Urinary peptidomics analysis reveals proteases involved in diabetic nephropathy

Mechanisms underlying the onset and progression of nephropathy in diabetic patients are not fully elucidated. Deregulation of proteolytic systems is a known path leading to disease manifestation, therefore we hypothesized that proteases aberrantly expressed in diabetic nephropathy (DN) may be involved in the generation of DN-associated peptides in urine. We compared urinary peptide profiles of DN patients (macroalbuminuric, n = 121) to diabetic patients with no evidence of DN (normoalbuminuric, n = 118). 302 sequenced, differentially expressed peptides (adjusted p-value < 0.05) were analysed with the Proteasix tool predicting proteases potentially involved in their generation. Activity change was estimated based on the change in abundance of the investigated peptides. Predictions were correlated with transcriptomics (Nephroseq) and relevant protein expression data from the literature. This analysis yielded seventeen proteases, including multiple forms of MMPs, cathepsin D and K, kallikrein 4 and proprotein convertases. The activity of MMP-2 and MMP-9, predicted to be decreased in DN, was investigated using zymography in a DN mouse model confirming the predictions. Collectively, this proof-of-concept study links urine peptidomics to molecular changes at the tissue level, building hypotheses for further investigation in DN and providing a workflow with potential applications to other diseases

Comparison of urine and plasma peptidome indicates selectivity in renal peptide handling

Purpose: Urine is considered to be produced predominantly as a result of plasma filtration in the kidney. However, the origin of the native peptides present in urine has never been investigated in detail. Therefore, we aimed to obtain a first insight into the origin of urinary peptides based on a side‐by‐side comprehensive analysis of the plasma and urine peptidome. Methods: Twenty‐two matched urine and plasma samples were analyzed for their peptidome using capillary electrophoresis coupled to mass spectrometry (CE‐MS; for relative quantification) and CE‐ or LC coupled to tandem mass spectrometry (CE‐ or LC‐ MS/MS; for peptide identification). The overlap and association of abundance of the different peptides present in these two body fluids were evaluated. Results: We were able to identify 561 plasma and 1461 urinary endogenous peptides. Only 90 peptides were detectable in both urine and plasma. No significant correlation was found when comparing the abundance of these common peptides, with the exception of collagen fragments. This observation was also supported when comparing published peptidome data from both plasma and urine. Conclusions and clinical relevance: Most of the plasma peptides are not detectable in urine, possibly due to tubular reabsorption. The majority of urinary peptides may in fact originate in the kidney. The notable exception is collagen fragments, which indicates potential selective exclusion of these peptides from tubular reabsorption. Experimental verification of this hypothesis is warranted

Rivaroxaban for Venous Thromboembolism Prophylaxis in Abdominoplasty: A Multicenter Experience

BACKGROUND: Abdominoplasty, a commonly performed aesthetic procedure, is considered to have an increased risk of venous thromboembolism (VTE) events. At present, routine VTE chemoprophylaxis following abdominoplasty remains controversial. OBJECTIVES: This study evaluates the authors' experience with rivaroxaban, an oral Factor Xa inhibitor, for VTE prophylaxis in abdominoplasty patients. METHODS: A retrospective case series was conducted. All patients who underwent abdominoplasty and received rivaroxaban were included. The prophylactic dose was 10 mg daily for 7 days, beginning 12 hours postoperatively. Patient demographics, comorbidities, and type of surgery were recorded. The primary outcome measured was hematologic complication, including VTE, hematoma requiring operative evacuation, and need for blood transfusion. RESULTS: From September 2012 until July 2014, 132 patients (122 women and 10 men) underwent abdominoplasty surgery and received rivaroxaban postoperatively. Mean patient age was 43.7 years, and mean body mass index was 27.1. One hundred twenty-five patients also underwent abdominal muscle plication. Eleven patients underwent a fleur de lis vertical skin resection component. One hundred patients underwent concomitant abdominal liposuction, while 79 patients also had back liposuction. Only 1 patient had a symptomatic VTE event. Three patients had a hematoma requiring operative evacuation, and all went on to heal without sequelae. Two patients received a blood transfusion for anemia during their course of rivaroxaban. CONCLUSIONS: Oral rivaroxaban administration for chemoprophylaxis in abdominoplasty patients is safe, with low rates of symptomatic VTE and hematoma formation. The authors continue routine use of the medication for patients at increased risk for VTE events. LEVEL OF EVIDENCE 4: Risk

Molecular Evolution of the Infrared Sensory Gene TRPA1 in Snakes and Implications for Functional Studies

TRPA1 is a calcium ion channel protein recently identified as the infrared receptor in pit organ-containing snakes. Therefore, understanding the molecular evolution of TRPA1 may help to illuminate the origin of “heat vision” in snakes and reveal the molecular mechanism of infrared sensitivity for TRPA1. To this end, we sequenced the infrared sensory gene TRPA1 in 24 snake species, representing nine snake families and multiple non-snake outgroups. We found that TRPA1 is under strong positive selection in the pit-bearing snakes studied, but not in other non-pit snakes and non-snake vertebrates. As a comparison, TRPV1, a gene closely related to TRPA1, was found to be under strong purifying selection in all the species studied, with no difference in the strength of selection between pit-bearing snakes and non-pit snakes. This finding demonstrates that the adaptive evolution of TRPA1 specifically occurred within the pit-bearing snakes and may be related to the functional modification for detecting infrared radiation. In addition, by comparing the TRPA1 protein sequences, we identified 11 amino acid sites that were diverged in pit-bearing snakes but conserved in non-pit snakes and other vertebrates, 21 sites that were diverged only within pit-vipers but conserved in the remaining snakes. These specific amino acid substitutions may be potentially functional important for infrared sensing

Overcrowding in emergency department: an international issue

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Wpływ technologii uprawy na barwę miąższu surowych bulw ziemniaka

Results of the research were based on a field experiment carried out in 2014‒2016 at the Experimental Station of Cultivar Assessment in Uhnin (51°34'N, 23°02'E), on podzolic slightly acidic soil. The experiment was carried out using random sub-blocks, in a dependent split-plot system, in triplicate. The first-order factor was potato cultivars (‘Vineta’ and ‘Satina’), and the second-order factor consisted of six cultivation technologies: A − using fungicides to control potato blight, technologies: B, C, D, E − with the application of effective microorganisms, and technology F − without the use of fungicides and effective microorganisms as a control object. The scope of the research included assessing the color of the raw tubers pulp. To determine the color of raw potato, the method of trichromatic colorimetry was used applying the Konica Minolta CM-5 spectrophotometer. The color measurement of raw tubers was carried out in the CIEL*a*b* system. Cultivation technology with fungicide application significantly contributed to the brightness change of the raw tuber flesh compared to the technology (D), where for the treatment, as in the growing season, effective microorganisms were used. Genetic properties of cultivars determined the color brightness, as well as its trichromatic coordinates

Urinary peptidomics in kidney disease and drug research

Introduction: Due to its close connection with the renal system, urine is considered a valuable source of information in kidney disease research. Peptidomics methods focus on the discovery of endogenous peptides, given their wide range of biological functions and diagnostic and therapeutic potential. Representing a non-invasive and sensitive method, technological prospects of urinary peptidomics should be evaluated in the context of drug discovery and research. Areas covered: This review describes urinary peptidomics with focus on its application in drug research in the field of kidney diseases. The authors provide an overview of current achievements and potential future applications. Expert opinion: The urinary peptidome is a dynamically changing source of information, able to reflect sudden and long-term changes affecting the renal system. Studies utilizing urinary peptidomics techniques have demonstrated their value in patient stratification and detection of early pathological changes in kidney disease. Serving as a liquid biopsy, urinary peptides are an invaluable tool for drug response monitoring. Nevertheless, peptidomics is largely underexplored in drug research in general, as evidenced by the scarce number of scientific publications on this topic. Further progress will be driven by the successful validation of current discoveries and continued efforts to improve the translation of results into therapeutic applications