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Journal of cancer Therapy 2013年第3期4卷 787-796页

作者： Huaquan Wang Xianghong chen Erika A. Eksioglu Junmin Zhou Nicole R. Fortenbery julie Djeu Alan List Sheng Wei Hematology Department General Hospital Tianjin Medical University Tianjin China Immunology Program and Malignant Hematology Program Moffitt Cancer Center and Research Institute Tampa USA.

Multiple myeloma (MM) is a plasma cell neoplasm characterized for its fast evolution and for being practically incurable, presenting a strong need for the development of therapies to target it. Among those under study are lenalidomide and arsenic trioxide (ATO) which show individual clinical promise, although never tested together. However, the combination of ATO with thalidomide, another immunomodulatory drug and lenalidomide’s structural albeit less potent analog, have been tried clinically with some success. Therefore, we investigated the effect the combination of lenalidomide and ATO have on the MM-derived U266 and RPMI 8226 cell lines. We observed that both compounds have separate, non-interfering, anti-myeloma mechanisms with ATO demonstrating strong cytotoxic effects while lenalidomide’s role remains cytostatic and immunomodulatory. However, ATO decreases cdc25c, which helps sensitize cells to lenalidomide effects enhancing the efficacy of their interaction. Mechanistically the combination of these two agents decreased the expression of MDM2, without affecting p53 activation or its expression. Therefore, this short study provides the foundation to continue mechanistic studies of the combination of lenalidomide and ATO as a foundation for future clinical application.

关键词： Multiple Myeloma Lenalidomide Arsenic Trioxide cdc25c

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第四纪地质年代学研究的现行趋势

宝石和宝石学杂志(中英文) 1988年第1期 50-52页

作者： julie Brigham-Grette 杜远生

过去十年在测定第四纪沉积物年龄的方法方面取得了巨大进展.新的同位素方法和化学方法现已得到广泛的应用,如放射性碳、裂变径迹、铀趋势法、热释光和氨基酸法,配合氧同位素和古地磁研究,校正地层层序和测定特殊沉积物的年龄.然而,所有... 详细信息

过去十年在测定第四纪沉积物年龄的方法方面取得了巨大进展.新的同位素方法和化学方法现已得到广泛的应用,如放射性碳、裂变径迹、铀趋势法、热释光和氨基酸法,配合氧同位素和古地磁研究,校正地层层序和测定特殊沉积物的年龄.然而,所有这些方法都是有限制的,因而,在正确采用这些年龄测定方法之前,必须了解这一点.

关键词：地质年代学地质学放射性碳年龄 c14年龄同位素地质年龄年龄测定年龄值威斯康星冰期裂变径迹粒子径迹测年

Estimated Binding Energies of Drug-Like and Nondrug-Like Molecules in the Active Site of HIV-1 Integrase, ***, and Two Mutant Models: Y143R and N155H

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Advances in Bioscience and Biotechnology 2017年第5期8卷 163-183页

作者： julie B. Ealy Noorhaan Abouomar Justin cogan Paolo Flauta Liliana Nassar Matthew Mekolochik Sarah Ramzy christopher Shannon Habib Yazgi Penn State Lehigh Valley Center Valley PA USA

Lipinski’s “Rule of Five” was introduced for predicting oral bioavailability to describe drug-like molecules. For the purpose of this research the rules were used to separate potential inhibitors of HIV-1 integrase (***) into two groups: drug-like and nondrug-like. If one of Lipinski’s “Rule of Five” was not followed the potential inhibitor was classified as nondrug-like. Thirty molecules were identified from the literature, twenty-four drug-like and six nondrug-like, that were docked into the active site of *** (considered the non-mutated protein) and two mutant models, Y143R and N155H. These are two of the mutations that have led to increased resistance to HIV-1 integrase drugs such as raltegravir and elvitegravir. The computational software, IcM-Pro (Molsoft L.L.c.), was used to determine the estimated binding energy (EBE) of the drug/protein complex. It was found that the nondrug-like molecules generally had a more negative EBE, that is, tighter binding with 1BIS. pdb, though there were several exceptions in the drug-like group. With the protein mutant model Y143R, the majority of drug-like (58%) and nondrug-like molecules (67%) had tighter binding. However, for the mutant model N155H, there was the same percent (46%) of drug-like molecules with tighter binding with the mutant model as with ***. The drug-like molecules were used when there was a ≥1 kcal/mole difference between *** and either of the two mutant models to suggest a pharmacophore with structural characteristics for an HIV-1 integrase inhibitor.

关键词： Lipinski’s “Rule of Five” Drug-Like and Nondrug-Like Molecules HIV-1 Integrase Estimated Binding Energy Pharmacophore

Sieving characteristics of cytokine-and peroxide-induced epithelial barrier leak:Inhibition by berberine

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World Journal of Gastrointestinal Pathophysiology 2016年第2期7卷 223-234页

作者： Katherine M DiGuilio christina M Mercogliano Jillian Born Brendan Ferraro julie To Brittany Mixson Allison Smith Mary carmen Valenzano James M Mullin Lankenau Institute for Medical Research Lankenau Medical Center Departments of Biology and Biomedical Engineering Drexel University

AIM: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak. METHODS: We examined the effects of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1-β (IL1β) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of cAcO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of 14c-D-mannitol, 3H-Lactulose and 14c-Polyethylene glycol as radiolabeled probe molecules. The isoquinoline alkaloid, berberine, was then examined for its ability to reduce specific types of transepithelial leak. RESULTS: Exposure to TNF-α alone (200 ng/mL; 48 h) induced a 50% decrease in TER, i.e., increased leak of Na+ and cl- - with only a marginal but statistically significant increase in transepithelial leak of 14c-mannitol (Jm). Exposure to TNF-α + IFN-γ (200 ng/mL; 48 h) + IL1β (50 ng/mL; 48 h) did not increase the TER change (from TNF-α alone), but there was now a 100% increase in Jm. There however was no increase in transepithelial leak of two larger probe molecules, 3H-lactulose and 14c-polyethylene glycol (PEG). However, exposure to TNF-α + IFN-γ + IL1β followed by a 5 h exposure to 2 mmol/L H2O2 resulted in a 500% increase in 14c-PEG leak as well as leak to the luminal mitogen, epidermal growth factor. cONcLUSION: This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances.

关键词： Intestine crohn’s disease Tight junction Ulcerative colitis cAcO-2 Berberine Micronutrient cytokine

Randomized, double-blinded, placebo-controlled trial evaluating simethicone pretreatment with bowel preparation during colonoscopy

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World Journal of Gastrointestinal Endoscopy 2019年第6期11卷 413-423页

作者： Mohit Rishi Jaskarin Kaur Mark Ulanja Nicholas Manasewitsch Molly Svendsen Abubaker Abdalla Shashank Vemala julie Kewanyama Karmjit Singh Nirmal Singh Nageshwara Gullapalli Eric Osgard Department of Internal Medicine University of NevadaReno School of MedicineRenown Regional Medical CenterRenoNV 89502 United States Gastroenterology consultants LTDRenoNV 89502United States Aureus Univeristy School of Medicine Oranjestad 31CAruba American International Medical University Gross Islet 7610Saint Lucia

BAcKGROUND The presence of small air bubbles and foam are an impediment to a successful colonoscopy. They impair an endoscopist’s view and diminish the diagnostic accuracy of the study. This has been particularly noted to be of concern with the switch to lower volume polyethylene glycol (PEG) and bisacodyl combination preparation. AIM To evaluate the effect of oral simethicone addition to bowel preparation on intraluminal bubbles reduction during colonoscopy. METHODS Described is a prospective, randomized, multi-center, double-blinded, placebocontrolled study to evaluate the use of premixed simethicone formulation with split-regimen, low-volume PEG-bisacodyl combination bowel preparation for 168 outpatients undergoing screening, surveillance, and diagnostic colonoscopies. Primary outcome includes evaluation of bubbles during colonoscopy graded using the Intraluminal Bubbles Scale. Secondary outcomes include evaluation of the Boston Bowel Preparation Scale (BBPS), total number of polyps, polyp size differentiation, polyp laterality, adenoma detection, mass detection, cecal insertion time, withdrawal time, and patient-reported adverse events. RESULTS Higher Intraluminal Bubbles grades III and IV (less than 75% of the mucosa cleared of bubbles/foam requiring intervention with simethicone infused wash) were detected in the placebo group [Simethicone n = 4/84 vs Placebo n = 20/84 (P = 0.007)]. BBPS total score was 7.42 [standard deviation (SD)=± 1.51] in the simethicone group and 7.28 (SD =± 1.44) in the placebo group (P = 0.542) from a total of 9. Significantly higher number of adenomas were detected in the simethicone group (P = 0.001). cONcLUSION The addition of simethicone to bowel preparation is well advised for its antifoaming properties. The results of this study suggest that addition of oral simethicone can improve bowel wall visibility.

关键词： Simethicone Intraluminal bubbles colonoscopy Adenoma detection

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The USTc complex co-opts an ancient machinery to drive piRNA transcription in ***

2020年

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The USTC complex co-opts an ancient machinery to drive piRNA...

comparison of the fatty acid composition of the serum phospholipids of controls, prediabetics and adults with type 2 diabetes

第五届中国秀丽线虫大会

作者： chenchun Weng Asia Kosalka Ahmet c.Berkyurek Przemislaw Stempor Xuezhu Feng Hui Mao chenming Zeng Wen-jun Li Yong-hong Yan Meng-qiu Dong cecilia Zuliani Orsolya Barabas julie Ahringer Shouhong Guang Eric A.Miska Hefei National Laboratory for Physical Sciences at the Microscale School of Life SciencesUniversity of Science and Technology of China Wellcome cancer Research UK Gurdon Institute University of Cambridge Department of Genetics University of Cambridge National Institute of Biological Sciences

＜正＞Piwi-interacting RNAs（piRNAs） engage Piwi proteins to suppress transposons and non-self nucleic acids,maintain genome integrity,and are essential for fertility in a variety of *** *** most piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units.

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Journal of Diabetes Mellitus 2012年第4期2卷 393-401页

作者： Lu-Te chuang Robert H. Glew chia-chun Li Dorothy J. VanderJagt julie S. Broyles Gretchen M. Ray Vallabh O. Shah Department of Biochemistry and Molecular Biology University of New Mexico Albuquerque USA Department of Biotechnology Yuanpei University Hsinchu Taiwan Department of Internal Medicine School of Medicine University of New Mexico Albuquerque USA Department of Pharmacy Practice and Administrative Sciences College of Pharmacy University of New Mexico Albuquerque USA

Objective: Although abnormalities in the fatty acid composition of serum and red cell membrane phospholipids of patients with type 2 diabetes are well-documented, lacking are studies of this issue in prediabetic individuals. Materials/Methods: For this cross-sectional study, we recruited 180 subjects (30 - 80 years), 56 of whom were normal with regard to glucose control (HbA1c, 6.5%). Serum phospholipids were isolated and analyzed for fatty acids. Results: Most importantly, the fatty acid compositions of the controls and prediabetic subjects were not different for 19 fatty acids. However, the fatty acid profile of the phospholipids of the patients with diabetes differed from the other two groups;the 14 to 18-carbon saturated fatty acids were decreased by 12% - 26% whereas the unsaturated fatty acids 16:1n-7, 18:1n-9, 18:2n-6, 20:3n-6 and 20:4n-6 were increased by 45% - 64%. Of note, the docosahexaenoic acid (DHA) status of individuals in all three study groups was remarkably low compared with international values, as indicated by DHA proportions in the 1.62% - 2.07% range, and there were no differences between groups. The mean melting point of the phospholipid fatty acids of the diabetic patients (32.2℃) was significantly lower (p c subjects (38.1℃) and the controls (39.9℃) which were not different from each other. conclusion: These observations indicate that the fatty acid changes associated with type 2 diabetes follow the onset of the disease as opposed to being a causative factor of poor glucose control and insulin insensitivity.

关键词： Pre-Diabetes Type 2 Diabetes Fatty Acids Phospholipids Fluidity

Beta-adrenergic receptor polymorphisms: A basis for pharmacogenetics

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World Journal of cardiovascular Diseases 2013年第6期3卷 406-411页

作者： Efstratios K. Theofilogiannakos Konstantinos Dean Boudoulas Brian E. Gawronski Taimour Y. Langaee Timotheos G. Kelpis Antonios A. Pitsis julie A. Johnson Harisios Boudoulas Agios Lukas Hospital Thessaloniki Greece The Ohio State University Division of Cardiovascular Medicine Columbus Ohio USA The Ohio State University Division of Cardiovascular Medicine Columbus Ohio USA Aristotelian University of Thessaloniki Thessaloniki Greece University of Florida Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics Gainesville Florida USA

Aims: Polymorphisms of the β-adrenergic receptor, the frequency of which may differ in ethnic groups, alters β-receptor function. The aim of this study was to elucidate the frequency of β1 and β2-adrenergic receptor polymorphisms in healthy Greeks and to compare with those of caucasian European (Euro) and African American (AA) origin. Methods: Ninety-nine individuals with a median age of 63 without clinical evidence of any disease were studied. Blood samples were obtained and common β1 and β2-adrenergic receptor polymorphisms that change the en-coded amino acid were determined by pyrosequencing. Results: The most common β1-adrenergic receptor polymorphism in Greeks is nucleotide substitution cytosine for guanine at position 1165 (1165 c/G) resulting in amino acid substitution arginine for glycine at position 389 (389 Arg/Gly) with a minor allele frequency of 28% (Euro 27%, AA 42%);this polymorphism increases the sensitivity of the β1-receptor. The most common β2-adrenergic receptor polymorphism in Greeks is the nucleotide substitution guanine for adenine at position 46 (46 G/A) resulting in amino acid substitution glycine for arginine at position 16 (16 Gly/Arg) with a minor allele frequency of 38% (Euro 41%, AA 50%);this polymerphism facilitates receptor down-regulation during chronic adrenergic stimulation. conclusion: The most common β1 and β2-adrenergic receptor polymorphisms in the Greek population are similar to those of other European ancestry, and less common than in those of African origin indicating variability in ethnic groups. This information provides insight into common polymorphisms that may assist in optimizing β-antagonist and agonist therapy.

关键词： β1 and β2-Adrenergic Receptor Polymorphism Ethnic Variability

contribution of colposcopy in the Diagnosis of Precancerous Lesions of the Uterine cervix at the Douala Gynaeco-Obstetric and Pediatric Hospital, cameroon

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Open Journal of Obstetrics and Gynecology 2022年第10期12卷 1031-1041页

作者： Diane Estelle Modjo Kamdem Alphonse Nyong Ngalame Inna Rakya Robert Tchounzou Darolles Wekam Mwadjie Humphry Tatah Neng Bilkissou Moustapha julie Batta Patricia Metouom Kamdem charlotte Nguefack Tchente Emile Mboudou Douala Gynaeco-Obstetric and Pediatric Hospital Douala Cameroon Faculty of Health Sciences University of Buea Buea Cameroon Faculty of Medicine and Biomedical Sciences University of Garoua Garoua Cameroon Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon University of Pittsburg Medical center-Mckeesport Pittsburg USA Faculty of Medicine and Biomedical Sciences University of Yaounde I Yaounde Cameroon

Introduction: cervical cancer is a public health problem in cameroon, due to low screening and late diagnosis. We sought to assess practice of colposcopy at the Douala Gyneco-Obstetric and Pediatric Hospital (DGOPH) in cameroon and its contribution to the fight against cervical cancer in our context. Method: This is a retrospective cross-sectional study of 99 colposcopies after which 71 exploitable biopsies were retained at the Douala for a period of 1year (December 1, 2019-December 1, 2020). The nomenclature of the French Society of colposcopy and cervico-Vaginal Pathology (SFcPcV) was used. Results: Mean age of the participants was 44 years, mostly multiparous (80%). cytological abnormalities were the main reference pattern. During the examination 22% of colposcopies were found to be normal, 37% of TAG 1-2A, 31% of TAG 2B-c, and 5% suspected of cancer. After histological analysis of biopsies guided by colposcopy, we found 42% (30/71) of cervical Intraepithelial Neoplasia (cIN) 1, 15.5% (11/71) of cIN 2 - 3, and 24% (17/71) cancer. Upon analysis of the diagnosed cIN1/cIN2-3/cancers, we noted a concordance with colposcopy in 62% (23/37), 37% (10/27) and 85% (6/7) respectively. colposcopic performance in the detection of high-grade lesions and above was 36% (26/71), with a sensitivity of 92.86%, specificity 83.33%, PPV 78.79% and NPV 94.59%. conclusion: Despite the difficult socioeconomic context, colposcopy retains all its importance in the diagnosis of precancerous lesions of the uterine cervix. With the imminent putting in place of a national health policy, the goals 90-70-90 by 2030 of the World Health Organization for the fight against cervical cancer can be achieved in our sub-Saharan African countries.

关键词： colposcopy cervix Dysplasia cancer DGOPH