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Shaping of the nephron - a complex, vulnerable, and poorly explored backdrop for noxae impairing nephrogenesis in the fetal human kidney. 肾元的形成-一个复杂的,脆弱的,并且在胎儿肾脏中对noxae损害肾形成的研究很少。
Pub Date : 2020-01-22 DOI: 10.1186/s40348-020-0094-9
Will W Minuth

Background: The impairment of nephrogenesis is caused by noxae, all of which are significantly different in molecular composition. These can cause an early termination of nephron development in preterm and low birth weight babies resulting in oligonephropathy. For the fetal human kidney, there was no negative effect reported on the early stages of nephron anlage such as the niche, pretubular aggregate, renal vesicle, or comma-shaped body. In contrast, pathological alterations were identified on subsequently developing S-shaped bodies and glomeruli. While the atypical glomeruli were closely analyzed, the S-shaped bodies and the pre-stages received little attention even though passing the process of nephron shaping. Since micrographs and an explanation about this substantial developmental period were missing, the shaping of the nephron in the fetal human kidney during the phase of late gestation was recorded from a microanatomical point of view.

Results: The nephron shaping starts with the primitive renal vesicle, which is still part of the pretubular aggregate at this point. Then, during extension of the renal vesicle, a complex separation is observed. The medial part of its distal pole is fixed on the collecting duct ampulla, while the lateral part remains connected with the pretubular aggregate via a progenitor cell strand. A final separation occurs, when the extended renal vesicle develops into the comma-shaped body. Henceforth, internal epithelial folding generates the tubule and glomerulus anlagen. Arising clefts at the medial and lateral aspect indicate an asymmetrical expansion of the S-shaped body. This leads to development of the glomerulus at the proximal pole, whereas in the center and at the distal pole, it results in elongation of the tubule segments.

Conclusions: The present investigation deals with the shaping of the nephron in the fetal human kidney. In this important developmental phase, the positioning, orientation, and folding of the nephron occur. The demonstration of previously unknown morphological details supports the search for traces left by the impairment of nephrogenesis, enables to refine the assessment in molecular pathology, and provides input for the design of therapeutic concepts prolonging nephrogenesis.

背景:肾形成障碍是由诺科菌引起的,它们的分子组成有显著差异。这些可导致早产儿和低出生体重婴儿肾细胞发育的早期终止,从而导致少肾病。对于胎儿人肾,未见对早期肾元基质(如生态位、肾小管前聚集体、肾小泡或逗号形体)有负面影响的报道。相反,在随后形成的s形体和肾小球上发现了病理改变。非典型肾小球虽经过肾元成形过程,但其s型体和前期却很少受到关注。由于缺乏显微照片和对这一重要发育时期的解释,因此从显微解剖学的角度记录了妊娠后期胎儿肾脏肾元的形成。结果:肾元形成始于原始肾小泡,此时仍是肾小泡前聚集体的一部分。然后,在肾囊延伸期间,观察到复杂的分离。其远端极的内侧部分固定在集合管壶腹上,而其外侧部分通过祖细胞链与前管聚集体保持连接。当延伸的肾囊发育成逗号状体时,发生最后的分离。此后,内部上皮折叠产生小管和肾小球的原素。在内侧和外侧出现的裂缝表明s形体的不对称扩张。这导致近端肾小球的发育,而在中心和远端,它导致小管段的延长。结论:本研究涉及胎儿肾脏肾元的形成。在这个重要的发育阶段,肾元的定位、定向和折叠发生了。先前未知的形态学细节的展示支持了对肾发生损伤留下的痕迹的研究,使分子病理学的评估得以完善,并为延长肾发生的治疗概念的设计提供了输入。
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引用次数: 8
Functional analysis of granulocyte and monocyte subpopulations in neonates 新生儿粒细胞和单核细胞亚群的功能分析
Pub Date : 2019-11-28 DOI: 10.1186/s40348-019-0092-y
I. Hegge, Ferry Niepel, A. Lange, A. Vogelgesang, M. Heckmann, J. Ruhnau
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引用次数: 9
Vegetarian diets in childhood and adolescence : Position paper of the nutrition committee, German Society for Paediatric and Adolescent Medicine (DGKJ). 儿童和青少年的素食饮食
IF 2.4 Q1 PEDIATRICS Pub Date : 2019-11-12 DOI: 10.1186/s40348-019-0091-z
Silvia Rudloff, Christoph Bührer, Frank Jochum, Thomas Kauth, Mathilde Kersting, Antje Körner, Berthold Koletzko, Walter Mihatsch, Christine Prell, Thomas Reinehr, Klaus-Peter Zimmer

In Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whether the corresponding health benefits in vegetarians outweigh the risks of nutrient deficiencies has not been fully clarified. It should be noted that vegetarians often have a higher socioeconomic status, follow a more health-conscious lifestyle with higher physical activity, and refrain from smoking more often than non-vegetarians. The nutritional needs of growing children and adolescents can generally be met through a balanced, vegetable-based diet; however, due to their higher nutrient requirements per kilogramme of body weight, vegetarian children have a higher risk for developing nutrient deficiencies than adults. With a vegetarian diet, the mean intakes of some nutrients, such as the omega-3 fatty acid docosahexaenoic acid (DHA), are lower than in omnivores or those eating fish. For other nutrients, such as iron and zinc, the bioavailability from vegetable foodstuffs is reduced when the intake of phytates and fibre is high; thus, the prevalence of iron deficiency can be increased despite high vitamin C intake. In addition, vitamin B12 is only found in animal-source foods. Vitamin B12 should be supplemented in people of all age groups who follow a strict vegan diet without consuming animal products. A vegetarian diet in childhood and adolescence requires good information and supervision by a paediatrician, if necessary, in cooperation with an appropriately trained dietary specialist.

在西方国家,与杂食饮食相比,素食摄入的能量、饱和脂肪酸和动物蛋白质较低,而纤维和植物化学物质的摄入量较高。素食者的相应健康益处是否大于营养素缺乏的风险尚未完全明确。值得注意的是,素食者的社会经济地位通常较高,他们的生活方式更注重健康,体育锻炼更多,而且与非素食者相比,他们更经常戒烟。一般来说,以蔬菜为基础的均衡饮食可以满足成长中的儿童和青少年的营养需求;然而,由于每公斤体重对营养素的需求量较高,素食儿童患营养素缺乏症的风险高于成人。在素食饮食中,某些营养素的平均摄入量(如欧米茄-3 脂肪酸二十二碳六烯酸 (DHA))低于杂食者或吃鱼的人。至于其他营养素,如铁和锌,如果植酸盐和纤维摄入量高,从蔬菜食品中摄取的生物利用率就会降低;因此,尽管维生素 C 摄入量高,缺铁症的发病率也会增加。此外,维生素 B12 只存在于动物源性食品中。各年龄段的人如果严格遵守素食原则,不食用动物产品,就应补充维生素 B12。儿童和青少年时期的素食需要儿科医生提供良好的信息和指导,必要时还应与经过适当培训的饮食专家合作。
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引用次数: 0
Vitamin D supplementation after the second year of life: joint position of the Committee on Nutrition, German Society for Pediatric and Adolescent Medicine (DGKJ e.V.), and the German Society for Pediatric Endocrinology and Diabetology (DGKED e.V.). 2岁后补充维生素D:营养委员会、德国儿科和青少年医学学会(DGKJ e.v.)和德国儿科内分泌学和糖尿病学会(DGKED e.v.)的联合立场。
Pub Date : 2019-05-06 DOI: 10.1186/s40348-019-0090-0
Thomas Reinehr, Dirk Schnabel, Martin Wabitsch, Susanne Bechtold-Dalla Pozza, Christoph Bührer, Bettina Heidtmann, Frank Jochum, Thomas Kauth, Antje Körner, Walter Mihatsch, Christine Prell, Silvia Rudloff, Bettina Tittel, Joachim Woelfle, Klaus-Peter Zimmer, Berthold Koletzko

Background: Low vitamin D serum concentrations have been associated with rickets and other disorders in observational studies. Since vitamin D serum concentrations in children and adolescents are frequently below reference values, it is debated whether vitamin D should be supplemented after infancy.

Methods: The effects of vitamin D supplementation in children > 2 years of age are analyzed based on a literature review of randomized controlled trials (RCTs).

Results: Vitamin D supplementation can potentially reduce the risk for influenza infections and improve asthma bronchiale exacerbation; however, it has no impact on asthma bronchiale severity. Vitamin D supplementation has no relevant effect on attention-deficit/hyperactivity disorders, cardiac failure, hypertension, or incidence of type II diabetes mellitus. Vitamin D supplementation has no effect on the rate of multiple sclerosis relapses, but on the number of new lesions detected by MRI. For other endpoints, RCTs are lacking.

Conclusion: Based on currently available studies, routine vitamin D supplementation is not be recommended for children aged > 2 years, even when they have serum concentrations below reference values. Routine vitamin D supplementation is not recommended in children who do not have risk factors and chronic diseases which are associated with calcium or vitamin D resorption disorders.

背景:在观察性研究中,低维生素D血清浓度与佝偻病和其他疾病有关。由于儿童和青少年的维生素D血清浓度经常低于参考值,因此在婴儿期后是否应该补充维生素D一直存在争议。方法:通过随机对照试验(RCTs)的文献综述,分析维生素D补充剂对> 2岁儿童的影响。结果:补充维生素D可以潜在地降低流感感染的风险,改善哮喘支气管恶化;然而,它对支气管哮喘的严重程度没有影响。补充维生素D对注意缺陷/多动障碍、心力衰竭、高血压或II型糖尿病的发病率没有相关影响。补充维生素D对多发性硬化症的复发率没有影响,但对MRI检测到的新病变数量有影响。对于其他终点,缺乏随机对照试验。结论:根据现有的研究,不建议2岁以上的儿童常规补充维生素D,即使他们的血清浓度低于参考值。对于没有与钙或维生素D吸收障碍相关的危险因素和慢性疾病的儿童,不建议常规补充维生素D。
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引用次数: 13
Complementary foods in baby food pouches: position statement from the Nutrition Commission of the German Society for Pediatrics and Adolescent Medicine (DGKJ, e.V.). 婴儿食品袋中的辅食:德国儿科和青少年医学学会营养委员会(DGKJ, e.v.)的立场声明。
Pub Date : 2019-03-06 DOI: 10.1186/s40348-019-0089-6
Berthold Koletzko, Christoph Bührer, Regina Ensenauer, Frank Jochum, Hermann Kalhoff, Burkhard Lawrenz, Antje Körner, Walter Mihatsch, Silvia Rudloff, Klaus-Peter Zimmer

Pureed complementary feeding products packed in squeezable plastic pouches, usually with a spout and a screw cap, have been increasingly marketed. The Committee on Nutrition recommends that infants and young children should not suck pureed or liquid complementary foods from baby food pouches. Complementary foods should be offered with a spoon or should be fed as finger foods. Infants and young children should be given the opportunity to get to know a variety of foods and food textures including pieces of foods, supported by responsive feeding between the child and their parents or caregivers. Complementary foods marketed in baby food pouches often have a high energy density and are predominantly extremely high in sugar content, with up to almost 90% of the total energy content. Regular consumption bears the risks of imbalanced nutrient provision and increased risks for dental caries and overweight. Complementary foods for infants and young children should have a balanced composition following the recommendations of the German Society of Pediatrics and Adolescent Medicine (DGKJ) and should contain only limited amounts of sugar. We discourage the feeding of pureed complementary foods from baby food pouches.

糊状辅食产品包装在可挤压的塑料袋,通常有一个喷嘴和一个螺旋盖,已经越来越多地推向市场。营养委员会建议,婴幼儿不应从婴儿食品袋中吮吸浆糊或液体辅食。辅食应该用勺子提供,或者应该作为手指食物来喂。婴儿和幼儿应该有机会了解各种食物和食物质地,包括食物的碎片,并通过儿童与其父母或照顾者之间的反应性喂养来支持。在婴儿食品袋中销售的辅食通常具有高能量密度,主要是极高的糖含量,几乎占总能量含量的90%。经常食用会带来营养供应不平衡的风险,增加患龋齿和超重的风险。婴儿和幼儿的辅食应按照德国儿科和青少年医学协会(DGKJ)的建议,具有均衡的成分,并且应只含有有限数量的糖。我们不鼓励从婴儿食品袋中喂养泥状辅食。
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引用次数: 28
KUNO-Kids birth cohort study: rationale, design, and cohort description. kuno -儿童出生队列研究:基本原理、设计和队列描述。
Pub Date : 2019-01-09 DOI: 10.1186/s40348-018-0088-z
Susanne Brandstetter, Antoaneta A Toncheva, Jakob Niggel, Christine Wolff, Silvia Gran, Birgit Seelbach-Göbel, Christian Apfelbacher, Michael Melter, Michael Kabesch

Background: Birth cohort studies can contribute substantially to the understanding of health and disease - in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various aspects of child health, using novel omics technologies in a systems medicine approach.

Results: After 3 years of recruitment, 2515 infants and their families have joined the study. Parents with higher education are overrepresented as in many other birth cohorts and are more likely to complete follow-up assessments via self-report questionnaires. The vast majority of participants consented to clinical examinations of their child and to the non-invasive collection of diverse biosamples, which were processed specifically for their integrated use in omics technology covering genomics, epigenomics, transcriptomics, metabolomics, and microbiome analyses of the skin, oral cavity, and stool.

Conclusions: The data and diverse biomaterial collected in the KUNO-Kids birth cohort study will provide extensive opportunities for investigating child health and its determinants in a holistic approach. The combination of a broad range of research questions in one study will allow for a cost-effective use of biomaterial and omics results and for a comprehensive analysis of biological and social determinants of health and disease. Aiming for low attrition and ensuring participants' long-term commitment will be crucial to fully exploit the potential of the study.

背景:出生队列研究可以大大有助于了解儿童时期和整个生命过程中的健康和疾病。KUNO-Kids出生队列研究的建立是为了调查儿童健康的各个方面,在系统医学方法中使用新的组学技术。结果:经过3年的招募,2515名婴儿及其家庭加入了研究。与许多其他出生队列一样,受过高等教育的父母比例过高,而且更有可能通过自我报告问卷完成后续评估。绝大多数参与者同意对他们的孩子进行临床检查,并非侵入性地收集各种生物样本,这些样本经过专门处理,用于组学技术的综合应用,包括基因组学、表观基因组学、转录组学、代谢组学和皮肤、口腔和粪便的微生物组学分析。结论:在KUNO-Kids出生队列研究中收集的数据和各种生物材料将为以整体方法调查儿童健康及其决定因素提供广泛的机会。在一项研究中结合广泛的研究问题,将能够以具有成本效益的方式利用生物材料和组学结果,并对健康和疾病的生物和社会决定因素进行全面分析。以低流失率为目标,确保参与者的长期投入,将是充分利用研究潜力的关键。
{"title":"KUNO-Kids birth cohort study: rationale, design, and cohort description.","authors":"Susanne Brandstetter,&nbsp;Antoaneta A Toncheva,&nbsp;Jakob Niggel,&nbsp;Christine Wolff,&nbsp;Silvia Gran,&nbsp;Birgit Seelbach-Göbel,&nbsp;Christian Apfelbacher,&nbsp;Michael Melter,&nbsp;Michael Kabesch","doi":"10.1186/s40348-018-0088-z","DOIUrl":"https://doi.org/10.1186/s40348-018-0088-z","url":null,"abstract":"<p><strong>Background: </strong>Birth cohort studies can contribute substantially to the understanding of health and disease - in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various aspects of child health, using novel omics technologies in a systems medicine approach.</p><p><strong>Results: </strong>After 3 years of recruitment, 2515 infants and their families have joined the study. Parents with higher education are overrepresented as in many other birth cohorts and are more likely to complete follow-up assessments via self-report questionnaires. The vast majority of participants consented to clinical examinations of their child and to the non-invasive collection of diverse biosamples, which were processed specifically for their integrated use in omics technology covering genomics, epigenomics, transcriptomics, metabolomics, and microbiome analyses of the skin, oral cavity, and stool.</p><p><strong>Conclusions: </strong>The data and diverse biomaterial collected in the KUNO-Kids birth cohort study will provide extensive opportunities for investigating child health and its determinants in a holistic approach. The combination of a broad range of research questions in one study will allow for a cost-effective use of biomaterial and omics results and for a comprehensive analysis of biological and social determinants of health and disease. Aiming for low attrition and ensuring participants' long-term commitment will be crucial to fully exploit the potential of the study.</p>","PeriodicalId":74215,"journal":{"name":"Molecular and cellular pediatrics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s40348-018-0088-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36850617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 37
Gene correction of HBB mutations in CD34+ hematopoietic stem cells using Cas9 mRNA and ssODN donors. 使用Cas9 mRNA和ssODN供体对CD34+造血干细胞HBB突变进行基因校正。
Pub Date : 2018-11-14 DOI: 10.1186/s40348-018-0086-1
Justin S Antony, Ngadhnjim Latifi, A K M Ashiqul Haque, Andrés Lamsfus-Calle, Alberto Daniel-Moreno, Sebastian Graeter, Praveen Baskaran, Petra Weinmann, Markus Mezger, Rupert Handgretinger, Michael S D Kormann

Background: β-Thalassemia is an inherited hematological disorder caused by mutations in the human hemoglobin beta (HBB) gene that reduce or abrogate β-globin expression. Although lentiviral-mediated expression of β-globin and autologous transplantation is a promising therapeutic approach, the risk of insertional mutagenesis or low transgene expression is apparent. However, targeted gene correction of HBB mutations with programmable nucleases such as CRISPR/Cas9, TALENs, and ZFNs with non-viral repair templates ensures a higher safety profile and endogenous expression control.

Methods: We have compared three different gene-editing tools (CRISPR/Cas9, TALENs, and ZFNs) for their targeting efficiency of the HBB gene locus. As a proof of concept, we studied the personalized gene-correction therapy for a common β-thalassemia splicing variant HBBIVS1-110 using Cas9 mRNA and several optimally designed single-stranded oligonucleotide (ssODN) donors in K562 and CD34+ hematopoietic stem cells (HSCs).

Results: Our results exhibited that indel frequency of CRISPR/Cas9 was superior to TALENs and ZFNs (P < 0.0001). Our designed sgRNA targeting the site of HBBIVS1-110 mutation showed indels in both K562 cells (up to 77%) and CD34+ hematopoietic stem cells-HSCs (up to 87%). The absolute quantification by next-generation sequencing showed that up to 8% site-specific insertion of the NheI tag was achieved using Cas9 mRNA and a chemically modified ssODN in CD34+ HSCs.

Conclusion: Our approach provides guidance on non-viral gene correction in CD34+ HSCs using Cas9 mRNA and chemically modified ssODN. However, further optimization is needed to increase the homology directed repair (HDR) to attain a real clinical benefit for β-thalassemia.

背景:β-地中海贫血是一种遗传性血液学疾病,由人血红蛋白β (HBB)基因突变导致β-珠蛋白表达减少或消除引起。虽然慢病毒介导的β-珠蛋白表达和自体移植是一种很有前景的治疗方法,但插入突变或低转基因表达的风险是显而易见的。然而,使用可编程核酸酶(如CRISPR/Cas9、TALENs和ZFNs)和非病毒修复模板对HBB突变进行靶向基因校正可确保更高的安全性和内源性表达控制。方法:我们比较了三种不同的基因编辑工具(CRISPR/Cas9、TALENs和ZFNs)对HBB基因位点的靶向效率。为了证明这一概念,我们研究了在K562和CD34+造血干细胞(hsc)中使用Cas9 mRNA和几种优化设计的单链寡核苷酸(ssODN)供体对常见的β-地中海贫血剪接变体HBBIVS1-110的个性化基因校正治疗。结果:我们的研究结果显示,CRISPR/Cas9的indel频率优于TALENs和ZFNs (P IVS1-110突变在K562细胞(高达77%)和CD34+造血干细胞- hsc(高达87%)中均显示indel。下一代测序的绝对定量显示,在CD34+ hsc中,使用Cas9 mRNA和化学修饰的ssODN可实现高达8%的NheI标签位点特异性插入。结论:我们的方法为利用Cas9 mRNA和化学修饰的ssODN对CD34+造血干细胞进行非病毒基因校正提供了指导。然而,需要进一步优化以增加同源定向修复(HDR)以获得β-地中海贫血的真正临床益处。
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引用次数: 43
Chemotherapy and the pediatric brain. 化疗和儿童大脑。
Pub Date : 2018-11-06 DOI: 10.1186/s40348-018-0087-0
Chrysanthy Ikonomidou

Survival rates of children with cancer are steadily increasing. This urges our attention to neurocognitive and psychiatric outcomes, as these can markedly influence the quality of life of these children. Neurobehavioral morbidity in childhood cancer survivors affects diverse aspects of cognitive function, which can include attention, memory, processing speed, intellect, academic achievement, and emotional health. Reasons for neurobehavioral morbidity are multiple with one major contributor being chemotherapy-induced central nervous system (CNS) toxicity. Clinical studies investigating the effects of chemotherapy on the CNS in children with cancer have reported causative associations with the development of leukoencephalopathies as well as smaller regional grey and white matter volumes, which have been found to correlate with neurocognitive deficits.Preclinical work has provided compelling evidence that chemotherapy drugs are potent neuro- and gliotoxins in vitro and in vivo and can cause brain injury via excitotoxic and apoptotic mechanisms. Furthermore, chemotherapy triggers DNA (deoxyribonucleic acid) damage directly or through increased oxidative stress. It can shorten telomeres and accelerate cell aging, cause cytokine deregulation, inhibit hippocampal neurogenesis, and reduce brain vascularization and blood flow. These mechanisms, when allowed to operate on the developing brain of a child, have high potential to not only cause brain injury, but also alter crucial developmental events, such as myelination, synaptogenesis, neurogenesis, cortical thinning, and formation of neuronal networks.This short review summarizes key publications describing neurotoxicity of chemotherapy in pediatric cancers and potential underlying pathomechanisms.

儿童癌症患者的存活率正在稳步上升。这促使我们关注神经认知和精神方面的结果,因为这些会显著影响这些儿童的生活质量。儿童癌症幸存者的神经行为疾病影响认知功能的各个方面,包括注意力、记忆力、处理速度、智力、学业成就和情绪健康。神经行为发病的原因是多种多样的,其中一个主要原因是化疗引起的中枢神经系统(CNS)毒性。临床研究调查了化疗对癌症儿童中枢神经系统的影响,报告了与白质脑病的发展以及区域灰质和白质体积较小的因果关系,这与神经认知缺陷有关。临床前工作提供了令人信服的证据,表明化疗药物在体内和体外都是强效的神经和胶质毒素,并可通过兴奋毒性和细胞凋亡机制引起脑损伤。此外,化疗直接或通过增加氧化应激触发DNA(脱氧核糖核酸)损伤。它可以缩短端粒,加速细胞老化,引起细胞因子失调,抑制海马神经发生,减少脑血管和血液流动。这些机制,当被允许在儿童发育中的大脑上进行操作时,不仅有可能导致脑损伤,而且还可能改变关键的发育事件,如髓鞘形成、突触发生、神经发生、皮质变薄和神经元网络的形成。这篇简短的综述总结了描述化疗在儿童癌症中的神经毒性和潜在的潜在病理机制的主要出版物。
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引用次数: 34
The role of S100 proteins in the pathogenesis and monitoring of autoinflammatory diseases. S100蛋白在自身炎症性疾病发病机制和监测中的作用。
Pub Date : 2018-09-25 DOI: 10.1186/s40348-018-0085-2
Dirk Holzinger, Dirk Foell, Christoph Kessel

S100A8/A9 and S100A12 are released from activated monocytes and granulocytes and act as proinflammatory endogenous toll-like receptor (TLR)4-ligands. S100 serum concentrations correlate with disease activity, both during local and systemic inflammatory processes. In some autoinflammatory diseases such as familial Mediterranean fever (FMF) or systemic juvenile idiopathic arthritis (SJIA), dysregulation of S100 release may be involved in the pathogenesis. Moreover, S100 serum levels are a valuable supportive tool in the diagnosis of SJIA in fever of unknown origin. Furthermore, S100 levels can be used to monitor disease activity to subclinical level, as their serum concentrations decrease with successful treatment.

S100A8/A9和S100A12从活化的单核细胞和粒细胞中释放,作为促炎内源性toll样受体(TLR)4配体。在局部和全身炎症过程中,血清S100浓度与疾病活动性相关。在一些自身炎症性疾病,如家族性地中海热(FMF)或系统性青少年特发性关节炎(SJIA)中,S100释放的失调可能参与了发病机制。此外,血清S100水平是诊断不明原因发热中SJIA的宝贵支持工具。此外,S100水平可用于监测疾病活动至亚临床水平,因为其血清浓度随着治疗成功而降低。
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引用次数: 36
Precision medicine in pediatric oncology. 儿科肿瘤学的精准医学。
Pub Date : 2018-08-31 DOI: 10.1186/s40348-018-0084-3
Stefan E G Burdach, Mike-Andrew Westhoff, Maximilian Felix Steinhauser, Klaus-Michael Debatin

Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.

自20世纪70年代以来,儿童癌症的治疗效果有了显著改善。这一成功在很大程度上是由于实施了标准化和发展儿童癌症治疗的合作临床研究试验组。然而,某些类型的恶性肿瘤的结果仍然是不利的。以急性和长期副作用为代价,常规化疗和放疗的强化只能略微改善预后。因此,有必要制定针对性的治疗策略。在此,我们回顾了儿科肿瘤精准医学的发展和前景,特别关注激酶抑制剂和细胞凋亡诱导剂等靶向药物治疗,癌症基因组测序和免疫治疗的影响。
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引用次数: 25
期刊
Molecular and cellular pediatrics
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