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1.
Miriam Banas Sindy Neumann Johannes Eiglsperger Eric Schiffer Franz Josef Putz Simone Reichelt-Wurm Bernhard Karl Krämer Philipp Pagel Bernhard Banas 《Metabolomics : Official journal of the Metabolomic Society》2018,14(9):116
Introduction
Allograft rejection is still an important complication after kidney transplantation. Currently, monitoring of these patients mostly relies on the measurement of serum creatinine and clinical evaluation. The gold standard for diagnosing allograft rejection, i.e. performing a renal biopsy is invasive and expensive. So far no adequate biomarkers are available for routine use.Objectives
We aimed to develop a urine metabolite constellation that is characteristic for acute renal allograft rejection.Methods
NMR-Spectroscopy was applied to a training cohort of transplant recipients with and without acute rejection.Results
We obtained a metabolite constellation of four metabolites that shows promising performance to detect renal allograft rejection in the cohorts used (AUC of 0.72 and 0.74, respectively).Conclusion
A metabolite constellation was defined with the potential for further development of an in-vitro diagnostic test that can support physicians in their clinical assessment of a kidney transplant patient.2.
HaJeung Park Tuan Tran Jun Hyuck Lee Hyun Park Matthew D. Disney 《BMC structural biology》2016,16(1):19
Background
Post-crystallization dehydration methods, applying either vapor diffusion or humidity control devices, have been widely used to improve the diffraction quality of protein crystals. Despite the fact that RNA crystals tend to diffract poorly, there is a dearth of reports on the application of dehydration methods to improve the diffraction quality of RNA crystals.Results
We use dehydration techniques with a Free Mounting System (FMS, a humidity control device) to recover the poor diffraction quality of RNA crystals. These approaches were applied to RNA constructs that model various RNA-mediated repeat expansion disorders.Conclusion
The method we describe herein could serve as a general tool to improve diffraction quality of RNA crystals to facilitate structure determinations.3.
Wenzel Schoening Volker Schmitz Jelena Klawitter Uwe Christians Jost Klawitter 《Metabolomics : Official journal of the Metabolomic Society》2017,13(9):102
Introduction
Although current immunosuppressive protocols have dramatically improved 1-year survival of kidney transplants, there has been less progress in terms of long-term graft survival over the last two decades. The key to avoiding late graft loss is early diagnosis and differentiation between anti-allograft immune processes and immunosuppressant toxicity (IS-Tox). Modern bioanalytical technologies have opened new opportunities for the development of sensitive and specific diagnostic tools. There is an immediate need for biomarkers that are able to differentiate between renal allograft rejection and immunosuppressant toxicity.Objective
To test our hypothesis that changes of metabolite patterns in urine have the potential to serve as a non-invasive combinatorial biomarker that can differentiate between allograft immune reactions and IS-Tox.Methods
We used 1H-NMR spectroscopy and Luminex multiplexing for metabolic profiling of rat urine and the analysis of protein biomarkers in urine and plasma, respectively, to compare the effects of chronic allograft rejection in a Fisher-to-Lewis rat transplant model with IS-Tox induced by cyclosporine, tacrolimus and/or sirolimus in Lewis rats.Results
Our results showed that, while IS-Tox caused changes in metabolite patterns that are typically associated with proximal tubule damage, rejection caused more profuse changes not specifically focused on a particular kidney region. Moreover, metabolite pattern changes were more sensitive than changes in protein markers that were evident only during the later stages of rejection.Conclusion
The present study provides first proof-of-concept that longitudinal monitoring of urine metabolite markers has the potential to differentiate between early renal allograft rejection and immunosuppressant nephrotoxicity.4.
Jing Xiong Tiefen Su Pengcheng Zhu Qilin Ao Qiurong Ruan Guoping Wang 《Diagnostic pathology》2017,12(1):86
Background
Renal transplant recipients have increased risk for developing malignant diseases because of immunosuppression or donor-to-recipient transmission. Malignant rhabdoid tumor (MRT) is a rare, highly aggressive and lethal tumor primarily affecting the kidney of infants and young children. MRT has not been reported in the renal allograft of an adult recipient after kidney transplantation.Case presentation
In this report, a 47-year-old woman who received a kidney transplantation from an infant donor and developed a mass in the transplanted kidney is presented. Pathological examinations revealed a malignant tumor with rhabdoid cells morphologically and the loss of INI1 expression immunohistochemically. The diagnosis of malignant rhabdoid tumor in the transplanted kidney was made. We confirmed that donor-to-recipient malignancy transmission was the cause of MRT in the transplanted kidney by fluorescence in situ hybridization (FISH) and short tandem repeat (STR) analysis.Conclusion
To our knowledge, this is the first case of MRT in an adult renal allograft recipient. This report highlights the importance of the criteria for selection of donors to screen possible malignant tumors transmission.5.
Yuvaraja B Thyavihally Hemant B Tongaonkar Sangeeta B Desai 《International Seminars in Surgical Oncology : ISSO》2005,2(1):18
Background
Mixed epithelial and stromal tumor (MEST) is a distinctive benign composite neoplasm of the kidney predominantly seen in females mostly in the perimenopausal period. Although these tumors are known to arise from renal pelvis, our case was distinct in that it had no intrapelvic component growing in exophytic fashion.Case report
A 35 year old female patient presented to us with vague abdominal pain. She had undergone excision of bilateral ovarian cystic masses for cystic teratoma twelve years earlier. A computed tomography scan of abdomen and pelvis showed a 9 × 7 cm uniformly solid mass with poor contrast enhancement situated in the inferomedial aspect of the left kidney. On exploration, the mass was arising from the inferior and anterior aspect of left renal pelvis, and was attached to it with a narrow pedicle. There was no adherence or attachment to the renal parenchyma. The mass was excised preserving the kidney. Microscopically, the tumor was composed of large collagenized areas containing bundles of spindle cells and several 'microcysts' lined by cuboidal epithelium suggestive of a benign mixed epithelial stromal tumor.Discussion
Mixed epithelial tumors usually present in perimenopausal women as a partially cystic mass. Tumors are composed of irregular mixtures of cystic and solid areas, glands with variable complexity and distribution and the stromal component is characterized by a spindle cell proliferation. Commonly, it arises from the renal parenchyma and pelvis and nephrectomy is advocated to manage these tumors.Conclusion
MEST is a distinctive benign tumor of the kidney that should be distinguished from other renal neoplasms. MEST arising from the renal pelvis and growing exophytically is a rare entity. The overall prognosis is favorable.6.
Mohamed Ali Essid Abderrazak Bouzouita Ahlem Blel Maroua Gharbi Marouen Chakroun Aycha Ben Miled Haroun Ayed Mohamed Cherif Mohamed Riadh Ben Slama Amine Derouiche Mohamed Chebil 《Journal of medical case reports》2018,12(1):376
Background
Intravascular papillary endothelial hyperplasia (known also as Masson’s tumor) is a benign vascular lesion that commonly occurs in the skin and is rarely found in solid organs, especially in the kidney. In what follows, we will look into the first case of an unexpectedly diagnosed Masson’s tumor of the kidney presenting as a suspicious renal cyst.Case presentation
A 61-year-old Arab man presented with a left renal cyst, incidentally revealed by ultrasonography. The laboratory values were unremarkable. Computed tomography and magnetic resonance imaging demonstrated a 38 mm left renal midportion Bosniak IV cyst. Our patient underwent a radical nephrectomy. Histopathology revealed the diagnosis of intravascular papillary endothelial hyperplasia. There was no recurrence detected after 9 years of follow-up.Conclusions
Renal intravascular papillary endothelial hyperplasia is a rare benign tumor which can mimic a suspicious renal mass on radiological findings. Thus, this entity should be considered more often in the thick of the diagnostic possibilities in order to avoid unnecessary nephrectomies.7.
Jamie V. de Seymour Stephanie Tu Xiaoling He Hua Zhang Ting-Li Han Philip N. Baker Karolina Sulek 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):79
Introduction
Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.Objective
Investigate the maternal hair metabolome for predictive biomarkers of ICP.Methods
The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.Results
Of 105 metabolites detected in hair, none were significantly associated with ICP.Conclusion
Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.8.
Background
Evidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development.Methods
The renal effects of the selective antagonist to AT1R, ZD 7155 and to AT2R, PD 1233319 were evaluated in two groups of conscious chronically instrumented lambs aged?~?one week (N?=?8) and?~?six weeks (N?=?10). Two experiments were carried out in each animal and consisted of the assessment of renal variables including glomerular and tubular function, for 30 min before (Control) and 60 min after infusion of ZD 7155 and PD 123319, respectively. Statistical significance was determined using parametric testing (Student t-test, analysis of variance ANOVA) as appropriate.Results
ZD 7155 infusion was associated with a significant decrease in glomerular filtration rate and filtration fraction at one but not six weeks; urinary flow rate decreased significantly in older animals, whereas sodium excretion and free water clearance were not altered. There was an age-dependent effect on potassium handling along the nephron, potassium excretion decreasing after ZD 7155 infusion in younger but not in older lambs. PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group.Conclusions
These results provide evidence to support an important role for AT1Rs in mediating the renal effects of angiotensin II during postnatal maturation in conscious developing animals. In contrast to a role for AT2Rs later in life, there appears to be no role for AT2Rs in influencing the renal effects of Angiotensin II in the postnatal period.9.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.10.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.11.
Background
Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a rare variant of renal tumor. The current data show most of MTSCCs are of low malignant potential and rare cases metastatic to lymph nodes have been reported; however, the recorded computed tomography (CT) and follow up data are limited.Material and method
In the present study, we retrospectively analyzed CT and clinicopathological data of eight patients with renal MTSCC-K.Results
A total of eight cases, including six females and two males, were included in this analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2 (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were slightly enhanced on both corticomedullary and nephrographic phase, which was different from many other renal cell carcinomas. Three of them were treated with open radical nephrectomy, three with laparoscopic radical nephrectomy and the other two with laparoscopic partial nephrectomy. No postoperative therapy was applied. Patients were followed up for 15 to 64 months and there was no evidence of recurrence and metastasis.Conclusions
The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis. The diagnosis mainly depends on the histopathological examination and CT may help to differentiate with papillary renal cell carcinoma. Surgical treatment is recommended and additional therapies are not necessary.Virtual slides
The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249.12.
Vanessa Drendel Bianca Heckelmann Christoph Schell Lucas Kook Martin L. Biniossek Martin Werner Cordula A. Jilg Oliver Schilling 《Clinical proteomics》2018,15(1):25
Background
Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5–7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.Methods
We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.Results
At 1% false discovery rate, we identified?>?3900 proteins, of which?>?2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.Conclusion
We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.13.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.14.
Justine Leenders Antoine Buemi Michel Mourad Pascal de Tullio François Jouret 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):94
Introduction
Pre-analytical processing significantly affects tissue metabolomes. Since most frozen kidney samples are stored after embedding, standardization of cryoprotective medium removal before metabolomics is essential.Objectives
We used rodent and human kidney samples to develop an easy and robust pre-analytical procedure compatible with 1H-nuclear magnetic resonance (NMR)-based metabolomics.Methods
In mice, renal ischemia was induced for 30 min, followed by 48-h reperfusion (I/R, n?=?6). Right kidneys were transversally cut in two fragments, and snap-frozen in liquid nitrogen (LN2) or in Optimal Cutting Temperature ® (OCT) fixative. In man, double kidney biopsies were simultaneously obtained before transplantation (n?=?15), and snap-frozen in LN2 or OCT.Results
1H-NMR spectrum of pure OCT highlighted two major peaks, i.e. from 3.4 to 4.2 ppm (47.2%) and from 1.2 to 2.2 ppm (42.5%). 1H-NMR spectra of mouse OCT kidneys were biased at 3.7. By contrast, 1H-NMR analyses of mouse OCT kidneys iteratively rinsed in saline significantly discriminated sham versus I/R groups, with Q² at 0.695 (to be compared with Q² at 0.866 for LN2 sham vs. I/R kidneys). Discriminant metabolites were analogous in both OCT and LN2 kidneys, with a correlation coefficient of 0.83. In man, iteratively rinsing OCT kidneys in saline eliminated the spectral 3.7-peak, thereby making metabolomes of OCT kidneys interpretable and similar to LN2 samples, with a correlation coefficient of 0.73.Conclusion
NMR metabolomics using OCT-frozen kidney samples is valuable in mouse and man, following standardized OCT removal. This may help use residual biobanked human tissues to better understand renal pathophysiology.15.
Biswapriya B. Misra Ram P. Upadhayay Laura A. Cox Michael Olivier 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):75
Introduction
Metabolomics is a promising approach for discovery of relevant biomarkers in cells, tissues, organs, and biofluids for disease identification and prediction. The field has mostly relied on blood-based biofluids (serum, plasma, urine) as non-invasive sources of samples as surrogates of tissue or organ-specific conditions. However, the tissue specificity of metabolites pose challenges in translating blood metabolic profiles to organ-specific pathophysiological changes, and require further downstream analysis of the metabolites.Objectives
As part of this project, we aim to develop and optimize an efficient extraction protocol for the analysis of kidney tissue metabolites representative of key primate metabolic pathways.Methods
Kidney cortex and medulla tissues of a baboon were homogenized and extracted using eight different extraction protocols including methanol/water, dichloromethane/methanol, pure methanol, pure water, water/methanol/chloroform, methanol/chloroform, methanol/acetonitrile/water, and acetonitrile/isopropanol/water. The extracts were analyzed by a two-dimensional gas chromatography time-of-flight mass-spectrometer (2D GC–ToF-MS) platform after methoximation and silylation.Results
Our analysis quantified 110 shared metabolites in kidney cortex and medulla tissues from hundreds of metabolites found among the eight different solvent extractions spanning low to high polarities. The results revealed that medulla is metabolically richer compared to the cortex. Dichloromethane and methanol mixture (3:1) yielded highest number of metabolites across both the tissue types. Depending on the metabolites of interest, tissue type, and the biological question, different solvents can be used to extract specific groups of metabolites.Conclusion
This investigation provides insights into selection of extraction solvents for detection of classes of metabolites in renal cortex and medulla, which is fundamentally important for identification of prognostic and diagnostic metabolic kidney biomarkers for future therapeutic applications.16.
Introduction
Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.Objectives
Assessment of the quality of raw data processing in untargeted metabolomics.Methods
Five published untargeted metabolomics studies, were reanalyzed.Results
Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.Conclusion
Incomplete raw data processing shows unexplored potential of current and legacy data.17.
J. C. Martínez-Ávila A. García Bartolomé I. García I. Dapía Hoi Y. Tong L. Díaz P. Guerra J. Frías A. J. Carcás Sansuan A. M. Borobia 《Metabolomics : Official journal of the Metabolomic Society》2018,14(5):70
Introduction
Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route.Objectives
Our objective was to evaluate the utility of pharmacometabolomics in the detection of zonisamide metabolites that could be related to its disposition and therefore, to its efficacy and toxicity.Methods
This study was nested to a bioequivalence clinical trial with 28 healthy volunteers. Each participant received a single dose of zonisamide on two separate occasions (period 1 and period 2), with a washout period between them. Blood samples of zonisamide were obtained from all patients at baseline for each period, before volunteers were administered any medication, for metabolomics analysis.Results
After a Lasso regression was applied, age, height, branched-chain amino acids, steroids, triacylglycerols, diacyl glycerophosphoethanolamine, glycerophospholipids susceptible to methylation, phosphatidylcholines with 20:4 FA (arachidonic acid) and cholesterol ester and lysophosphatidylcholine were obtained in both periods.Conclusion
To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.18.
Renato de Souza Pinto Lemgruber Kaspar Valgepea Mark P. Hodson Ryan Tappel Sean D. Simpson Michael Köpke Lars K. Nielsen Esteban Marcellin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):35
Introduction
Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.Objective
To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.Methods
Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.Results
Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.Conclusion
Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.19.
Amir Abdoli 《生物学前沿》2017,12(6):387-391
Background
Inflammatory conditions are involved in the pathophysiology of cancer. Recent findings have revealed that excessive salt and fat intake is involved in the development of severe inflammatory reactions.Methods
literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of high salt and fat intake in the induction of inflammatory reactions and their roles in the etiopathogenesis of cancer.Results
The results indicate that high salt and fat intake can induce severe inflammatory conditions. However, various inflammatory conditions have been strongly linked to the development of cancer. Hence, high salt and fat intake might be involved in the pathogenesis of cancer progression via putative mechanisms related to inflammatory reactions.Conclusion
Reducing salt and fat intake may decrease the risk of cancer.20.
Da-Yong Hu Ying Luo Chang-Bin Li Chun-Yu Zhou Xin-Hua Li Ai Peng Jun-Yan Liu 《Metabolomics : Official journal of the Metabolomic Society》2018,14(8):104