B7-H3 is widely expressed in soft tissue sarcomas.

Purpose: Targeted therapy development in soft tissue sarcoma (STS) has been burdened by the heterogeneity of this group of rare tumors. B7 homolog 3 protein (B7-H3) is a molecule in the same family as programmed death-ligand 1 (PD-L1). It has limited expression in noncancerous tissues and is overexpressed in many cancers, making it an attractive target for cancer therapy, and clinical trials targeting B7-H3 are actively underway.

Metabolome panels as potential noninvasive biomarkers for primary glomerulonephritis sub-types: meta-analysis of profiling metabolomics studies.

Primary glomerulonephritis diseases (PGDs) are known as the top causes of chronic kidney disease worldwide. Renal biopsy, an invasive method, is the main approach to diagnose PGDs. Studying the metabolome profiles of kidney diseases is an inclusive approach to identify the disease's underlying pathways and discover novel non-invasive biomarkers.

The potential of cardiac biomarkers, NT-ProBNP and troponin T, in predicting the progression of nephropathy in diabetic patients: A meta-analysis of prospective cohort studies.

Aims: A meta-analysis was done to investigate the association of two cardiac biomarkers of N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and circulating troponin T (TnT) with the progression of diabetic nephropathy (DN).

Methods: A thorough search of the PubMed, Scopus, and Web of Science databases was done until June 2022. The outcome (progression of DN) was described as either of the followings: a) eGFR decline, b) albuminuria, c) end-stage renal disease, or d) mortality.

What the BTBR/J mouse has taught us about diabetes and diabetic complications.

Human and mouse genetics have delivered numerous diabetogenic loci, but it is mainly through the use of animal models that the pathophysiological basis for their contribution to diabetes has been investigated. More than 20 years ago, we serendipidously identified a mouse strain that could serve as a model of obesity-prone type 2 diabetes, the BTBR (Black and Tan Brachyury) mouse (BTBR T+ Itpr3tf/J, 2018) carrying the mutation. We went on to discover that the BTBR- mouse is an excellent model of diabetic nephropathy and is now widely used by nephrologists in academia and the pharmaceutical industry.

Candidate MicroRNA Biomarkers in Lupus Nephritis: A Meta-analysis of Profiling Studies in Kidney, Blood and Urine Samples.

Context: Lupus nephritis (LN) is a kidney disease caused by systemic lupus erythematosus in which kidneys are attacked by the immune system. So far, various investigations have reported altered miRNA expression profiles in LN patients and different miRNAs have been introduced as biomarkers and/or therapeutic targets in LN. The aim of this study was to introduce a consensus panel of potential miRNA biomarkers by performing a meta-analysis of miRNA profiles in the LN patients.

Regression of diabetic nephropathy by treatment with empagliflozin in BTBR ob/ob mice.

Background: The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin lowers blood glucose via reduced tubular reabsorption of filtered glucose and is an important new therapy for diabetic nephropathy (DN). This study tested whether treatment with empagliflozin would ameliorate proteinuria and the pathologic alterations of DN including podocyte number and integrity in the leptin-deficient BTBR ob/ob mouse model of DN.

Methods: Study cohorts included wild-type (WT) BTBR mice, untreated diabetic BTBR ob/ob mice and mice treated with empagliflozin for 6 weeks after development of established DN at 18 weeks of age.

TACI haploinsufficiency protects against BAFF-driven humoral autoimmunity in mice.

Polymorphisms in TACI, a BAFF family cytokine receptor, are linked to diverse human immune disorders including common variable immunodeficiency (CVID) and systemic lupus erythematosus (SLE). Functional studies of individual variants show modest impacts on surface TACI expression and/or downstream signal transduction, indicating that relatively subtle variation in TACI activity can impact human B-cell biology. However, significant complexity underlies TACI biology, including both positive and negative regulation of physiologic and pathogenic B-cell responses.

Non-invasive metabolic biomarkers for early diagnosis of diabetic nephropathy: Meta-analysis of profiling metabolomics studies.

Aim: Diabetic nephropathy (DN) is one of the worst complications of diabetes. Despite a growing number of DN metabolite profiling studies, most studies are suffering from inconsistency in their findings. The main goal of this meta-analysis was to reach to a consensus panel of significantly dysregulated metabolites as potential biomarkers in DN.

Reversal of hypertriglyceridemia in diabetic BTBR ob/ob mice does not prevent nephropathy.

The etiology of diabetic nephropathy in type 2 diabetes is multifactorial. Sustained hyperglycemia is a major contributor, but additional contributions come from the hypertension, obesity, and hyperlipidemia that are also commonly present in patients with type 2 diabetes and nephropathy. The leptin deficient BTBR ob/ob mouse is a model of type 2 diabetic nephropathy in which hyperglycemia, obesity, and hyperlipidemia, but not hypertension, are present.

Beneficial effect on podocyte number in experimental diabetic nephropathy resulting from combined atrasentan and RAAS inhibition therapy.

Podocyte loss and proteinuria are both key features of human diabetic nephropathy (DN). The leptin-deficient BTBR mouse strain with the mutation develops progressive weight gain, type 2 diabetes, and diabetic nephropathy that has many features of advanced human DN, including increased mesangial matrix, mesangiolysis, podocyte loss, and proteinuria. Selective antagonism of the endothelin-1 type A receptor (ETR) by atrasentan treatment in combination with renin-angiotensin-aldosterone system inhibition with losartan has been shown to have the therapeutic benefit of lowering proteinuria in patients with DN, but the underlying mechanism for this benefit is not well understood.

Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury.

Lupus nephritis (LN) is a major contributor to morbidity and mortality in lupus patients, but the mechanisms of kidney damage remain unclear. In this study, we introduce, to our knowledge, novel models of LN designed to resemble the polygenic nature of human lupus by embodying three key genetic alterations: the interval leading to anti-chromatin autoantibodies; , leading to defective clearance of apoptotic cells; and either or , leading to low complement levels. We report that proliferative glomerulonephritis arose only in the presence of all three abnormalities (i.

High-protein diet accelerates diabetes and kidney disease in the BTBR mouse.

There is a need for improved animal models that better translate to human kidney disease to predict outcome of pharmacological effects in the patient. The diabetic BTBR mouse model mimics key features of early diabetic nephropathy in humans, but with chronic injury limited to glomeruli. To explore if we could induce an accelerated and more advanced disease phenotype that closer translates to human disease, we challenged BTBR mice with a high-protein diet (HPD; 30%) and followed the progression of metabolic and renal changes up to 20 wk of age.

Differential expression of parietal epithelial cell and podocyte extracellular matrix proteins in focal segmental glomerulosclerosis and diabetic nephropathy.

In healthy glomeruli, parietal epithelial cell (PEC)-derived extracellular matrix (ECM) proteins include laminin-β, perlecan, and collagen type IV-α and podocyte-specific ECM proteins include laminin-β, agrin, and collagen type IV-α. This study aimed to define individual ECM protein isoform expression by PECs in both experimental and human focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN) and to determine if changes were CD44 dependent. In experimental FSGS induced with a cytotoxic podocyte antibody and in the BTBR mouse model of DN, PEC-derived protein staining was significantly increased in PECs.

Gene deletion of the Na-glucose cotransporter SGLT1 ameliorates kidney recovery in a murine model of acute kidney injury induced by ischemia-reperfusion.

Renal Na-glucose cotransporter SGLT1 mediates glucose reabsorption in the late proximal tubule, a hypoxia-sensitive tubular segment that enters the outer medulla. Gene deletion in mice () was used to determine the role of the cotransporter in acute kidney injury induced by ischemia-reperfusion (IR), including the initial injury and subsequent recovery phase. On and after IR, absolute and fractional urinary glucose excretion remained greater in mice versus wild-type (WT) littermates, consistent with a sustained contribution of SGLT1 to tubular glucose reabsorption in WT mice.

Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci.

Background: Linking genetic risk loci identified by genome-wide association studies (GWAS) to their causal genes remains a major challenge. Disease-associated genetic variants are concentrated in regions containing regulatory DNA elements, such as promoters and enhancers. Although researchers have previously published DNA maps of these regulatory regions for kidney tubule cells and glomerular endothelial cells, maps for podocytes and mesangial cells have not been available.

Pathology identifies glomerular treatment targets in diabetic nephropathy.

The development of the glomerular injury in diabetic nephropathy involves interactions between podocytes, endothelium, and the mesangium. Loss of podocytes is an early and critical step in the development of diabetic nephropathy, and analysis of structural lesions within the mesangium such as mesangiolysis implicate the loss of podocytes as a key mediating event. The BTBR / mouse has proved a useful tool to demonstrate that restoration of podocyte density, once thought to be an absolute barrier to glomerular repair, can be achieved with replacement of the hormone leptin that is constitutively absent in these mice.

TACI deletion protects against progressive murine lupus nephritis induced by BAFF overexpression.

B cells are known to promote the pathogenesis of systemic lupus erythematosus (SLE) via the production of pathogenic anti-nuclear antibodies. However, the signals required for autoreactive B cell activation and the immune mechanisms whereby B cells impact lupus nephritis pathology remain poorly understood. The B cell survival cytokine B cell activating factor of the TNF Family (BAFF) has been implicated in the pathogenesis of SLE and lupus nephritis in both animal models and human clinical studies.

A Novel Type 2 Diabetes Mouse Model of Combined Diabetic Kidney Disease and Atherosclerosis.

Diabetic kidney disease and atherosclerotic disease are major causes of morbidity and mortality associated with type 2 diabetes (T2D), and diabetic kidney disease is a major cardiovascular risk factor. The black and tan, brachyury (BTBR) mouse strain with leptin deficiency (Lep) has emerged as one of the best models of human diabetic kidney disease. However, no T2D mouse model of combined diabetic kidney disease and atherosclerosis exists.

Histopathology of Veins Obtained at Hemodialysis Arteriovenous Fistula Creation Surgery.

Stenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study.

LR8 Expression in fibroblasts of healthy and fibrotic human tissues.

LR8 gene was first reported in a subpopulation of cultured human lung fibroblasts expressing the receptor for C1q-globular domain, and it was not detectable in cultured endothelial cells and smooth muscle cells. LR8 mRNA levels were higher in fibrotic lungs. In this study we assessed LR8 production in human tissues and determined if the distribution of fibroblasts producing LR8 is affected in fibrosis.

The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age.

Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 months (equivalent to a 79-year-old human).

The role of PDGF-D in healthy and fibrotic kidneys.

Platelet-derived growth factor (PDGF)-D, a specific PDGF receptor β (PDGFR-β) ligand, mediates mesangial proliferation in vitro and in vivo. However, its role in renal development, physiology, and fibrosis is relatively unknown. In healthy murine kidneys, PDGF-D was found to be expressed on renal mesenchymal cells (mesangial cells, fibroblasts, and vascular smooth muscle cells).

Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E.

Macrophages play a key role in the development of atherosclerosis. Murine noroviruses (MNV) are highly prevalent in research mouse colonies and infect macrophages and dendritic cells. Our laboratory found that MNV4 infection in mice lacking the LDL receptor alters the development of atherosclerosis, potentially confounding research outcomes.

The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy.

Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes.