Identification of Periostin as a Critical Marker of Progression/Reversal of Hypertensive Nephropathy

Progression of chronic kidney disease (CKD) is a major health issue due to persistent accumulation of extracellular matrix in the injured kidney. However, our current understanding of fibrosis is limited, therapeutic options are lacking, and progressive degradation of renal function prevails in CKD patients. Uncovering novel therapeutic targets is therefore necessary

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Expression of the transcriptional regulator snail1 in kidney transplants displaying epithelial-to-mesenchymal transition features

International audienc

Epithelial-to-Mesenchymal Transition Predicts Cyclosporine Nephrotoxicity in Renal Transplant Recipients

Maintenance immunosuppression with cyclosporine A (CsA) can cause nephrotoxicity in renal transplant recipients. Identifying patients at increased risk for CsA nephrotoxicity may allow interventions to prolong graft survival. Here, we studied the effect of early CsA withdrawal or maintenance among 96 kidney recipients at risk for interstitial fibrosis and tubular atrophy (IF/TA) on the basis of tubular expression of vimentin and β-catenin in a protocol biopsy performed 3 months after transplant. In this retrospective analysis of biopsies collected during a randomized trial of early withdrawal of CsA or mycophenolate mofetil, the semiquantitative score of early phenotypic changes suggestive of epithelial-to-mesenchymal transition (EMT) progressed with time among those maintained on a CsA-containing regimen. EMT-positive grafts displayed a significantly higher IF/TA score and greater progression of the IF/TA score at 12 months (P = 0.001 and 0.008, respectively). EMT-positive grafts exposed to CsA also had a greater decrease in estimated GFR compared with EMT-negative grafts exposed to CsA and EMT-positive grafts withdrawn from CsA exposure. Multivariable analysis revealed that the presence of EMT was an independent risk factor for a 10% decline in graft function up to 4 years posttransplant (odds ratio 4.49; 95% confidence interval 1.02 to 19.9). Collectively, these data demonstrate that changes consistent with EMT are strong prognostic biomarkers in renal transplant recipients exposed to CsA

La transition épithélio-mésenchymateuse et la fibrose du transplant rénal

La transition épithélio-mésenchymateuse (TEM) est un processus par lequel les cellules épithéliales différenciées subissent une conversion phénotypique et acquièrent un phénotype de cellules mésenchymateuses. Outre la morphologie allongée, s’y associent une capacité migratoire et une production accrue des composants de la matrice extracellulaire (MEC). Ce phénomène joue un rôle essentiel dans le développement embryonnaire, la cicatrisation et la régénération tissulaire. Certaines études ont suggéré que les cellules épithéliales tubulaires rénales, en réponse à une agression, se transforment en cellules mésenchymateuses, constituant une source importante de nouveaux myofibroblastes qui envahissent l’interstitium rénal et contribuent à la fibrose au sein de celui-ci. Cependant, un nombre croissant de travaux ont remis en question l’existence réelle de ce processus in vivo, qui reste un sujet de débat intense, et pourrait dépendre du modèle étudié. Dans cette revue, nous faisons le point sur le rôle de la TEM dans le développement de la fibrose du greffon rénal, puis nous proposons des approches pour la détection et le traitement de la fibrogenèse rénale, basées sur ce processus de TEM

Expression of periostin by immunohistochemistry in renal cortex during L-NAME-induced hypertensive nephropathy.

<p>Original magnification ×20.</p

Markers of endothelial dysfunction, epithelial mesenchymal transition and fibrosis during progression/regression of renal disease.

<p>Real-time quantitative PCR for endothelin-1 (ET1, A) and E-selectin (ESel, B) Col3A1 (C) and vimentin (D). Results are expressed as arbitrary units. Error bars represent SEM. * <i>p</i><0.05 <i>vs</i> C ; # <i>p</i><0.05 <i>vs</i> LN Reg.</p

Descriptive statistics for functional and structural parameters of hypertensive nephropathy.

<p>C: Control, LOS: Losartan, LN: L-NAME, LN Reg: L-NAME Regression, LN No Reg: L-NAME No Regression.</p><p>MAP: Mean Arterial Pressure, P/C: Proteinuria/Creatininuria, pCr: Plasma Creatinine, RBF: Renal Blood Flow.</p><p>N for each group is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031974#pone-0031974-g003" target="_blank">Figure 3</a>. Values are mean ± SEM.</p>*<p><i>p</i><0.05 <i>vs</i> C:</p>#<p><i>p</i><0.05 <i>vs</i> LN Reg.</p