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Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

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International Journal of Oral Science 2013年第3期5卷 130-140页

作者： carol l fischer Katherine S Walters David R Drake Deborah V Dawson Derek R Blanchette Kim A Brogden Philip W Wertz Dows Institute for Dental Research College of Dentistry The University of Iowa Central Microscopy Research Facility College of Dentistry The University of Iowa Department of Endodontics College of Dentistry The University of Iowa Department of Pediatric Dentistry College of Dentistry The University of Iowa Department of Periodontics College of Dentistry The University of Iowa Department of Oral Pathology Radiology & Medicine College of Dentistry The University of Iowa

Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however,little is known about their spectrum of antimicrobial activity or mechanisms of action against oral *** this study,we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis,an important colonizer of the oral cavity implicated in *** inhibitory concentrations,minimal bactericidal concentrations,and kill kinetics revealed variable,but potent,activity of oral mucosal and salivary lipids against ***,indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria,although specific components of bacterial membranes are also likely *** micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma *** information,coupled with the association of treatment lipids with *** lipids revealed via thin layer chromatography,suggests that the plasma membrane is a likely target of lipid antibacterial *** a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique *** stress response,including proteins important in fatty acid biosynthesis,metabolism and energy production,protein processing,cell adhesion and *** or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

关键词： antimicrobial lipid fatty acid Porphyromonasgingivalis sphingoid base sphingolipid ultrastructure

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New insights into the vitamin D requirements during pregnancy

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Bone Research 2017年第3期5卷 161-176页

作者： Bruce W Hollis carol l Wagner Department of Pediatrics Darby Children's Research Institute Medical University of South Carolina

Pregnancy represents a dynamic period with physical and physiological changes in both the mother and her developing fetus. The dramatic 2-3 fold increase in the active hormone 1,25（OH）2D concentrations during the early weeks of pregnancy despite minimal increased calcium demands during that time of gestation and which are sustained throughout pregnancy in both the mother and fetus suggests an immunomodulatory role in preventing fetal rejection by the mother. While there have been numerous observational studies that support the premise of vitamin D＇s role in maintaining maternal and fetal well-being, until recently, there have been few randomized clinical trials with vitamin D supplementation. One has to exhibit caution, however, even with RCTs, whose results can be problematic when analyzed on an intent-to-treat basis and when there is high non-adherence to protocol （as if often the case）, thereby diluting the potential good or harm of a given treatment at higher doses. As such, a biomarker of a drug or in this case ＂vitamin＂ or pre-prohormone is better served. For these reasons, the effect of vitamin D therapies using the biomarker circulating 25（OH）D is a far better indicator of true ＂effect.＂ When pregnancy outcomes are analyzed using the biomarker 25（OH）D instead of treatment dose, there are notable differences in maternal and fetal outcomes across diverse racial/ethnic groups, with improved health in those women who attain a circulating 25（OH）D concentration of at least 100 nmol. l-1 （40 ng. ml-1）. Because ,an important issue is the timing or initiation of vitamin D treatment/supplementation, and given the potential effect of vitamin D on placental gene expression and its effects on inflammation within the placenta, it appears crucial to start vitamin D treatment before placentation （and trophoblast invasion）; however, this question remains unanswered. Additional work is needed to decipher the vitamin D requirements of pregnant women and the optimal timing of s

关键词： New insights into the vitamin D requirements during pregnancy

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Impact of asialoglycoprotein receptor deficiency on the development of liver injury

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World Journal of Gastroenterology 2009年第10期15卷 1194-1200页

作者： Serene Ml lee carol A Casey Benita l McVicker Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

The asialoglycoprotein （ASGP） receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis （RME）. The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease （AlD）. The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice （lacking a functional ASGP receptor） to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas （CD95） antibody, carbon tetrachloride （CCh） and lipopolysaccharide （lPS）/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.

关键词： Asialoglycoprotein receptor Asialoglycoproteinreceptor deficient mice Receptor-mediatedendocytosis Alcohol Carbon tetrachloride Anti-Fas lipopolysaccharide/galactosamine Toxicant-induced liverinjury

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Effect of ethanol on pro-apoptotic mechanisms in polarizedhepatic cells

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World Journal of Gastroenterology 2007年第37期13卷 4960-4966页

作者： Benita l McVicker Dean J Tuma carol A Casey liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

Chronic ethanol consumption is associated with serious and potentially fatal alcohol-related liver injuries such as hepatomegaly, alcoholic hepatitis and cirrhosis. Moreover, it has been documented that the clinical progression of alcohol-induced liver damage may be associated with an increase in hepatocellular death that involves apoptotic mechanisms. Although much information has been learned about the clinical manifestations associated with alcohol-related diseases, the search continues for a better understanding of the molecular and/or cellular mechanisms by which ethanol exerts its deleterious effects such as the induction of pro-apoptotic mechanisms and related cell damaging events. As part of the effort to enhance our understanding of those particular cellular pathways and mechanisms associated with ethanol toxicity, researchers over the years have utilized a variety of model systems. Recently, work has come forth demonstrating the utility of a hybrid cell line (WIF-B) as a cell culture model system for the study of alcohol-associated alterations in hepatocellular mechanisms. Success with such emerging model systems could aid in the development of potential therapeutic treatments for the prevention of alcohol- induced apoptotic cell death that may ultimately serve as a significant target in delaying the onset and/or progression of clinical symptoms of alcohol-mediated liver disease. This review article summarizes the current understanding of ethanol-mediated modifications in cell survival and thus the promotion of pro-apoptotic events with emphasis on analyses made in various experimental model systems, particularly the more recently characterized WIF-B cell system.

关键词： Hepatoma hybrid cells Ethanol Apoptosis Fas receptor Caspase

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RNAi,a new therapeutic strategy against viral infection

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Cell Research 2004年第6期14卷 460-466页

作者： fischer l.TAN,James Q.YIN Institute of Biophysics Institute of Biophysics Chinese Academy of Sciences 15 Datun Road Beijing 100101 China. Chinese Academy of Sciences 15 Datun Road Beijing 100101 China.

RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells. RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently, small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.

关键词： RNAi siRNA viral infection gene therapy.

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Optical coherence tomography for ocular surface and corneal diseases: a review

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Eye and Vision 2018年第1期5卷 126-136页

作者： Nandini Venkateswaran Anat Galor Jianhua Wang carol l.Karp Bascom Palmer Eye Institute University of Miami Miller School of MedicineMcKnight Building Room 202A1638 NW 10th Avenue900 NW 17th StreetMiamiFL 33136USA Department of Ophthalmology Miami Veterans Administration Medical Center1201 NW 16th StreetMiamiFL 33125USA

The advent of optical coherence tomography(OCT)imaging has changed the way ophthalmologists image the ocular surface and anterior segment of the *** ability to obtain dynamic,high and ultra-high resolution,cross-sectional images of the ocular surface and anterior segment in a noninvasive and rapid manner allows for ease of *** this review,we focus on the use of anterior segment OCT,which provides an“optical biopsy”or in vivo imaging of various ocular surface and corneal pathologies,allowing the clinician to diagnose diseases otherwise not visualized by traditional *** utility of anterior segment OCT for various anterior segment pathologies is reviewed.

关键词： Anterior segment optical coherence tomography Ocular surface imaging Ocular surface lesions

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Performance evaluation of operational atmospheric correction algorithms over the East China Seas

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Chinese Journal of Oceanology and limnology 2017年第1期35卷 1-22页

作者： HE Shuangyan[l,2,3] HE Mingxia fischer Jurgen Ocean Remote Sensing Institute Ocean University of China Qingdao 266003 China Institute for Space Sciences Freie Universitdt Berlin Berlin D-12165 Germany Ocean College Zhejiang University Hangzhou 310058 China

To acquire high-quality operational data products for Chinese in-orbit and scheduled ocean color sensors, the performances of two operational atmospheric correction(AC) algorithms(ESA MEGS 7.4.1 and NASA Sea DAS 6.1) were evaluated over the East China Seas(ECS) using MERIS data. The spectral remote sensing reflectance R_(rs)(λ), aerosol optical thickness(AOT), and ?ngstr?m exponent(α) retrieved using the two algorithms were validated using in situ measurements obtained between May 2002 and October 2009. Match-ups of R_(rs), AOT, and α between the in situ and MERIS data were obtained through strict exclusion criteria. Statistical analysis of R_(rs)(λ) showed a mean percentage difference(MPD) of 9%–13% in the 490–560 nm spectral range, and significant overestimation was observed at 413 nm(MPD>72%). The AOTs were overestimated(MPD>32%), and although the ESA algorithm outperformed the NASA algorithm in the blue-green bands, the situation was reversed in the red-near-infrared bands. The value of α was obviously underestimated by the ESA algorithm(MPD=41%) but not by the NASA algorithm(MPD=35%). To clarify why the NASA algorithm performed better in the retrieval of α, scatter plots of the α single scattering albedo(SSA) density were prepared. These α-SSA density scatter plots showed that the applicability of the aerosol models used by the NASA algorithm over the ECS is better than that used by the ESA algorithm, although neither aerosol model is suitable for the ECS region. The results of this study provide a reference to both data users and data agencies regarding the use of operational data products and the investigation into the improvement of current AC schemes over the ECS.

关键词： validation remote sensing reflectance aerosol optical thickness ocean color atmospheric correction remote sensing

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Utility of high-resolution anterior segment optical coherence tomography in the diagnosis and management of sub-clinical ocular surface squamous neoplasia

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Eye and Vision 2019年第1期6卷 229-235页

作者： Ann Q.Tran Nandini Venkateswaran Anat Galor carol l.Karp Department of Ophthalmology Bascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine900 NW 17th StMiamiFL 33136USA

Background:To evaluate the frequency and characteristics of sub-clinical ocular surface squamous neoplasia(OSSN)detected by high-resolution anterior segment tomography(HR-OCT)in patients with clinically unapparent disease following topical ***:A retrospective chart review of patients with OSSN identified through a pharmacy database at the Bascom Palmer Eye Institute from January 2013 to December 2018 was *** undergoing primary therapy with topical 5-fluorouracil 1%(5-FU)(4 times a day for 7 days with a 21-day break)or interferon-alpha-2b(IFN)(4 times a day)were *** were separated into two *** 1 included individuals whose clinical resolution of OSSN aligned with complete resolution on *** 2(sub-clinical OSSN group)included individuals with clinical OSSN resolution but with features of persistent disease on *** excluded included those treated at an outside institution and those who used topical therapy as a surgical ***:A total of 95 patients(95 eyes)were ***-clinical OSSN was detected at a frequency of 17%in our study patients(n=16 patients,9 treated with 5-FU and 7 treated with IFN).In the 16 individuals,the mean time to clinical resolution was 3.6±1.0 cycles for 5-FU and 4.0±0.0 months for *** additional 2.1±0.8 cycles for 5-FU and 1.2±0.4 months for IFN were needed to achieve HR-OCT resolution of *** in Group 1 was noted in 10 patients(12%)while no recurrences occurred in Group 2,the cohort with subclinical disease that received the extended medical *** mean follow-up was 24.0±17.9 ***:We found that at least 17%of individuals with apparent clinical resolution of OSSN have sub-clinical disease detected on *** information can be used to optimize treatment and extend therapy past the point of clinical resolution.

关键词： Ocular surface squamous neoplasia,High-resolution optical coherence tomography,Sub-clinical ocular surface squamous neoplasia,Ocular surface imaging ocular surface lesions

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Update on Diagnosis and Management of Conjunctival Papilloma

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Eye and Vision 2019年第1期6卷 131-147页

作者： Despoina Theotoka Melina I.Morkin Anat Galor carol l.Karp Department of Ophthalmology Bascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine900 NW 17th StreetMiamiFL 33136USA Miami Veterans Administration Medical Center 1201 NW 16th StreetMiami 33125FLUSA

Conjunctival papilloma is an acquired benign squamous cell tumor that can present at any age,but most frequently in the third and fourth decades of *** have been associated with human papilloma virus(HPV)infection,usually types 6 and *** histopathological diagnosis remains the gold standard,the advent of newer non-invasive imaging modalities such as optical coherence tomography(OCT)is transforming the way we diagnose and treat ocular surface tumors,including conjunctival *** of these lesions can prove a challenge to the treating physician since not all lesions respond to medical and/or surgical therapy and in fact may worsen after surgical *** this review,the epidemiology,pathophysiology,clinical characteristics,and diagnosis of conjunctival papilloma including the use of OCT are ***,efficacy,and side effects of currently available management options are also reviewed to guide the selection of the best treatment approach.

关键词： Conjunctival papilloma Squamous cell papilloma Optical coherence tomography Treatment Interferon Mitomycin Surgery Cryotherapy Human papilloma virus

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Epidemiology of ocular surface squamous neoplasia in veterans: a retrospective casecontrol study

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Eye and Vision 2019年第1期6卷 99-104页

作者： logan M.Smith Shiv lamba carol l.Karp Anat Galor Miami Veterans Administration Medical Center 1201 NW 16th StMiamiFL 33125USA Bascom Palmer Eye Institute Department of OphthalmologyUniversity of Miami900 NW 17th StreetMiamiFL 33136USA Flint Hill School OaktonVirginiaUSA

Background:A number of risk factors have been evaluated in ocular surface squamous neoplasia,but few studies have assessed risk factors specific to the armed forces veteran ***:We conducted a retrospective case-control study on 55 patients and 55 age-matched controls with biopsy-proven ocular surface squamous neoplasia from the Miami Veterans Administration Hospital Eye Clinic to investigate potential risk factors encountered by veterans,including service-specific ***-specific risk factors included ionizing radiation exposure,Agent Orange exposure,deployment to Southwest Asia,and exposure to the series of biochemical warfare tests known as Project Shipboard Hazard and *** was analyzed with SPSS(SPSS Inc.,Chicago,Il)using t-tests,chi-squared,and logistic regression analysis,with a p-value oflly ***:The strongest risk factor for ocular surface squamous neoplasia was lifetime sun exposure both directly assessed via historical quantification of exposure by dermatology practitioners(Odds Ratio(OR)5.4,95%Confidence Interval(CI)2.27–12.847,pl cell carcinoma(OR 3.157,95%CI 1.286–7.748,p=0.010)and pingueculae(OR 5.267,95%CI 2.104–13.186,ployment were not associated with an increased risk of ocular surface squamous *** to ionizing radiation and involvement in Project Shipboard Hazard and Defense were not documented among any cases or ***:The results of our study are consistent with prior established risk factors,namely highlighting the important role of sun exposure in ocular surface squamous neoplasia among veterans.

关键词： Ocular surface squamous neoplasia Risk factors Veteran population

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