A Novel Regulatory Role of TRAPPC9 in In Inflammatory Chondrocytes and Osteoarthritis
Hussein Nazar; Zepeda Ernesto Solorzano; Safadi Fayez
Journal of Bone and Mineral Research
2019
2019-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
Adolescents with urinary stones have elevated urine levels of inflammatory mediators
Biomarker; Cytokine; Innate immunity; Interleukin
Urinary stones are increasing in children, primarily during adolescence. Although urinary stones are often viewed in the context of intermittent stone events, increasing evidence indicates that stones are a metabolic process associated with chronic kidney disease and cardiovascular disease. These aforementioned stone-associated conditions may have pediatric origins. To compare urine inflammatory markers in otherwise healthy stone forming children versus matched controls. Urine samples were collected from 12 adolescents with urinary stones along with 15 controls. The levels of 30 urine cytokines were measured using a Mesoscale 30-Plex Human Cytokine panel and normalized to urine creatinine levels. Macrophage inflammatory protein 1β and interleukin 13 levels were significantly elevated in the urine of the stone forming adolescents compared to controls. Interleukin 17A was elevated in the urine of controls. This study indicates that urine levels of cytokines involved in chronic inflammation and fibrosis are elevated in urinary stone formers as early as adolescence. Because stone formers are at risk for chronic kidney disease, macrophage inflammatory protein 1β and interleukin 13 represent investigative targets.
Kusumi Kirsten; Ketz John; Saxena Vijay; Spencer John David; Safadi Fayez; Schwaderer Andrew
Urolithiasis
2019
2019-04
<a href="http://doi.org/10.1007/s00240-019-01133-1" target="_blank" rel="noreferrer noopener">10.1007/s00240-019-01133-1</a>
Comparison of Risk Factors for Pediatric Kidney Stone Formation: The Effects of Sex.
pediatrics; age; sex; kidney stones; urolithiasis
Background: Urinary stones are affecting more children, and pediatric stone formers have unique pathophysiology compared to adults. While adult stone formers are most frequently male, children have an age dependent sex prevalence. Under 10 years, a majority of stone formers are boys; adolescent stone formers are mostly female. Previous adult studies have shown that stone composition is influenced by the sex and age of the stone former. Thus, we hypothesize that female and male stone forming children will also have sex and age specific stone phenotypes. Methods: Retrospective chart review of a large pediatric center's stone forming children 6/1/2009 to 6/1/2016. Patients were identified by ICD 9 codes: N20, N20.1, and N20.9. Charts were reviewed for radiographic evidence of stones or documented visualized stone passage. Results: One hundred and thirty six subjects: 54 males and 82 females. Females were older, median age 14 years [interquartile range (IQR): 11, 15] vs. males' median age 12 years (IQR: 11, 14) (p < 0.01). Females had lower height z-scores, median 0.2 (IQR: -0.8, 0.8) vs. males' median 0.8 (IQR: -0.2, 1.8) (p < 0.01). Presenting symptoms were similar except flank pain affecting 39% of females vs. 22% of males (p = 0.04). Leukocyte esterase was positive in more females than males (33 vs. 4%) (p < 0.001). Males had a higher BUN/Cr ratio, mean +/- standard deviation of 19.8 +/- 6.3 vs. 16.6 +/- 6.5 in females (p = 0.01). Glomerular hyperfiltration was present in 9% of patients while 35% of patients had estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2). Treatment strategies and clinical course were similar except females were told to increase dietary citrate more frequently than males (21 vs. 4%) (p < 0.01). Conclusion: We have provided a novel analysis and demonstrated that low height z-score and pyuria are more common in female stone formers. We have also shown that 9% of pediatric stone formers have labs consistent with hyperfiltration. Whether high protein intake and/or chronic dehydration are associated with hyperfiltration and long-term renal function in children with kidney stones will be an area for future research.
Schwaderer Andrew L; Raina Rupesh; Khare Anshika; Safadi Fayez; Moe Sharon M; Kusumi Kirsten
Frontiers in pediatrics
2019
2019
<a href="http://doi.org/10.3389/fped.2019.00032" target="_blank" rel="noreferrer noopener">10.3389/fped.2019.00032</a>
Glycoprotein Nonmelanoma Clone B Regulates the Crosstalk between Macrophages and Mesenchymal Stem Cells toward Wound Repair.
The process of wound repair requires the coordinated participation of multiple types of cells, which are sequentially recruited during the healing process. In response to tissue injury, both macrophages and mesenchymal stem cells (MSCs) are recruited to the site of injury, where they participate in the repair process. Despite considerable understanding of the role of each cell type in the process of wound repair, the nature of the dynamic interplay between these two cell types and how this interaction influences the process of wound repair are not well understood. Here, using an in vivo model of cutaneous wound healing in mice, we provide evidence that GPNMB is functionally important in promoting the recruitment of MSCs to the site of skin injury, which in turn modulates inflammatory responses by directing the M2 polarization of macrophages in acute wound healing. Furthermore, we show that GPNMB activity is impaired in a diabetic wound environment, which is associated with impaired MSC recruitment that is reversed by the topical administration of recombinant GPNMB protein to the wounds of diabetic mice. Our study provides important insight into the crosstalk between macrophages and endogenous MSCs toward wound repair.
Yu Bing; Alboslemy Talib; Safadi Fayez; Kim Min-Ho
The Journal of investigative dermatology
2018
2018-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.jid.2017.08.034" target="_blank" rel="noreferrer noopener">10.1016/j.jid.2017.08.034</a>
Glycoprotein Nonmelanoma Clone B Regulates the Crosstalk between Macrophages and Mesenchymal Stem Cells toward Wound Repair.
Humans; Male; Animals; Mice; Cell Differentiation; Wound Healing/*physiology; Macrophages/*physiology; Diabetes Mellitus; Cells; Cultured; Inbred C57BL; Animal; Disease Models; Administration; Cutaneous; Cell Communication/*physiology; Eye Proteins/administration & dosage/genetics/*physiology; Membrane Glycoproteins/administration & dosage/genetics/*physiology; Mesenchymal Stem Cells/*physiology; Recombinant Proteins/administration & dosage/genetics/metabolism; Skin/*injuries/metabolism; Type 2/complications/pathology
The process of wound repair requires the coordinated participation of multiple types of cells, which are sequentially recruited during the healing process. In response to tissue injury, both macrophages and mesenchymal stem cells (MSCs) are recruited to the site of injury, where they participate in the repair process. Despite considerable understanding of the role of each cell type in the process of wound repair, the nature of the dynamic interplay between these two cell types and how this interaction influences the process of wound repair are not well understood. Here, using an in vivo model of cutaneous wound healing in mice, we provide evidence that GPNMB is functionally important in promoting the recruitment of MSCs to the site of skin injury, which in turn modulates inflammatory responses by directing the M2 polarization of macrophages in acute wound healing. Furthermore, we show that GPNMB activity is impaired in a diabetic wound environment, which is associated with impaired MSC recruitment that is reversed by the topical administration of recombinant GPNMB protein to the wounds of diabetic mice. Our study provides important insight into the crosstalk between macrophages and endogenous MSCs toward wound repair.
Yu Bing; Alboslemy Talib; Safadi Fayez; Kim Min-Ho
The Journal of investigative dermatology
2018
2018-01
<a href="http://doi.org/10.1016/j.jid.2017.08.034" target="_blank" rel="noreferrer noopener">10.1016/j.jid.2017.08.034</a>
Members of the novel UBASH3/STS/TULA family of cellular regulators suppress
Animals; Antigen; Colitis/*immunology; Humans; Knockout; Mice; Phosphorylation; Protein Tyrosine Phosphatases/genetics/*physiology; Receptors; T-Cell/genetics/*physiology; T-Lymphocytes/*immunology; ZAP-70 Protein-Tyrosine Kinase/metabolism
The UBASH3/STS/TULA family consists of two members sharing substantial homology and a similar multi-domain architecture, which includes a C-terminal histidine phosphatase domain capable of dephosphorylating phosphotyrosine-containing substrates. TULA-family proteins act as downregulators of receptor-induced activation in several cell types, including T cells and platelets. Deletion of both family members in mice has been shown to result in hyperresponsiveness of T cells to T-cell receptor (TCR)/CD3 complex engagement, but little is known about the biological consequences of double knockout (dKO) and especially of either single KO (sKO). We elucidated the biological consequences of the lack of
Newman Tiffanny N; Liverani Elisabetta; Ivanova Elitza; Russo Gian L; Carpino Nick; Ganea Doina; Safadi Fayez; Kunapuli Satya P; Tsygankov Alexander Y
Immunology and cell biology
2014
2014-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1038/icb.2014.60" target="_blank" rel="noreferrer noopener">10.1038/icb.2014.60</a>