospital for Sick Children Toronto Canada Department of Clinical Biochemistry University of Toronto Toronto Canada Department of Molecular Oncology MD Anderson Cancer Center University of Texas Houston

Recent studies have revealed that the γ-chain of theIL-2 receptor is shared by the receptors for IL-4, IL7, IL-9, IL-13, and IL-15, and it is therefore also referred toas the common γ-chain (γc). Mutations of γc result inX-linked severe combined immunodeficiency syndrome inhumans, indicating that rye is essential for normal development and function of the immune system. We demonstratethat human hematopoietic cells express two γc transcriptsdiffering in their carboxyl terminal coding region. Onetranscript is the previously reported sequence (γc-long),whereas the newly identified sequence exhibits a deletion of72 nucleotides close to the 3'-end of the open reading frame(γc-short). This alteration predicts a loss of 24 amino acidsincluding a conserved tyrosine residue which is shared byseveral members of the cytokine receptor family. Thepresence of these two distinct forms of rye transcripts wasdemonstrated by sequencing of reversely transcribed andpolymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines andhuman peripheral blood lymphocytes. Furthermore, thetwo variants were present in peripheral blood lymphocytesfrom both female and male donors, which rules out allelicvariants since rye is a single copy gene located on the Xchromosome. A truncation mutant at a site near the observed changes in γc-short has been reported by othersto alter biochemical events activated by cytokines. Thiscombined with the loss of a potential sh2 "docking" sitein γc-short suggests that γc-long and γc-short may link todifferent signaling pathways and may play an importantrole in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.

关键词： IL-2 receptor γ-chain cytokine receptor common γ-chain IL-2 receptor cytokine receptors RNA splicing