A5021277525- Acute Kidney Injury Research
- Cholesterol and Lipid Metabolism
- Chronic Kidney Disease and Diabetes
- Dendrimers and Hyperbranched Polymers
- RNA Interference and Gene Delivery
- Cancer, Lipids, and Metabolism
- Dialysis and Renal Disease Management
- Lipid metabolism and biosynthesis
- Advanced biosensing and bioanalysis techniques
- Renal and related cancers
- Drug Transport and Resistance Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Liver Disease Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Phagocytosis and Immune Regulation
- Click Chemistry and Applications
- Pancreatic function and diabetes
- Phase Equilibria and Thermodynamics
- Chemical Synthesis and Analysis
- Nanoparticle-Based Drug Delivery
- Organ Donation and Transplantation
- Scientific Measurement and Uncertainty Evaluation
- Organ Transplantation Techniques and Outcomes
- Drug-Induced Hepatotoxicity and Protection
- Lipoproteins and Cardiovascular Health
Yale University
2016-2024
Mount Auburn Hospital
2022
Harvard University
2022
Business Academy Aarhus
2022
Shandong Agricultural University
2022
Virginia Commonwealth University
2009-2017
Pediatric Nephrology of Alabama
2017
University of Richmond
2015
Hunter Holmes McGuire VA Medical Center
2009-2013
Shanghai Medical College of Fudan University
2009
Significance Statement Clinical evidence suggests that monocyte chemoattractant protein-1 (MCP-1) may be a useful biomarker to identify patients at risk for kidney fibrosis and CKD progression. Using mouse model of unilateral ischemia/reperfusion injury (U-IRI), the authors show sustained GM-CSF expression by renal tubular cells markedly increases Mcp-1 in macrophages during transition from normal repair maladaptive fibrosis. Eliminating CCR2, receptor MCP-1, using genetic engineering or...
INTRODUCTION. Acute kidney injury and chronic disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term progression to failure is required.
Abstract Incomplete repair after acute kidney injury can lead to development of chronic disease. To define the mechanism this response, we compared mice subjected identical unilateral ischemia-reperfusion with either contralateral nephrectomy (where tubule predominates) or intact atrophy predominates). By day 14, kidneys undergoing had more macrophages higher expression chemokines, correlating a second wave proinflammatory neutrophil and T cell recruitment accompanied by increased tubular...
BACKGROUNDLongitudinal investigations of murine acute kidney injury (AKI) suggest that and inflammation may persist long after the initial insult. However, evolution these processes their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort 656 participants hospitalized AKI, we measured 7 urine 2 plasma biomarkers injury, inflammation, tubular health at multiple time points from diagnosis to 12 months AKI. We used linear mixed-effect models estimate biomarker...
Repeated administration of cisplatin causes CKD. In previous studies, we reported that the kidney-secreted survival protein renalase (RNLS) and an agonist peptide protected mice from cisplatin-induced AKI.To investigate whether kidney-targeted delivery RNLS might prevent CKD in a mouse model, achieved specific (RP81) to renal proximal tubule by encapsulating mesoscale nanoparticles (MNPs). We used genetic deletion RNLS, single-cell RNA sequencing analysis, Western blotting determine efficacy...
Background and objectives Uromodulin, produced exclusively in the kidney’s thick ascending limb, is a biomarker of kidney tubular health. However, relationship between urine uromodulin histologic changes tubulointerstitium has not been characterized. In this study, we test association with findings humans mice. Design, setting, participants, & measurements We investigated independent measured at time biopsy features 364 participants two academic medical centers from 2015 to 2018 using...
The oxysterol receptor LXR is a key transcriptional regulator of lipid metabolism. increases expression SREBP-1, which in turn regulates at least 32 genes involved synthesis and transport. We recently identified 25-hydroxycholesterol-3-sulfate (25HC3S) as an important regulatory molecule the liver. have now studied effects 25HC3S its precursor, 25-hydroxycholesterol (25HC), on metabolism mediated by LXR/SREBP-1 signaling macrophages. Addition to human THP-1-derived macrophages markedly...
Dysregulation of lipid metabolism is frequently associated with inflammatory conditions. The mechanism this association still not clearly defined. Recently, we identified a nuclear oxysterol, 25-hydroxycholesterol-3-sulfate (25HC3S), as an important regulatory molecule involved in hepatocytes. present study shows that 25HC3S and its precursor, 25-hydroxycholesterol (25HC), diametrically regulate response via LXR/SREBP-1 IkappaBalpha/NFkappaB signaling Addition to primary rat hepatocytes...
Free-radical photopolymerization initiated by photoinitiators is an important method to make tissue engineering scaffolds. To advance understanding of photoinitiator cytocompatibility, we examined three including 2,2-dimethoxy-2-phenylacetophenone (DMPA), Irgacure 2959 (I-2959), and eosin Y photoinitiating system (EY) in terms their effects on viability HN4 cells expression levels intracellular AKT its phosphorylated form p-AKT. Our results show that the UV-exposed counterparts affect...
Significance Statement Proinflammatory macrophages that infiltrate the kidney after ischemia-reperfusion injury later transition to a proreparative state characterized by expression of multiple proteins including arginase-1 ( Arg1 ). By comparing repair response in mice lack macrophage with littermate controls, we show plays critical role renal recovery part promoting epithelial cell proliferative repair. Thus, therapeutic interventions enhance may improve injury. Background After injury,...
The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein–39 (BRP-39), also known as chitinase 3–like 1 (CHI3L1) encoded by Chi3l1 gene, is expressed at high levels macrophages during early stages repair promotes tubular cell survival via IL-13 receptor α 2 (IL13R 2)–mediated signaling. Here, we investigated role BRP-39 in profibrotic responses after AKI. In wild-type...
Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort hospitalized with without AKI. Cox proportional hazards regression was used to investigate...
Sulfotransferase (SULT)-mediated sulfation represents a critical mechanism in regulating the chemical and functional homeostasis of endogenous exogenous molecules. The cholesterol sulfotransferase SULT2B1b catalyzes sulfoconjugation to synthesize sulfate (CS). In this study, we showed that expression liver was induced obese mice during transition from fasted fed state, suggesting regulation is physiologically relevant. CS inhibited gluconeogenesis by targeting gluconeogenic factor hepatocyte...
The nuclear receptor peroxisome proliferator-activated receptors (PPARs) are important in regulating lipid metabolism and inflammatory responses macrophages. Activation of PPARγ represses key response gene expressions. Recently, we identified a new cholesterol metabolite, 25-hydroxycholesterol-3-sulfate (25HC3S), as potent regulatory molecule metabolism. In this paper, report the effect 25HC3S its precursor 25-hydroxycholesterol (25HC) on activity responses. Addition to human macrophages...
We developed novel dendrimer hydrogels (DHs) on the basis of bioorthogonal chemistry, in which polyamidoamine (PAMAM) generation 4.0 (G4) functionalized with strained alkyne, i.e., dibenzocyclooctyne (DBCO), via a PEG spacer (Mn = 2000 g/mol) underwent strain-promoted azide–alkyne cycloaddition (SPAAC) polyethylene glycol bisazide (PEG-BA) (Mn= 20 000 to generate dendrimer-PEG cross-linked network. This platform offers high degree functionality and modularity. A wide range structural...
Folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) was synthesized and studied for targeted delivery of genes to head neck cancer cells expressing high levels folate receptors (FRs).Cellular uptake, targeting specificity, cytocompatibility transfection efficiency were evaluated.G4-FA competes with free FA the same binding site. G4-FA facilitates cellular uptake DNA plasmids in a FR-dependent manner selectively delivers FR-high cells, leading enhanced gene expression.G4-FA is...
In the present work we report on click synthesis of a new camptothecin (CPT) prodrug based an anionic polyamidoamine (PAMAM) dendrimer intended for cancer therapy.
Sterol regulatory element-binding protein-1c (SREBP-1c) increases lipogenesis at the transcriptional level, and its expression is upregulated by liver X receptor α (LXRα). The LXRα/SREBP-1c signaling may play a crucial role in pathogenesis of nonalcoholic fatty disease (NAFLD). We previously reported that cholesterol metabolite, 5-cholesten-3β,25-diol 3-sulfate (25HC3S), inhibits LXRα reduces decreasing SREBP-1c primary hepatocytes. present study aims to investigate effects 25HC3S on lipid...
Immobilizing highly branched polyamidoamine (PAMAM) dendrimers to the cell surface represents an innovative method of enhancing loading capacity deliver therapeutic and imaging agents. In this work, hybridized immune cells, that is, macrophage RAW264.7 (RAW), with PAMAM dendrimer G4.0 (DEN) on basis bioorthogonal chemistry are clicked. Efficient selective immobilization is confirmed by confocal microscopy. Viability motility RAW‐DEN hybrids remain same as untreated RAW cells according WST‐1...