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Loss of Hox5 function results in myofibroblast mislocalization and distal lung matrix defects during postnatal development

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Science China(Life Sciences) 2018年第9期61卷 1030-1038页

作者： Steven M.Hrycaj Leilani marty-Santos ANDrew J.Rasky Nicholas W.Lukacs Deneen M.Wellik Department of Internal Medicine Division of Molecular Medicine and Genetics University of Michigan Department of Pathology University of Michigan Department of Cell and Developmental Biology University of Michigan

Alveologenesis is the final stage of lung development and is responsible for the formation of the principle gas exchange units called alveoli. The lung mesenchyme, in particular the alveolar myofibroblasts, are drivers of alveolar development, however,few key regulators that govern the proper distribution and behavior of these cells in the distal lung during alveologenesis have been identified. While Hox5 triple mutants(Hox5 aabbcc) exhibit neonatal lethality, four-allele, compound mutant mice(Hox5 AabbCc) are born in Mendelian ratios and are phenotypically normal at birth. However, they exhibit defects in alveologenesis characterized by a BPD-like phenotype by early postnatal stages that becomes more pronounced at adult stages. Invasive pulmonary functional analyses demonstrate significant increases in total lung volume and compliance and a decrease in elastance in Hox5 compound mutants. SMA+ myofibroblasts in the distal lung are distributed abnormally during peak stages of alveologenesis and aggregate, resulting in the formation of a disrupted elastin network. Examination of other key components of the distal lung ECM, as well as other epithelial cells and lipofibroblasts reveal no differences in distribution. Collectively, these data indicate that Hox5 genes play a critical role in alveolar development by governing the proper cellular behavior of myofibroblasts during alveologenesis.

关键词： Hox5 alveologenesis alveolar myofibroblasts lung ECM postnatal lung development

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Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson(Houpo) and its constituents

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2017年第3期18卷 194-214页

作者： melanie POIVRE Pierre DUEZ (Unit of Therapeutic Chemistry and Pharmacognosy Faculty of Medicine and Pharmacy Research Institute for Health Sciences and Technology University of Mons-UMONS Mons Belgium

Traditional Chinese herbal drugs have been used for thousands of years in Chinese pharmacopoeia. The bark of Magnolia officinalis Rehder ＆ E. Wilson, known under the pinyin name ＂Houpo＂, has been traditionally used in Chinese and Japanese medicines for the treatment of anxiety, asthma, depression, gastrointestinal disorders, headache, and more. Moreover, Magnolia bark extract is a major constituent of currently marketed dietary supplements and cosmetic products. Much pharmacological activity has been reported for this herb and its major compounds notably antioxidant, anti-inflammatory, antibiotic and antispasmodic effects. However, the mechanisms underlying this have not been elucidated and only a very few clinical trials have been published. In vitro and in vivo toxicity studies have also been published and indicate some intriguing features. The present review aims to summarize the literature on M. officinalis bark composition, utilisation, pharmacology, and safety.

关键词： Magnolia bark Houpo Chinese herb Traditional Chinese medicine

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Sexuality following trauma injury: A literature review

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Burns & Trauma 2014年第2期2卷 61-70页

作者： Kylie Marie Connell Rosemary Coates Fiona melanie Wood Department of Sexology School of Public HealthFaculty of Health SciencesCurtin UniversityPerthWestern Australia Fiona Wood Foundation PerthWestern Australia Burns Service of Western Australia Royal Perth HospitalWestern Australia4Burn Injury Research Unit University of Western Australia PerthWestern AustraliaAustralia

Restoration of the quality of life(QoL)of trauma injury survivors is the aim of trauma *** is generally acknowledged that sexuality is an important component of QoL;however,rehabilitation services frequently fall short of including sexuality as a matter of *** literature was reviewed to examine the experiences of trauma survivors from three groups:spinal cord injury(SCI),traumatic brain injury(TBI)and *** focus was on the impact of trauma on the QoL to identify future research directions and to advocate for the inclusion of sexuality as an integral part of *** searched were Proquest,Ovid,Cinahl,Medline,PsycInfo and Cochrane Central Register of controlled trials.A total of 36 eligible studies were included:SCI(n=25),TBI(n=6),burns(n=5).Four themes were identified across the three trauma groups that were labeled as physiological impact of trauma on sexuality,cognitive-genital dissociation(CGD),sexual disenfranchisement(SD)and sexual rediscovery(SR).Trauma injury has a significant impact on sexuality,which is not routinely addressed within rehabilitation *** sexuality research is required among all trauma groups to improve rehabilitation services and in turn QoL outcomes for all trauma survivors.

关键词： Burns rehabilitation spinal cord injury sexuality traumatic brain injury

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Helicobacter pylori arginase mutant colonizes arginase Ⅱ knockout mice

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World Journal of Gastroenterology 2011年第28期17卷 3300-3309页

作者： Songhee H Kim melanie L Langford Jean-Luc Boucher Traci L Testerman David J McGee Department of Microbiology and Immunology Louisiana State University Health Sciences Center-Shreveport University of Nebraska-Lincoln School of Biological SciencesLincoln Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques Université Paris Descartes

AIM: To investigate the role of host and bacterial arginases in the colonization of mice by Helicobacter pylori (***).METHODS: *** produces a very powerful urease that hydrolyzes urea to carbon dioxide and ammonium,which neutralizes *** is absolutely essential to *** pathogenesis;therefore,the urea substrate must be in ample supply for urease to work *** urea substrate is most likely provided by arginase activity,which hydrolyzes L-arginine to L-ornithine and *** work has demonstrated that *** arginase is surprisingly not required for colonization of wild-type ***,another in vivo source of the critical urea substrate must *** hypothesized that the urea source was provided by host arginase Ⅱ,since this enzyme is expressed in the stomach,and *** has previously been shown to induce the expression of murine gastric arginase Ⅱ.To test this hypothesis,wild-type and arginase (rocF) mutant *** strain SS1 were inoculated into arginase Ⅱ knockout ***: Surprisingly,both the wild-type and rocF mutant bacteria still colonized arginase Ⅱ knockout ***,feeding arginase Ⅱ knockout mice the host arginase inhibitor S-(2-boronoethyl)L-cysteine (BEC),while inhibiting > 50% of the host arginase Ⅰ?activity in several tissues,did not block the ability of the rocF mutant *** to *** contrast,BEC poorly inhibited *** arginase ***: The in vivo source for the essential urea utilized by *** urease is neither bacterial arginase nor host arginase Ⅱ;instead,either residual host arginase Ⅰ?or agmatinase is probably responsible.

关键词： Arginase Helicobacter pylori S-(2-boronoethyl)-L-cysteine Urease Mice

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Hepatotoxicity induced by cyproterone acetate:A report of three cases

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World Journal of Gastroenterology 2006年第46期12卷 7551-7555页

作者： Ioanna Savidou melanie Deutsch Aspasia S Soultati Dimitrios Koudouras Georgia Kafiri Spyridon P Dourakis 2nd Department of Medicine University of Athens Medical School Hippokration General Hospital 114 Vas Sofias Avenues 11527 Athens Greece Department of Pathology Hippokration General Hospital Greece

Cyproterone acetate (CPA) is a steroidal synthetic progestagen and anti-androgenic compound widely administered in prostate cancer which has been evidentially correlated with a severe hepatotoxic potency. Three male patients aged 78-83 years are presented, in whom severe hepatotoxic reactions emerged after CPA administration. Patients were treated with CPA at the doses of 200-300 mg/d for malignant prostate disease for 3-12 mo prior to the acute manifestation of the hepatic disease. Clinical features compatible with mixed hepatocellular and cholestatic liver disease including jaundice, white stools and dark urine, manifested in all three cases whereas encephalopathy and ascites were present in two of the patients. Other primary causes of hepatotoxicity (alcohol consumption and viral hepatitis) were also verified in two cases, and in those patients biopsy findings revealed the presence of cirrhotic lesions in liver parenchyma. Discontinuation of the therapeutic agent led to the amelioration of the clinical profile in all the patients whereas a patient died 40 d after hospital admission due to sepsis, despite acute liver disease improvement. The current article highlights the hepatotoxic potency of a widely administered therapeutic agent and illustrates the importance of clinical surveillance especially in patients with previous hepatic diseases. Three relevant cases are reported and a review of the published literature is made.

关键词： Cyproterone acetate Drug induced hepatotoxicity Prostate cancer Idiosyncratic drug reaction Hepatomitogen action

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Effects of financial incentives for treatment supporters on tuberculosis treatment outcomes in Swaziland: a pragmatic interventional study

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Infectious Diseases of Poverty 2015年第1期4卷 227-233页

作者： Merav Kliner Mamvura Canaan Sifiso Zwide Ndwwe Fred Busulwa William Welfare marty Richardson John Walley John Wright The Clinic Group Matsapha Health CarePO Box 1075MatsaphaManziniSwaziland Family Life Association of Swaziland PO Box 1051ManziniSwaziland Good Shepherd Hospital PO Box 2SitekiSwaziland Manchester Academic Health Science Centre University of ManchesterOxford RdManchester M139PLUK Cochrane Infectious Diseases Group Liverpool School of Tropical MedicinePembroke PlaceLiverpoolMerseyside L35QAUK Nuffield Centre for International Health and Development University of Leeds101 Clarendon RoadLeeds LS29LJUK Bradford Institute for Health Research Bradford Royal InfirmaryDuckworth LaneBradford BD96RJUK Mersey Deanery Summers RoadLiverpoolMerseyside L34BLUK

Background:Swaziland has the highest national incidence of tuberculosis(TB)in the world,with treatment success rates well below the 85%international *** support as part of comprehensive TB services is a core component of the Stop TB *** study investigated the effects of financial incentives for treatment supporters on TB treatment outcomes in ***:This was a controlled study that compared treatment outcomes for patients with a treatment supporter who received or did not receive a financial ***:The intervention group had a higher chance of treatment success as compared with the control group:73%(95%confidence intervals[CIs]66–80%)versus 60%(95%CIs 57–64%),respectively,p=*** improvement remained significant when treatment success rates were adjusted for differences in baseline characteristics,with the effect of incentivised treatment supporters on treatment outcomes having an odds ratio(OR)of *** was also a significant improvement in the death rate in the intervention group,as compared with the control group(10.6 versus 23.5%,p=<0.001).Conclusion:Incentives provided to TB treatment supporters appear to significantly improve TB treatment *** treatment support may be appropriate as an effective addition to support and supervision measures(199 words).

关键词： Tuberculosis Treatment success Swaziland Africa

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Predicting utility of a model for end stage liver disease in alcoholic liver disease

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World Journal of Gastroenterology 2006年第25期12卷 4020-4025页

作者： Aspasia S Soultati Spyridon P Dourakis Alexandra Alexopoulou melanie Deutsch Larissa Vasilieva Athanasios J Archimandritis 2nd Department of Internal Medicine University of Athens Medical School Hippokration General Hospital114 Vas Sofias AvenuesAthens 11527Greece

AIM： To validate the statistic utility of both the Maddrey Discriminant Function score and the Model for End-Stage Liver Disease as predictors of short term （30 d and 90 d） mortality in patients with alcoholic hepatitis and to assess prognostic factors among clinical characteristics and laboratory variables of patients with alcoholic hepatitis. METHODS： Thirty-four patients with the diagnosis of alcoholic hepatitis admitted to Hippokration University Hospital of Athens from 2000 to 2005 were assessed in the current retrospective study and a statistical analysis was conducted. RESULTS： 30- and 90-d mortality rates were reported at 5.9% （2/34） and 14.7% （5/34）, respectively. Significant correlation was demonstrated for the Model for End- Stage Liver Disease （P30 = 0.094, P90 = 0.046） and the Maddrey Discriminant Function score （P30 = 0.033, P90 = 0.038） with 30- and 90-d mortality whereas a significant association was also established for alanine aminotrans- ferase （P = 0.057）, fibrin degradation products （P = 0.048） and C-reactive protein （P = 0.067） with 90-d mortality. For 30-d mortality the Area Under the Curve was 0.969 （95%CI： 0.902-1.036, P = 0.028） for the Model for End-Stage Liver Disease score and 0.984 （95%CI： 0.942-1.027, P = 0.023） for the Maddrey Discriminant Function score with the optimal cut off point of 30.5 （sensitivity 1, specificity 0.937） and 108.68 （sensitivity 1, specificity 0.969）, respectively. Accordingly, for 90-d mortality the Area Under the Curve was 0.762 （95%CI： 0.559-0.965, P = 0.065） for the Model for End-Stage Liver Disease score and 0.752 （95%CI： 0.465-1.038, P = 0.076） for the Maddrey Discriminant Function score with the optimal cut off point of 19 （sensitivity 0.6, specificity 0.6） and 92 （sensitivity 0.6, specificity 0.946）, respectively. The observed Kaplan Meier survival rates for different score-categories were compared with logrank tests and higher score values were correlated with a lower survival. CONCLUSION： Equivale

关键词： Alcoholic liver disease Alcoholic hepatitis Maddrey discriminant function score Model for end-stage liver disease score

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pH-mediated synthesis of monodisperse gold nanorods with quantitative yield and molecular level insight

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Nano Research 2021年第4期14卷 1167-1174页

作者： Reese Gallagher Xing Zhang Anthony Altomare David Lawrence Jr. Nicholas Shawver Ninh Tran melanie Beazley Gang Chen Department of Chemistry University of Central FloridaOrlando32816USA

Although gold nanorods(GNRs)have been produced with different dimensions and aspect ratios,the current synthesis methods through seed-mediated growth are far from ideal,for instance,the quality(rod yield)and the quantity(gold conversion)cannot be simultaneously *** critically,there is no molecular level understanding of the growth ***,we solved the problem by employing the stoichiometric ratio of reactants and tuning the reactivity of the reductant through adjusting the initial pH value of the growth solution to achieve both good quality and high quantity *** also extended our strategy to other enols besides ascorbic acid,such as phenolic compounds,and found that the optimal pH for GNRs synthesis depends on the structure of the individual *** mechanistic insight greatly enriches the toolbox of reductants for GNRs growth and makes it possible to synthesize GNRs at both acidic and basic *** interesting phenomenon is that for most of the phenolic compounds we tested,the morphology of the final products follows the same sphere-rod-sphere trend as the initial pH value of the reaction increases,whether it is under acidic or basic conditions,which cannot be explained by any previously proposed *** effect of pH is mainly attributed to the regulation of the reduction potential of the reductants,and thus the reaction rate.A model has been proposed to explain the dependence of anisotropic growth of GNRs on the concentration gradient of reactants around the seeds,which is decided by both the reaction rate and diffusion rate.

关键词： gold nanorods gold conversion yield shape homogeneity pH value reduction potential concentration gradient

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Circulating biomarkers of hepatocellular carcinoma response after locoregional treatments: New insights

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World Journal of Hepatology 2015年第14期7卷 1834-1842页

作者： Maria Tampaki Polyxeni P Doumba melanie Deutsch John Koskinas Academic Department of Medicine Medical School of AthensHippokration General Hospital

Hepatocellular cancer is the 5th most common cancer in the world and the third cause of death by malignant disease. Locoregional therapies are the most usual treatment of choice for patients with early or intermediate stage of disease. The main diagnostictools for the detection of recurrence are the radiological techniques such as 4-phase computed tomography or dynamic contrast enhanced magnetic resonance imaging. However, in order to achieve best evaluation of treatment outcome and recurrence rates, there is a great need for the identification of specific and easily measured circulating biomarkers. The aim of this review is to analyze the existing data considering the prognostic significance of changes of serum diagnostic markers such as alpha-fetoprotein, des-gamma-carboxy prothrombin, alpha-fetoprotein-L3, angiogenetic factors(vascular endothelial growth factor, hypoxia inducible factor-1a) and immune parameters before and after radiofrequency ablation or transarterial chemoembolization.

关键词： Radiofrequency ablation Transarterialchemoembolization Hepatocellular cancer Circulatingbiomarkers Prognosis

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Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies

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Genes & Diseases 2019年第3期6卷 232-246页

作者： Hongxing Shen Eddy Shih-Hsin Yang marty Conry John Fiveash Carlo Contreras James A.Bonner Lewis Zhichang Shi Department of Radiation Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA O’Neal Comprehensive Cancer Center The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Medical Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Surgical Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Microbiology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Program in Immunology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA

Immune checkpoint blockade therapies(ICBs)are a prominent breakthrough in cancer immunotherapy in recent years(named the 2013“Breakthrough of the Year”by the Science magazine).Thus far,FDA-approved ICBs primarily target immune checkpoints CTLA-4,PD-1,and *** their impressive long-term therapeutic benefits,their efficacy is limited to a small subset of cancer *** addition,ICBs induce inadvertent immune-related adverse events(irAEs)and can be costly for long-term *** overcome these limitations,two strategies are actively being pursued:identification of predictive biomarkers for clinical response to ICBs and multi-pronged combination *** will allow clinicians to practice a precision medicine approach in ICBs(biomarker-based patient selection)such as treating triple-negative breast cancer patients that exhibit PD-L1 staining of tumor-infiltrating immune cells in1%of the tumor area with nanoparticle albumin-bound(nab)epaclitaxel plus anti-PD-L1 and treating patients of MSI-H or MMR deficient unresectable or metastatic solid tumors with pembrolizumab(anti-PD-1).Importantly,the insights gained from these biomarker studies can guide rational combinatorial strategies such as CDK4/6 inhibitor/fractionated radiotherapy/HDACi in conjunction with ICBs to maximize therapeutic ***,with the rapid technological advents(e.g.,ATCT-Seq),we predict more reliable biomarkers will be identified,which in turn will inspire more promising combination therapies.

关键词： IFN-γ Immune checkpoint Microbiota Microsatellite instability Neoantigen PD-L1 Radiotherapy

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