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Stem cell injection for complex anal fistula in Crohn’s disease: A single-center experience

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World Journal of Gastroenterology 2021年第24期27卷 3643-3653页

作者： oliver Schwandner Department of Proctology Krankenhaus Barmherzige BruederRegensburg 93049Germany

BACKGROUND Despite tremendous progress in medical therapy and optimization of surgical strategies,considerable failure rates after surgery for complex anal fistula in Crohn’s disease have been ***,stem cell therapy for the treatment of complex perianal fistula can be an innovative option with potential long-term *** To evaluate the results of local administration of allogenic,adipose-derived mesenchymal stem cells(darvadstrocel)for complex anal Crohn’s *** All patients with complex anal fistulas associated with Crohn’s disease who were amenable for definite fistula closure within a defined observation period were potential candidates for stem cell injection(darvadstrocel)if at least one conventional or surgical attempt to close the fistula had *** was only indicated in patients without active Crohn’s disease and without presence of anorectal *** injection of darvadstrocel was performed as a standardized procedure under general anesthesia including single-shot antibiotic prophylaxis,removal of seton drainage,fistula curettage,closure of the internal openings and local stem cell *** collection focusing on healing rates,occurrence of abscess and follow-up was performed on a regular basis of quality control and patient *** were retrospectively *** Between July 2018 and January 2021,12 patients(6 females,6 males)with a mean age of 42.5(range:26-61)years underwent stem cell *** patients had a minimum of one complex fistula,including patients with two complex fistulas in 58.3%(7/12).Two of the 12 patients had horse-shoe fistula and 3 had one complex *** to Parks classification,the majority of fistulas were transsphincteric(76%)or suprasphincteric(14%).All patients underwent removal of seton,fistula curettage,transanal closure of internal opening by suture(11/12)or mucosal flap(1/12)and stem cell *** a mean follow-up of 14.3(range:3-30)mo,a healing rate

关键词： Complex anal fistula Crohn’s disease Stem cell therapy Mesenchymal stem cells Darvadstrocel Treatment Surgery Outcomes

Mitochondrial dysfunction in a rat model and the related risk of metabolic disorders

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Journal of Traditional Chinese Medicine 2023年第1期43卷 95-104页

作者： LI Han HUANG Xiaomin CAI Haiyang HEROK George HE Jing SU Yixun LI Weihong YI Chenju oliver Brian G CHEN Hui Faculty of Basic Medical Sciences Chengdu University of Traditional Chinese MedicineChengdu 611137China Research Centre the Seventh Affiliated Hospital of Sun Yat-Sen UniversityShenzhen 518107China School of Life Sciences University of Technology SydneyNew South Wales 2059Australia

OBJECTIVE:To explore whether kidney Yang deficiency(KYD)is prone to metabolic disorders may be linked to impaired mitochondrial function in thermogenesis and metabolic ***:A rat model of KYD was used,which was established using Sprague Dawley rat dams with warm preference subjected to herbal treatment that can improve kidney *** human relevance was confirmed by reduced serum corticosterone levels,and increased preference for warm ***:KYD Rats were ***(ATP)production was reduced in the brown fat,but increased in the ***,oxidative phosphorylated complexes to generate ATP and mitochondrial biogenesis marker were reduced in both *** the second insult of high-fat diet(HFD)was introduced,KYD rats gained less weight yet developed more severe lipid and glucose metabolic *** may be driven by disregulated liver gluconeogenesis marker forkhead box protein O1 and lipid metabolic regulator cholesterol 7 ***:KYD rats exhibited reduced mitochondrial function in the brown fat,but were partially compensated by skeletal muscle,associated with the phenotype of warm preference and metabolic disorder,which was further exacerbated by additional HFD *** studies can focus on treatment targetting mitochondria function to reverse this phenotype.

关键词： kidney Yang deficiency DNA,mitochondrial adenosine triphosphate thermogenesis peroxisome proliferator-activated receptor gamma coactivator 1-alpha

Epitaxially aligned single-crystal gold nanoplates formed in large-area arrays at high yield

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Nano Research 2022年第1期15卷 296-303页

作者： Trevor B.Demille Robert D.Neal Arin S.Preston Zijuan Liang Allen G.oliver Robert A.Hughes Svetlana Neretina College of Engineering University of Notre DameNotre DameIndiana 46556USA Department of Chemistry and Biochemistry University of Notre DameNotre DameIndiana 46556USA

Well-tailored nanomaterials with a single-crystal character provide ideal building blocks for on-chip plasmonic *** colloidal methods have demonstrated mastery over the synthesis of such structures,it has proven quite difficult to deploy these same nanomaterials on substrate surfaces in a highly deterministic manner where precise control over position and orientation is ***,we demonstrate a room-temperature two-reagent liquid-phase seed-mediated synthesis of gold nanoplates directly on substrate surfaces in arrays over a square-centimeter *** synthesis is reliant on benchtop lithographic and directed-assembly processes that give rise to single-crystal seeds of gold that express both an epitaxial relationship with the underlying substrate and the internal defect structure required to promote a two-dimensional growth *** resulting structures are highly faceted and,because seed-substrate epitaxy is imposed upon the growing nanoplates,are identically aligned on the substrate *** yields are increased to values as high as 95%using a post-processing sonication procedure that selectively removes a small population of irregularly shaped nanostructures from the substrate surface,and in doing so,gives rise to an uncompromised plasmonic *** work,therefore,advances the techniques needed to integrate single-crystal nanomaterials with wafer-based technologies and provides leading-edge capabilities in terms of defining large-area arrays of plasmonic structures with the nanoplate geometry.

关键词： nanoplates epitaxial array plasmon Brij-700 block copolymer substrate

Chemistry-led investigations into the mode of action of NAMPT activators,resulting in the discovery of non-pyridyl class NAMPT activators

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Acta Pharmaceutica Sinica B 2023年第2期13卷 709-721页

作者： Siyuan Tang Miguel Garzon Sanz oliver Smith Andreas Krämer Daniel Egbase Paul W.Caton Stefan Knapp Sam Butterworth Division of Pharmacy and Optometry School of Health SciencesManchester Academic Health Sciences CentreUniversity of ManchesterManchester M139PLUK Structural Genomics Consortium(SGC) 60438 Frankfurt Am MainGermany Buchmann Institute for Life Sciences(BMLS) 60438 Frankfurt Am MainGermany Institut für Pharmazeutische Chemie Goethe University60438 Frankfurt Am MainGermany Frankfurt Cancer Institute(FCI) 60596 Frankfurt Am MainGermany Department of Diabetes School of Cardiovascular and Metabolic Medicine&SciencesFaculty of Life Sciences&MedicineKing's College LondonLondon SE11ULUK

The cofactor nicotinamide adenine dinucleotide(NAD+)plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+levels is an established approach to enhancing healthy ***,several classes of nicotinamide phosphoribosyl transferase(NAMPT)activators have been shown to increase NAD+levels in vitro and in vivo and to demonstrate beneficial effects in animal *** best validated of these compounds are structurally related to known urea-type NAMPT inhibitors,however the basis for the switch from inhibitory activity to activation is not well *** we report an evaluation of the structure activity relationships of NAMPT activators by designing,synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known *** results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site,resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead,which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

关键词： Nicotinamide phosphoribosyl transferase activator Healthy aging Drug discovery Bioisosteres Medicinal chemistry

A classical equation that accounts for observations of non-Arrhenius and cryogenic grain boundary migration

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npj Computational Materials 2022年第1期8卷 1492-1500页

作者： Eric R.Homer oliver K.Johnson Darcey Britton James E.Patterson Eric T.Sevy Gregory B.Thompson Department of Mechanical Engineering Brigham Young UniversityProvoUT84602USA Department of Chemistry and Biochemistry Brigham Young UniversityProvoUT84602USA Department of Metallurgical and Materials Engineering University of AlabamaTuscaloosaAL35401USA

Observations of microstructural coarsening at cryogenic temperatures,as well as numerous simulations of grain boundary motion that show faster migration at low temperature than at high temperature,have been troubling because they do not follow the expected Arrhenius *** work demonstrates that classical equations,that are not simplified,account for all these oddities and demonstrate that non-Arrhenius behavior can emerge from thermally activated *** to this classical model,this occurs when the intrinsic barrier energies of the processes become small,allowing activation at cryogenic *** thermal energy then allows the low energy process to proceed in reverse,so increasing temperature only serves to frustrate the forward *** classical form is shown to reconcile and describe a variety of diverse grain boundary migration observations.

关键词： cryogenic grain boundary

Spatiotemporal Dynamics of a Páramo Ecosystem in the Northern Ecuadorian Andes 1988-2007

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Journal of Mountain Science 2014年第3期11卷 708-716页

作者： oliver WIGMORE Jay GAO School of Environment University of Auckland Private Bag 92019 Auckland New Zealand Department of Geography The Ohio State University 1036 Derby Hall 154 N Oval Mall Columbus Ohio 43210 USA Byrd Polar Research Center The Ohio State University 108 Scott Hall 1090 Carmack Road Ohio 43210 USA School of Environment University of Auckland Private Bag 92019 Auckland New Zealand

Páramo is a term used to describe tropical alpine vegetation between the continuous timberline and the snow line in the Northern Andes. Páramo environments provide important species habitat and ecosystem services. Changes in spatial extent of the páramo ecosystem at Pambamarca in the Central Cordillera of the northern Ecuadorian Andes were analysed using multi-temporal Landsat TM/ETM+ satellite data. The region suffered a loss of 1826.6 ha or 20% of the total area at a rate of 100 ha/annum during 1988-2007 period. It is found that permanent páramo cover decreased from 8350 ha in 1988 to 5864 ha in 2007 at a fairly constant rate(R2=0.94). This loss is attributed to expansion of commercial agriculture and floriculture in the valleys coupled with increased population pressure. Land at higher elevations has been cleared for small scale agriculture. Loss of the páramo ecosystem will exert a number of negative impacts on ecosystem services and livelihoods of the local population at Pambamarca.

关键词：生态系统服务安第斯山脉厄瓜多尔时空动态 Landsat 规模农业高山植被空间范围

Treatment sequencing in metastatic castrate-resistant prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 426-431页

作者： oliver Sartor Silke Gillessen Department of Medicine and Urology Tulane University School of Medicine New Orleans Louisiana USA Department of Medical Oncology Kantonsspital St. Gallen St. Gallen Switzerland.

Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer （mCRPC）. Front-line therapeutic options for mCRPC include docetaxel, sipuleuceI-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

关键词： abiraterone cabazitaxel castrate-resistant docetaxel enzalutamide~ radium-223 sipuleuceI-T

Abandoned Altitudes? Decrease and Expansion of Grassland in the Hinterland of Popayán, Southern Colombian Andes

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Journal of Mountain Science 2015年第1期12卷 123-133页

作者： Andreas Haller oliver Bender Institute of Geography University of Innsbruck Institute for Interdisciplinary Mountain Research Austrian Academy of Sciences Technikerstrasse 21a 6020 InnsbruckAustria

Due to their ecological disadvantages,many mountain regions have experienced land-use abandonment and shrub encroachment on former grassland at higher altitudinal zones—especially during recent decades of urbanization. But does this trend also apply to the hinterland of urban settlements? By using the Southern Colombian example of Popayán, a medium-sized city located in the Northern Andes, we can show that the landscape changes observed between 1989 and 2010 can hardly be related to agricultural abandonment. Hypsometric variations of land-cover change indicate that, until 2001, woods or shrubland expanded faster at the lower altitudinal range adjacent to the city than at the more remote higher zones. In contrast, after 2001 grassland areas increased on former woods or shrubland at all altitudinal belts. Both periods thus present developments that can be interpreted as the result of land-use expansion below 2000 m asl and land-use persistence in the tierra fría of the mountain city's hinterland.

关键词：安第斯山脉海拔高度哥伦比亚腹地草原土地覆被变化草地面积土地使用

Long-term vegetation development on a wildfire slope in Innerzwain(Styria,Austria)

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Journal of Forestry Research 2014年第1期25卷 103-111页

作者： Bodo Malowerschnig oliver Sass Karl-Franzens-University Graz Department of Geography and Regional Science

Forest fires in mountainous areas can cause severe defores-tation which can potentially trigger secondary natural hazards like debris falls and avalanches. We documented an extreme case study for the range of possible post-fire land cover （LC） dynamics. We investigated a 15-ha, steep （10°-65°） burnt slope in Styria （Austria） at elevation of 760-1130 m, which burned in 1946 and has not fully recovered to date. Seven 8-class legend LC maps were produced （1954, 1966, 1973, 1982, 1998, 2004, 2009） and integrated in a vector-based GIS, mainly by on-screen interpretation of aerial photos. Our aim was to clarify how post-wildfire LC dynamics take place on a severely damaged, steep slope and to give a basic projection of the future vegetation recovery process. The pre-fire Pinus sylvestrisstands have been mainly replaced by Picea abies and Larix decidua. Regeneration proceeded mainly from the base of the slope upwards. All tree species together still cover no more than 40% of the slope after more than 60 years of recovery, while grassland communities and rock/debris areas have expanded. Multitemporal analysis showed a slow but steady increase in woodland cover. Degraded rock/debris areas, however, expanded as well because soil erosion and related debris flows remained active. Slope angle （with a threshold value of approx. 35-40°） seemed to control whether erosion or regeneration prevailed. According to a simple extrapolation, the slope will not reach its former condition before 2070. This extreme disturbance window of more than 120 years is owed to the steepness of the slope and to the shallow soils on dolomitic bedrock that were severely damaged by the fire. The neglect of any game fencing is a further factor slowing regeneration.

关键词： wildfire landcover change temperate forest aerial photos,soil degradation vegetation development