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Short-term nitisinone discontinuation of hereditary tyrosinemia type 1 mice causes metabolic alterations in glutathione metabolism/biosynthesis and multiple amino acid degradation pathways

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Genes & Diseases 2023年第5期10卷 1759-1762页

作者： Colemonts-Vroninks Haaike Norman P.Brendan Van laere sven Davison S.Andrew Marcélis lionel Casimir Georges Goyens Philippe Claes Paul De Bundel Dimitri Martens Geert Ranganath lakshminarayan Rao Vanhaecke Tamara Gallagher James A De Kock Joery Vrije Universiteit Brussel Liver Therapy&Evolution TeamIn Vitro Toxicology and Dermato-Cosmetology(IVTD)Research GroupFaculty of Medicine and PharmacyLaarbeeklaan 103Brussels B-1090Belgium Vrije Universiteit Brussel Experimental Pharmacology(EFAR)Research GroupFaculty of Medicine and PharmacyLaarbeeklaan 103Brussels B-1090Belgium University of liverpool Dept.of Musculoskeletal&Ageing ScienceInstitute of Life Course&Medical SciencesLiverpool L78TXUnited Kingdom Vrije Universiteit Brussel Interfaculty Center Data Processing and StatisticsFaculty of Medicine and PharmacyLaarbeeklaan 103Brussels B-1090Belgium liverpool University Hospitals NHS Foundation Trust Clinical Biochemistry and Metabolic MedicineLiverpool L35PSUnited Kingdom Universitélibre de Bruxelles Laboratoire de PédiatrieBrussels B-1050Belgium Vrije Universiteit Brussel In Vitro Liver Disease Modelling TeamIn Vitro Toxicology and Dermato-Cosmetology(IVTD)Research GroupFaculty of Medicine and PharmacyLaarbeeklaan 103Brussels B-1090Belgium AZ Delta General Hospital Department of Laboratory MedicineRoeselare 8800Belgium Ghent University Department of Biomolecular MedicineGhent 9052Belgium

Hereditary tyrosinemia type 1(HT1)is a life-threatening disease caused by the patient's inability to break down tyrosine due to loss-of-function mutations in the fumarylacetoacetate hydrolase(FAH)enzyme(Fig.S1).Currently,the only available life-saving treatment is nitisinone(NTBC).However,nitisinone therapy comes with debilitating side effects and requires a strict drug regime combined with a tyrosine-and phenylalanine-restricted ***,therapy adherence is often experienced as an additional *** this study,transcriptional profiling was conducted parallel to high-resolution metabolomics on,respectively,liver tissue and serum samples of Fah-deficient *** experimental workflow of our study is shown in Figure *** pathway analyses showed manifest activation of the NRF2-stress response,associated with hepatocellular damage and mainly driven by a markedly increased oxidative *** altered canonical pathways were primarily a downstream consequence of the ***,we observed an overall aminoacidemia and changes related to aminoacyl-tRNA biosynthesis,which postulates that short-term nitisinone discontinuation can already put the patient at risk for hepatocellular carcinoma ***,we did not only identify changes in numerous pathways,directly and indirectly,related to the metabolism of tyrosine and glutathione but also the presence of“side-chain”metabolites,such as y-glutamyl-and N-acetyl-coupled amino acids,indicating that non-directly related pathways like phase II biotransformation reactions are also affected.

关键词： continuation Figure hereditary

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The Use of Restriction Fragment length Polymorphism and Fluorescence in Situ Hybridization to Investigate Microbiota of Piglets after Feeding Oregano

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Food and Nutrition Sciences 2014年第17期5卷 1628-1636页

作者： Katrin Stelter Andreas Berk lutz Geue Stefanie Barth Petra Schlien Alexander Swidsinski sven Danicke Institute of Animal Nutrition Friedrich-Loeffler-Institute(FLI)Federal Research Institute for Animal HealthBraunschweigGermany Institute of Molecular Pathogenesis Friedrich-Loeffler-Institute(FLI)Federal Research Institute for Animal HealthJenaGermany Charite Hospital CCMLaboratory for Molecular GeneticsPolymicrobial Infections and Bacterial BiofilmsDepartment of MedicineGastroenterologyUniversitatsmedizin BerlinBerlinGermany

A total of 80 piglets (7.9 ± 1.0 kg) were used in a feeding experiment with dried oregano. The diets differed in their oregano content: 0 g, 2 g, 4 g and 8 g oregano/kg feed, corresponding to 0, 23.5, 46.9 and 93.9 mg carvacrol/kg DM. After the experimental period of 5 weeks, 20 piglets of both extreme feeding groups were slaughtered: 10 animals of the control group and 10 animals of the group that received 8 g oregano/kg. Ingesta samples of jejunum, caecum and colon were collected and analyzed by FISH and PCR RFlP to compare the diversity of microbiota. The results showed no significant changes in microbiota in response to oregano. The patterns of the PCR-RFlP showed a similarity of 61.8% - 91.8% in both feeding groups. In conclusion, an effect of oregano on the in- testinal microbiota could not be shown under the methods used.

关键词： Piglets Origanum vulgare l. Fluorescence in Situ Hybridization Restriction Fragment length Polymorphism Intestinal Microorganisms

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血清胸苷激酶1检测对肺癌患者诊断与预后评估的意义

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江苏医药 2012年第3期38卷 310-312页

作者：周源汪栋杨爱珍 Ellen He sven Skog 张旻解放军第八一医院胸心外科江苏省210002 解放军第八一医院中心实验科江苏省210002 华瑞同康生物技术(深圳)有限公司

目的探讨血清胸苷激酶1(TK1)检测对肺癌患者诊断与预后评估的意义。方法应用免疫印迹-增强化学发光法检测63例肺癌患者(A组)和14例健康体检者(B组)血清TK1水平。24例术后获随访6-18个月。其中,无肿瘤复发15例(无复发组),肿瘤复发9例(复... 详细信息

目的探讨血清胸苷激酶1(TK1)检测对肺癌患者诊断与预后评估的意义。方法应用免疫印迹-增强化学发光法检测63例肺癌患者(A组)和14例健康体检者(B组)血清TK1水平。24例术后获随访6-18个月。其中,无肿瘤复发15例(无复发组),肿瘤复发9例(复发组);随访期同时检测了其他相关肿瘤标记物。结果 A组血清TK1水平明显高于B组[(2.37±3.74)pmol/lvs.(0.32±0.42)pmol/l](P<0.01)。A组手术治疗后血清TK1水平显著降低(P<0.05)。复发组血清TK1均较术前升高;无复发组中1例血清TK1升高,其余14例均较术前降低。TK1与其他肿瘤标志物联合检测提高了预后评估的准确性。结论血清TK1水平升高对肺癌有辅助诊断价值,连续跟踪监测有利于肺癌治疗效果和预后的判断。

关键词：胸苷激酶1 肺癌

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父亲使用抗抑郁药物与子代结局:瑞典全国前瞻性队列研究

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英国医学杂志中文版 2022年第7期25卷 376-377页

作者： Alexander Viktorin Stephen Z levine Margret Atemus Abraham Reichenberg sven Sandin 李和程(译) 王忠(校) Departnent of Medical Epidemiology and Biostatistics Karolinska InstitutetStockholmSweden Department of Community Mental Health University of HaifaHaifaIsrael Department of Psychiatry Yale School of MedicineNew HavenCTUSA Department of Psychiatry Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Seaver Autism Center for Research and Treatment at Mount Sinai New YorkNYUSA 西安交通大学第二附属医院泌尿外科上海交通大学医学院附属第九人民医院

目的探究父亲在母亲受孕期间使用抗抑郁药与子代早产、畸形、自闭症谱系障碍和智力残疾之间的关系。设计利用回归方法和阴性对照进行观察性前瞻性队列研究。研究地点瑞典全国。

关键词：前瞻性队列研究自闭症谱系障碍抗抑郁药物智力残疾回归方法观察性阴性对照子代

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Spiegelmer NOX 1255对lHRH-PE40与Hela细胞上lHRH受体结合的抑制作用

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中国生物制品学杂志 2011年第6期24卷 657-659,664页

作者：邓欣 sven Klussmann 李亘松聂志伟宋阳张国利朱平中国医科大学基础医学院机能实验中心沈阳110001 德国柏林NOXXON制药公司军事医学科学院军事兽医研究所生物技术应用研究室长春130062

目的探讨Spiegelmer NOX 1255对促黄体激素释放激素-绿脓杆菌外毒素40(luteinizing hormone-releasing hor-mone-Pseudomonas aeruginosa exotoxin 40,lHRH-PE40)与Hela细胞上促黄体激素释放激素(lHRH)受体结合的抑制作用。方法分别将25μmol/l的lHRH-PE40、PEA和PE40与Hela细胞共孵育24 h后,观察细胞的形态学变化;用Spiegelmer NOX1255特异性结合lHRH-PE40上的lHRH,光学显微镜观察Spiegelmer NOX 1255对lHRH-PE40的抑制作用,ElISA检测Spiege-lmer NOX 1255对lHRH-PE40与lHRH受体结合的抑制作用。结果 lHRH-PE40和PEA可直接杀伤Hela细胞,而PE40不能对Hela细胞产生毒性作用;Spiegelmer NOX 1255能够结合lHRH-PE40中的lHRH,抑制lHRH-PE40与lHRH受体的结合及PE40的毒性作用。结论 lHRH-PE40对Hela细胞的毒性作用是通过细胞表面的lHRH受体产生的;Spiegelmer NOX 1255可阻断lHRH-PE40与Hela细胞表面lHRH受体的结合。

关键词：受体 lHRH Hela细胞 Spiegelmer NOX 1255 lHRH-PE40

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Dukan Dam Reservoir Bed Sediment, Kurdistan Region, Iraq

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Engineering（科研） 2016年第9期8卷 582-596页

作者： Rebwar Hassan Nadhir Al-Ansari Salahalddin S. Ali Ammar A. Ali Twana Abdullah sven Knutsson luleå University of Technology Lulea Sweden Department of Geology University of Sulaimani Sulaymaniyah Iraq

The Dukan Dam Reservoir (DDR) in the Kurdistan Region of Iraq has been studied to determine the characteristics and nature of the reservoir and the deposited sediments on its bottom surface. This study was achieved by doing a field survey and grain size analyses of the collected sediment samples at 32 locations representing the whole reservoir area that had been created when the lesser Zab River was dammed in 1959. The Dukan Dam, which is a multi-purpose concrete arch dam, was built on the lesser Zab River for controlling its flood during high rainfall seasons, irrigation and power generation. The catchment area is 11,690 km2. The surface area of the reservoir is 270 square kilometers and the volume is 6.870 × 106 m3 at normal operation level (El. 511.00 m. a.s.l.). The minimum drawdown level is at elevation 469 m above sea level (a.s.l.). The live storage is 6.14 × 106 m3 while the remainder is dead storage. The reservoir has a surface area that reaches 270 square kilometers and is composed of two sub-reservoirs connected by a narrow channel that has a length of 5 kilometers. The relatively bigger reservoir is located in the north and has a triangular shape with a surface area approximately 250 square kilometers. The smaller sub-reservoir is located down south where the dam exists and it has irregular rectangular shape. Thirty-two sediment samples were collected from the bottom of Dukan reservoir. The bed of the reservoir is mainly composed of 15% gravel, 14% sand, 48% silt and 23% clay respectively. Most of the sediments are very fine grained, very poorly sorted, strongly coarse skewed and mesokurtic.

关键词： Sediment Dukan Reservoir Iraq

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Esophagogastric anastomosis in rats: Improved healing by BPC 157 and l-arginine, aggravated by l-NAME

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World Journal of Gastroenterology 2016年第41期22卷 9127-9140页

作者： Zeljko Djakovic Ivka Djakovic Vedran Cesarec Goran Madzarac Tomislav Becejac Goran Zukanovic Domagoj Drmic lovorka Batelja Anita Zenko Sever Danijela Kolenc Alen Pajtak Nikica Knez Mladen Japjec Kresimir luetic Dinko Stancic-Rokotov sven Seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb 10000 Zagreb Croatia

AIM To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NOsystem. In the 4 d after esophagogastric anastomosis creation, rats received medication(/kg intraperitoneallyonce daily: BPC 157(10 μg, 10 ng), l-NAME(5 mg), or l-arginine(100 mg) alone and/or combined or BPC 157(10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage(sum of the longest diameters, mm), esophagitis(scored 0-5), weak anastomosis(m l H2 O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter(cm H2O), progressive weight loss(g) and mortality. Immediate effect assessed blood vessels disappearance(scored 0-5) at the stomach surface immediately after anastomosis creation. RESUlTS BPC 157(all regimens) fully counteracted the perilous disease course from the very beginning(i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with l-NAME nullified any effect of l-NAME that otherwise intensified the regular course. Consistently, with worsening(with l-NAME administration) and amelioration(with l-arginine), either l-arginine amelioration prevails(attenuated esophageal and gastric lesions) or they counteract each other(l-NAME + l-arginine); with the addi

关键词： Esophagogastric anastomosis l-NAME Aggravation BPC 157 l-arginine Curative treatment Rats

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Vitamin D Insufficiency among Women Post-Partum in Northern Sweden—A Public Health Concern

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Food and Nutrition Sciences 2017年第1期8卷 99-109页

作者： Pamela Hasslof Frida Karlsson Videhult sven Arne Silfverdal Christina E.West Christina Stecksén-Blicks Department of Odontology Pediatric DentistryUmea UniversityUmeaSweden Department of Clinical Sciences PediatricsUmea UniversityUmeaSweden

Pregnancy and post-partum represent a period of susceptibility for vitamin D insufficiency. This study investigated S-25 [OH] D levels in women in northern Sweden 4 weeks post-partum and its association with selected background factors. Blood from 100 healthy women were analyzed for iron status and serum levels of S-25[OH] D using ionization-mass spectrometry (HPlC-APCI-MS). <50 nmol/l was categorized as insufficiency and <25 nmol/l as deficiency. Maternal BMI, dietary habits, fungal infections during pregnancy, and infant birth characteristics were collected using questionnaires and medical charts. 58% were vitamin D insufficient whereas 10% had deficiency. Insufficiency was most common during winter (OR = 2.77;95% CI = 1.1-6.96) and women with deficiency reported lower milk consumption;11.3 ± 22.8 intakes per months vs. 34.0 ± 28.9 for those above 25 nmol/l (p °49'N. The odds of being insufficient were increased during winter whereas milk consumption was negatively associated with deficiency. The low vitamin D-levels particularly during winter is a public health concern. From a public health perspective it has to be considered whether dietary advices alone should be modified or if supplementation with vitamin D during pregnancy and the post-partum period also is needed.

关键词： Vitamin D Insufficiency Fungal Infection Postpartum Public Health Season

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Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, l-NAME and l-arginine

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World Journal of Gastroenterology 2018年第47期24卷 5366-5378页

作者： Fedor Amic Domagoj Drmic Zdenko Bilic Ivan Krezic Helena Zizek Marina Peklic Robert Klicek Alen Pajtak Enio Amic Tinka Vidovic Mislav Rakic Marija Milkovic Perisa Katarina Horvat Pavlov Antonio Kokot Ante Tvrdeic Alenka Boban Blagaic Mario Zovak sven Seiwerth Predrag Sikiric Department of Pharmacology Medical Faculty University of Zagreb Department of Pathology Medical Faculty University of Zagreb

AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system *** Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 ml bath/rat; l-NAME 5 mg/kg per 1 m l bath/rat; l-arginine 100 mg/kg per 1 ml bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in *** Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of l-NAME and l-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, l-NAME+l-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving l-NAME and/or l-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal *** BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and

关键词： Major venous occlusion Duodenal lesions BPC 157 l-NAME Bypassing l-arginine Reduction of free radical formation Rats

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数字词典学视阈下“有意学习”与“附带学习”新探

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辞书研究 2022年第6期 1-11,I0002页

作者： sven Tarp 陈汝(译) 耿云冬(译) 丹麦奥胡斯大学词典学中心奥胡斯华中农业大学外国语学院武汉430070

文章在数字词典场域中重新审视二语习得经典概念“有意学习”与“附带学习”的内涵与差异,并结合欧洲数字词典研发前沿案例,探讨大数据时代如何优化数字词典的语言知识服务功能。

关键词：有意学习附带学习写作助手数字辞书

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