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| 1 | Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a^(-/-) mice显示文摘AIM: To investigate the ability of a Prunella vulgaris(P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle(5% ethanol) or P. vulgaris ethanolic extract(2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencingweight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced(P < 0.05) serum levels of IL-10(4.6 ± 2 vs 19.4 ± 4), CXCL9(1319.0 ± 277 vs 3901.0 ± 858), and TNFα(9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/-mice. Histologically, several microscopic parameters were reduced(P < 0.05) in P. vulgaris-treated mdr1a-/-mice, as was myeloperoxidase activity in the colon(2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4+ T cells(2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells(2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris-treated mdr1a-/- were significantly reduced(P < 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris-treated mdr1a-/- mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a-/- mice. | Kelley MK Haarberg Meghan J Wymore Brand Anne-Marie C Overstreet Catherine C Hauck Patricia A Murphy Jesse M Hostetter Amanda E Ramer-Tait Michael J Wannemuehler | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 8 |
| 2 | Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies显示文摘在地岬基因的 Oncogenic 变化在人的癌症是很普通的,导致有描绘得好的选择优点,而且不太听说得好的危险的房间。我们执行了一幅大规模 loss-of-function 屏幕识别被转变 KRAS 的结肠癌房间,然而并非由缺乏这 oncogene 的衍生物要求的基因。最高得分的基因然后在 KRAS 变异、野类型的癌症房间的一块更大的面板被测试。表示 oncogenic KRAS 的癌症房间被发现高度依赖于抄写因素 GATA2 和 DNA 复制开始管理者 CDC6。与已知的目标用许多药扩大这分析,我们发现有变异的 KRAS 的癌症房间与 topoisomerase 抑制显示出选择嗜好到 proteasome 功能,以及合成致命性。联合指向引起的这些功能改善了相对野类型的房间 KRAS 变异的房间杀死。这些观察建议新奇目标和在地岬变异的癌症为最佳的效果联合存在治疗的新方法,它传统地被看作对治疗高度倔强。 | Michael Steckel Miriam Molina-Arcas Britta Weigelt Michaela Marani Patricia H Warne Hanna Kuznetsov Gavin Kelly Becky Saunders Michael Howell Julian Downward David C Hancock | 2012 | Cell Research2012，22，8： | 5 |
| 3 | Immunogenetic factors driving formation of ultralong VH CDR3 in Bos taurus antibodies显示文摘The antibody repertoire of Bos taurus is characterized by a subset of variable heavy(VH)chain regions with ultralong third complementarity determining regions(CDR3)which,compared to other species,can provide a potent response to challenging antigens like HIV env.These unusual CDR3 can range to over seventy highly diverse amino acids in length and form uniqueβ-ribbon‘stalk’and disulfide bonded‘knob’structures,far from the typical antigen binding site.The genetic components and processes for forming these unusual cattle antibody VH CDR3 are not well understood.Here we analyze sequences of Bos taurus antibody VH domains and find that the subset with ultralong CDR3 exclusively uses a single variable gene,IGHV1-7(VHBUL)rearranged to the longest diversity gene,IGHD8-2.An eight nucleotide duplication at the 3′end of IGHV1-7 encodes a longer V-region producing an extended Fβ-strand that contributes to the stalk in a rearranged CDR3.A low amino acid variability was observed in CDR1 and CDR2,suggesting that antigen binding for this subset most likely only depends on the CDR3.Importantly a novel,potentially AID mediated,deletional diversification mechanism of the B.taurus VH ultralong CDR3 knob was discovered,in which interior codons of the IGHD8-2 region are removed while maintaining integral structural components of the knob and descending strand of the stalk in place.These deletions serve to further diversify cysteine positions,and thus disulfide bonded loops.Hence,both germline and somatic genetic factors and processes appear to be involved in diversification of this structurally unusual cattle VH ultralong CDR3 repertoire. | Thaddeus C Deiss Melissa Vadnais Feng Wang Patricia L Chen Ali Torkamani Waithaka Mwangi Marie-Paule Lefranc Michael F Criscitiello Vaughn V Smider | 2019 | Cellular & Molecular Immunology2019，16，1： | 4 |
| 4 | Induced pluripotent stem cells for modeling neurological disorders显示文摘Several diseases have been successfully modeled since the development of induced pluripotent stem cell(i PSC) technology in 2006. Since then, methods for increased reprogramming efficiency and cell culture maintenance have been optimized and many protocols for differentiating stem cell lines have been successfully developed, allowing the generation of several cellular subtypes in vitro. Gene editing technologies have also greatly advanced lately, enhancing disease-specific phenotypes by creating isogenic cell lines, allowing mutations to be corrected in affected samples or inserted in control lines. Neurological disorders have benefited the most from i PSC-disease modeling for its capability for generating disease-relevant cell types in vitro from the central nervous system, such as neurons and glial cells, otherwise only available from post-mortem samples. Patient-specific i PSC-derived neural cells can recapitulate the phenotypes of these diseases and therefore, considerably enrich our understanding of pathogenesis, disease mechanism and facilitate the development of drug screening platforms for novel therapeutic targets. Here, we review the accomplishments and the current progress in human neurological disorders by using i PSC modeling for Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy, amyotrophic lateral sclerosis, duchenne muscular dystrophy, schizophrenia and autism spectrum disorders, which include Timothy syndrome, Fragile X syndrome, Angelman syndrome, Prader-Willi syndrome, PhelanMc Dermid, Rett syndrome as well as Nonsyndromic Autism. | Fabiele B Russo Fernanda R Cugola Isabella R Fernandes Graciela C Pignatari Patricia C B Beltrão-Braga | 2015 | World Journal of Transplantation2015，5，4： | 4 |
| 5 | Lack of microRNA‐101 causes E‐cadherin functional deregulation through EZH2 up‐regulation in intestinal gastric cancer显示文摘 | Joana Carvalho Nicole C van Grieken Patricia M Pereira Sónia Sousa Marianne Tijssen Tineke E Buffart Bego?a Diosdado Heike Grabsch Manuel AS Santos Gerrit Meijer Raquel Seruca Beatriz Carvalho Carla Oliveira | 2012 | J Pathol2012，，1： | 3 |
| 6 | Vaccinations in immunosuppressive-dependent pediatric inflammatory bowel disease显示文摘AIM To determine the vaccination rates in pediatric immunosuppression-dependent inflammatory bowel disease(IBD) and review the safety and efficacy of vaccinations in this population.METHODS The electronic medical records from October 2009 to December 2015 of patients diagnosed with IBD at 10 years of age or younger and prescribed antitumor necrosis factor alpha(anti-TNF-α) therapy were reviewed for clinical history, medication history, vaccination history, and hepatitis B and varicella titers. Literature discussing vaccination response in IBD patients were identified through search of the MEDLINE database and reviewed using the key words 'inflammatory bowel disease', 'immunization', 'vaccination', 'pneumococcal', 'varicella', and 'hepatitis B'. Non-human and non-English language studies were excluded. Search results were reviewed by authors toselect articles that addressed safety and efficacy of immunizations in inflammatory bowel disease.RESULTS A total of 51 patients diagnosed with IBD prior to the age of 10 and receiving anti-TNF-α therapy were identified. Thirty-three percent of patients(17/51) had incomplete or no documentation of vaccinations. Sixteen case reports, cohort studies, cross-sectional studies, and randomized trials were determined through review of the literature to describe the safety and efficacy of hepatitis B, pneumococcal, and varicella immunizations in adult and pediatric patients with IBD. These studies showed that patients safely tolerated the vaccines without significant adverse effects. Importantly, IBD patients receiving immunosuppressive medications, particularly anti-TNF-α treatment, have decreased vaccine response compared to controls. However, the majority of patients are still able to achieve protective levels of specific antibodies. CONCLUSION Immunizations have been shown to be well-tolerated and protective immunity can be achieved in patients with IBD requiring immunosuppressive therapy. | Huyen-Tran Nguyen Phillip Minar Kimberly Jackson Patricia C Fulkerson | 2017 | World Journal of Gastroenterology2017，23，42： | 2 |
| 7 | Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression显示文摘 | Brian J Reid Laura J Prevo Patricia C Galipeau Carissa A Sanchez Gary Longton Douglas S Levine Patricia L Blount Peter S Rabinovitch | 2001 | The American Journal of Gastroenterology2001，，10： | 2 |
| 8 | The potential leaching and mobilization of trace elements from FGD-gypsum of a coal-fired power plant under water re-circulation conditions显示文摘Experimental and geochemical modelling studies were carried out to identify mineral and solid phases containing major, minor, and trace elements and the mechanism of the retention of these elements in Flue Gas Desulphurisation(FGD)-gypsum samples from a coal-fired power plant under filtered water recirculation to the scrubber and forced oxidation conditions. The role of the p H and related environmental factors on the mobility of Li, Ni, Zn, As, Se, Mo, and U from FGD-gypsums for a comprehensive assessment of element leaching behaviour were also carried out. Results show that the extraction rate of the studied elements generally increases with decreasing the p H value of the FGD-gypsum leachates. The increase of the mobility of elements such as U, Se, and As in the FGD-gypsum entails the modification of their aqueous speciation in the leachates; UO2SO4, H2 Se, and HAs O2 are the aqueous complexes with the highest activities under acidic conditions.The speciation of Zn, Li, and Ni is not affected in spite of p H changes; these elements occur as free cations and associated to SO42 in the FGD-gypsum leachates. The mobility of Cu and Mo decreases by decreasing the p H of the FGD-gypsum leachates, which might be associated to the precipitation of Cu Se2 and Mo Se2, respectively. Time-of-Flight mass spectrometry of the solid phase combined with geochemical modelling of the aqueous phase has proved useful in understanding the mobility and geochemical behaviour of elements and their partitioning into FGD-gypsum samples. | Patricia Córdoba Iria Castro Mercedes Maroto-Valer Xavier Querol | 2015 | Journal of Environmental Sciences2015，27，6： | 2 |
| 9 | Identification of patients at-risk for Lynch syndrome in a hospital-based colorectal surgery clinic显示文摘AIM:To determine the prevalence of a family history suggestive of Lynch syndrome (LS) among patients with colorectal cancer (CRC) followed in a coloproctology outpatient clinic in Southern Brazil.METHODS:A consecutive sample of patients with CRC were interviewed regarding personal and family histories of cancer.Clinical data and pathology features of the tumor were obtained from chart review.RESULTS:Of the 212 CRC patients recruited,61 (29%) reported a family history of CRC,45 (21.2%) were diagnosed under age 50 years and 11 (5.2%) had more than one primary CRC.Family histories consistent with Amsterdam and revised Bethesda criteria for LS were identified in 22 (10.4%) and 100 (47.2%) patients,respectively.Twenty percent of the colorectal tumors had features of the high microsatellite instability phenotype,which was associated with younger age at CRC diagnosis and with Bethesda criteria (P < 0.001).Only 5.3% of the patients above age 50 years had been previously submitted for CRC screening and only 4% of patients with suspected LS were referred for genetic risk assessment.CONCLUSION:A significant proportion of patients with CRC were at high risk for LS.Education and training of health care professionals are essential to ensure proper management. | Patrícia Koehler-Santos Patricia Izetti Jamile Abud Carlos Eduardo Pitroski Silvia Liliana Cossio Suzi Alves Camey Cláudio Tarta Daniel C Damin Paulo Carvalho Contu Mario Antonello Rosito Patricia Ashton-Prolla Joāo Carlos Prolla | 2011 | World Journal of Gastroenterology2011，17，6： | 2 |
| 10 | Determination of As, Sb, Se, Te and Bi in milk by slurry sampling hydride atomic fluorescence spectrometry 显示文摘 | Patricia C M Luisa C Agustin P | 2004 | Talanta2004，62，1： | 1 |
| 11 | Glibert,Effects of light on nitrogen and carbon uptake during a Prorocentrum minimum bloom显示文摘 | PATRICIA M | 2005 | Harmful Algae2005，，4： | 1 |
| 12 | Enhancing the Trust-based Recommendation Process with Explicit Dis-trust显示文摘 | Patricia V Nele V Chris C | 2013 | ACM Transactions on the Web2013，7，2： | 1 |
| 13 | LIGHT, a New Member of the TNF Superfamily, and Lymphotoxin α Are Ligands for Herpesvirus Entry Mediator显示文摘 | Davide N Mauri Reinhard Ebner Rebecca I Montgomery Kristine D Kochel Timothy C Cheung Guo-Liang Yu Steve Ruben Marianne Murphy Roselyn J Eisenberg Gary H Cohen Patricia G Spear Carl F Ware | 1998 | Immunity1998，，： | 1 |
| 14 | Effect of heparin on in vitro capacitation of boar sperm显示文摘 | DOEA G D PATRICIA M MARCEO C | 2006 | Biol Res2006，39，4： | 1 |
| 15 | Characteristics associated with longer breast显示文摘 | Tracie AB Tan C Patricia AB | 2009 | J Hum Lact2009，25，1： | 1 |
| 16 | Percutaneous transthoracic needle aspiration biopsy显示文摘 | RYAN C LARSCHEID PATRICIA E THORPE WALTER J SCOTT | 1998 | Chest1998，114，： | 1 |
| 17 | Training pharmacy workers in recognition,management,and prevention of STDs:district-randomized controlled trial显示文摘 | PATRICIA G JAMES H CESAR C | 2003 | Bull WHO2003，81，11： | 1 |
| 18 | Quantitative conversion of phytate to inorganic phosphorus in soybean seeds expressing a bacterial phytase显示文摘 | Peiyu Z Patricia C | 2008 | Plant Physiology2008，146，2： | 1 |
| 19 | Identification and characterization of pathogenic Aerornonas veronii biovar, sobria associated with epizootic ulcerative syndrome in fish in Bangladesh显示文摘 | MOKHLASUR R PATRICIA C INGER K | 2002 | Appl Environ Microbiol2002，68，2： | 1 |
| 20 | Solid phase microextraction capillary gas chromatography combined with furnace atomization plasma emission spectrometry for speciation of mercury in fish tissues显示文摘 | Patricia G Reinaldo C C Zoltan M | 2003 | Spectrochimica Acta Part B2003，，58： | 1 |
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