Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis

IgA nephropathy (IgAN) is the most prevalent among primary glomerular diseases worldwide. Although our understanding of IgAN has advanced significantly, its underlying biology and potential drug targets are still unexplored. We investigated a combinatorial approach for the analysis of IgAN-relevant -omics data, aiming at identification of novel molecular signatures of the disease. Nine published urinary proteomics datasets were collected and the reported differentially expressed proteins in IgAN vs. healthy controls were integrated into known biological pathways. Proteins participating in these pathways were subjected to multi-step assessment, including investigation of IgAN transcriptomics datasets (Nephroseq database), their reported protein-protein interactions (STRING database), kidney tissue expression (Human Protein Atlas) and literature mining. Through this process, from an initial dataset of 232 proteins significantly associated with IgAN, 20 pathways were predicted, yielding 657 proteins for further analysis. Step-wise evaluation highlighted 20 proteins of possibly high relevance to IgAN and/or kidney disease. Experimental validation of 3 predicted relevant proteins, adenylyl cyclase-associated protein 1 (CAP1), SHC-transforming protein 1 (SHC1) and prolylcarboxypeptidase (PRCP) was performed by immunostaining of human kidney sections. Collectively, this study presents an integrative procedure for -omics data exploitation, giving rise to biologically relevant results

PeptiCKDdb-peptide- and protein-centric database for the investigation of genesis and progression of chronic kidney disease

The peptiCKDdb is a publicly available database platform dedicated to support research in the field of chronic kidney disease (CKD) through identification of novel biomarkers and molecular features of this complex pathology. PeptiCKDdb collects peptidomics and proteomics datasets manually extracted from published studies related to CKD. Datasets from peptidomics or proteomics, human case/control studies on CKD and kidney or urine profiling were included. Data from 114 publications (studies of body fluids and kidney tissue: 26 peptidomics and 76 proteomics manuscripts on human CKD, and 12 focusing on healthy proteome profiling) are currently deposited and the content is quarterly updated. Extracted datasets include information about the experimental setup, clinical study design, discovery-validation sample sizes and list of differentially expressed proteins (P-value < 0.05). A dedicated interactive web interface, equipped with multiparametric search engine, data export and visualization tools, enables easy browsing of the data and comprehensive analysis. In conclusion, this repository might serve as a source of data for integrative analysis or a knowledgebase for scientists seeking confirmation of their findings and as such, is expected to facilitate the modeling of molecular mechanisms underlying CKD and identification of biologically relevant biomarkers.Database URL: www.peptickddb.com

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

Activity of different desoximetasone preparations compared to other topical corticosteroids in the vasoconstriction assay

Introduction: We report on a double-blind, vehicle-controlled, single-center confirmatory study with random assignment. The purpose of the study was to investigate the topical bioavailability of different topical corticosteroid formulations in healthy human beings focussing on desoximetasone (DM). Materials and Methods: Two DM 0.25% formulations {[}ointment (DM-o) and fatty ointment (DM-fo, water-free); class III corticosteroids], the corresponding active ingredient-free vehicles and three comparators of different strength {[}clobetasol propionate 0.05% (CP 0.05%), fatty ointment, class IV; hydrocortisone (HC) 1%, fatty ointment, class I, and betamethasone (BM) 0.05%, fatty ointment, class III] were tested using the vasoconstriction assay. The degree of vasoconstriction (blanching) in the treatment field was compared to the one found in untreated control fields using chromametric measurements and clinical assessment. Results/Conclusion: DM-o 0.25%, DM-fo 0.25% and BM 0.05% showed similar vasoconstrictive potential, i.e., clear blanching. In fact, both DM preparations were proven to be non-inferior to BM 0.05%, while CP 0.05% was found a little less active. HC 1.0% and the DM vehicles showed no clear-cut vasoconstrictive effect. No adverse events related to the study medications were observed. Good topical bioavailability of both DM formulations was detected by chromametric measurement and clinical assessment. Copyright (C) 2008 S. Karger AG, Basel

Lisa Krochmal to Mr. Meredith (1 October 1962)

https://egrove.olemiss.edu/mercorr_pro/1374/thumbnail.jp

Organic phase cyclopentadienylnickelthiolate sensor system for electrochemical determination of sulfur dioxide

A series of cyclopentadienylnickelthiolate complexes, [Ni(PBu3)(h 5 -C5H5)(SC6H4X-4)] (X ¼ F, Cl, Br, NH2), were shown to express stable reversible electrochemical properties even after formation of SO2 adducts in organic phase consisting of argon purged CH2Cl2/0.1 M [n-Bu4N][BF4]. The formal potentials (E8’) values of the compounds ranged from 265 to 431 mV/Ag-AgCl depending on the para substituent of the benzene thiolate ligand. Electrochemical, UVvis and 1 H NMR spectroscopic analyses show that the formation of SO2 adducts causes the perturbation of the electronic density of the nickel metal center, indicated by shifts in the E8’ values of the Ni II/III redox couple that is dependent on SO2 concentration. The detection limits of the resulting organic phase electrochemical gas sensor system was as low as 0.56 ppm SO2 for the fluoro complex, while the linear range was as high as 700 – 2000 ppm SO2 for the amino complex

Oral History Interview with Robert Horton (Part 1)

Robert Horton, a native of New Orleans, shared his life journey, highlighting his experiences from the 1980s to the present. He discussed his early education, his father\u27s incarceration, and the impact of Hurricane Katrina on his family. Horton\u27s involvement in grassroots organizing began with Black Men United and the People\u27s Institute for Survival and Beyond, focusing on economic justice, fatherhood, and community policing. He later worked with Critical Resistance and Step Up Louisiana, developing new leaders and advocating for the Workers Bill of Rights. Horton emphasized the importance of political education and civic engagement in community organizing. Robert Horton discusses the interconnectedness of racial capitalism and capitalism, emphasizing that capitalism inherently benefits white individuals due to racial biases. He identifies as a revolutionary, advocating for social change and anti-racism. Horton highlights the exploitation of the Latinx community, who perform jobs previously held by African Americans, and the potential for tension between the two groups. Horton stresses the importance of challenging white supremacy systemically to achieve true racial justice.https://scholarworks.uno.edu/ejrloh/1000/thumbnail.jp