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Evaluating the regulation of transporter proteins and P-glycoprotein in rats with cholestasis and its implication for digoxin clearance

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World Journal of Gastrointestinal Pathophysiology 2022年第3期13卷 73-84页

作者： Parker Giroux patrick B Kyle Chalet Tan Joseph d Edwards Michael J Nowicki Hua Liu division of Pediatric Gastroenterology Department of PediatricsUniversity of Mississippi Medical CenterJacksonMS 39216United States department of Pathology University of Mississippi Medical CenterJacksonMS 39216United States department of Pharmaceutics and drug delivery University of MississippiOxfordMS 38677United States

BACKGROUNd Cardiac and hepatic functionality are intertwined in a multifaceted *** processes involving one may affect the other through a variety of mechanisms,including hemodynamic and membrane transport *** To better understand the effect of extrahepatic cholestasis on regulations of membrane transporters involving digoxin and its implication for digoxin *** Twelve adult rats were included in this study;baseline hepatic and renal laboratory values and digoxin pharmacokinetic(PK)studies were established before evenly dividing them into two groups to undergo bile duct ligation(BdL)or a sham *** 7 d repeat digoxin PK studies were completed and tissue samples were taken to determine the expressions of cell membrane transport proteins by quantitative western blot and real-time polymerase chain *** were analyzed using SigmaStat *** between pre-surgery and post-surgery in the same experimental group were compared by paired t-test,while independent t-test was employed to compare the means between sham and BdL *** digoxin clearance was decreased and liver function,but not renal function,was impaired in BdL *** resulted in significant up-regulation of multidrug resistance 1 expression in the liver and kidney and its down-regulation in the small *** anion transporting polypeptides(OATP)1A4 was up-regulated in the liver but down-regulated in intestine after ***4C1 expression was markedly increased in the kidney following *** The results suggest that cell membrane transporters of digoxin are regulated during extrahepatic *** regulations are favorable for increasing digoxin excretion in the kidney and decreasing its absorption from the intestine to compensate for reduced digoxin clearance due to cholestasis.

关键词： Cholestasis digoxin clearance Organic anion transporting polypeptides P-glycoproteins/multidrug resistance 1 Bile duct ligation

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Construction of One-Lee Weight and Two-Lee Weight Codes over IF_p+vIF_p

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Journal of Systems Science & Complexity 2017年第2期30卷 484-493页

作者： SHI Minjia LUO Yong SOLE patrick Key Laboratory of Intelligent Computing&Signal Processing Ministry of EducationAnhui UniversityHefei 230039China School of Mathematical Sciences Anhui UniversityHefei 230601China National Mobile Communications Research Laboratory Southeast UniversityNanjing 210096China Telecom Paris Tech ParisFrance

This paper is devoted to the construction of one-Lee weight codes and two-Lee weight codes over IF_p+vIF_p(v^2=v) with type p^(2 k_1)p^(k2)p^(k3) based on two different distance-preserving Gray maps from((IF_p+vIF_p)~n, Lee weight) to(IF_p^(2 n), Hamming weight), where p is a prime. Moreover, the authors prove that the obtained two-Lee weight codes are projective only when p=2.

关键词： Generator matrix Gray map linear code one-Lee weight code two-Lee weight code

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Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma:Real-life data on Liver disease,Treatment and Prognosis

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1106-1117页

作者： Xavier Adhoute Olivia Pietri Guillaume Pénaranda Thomas Wolf patrick Beaurain Olivier Monnet Arthur Laquière Justine Bonomini Frédéric Neumann Olivier Levrel Jean-Pascal Buono Xavier Hanna Paul Castellani HervéPerrier Marc Bourliere Rodolphe Anty department of Gastroenterology and Hepatology Hôpital Saint-JosephMarseilleFrance department of Biostatistics AlphaBio-Biogroup LaboratoryMarseilleFrance department of Radiology Hôpital Saint-JosephMarseilleFrance department of Clinical Research Hôpital Saint-JosephMarseilleFrance Medipath EguillesFrance department of Hepatobiliary Surgery Hôpital Saint-JosephMarseilleFrance department of Gastroenterology and Hepatology Hôpital Universitaire de l’ArchetNiceFrance

Background and Aims:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)have common features and *** real-life study investigated their characteristics,treatment modalities,and ***:This retrospective comparative study was performed in 1,075 patients seen at one tertiary center between January 2008 and december *** survival(OS)was estimated by the Kaplan-Meier *** of iCCAs after histological and radiological review,and molecular profiling was ***:HCCs patients were more likely to have early-stage disease than iCCA *** patients were more likely to be female,especially those patients without cirrhosis(43%vs.17%).Cirrhosis was prominent among HCC patients(89%vs.34%),but no difference in underlying liver disease among cirrhotic patients was *** of HCC patients was 18.4(95%CI:6.4,48.3)months,that of iCCA patients was 7.0(95%CI:3.4,20.1)*** of Barcelona Clinic Liver Cancer C HCC patients was 7.8(95%CI:4.3,14.2)months,that of advanced/metastatic iCCA patients was 8.5(95%CI:5.7,12.3)*** patients treated with sorafenib,OS was longer in HCC patients who received subsequent tyrosine kinase inhibitor *** significant OS difference was found between iCCA patients with and without cirrhosis or according to histological subtype.A targetable molecular alteration was detected in 50%of the iCCA ***:In this French series,cirrhosis was common in iCCA,which showed etiological factors comparable to those of HCC,implying a distinct oncogenic *** entities had a dismal prognosis at advanced ***,systemic therapies sequencing in HCC and molecular profiling in iCCA offer new insights.

关键词： Intrahepatic cholangiocarcinoma Hepatocellular carcinoma Cirrhosis NASH Oncogenic alterations

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Understanding Health Worker Perspectives on Risk Screening for HIV Testing—A Qualitative Study from Zimbabwe

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Open Journal of Preventive Medicine 2022年第10期12卷 199-212页

作者： Hamufare d. Mugauri Joconiah Chirenda Kudakwashe Takarinda Owen Mugurungi Ishmael Chikondowa patrick Mantiziba Mufuta Tshimanga department of Primary Health-Care Sciences The University of Zimbabwe Harare Zimbabwe Ministry of Health and Child Care AIDS and TB Unit Harare Zimbabwe Organisation for Public Health Interventions and development (OPHId) Harare Zimbabwe Clinton Health Access Initiative (CHAI) Harare Zimbabwe

Background: Zimbabwe recorded a 55% increase in HIV testing from 2011 to 2018 but with decreasing HIV-testing yields from 20% to 6% respectively as we aim to identify the narrowing gap of undiagnosed people living with HIV. As such adoption of screening tools during targeted HIV testing services improves efficiency by identifying individuals who are likely to test positive. Effective utilization of screening tools requires an understanding of health care worker perception and willingness to use the tools. Methods: We conducted a qualitative study among healthcare workers at 8 selected primary healthcare facilities in Zimbabwe. Interviewer-guided, in-depth interviews were conducted with healthcare workers and their immediate supervisors. Thematic analysis was performed following a framework built around the grounded theory model to describe perspectives that influence the utilization of HIV screening tools and suggestions for improved eligibility screening. Results: Behavioural factors facilitating the utilisation of the screening tool included motivation to adhere to standard practice, awareness of screening in targeting testing, and its ability to manage workload through screening out ineligible clients. This was evident across service delivery levels. Barriers included limited healthcare capacity, confidentiality space, multiple screening tools and opaque screening in/out criteria and the potential of clients not responding to screening questions truthfully. Conclusions: Across geographical and service delivery levels, placing screening tools at HIV testing entry points, healthcare worker knowledge on screening in/out criteria emerged as enablers for correct and consistent utilization. Further, standardizing the tools and adopting a decision aid algorithm would improve the accurate utilisation of screening tools.

关键词： Screening Tool Qualitative HIV Testing Services Health Worker Perspectives Grounded Theory Framework

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Comprehensive chemical characterization of PM_(2.5) in the large East Mediterranean-Middle East city of Beirut,Lebanon

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Journal of Environmental Sciences 2023年第11期133卷 118-137页

作者： Nansi Fakhri Marc Fadel Fatma Ozturk Melek Keles Minas Iakovides Michael Pikridas Charbel Abdallah Cyril Karam Jean Sciare patrick L.Hayes Charbel Afif EMMA Research Group Centre d’Analyses et de RechercheFaculty of SciencesUniversitéSaint-JosephBeirutLebanon department of Chemistry Faculty of SciencesUniversitéde MontréalMontréalQuébecCanada Environmental Engineering department Faculty of EngineeringBolu Abant Izzet Baysal UniversityBoluTurkey Climate and Atmosphere Research Center(CARE-C) The Cyprus InstituteNicosiaCyprus

The chemical composition of PM_(2.5) at two sites in Lebanon,a country in the East Mediterranean-Middle East region,is investigated in the spring and summer *** average PM_(2.5) concentrations were of(29±16)μg/m 3 for Beirut urban site and(32±14)μg/m 3 for Beirut suburban *** study showed that the geographic location of the East Mediterranean region,such as its proximity to the Mediterranean Sea and the dust storm intrusion are a significant contributor to the high PM levels from natural sources,which cannot be mitigated,rendering the PM_(2.5) WHO annual Air Quality guideline unattainable due to high natural background,which also applies to the entire Middle East *** and Eastern Europe are the dominant origin of air masses throughout our sampling days,suggesting the long-range transport as an important potential contributor to the high observed concentrations of V,Ni,and sulfate in this region most probably in other East Mediterranean countries than Lebanon *** local sources determined through the chemical speciation including organics are road transport,resuspension of dust and diesel private generators.A health risk assessment of airborne metals was performed and the carcinogenic risk for all the metals exceeded by 42(adults)and 14(children)times the acceptable risk level(10^(-6))at both *** was the predominant carcinogenic metal,emphasizing the need to replace energy production with cleaner energy on a regional level and highlighting the severe impact of air pollution on the health of inhabitants in this region’s main cities.

关键词： Chemical composition PM_(2.5) Eastern Mediterranean Middle East Organic aerosols Health risk assessment

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Large-Size Honeycomb-Shaped and Iris-Like Liquid Crystal Elastomer Actuators

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CCS Chemistry 2022年第3期4卷 847-854页

作者： Bin Ni Gaoyu Liu Mengxue Zhang patrick Keller Michael Tatoulian Min-Hui Li Chimie ParisTech UniversitéParis Sciences&LettresCNRSInstitut de Recherche de Chimie ParisUMR824775005 Paris Institut Curie UniversitéParis Sciences&LettresCNRSSorbonne UniversitéLaboratoire Physico-Chimie CurieUMR16875005 Paris

Nature is providing inspiration for researchers to mimic its functions or existing structures,which could remarkably promote the development of new ***,a large-size honeycomb-shaped liquid crystal elastomer(LCE)actuator with LC orientation along the height of the honeycomb shape is built by combining magnetic field alignment and soft lithography *** homeotropic alignment allowed the height contraction of honeycomb and pore size expansion of hexagons in a reversible manner upon temperature ***,this LCE actuator can be used as a structure for temperature-gated separation of *** example is an iris-like LCE actuator,which has the capability of adjusting its aperture size with a temperature *** approach provides a simple way to design customizable sophisticated LCE actuators for various potential applications.

关键词： liquid crystal elastomers soft actuators biomimetic systems

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Congenital Absence of Pericardium:The Largest Systematic Review in the Field on 247 Worldwide Cases(1977-Now)

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Congenital Heart disease 2023年第6期18卷 595-610页

作者： Pier Paolo Bassareo Aurelio Secinaro Paolo Ciliberti Massimo Chessa Marco Alfonso Perrone Kevin patrick Walsh Colin Joseph Mcmahon Mater Misericordiae University Hospital National Adult Congenital Heart Disease ServiceDublinD07 R2WYIreland Children’s Health Ireland Crumlin DublinIreland School of Medicine University College of DublinDublinIreland Advanced Cardiovascular Imaging Unit Bambino GesùChildren’s HospitalIRCCSRomeItaly department of Cardiac Surgery CardiologyHeart and Lung Transplantation Bambino Gesu’Children’s HospitalIRCCSRomeItaly Adult Congenital Heart disease UNIT Paediatric and Adult Congenital Heart CentreIRCCS-Policlinico San DonatoSan Donato MilaneseMilanItaly School of Medicine Vita Salute San Raffaele UniversityMilanItaly division of Cardiology and CardioLab Department of Clinical Sciences and Translational MedicineUniversity of Rome Tor VergataRomeItaly

Background:Congenital absence of pericardium(CAP),also known as pericardial agenesis,represents an uncommon cardiac abnormality and mostly incidental *** can be subdivided into complete and partial(left or right-sided)*** of its infrequency,just case reports and a few case series have been released so *** paper represents the largest systematic review in the *** features(age at diagnosis,type,gender,clinical presentation,electrocardiography,imaging(ultrasounds,CT/MRI),concomitant cardiac defects,and outcome)were ***:The electronic database PubMed was investigated from its establishment up to July 15th,*** case reports and case series were *** studies,papers that were not in English,Spanish,and Italian,and those manuscripts not reporting at least seven of the nine analysed *** ruled *** analysed data were reported mostly in terms of ***:One hundred eighty studies were included encompassing 247 *** than half of reviewed CAP cases were in males(63.2%).The mean age at diagnosis was 31.8±19.3 years;a range of 32 weeks of gestation-81 years).23.5%of the patients did not report any *** most common clinical presentations were chest pain(35.2%)and dyspnoea(29.2%).The most commonly seen ECG changes were right axis deviation(28.7%)and right bundle branch block(23.9%).CAP was suspected or diagnosed by echocardiography in 20.1%of *** diagnosis was made by CT and/or MRI in 61.9%of *** was left-sided in 71.2%,complete in 23.1%,and right-sided in 5.7%.A concomitant congenital heart defect was found in 22.7%,especially in the form of atrial septal defect(6.5%)and patency of ductus arteriosus(2.8%).The pericardial repair was required in 12.9% of the incomplete forms of the *** did the complete form require surgical *** outcome appeared favourable in the vast majority of cases,with just 18 deaths(7.3%).discussion:The main limitation of this syste

关键词： Congenital absence pericardium pericardial agenesis electrocardiography echocardiography computed tomography cardiac magnetic resonance imaging

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The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy

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Acta Pharmaceutica Sinica B 2022年第1期12卷 50-75页

作者： patrick Kwabena Oduro Xianxian Zheng Jinna Wei Yanze Yang Yuefei Wang Han Zhang Erwei Liu Xiumei Gao Mei du Qilong Wang Institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of Component-Based Chinese Medicine Ministry of EducationTianjin 301617China department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China

The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure,myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns(mitochondrial dNA, dNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular *** derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

关键词： STING cGAS Cardiovascular diseases Metabolic diseases damage-associated molecular patterns Inflammation ER stress Mitochondria

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A Pivotal Role of dELLAs in Regulating Multiple Hormone Signals

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Molecular Plant 2016年第1期9卷 10-20页

作者： Jean-Michel daviere patrick Achard Institut de Biologie Moleculaire des Plantes (IBMP) UPR2357 associe avec l'Universite de Strasbourg 12 rue General Zimmer 67084 Strasbourg Cedex France

Plant phenotypic plasticity is controlled by diverse hormone pathways, which integrate and convey infor- mation from multiple developmental and environmental signals. Moreover, in plants many processes such as growth, development, and defense are regulated in similar ways by multiple hormones. Among them, gibberellins （GAs） are phytohormones with pleiotropic actions, regulating various growth processes throughout the plant life cycle. Previous work has revealed extensive interplay between GAs and other hor- mones, but the molecular mechanism became apparent only recently. Molecular and physiological studies have demonstrated that dELLA proteins, considered as master negative regulators of GA signaling, inte- grate multiple hormone signaling pathways through physical interactions with transcription factors or reg- ulatory proteins from different families. In this review, we summarize the latest progress in GA signaling and its direct crosstalk with the main phytohormone signaling, emphasizing the multifaceted role of dELLA proteins with key components of major hormone signaling pathways.

关键词： gibberellins dELLAs hormone crosstalk plant development phenotypic plasticity

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disturbance cues in freshwater prey fishes： does urea function as an ＇early warning cue＇ in juvenile convict cichlids and rainbow trout？

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Current Zoology 2012年第2期58卷 250-259页

作者： Grant E. BROWN Christopher d. JACKSON patrick H. MALKA Elisa JACQUES Marc-Andre COUTURIER department of Biology Concordia University 7141 Sherbrooke St. West Montreal Quebec H4B 1R6 CANADA

Freshwater vertebrate and invertebrate prey species commonly rely on chemosensory information, including non-injury released disturbance cues, to assess local predation threats. We conducted laboratory studies to (1) determine if urea can function as a disturbance cue in juvenile convict cichlids and rainbow trout and (2) determine if the background level of urea influences the behavioral response to a subsequent pulse of urea (‘background noise’ hypothesis). In the first series of trials, juvenile cichlids and trout were exposed to urea at varying concentrations (0 to 0.5 mg L-1for cichlids and 0 to 1.0 mg L-1for trout). Our results suggest that both cichilds and trout exhibited functionally similar responses to urea and conspecific disturbance cues and that increasing the concentration of urea results in an increase intensity of antipredator behaviour. In the second series of trials, we pre-exposed cichlids or trout to intermediate or high concentrations of urea (or a distilled water control) and then tested for the response to a second pulse of urea at at intermediate or high concentrations (versus a distilled water control). Our results demonstrate that pre-exposure to urea reduces or eliminates the response to a second pulse of urea, supporting the background noise hypothesis. Together, our results suggest that pulses of urea, released by disturbed or stressed individuals, may function as an early warning signal in freshwater prey species [Current Zoology58 (2): 250–259 , 2012].

关键词：虹鳟鱼尿素鲷鱼干扰淡水罪犯少年预警

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