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https://www.readbyqxmd.com/read/28931758/molecular-characterization-of-the-transition-from-acute-to-chronic-kidney-injury-following-ischemia-reperfusion
#1
Jing Liu, Sanjeev Kumar, Egor Dolzhenko, Gregory F Alvarado, Jinjin Guo, Can Lu, Yibu Chen, Meng Li, Mark C Dessing, Riana K Parvez, Pietro E Cippà, A Michaela Krautzberger, Gohar Saribekyan, Andrew D Smith, Andrew P McMahon
Though an acute kidney injury (AKI) episode is associated with an increased risk of chronic kidney disease (CKD), the mechanisms determining the transition from acute to irreversible chronic injury are not well understood. To extend our understanding of renal repair, and its limits, we performed a detailed molecular characterization of a murine ischemia/reperfusion injury (IRI) model for 12 months after injury. Together, the data comprising RNA-sequencing (RNA-seq) analysis at multiple time points, histological studies, and molecular and cellular characterization of targeted gene activity provide a comprehensive profile of injury, repair, and long-term maladaptive responses following IRI...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28809130/long-noncoding-rna-a-new-contributor-and-potential-therapeutic-target-in-fibrosis
#2
Xiaoying Jiang, Fujun Zhang
Fibrosis is the excess deposition of extracellular matrix components which occur in multiple organs and ultimately leads to organ failure. Long noncoding RNAs (lncRNAs) are a kind of noncoding RNAs longer than approximately 200 nucleotides with no protein-encoding capacity. A growing body of evidence suggests that lncRNAs are also involved in tissues fibrosis in several organs, such as lungs fibrosis, liver fibrosis, renal fibrosis and cardiac fibrosis. In this review, we summarized the current studies of lncRNAs in the process of fibrosis and hopefully aid in better understanding the molecular mechanism of fibrosis and provide a basis to explore new therapeutic targets of fibrosis...
August 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28780716/epigenetics-a-potential-key-mechanism-involved-in-the-pathogenesis-of-cardiorenal-syndromes
#3
REVIEW
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Massimo de Cal, Claudio Ronco
Epigenetics is defined as the heritable changes in gene expression patterns which are not directly encoded by modifications in the nucleotide DNA sequence of the genome, including higher order chromatin organization, DNA methylation, cytosine modifications, covalent histone tail modifications, and short non-coding RNA molecules. Recently, much attention has been paid to the role and the function of epigenetics and epimutations in the cellular and subcellular pathways and in the regulation of genes in the setting of both kidney and cardiovascular disease...
August 5, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28762541/real-world-effectiveness-and-safety-of-paritaprevir-ritonavir-ombitasvir-and-dasabuvir-with-or-without-ribavirin-for-patients-with-chronic-hepatitis-c-virus-genotype-1b-infection-in-taiwan
#4
Chen-Hua Liu, Chun-Jen Liu, Tung-Hung Su, Hung-Chih Yang, Chun-Ming Hong, Tai-Chung Tseng, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
BACKGROUND AND AIM: The real-world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) remain limited for East Asian hepatitis C virus genotype 1b (HCV-1b) patients. We aimed to evaluate the anti-viral responses of PrOD-based regimens for HCV-1b patients in Taiwan. METHODS: We performed a retrospective analysis of 103 HCV-1b patients receiving PrOD with or without ribavirin (RBV) for 12 weeks. Data were analyzed to assess the on-treatment and off-therapy HCV viral load, and on-treatment adverse events (AEs)...
August 1, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28703905/successful-treatment-of-chronic-hepatitis-c-infection-with-directly-acting-antivirals-in-renal-transplant-recipients
#5
Sunil Taneja, Ajay Duseja, Arka De, Vivek Kumar, Raja Ramachandran, Ashish Sharma, Radha K Dhiman, Krishan L Gupta, Yogesh Chawla
AIMS: The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia-Pacific region. Aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. METHODS: A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016...
July 13, 2017: Nephrology
https://www.readbyqxmd.com/read/28676554/diabetic-rats-present-higher-urinary-loss-of-proteins-and-lower-renal-expression-of-megalin-cubilin-clc-5-and-cftr
#6
Miriam F Figueira, Raquel C Castiglione, Carolina M de Lemos Barbosa, Felipe M Ornellas, Geórgia da Silva Feltran, Marcelo M Morales, Rodrigo N da Fonseca, Jackson de Souza-Menezes
Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28662883/paritaprevir-ritonavir-ombitasvir-plus-dasabuvir-with-ribavirin-for-treatment-of-recurrent-chronic-hepatitis-c-genotype-1-infection-after-liver-transplantation-real-world-experience
#7
Ming-Lung Yu, Yao-Li Chen, Chung-Feng Huang, Kuo-Hua Lin, Ming-Lun Yeh, Ching-I Huang, Meng-Hsuan Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang
BACKGROUND/AIMS: The registered trial has demonstrated that paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD) with ribavirin was effective for recurrent hepatitis C virus genotype 1 (HCV-1) infection after liver transplantation in patients with mild fibrosis; however, the real-world efficacy and safety of this regimen have not been determined. METHODS: The efficacy (sustained virological response, SVR12, undetectable HCV RNA 12 weeks post-treatment) and safety were evaluated in 12 patients with recurrent HCV-1 infection after liver transplantation...
June 26, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28620300/novel-anti-fibrotic-therapies
#8
REVIEW
Benita L McVicker, Robert G Bennett
Fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease, as well as a post-injury response that drives progression. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Novel treatments have recently been identified that hold promise as potential therapeutic agents for cardiovascular diseases associated with fibrosis, as well as other fibrotic conditions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28620270/flucytosine-and-amphotericin-b-coadministration-induces-dose-related-renal-injury
#9
Alexandra Folk, Cornel Balta, Hildegard Herman, Alexandra Ivan, Oana Maria Boldura, Lucian Paiusan, Aurel Ardelean, Anca Hermenean
Invasive fungal infections remain an important clinical problem, and despite recent approaches, they bring high morbidity and mortality. Combination therapies are the most effective; however, adverse effects need to be considered. In this study, we aimed to evaluate the nephrotoxicity induced by combined therapy of flucytosine (FL) and amphotericin B (AMF) at 3 different doses administered to mice for 14 days: 300 μg/kg AMF+50 mg/kg FL; 600 μg/kg AMF+100 mg/kg FL; 900 μg/kg AMF+150 mg/kg FL. Antifungal coadministration triggered nuclear translocation of NF-κB and upregulated nuclear factor kappa-light-chain-enhancer of activated B cells subunit p65 (NF-κB p65) messenger RNA mRNA level in dose-dependent manner...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28618421/identification-of-tisp40-as-an-essential-regulator-of-renal-tubulointerstitial-fibrosis-via-tgf-%C3%AE-smads-pathway
#10
Cheng-Cheng Xiao, Jie Zhang, Peng-Cheng Luo, Cong Qin, Yang Du, Jin-Zhuo Ning, Hai-Zhou Zheng
BACKGROUND: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown. METHODS: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT) and the underlying molecular mechanisms in transforming growth factor-β (TGF-β)-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R) by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28611273/racial-disparities-in-hepatitis-c-treatment-eligibility
#11
Omar Sims, David Pollio, Barry Hong, Carol North
BACKGROUND: Hepatitis C (HCV) is more prevalent in African Americans than in any other racial group in the United States. However, African Americans are more likely to be deemed ineligible for HCV treatment than non-African Americans. There has been limited research into the origins of racial disparities in HCV treatment eligibility. AIM: The purpose of this study was to compare medical and non-medical characteristics commonly assessed in clinical practice that could potentially contribute to HCV treatment ineligibility disparities between African American and non-African American patients...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28596300/clear-cell-renal-cell-carcinoma-is-linked-to-epithelial-to-mesenchymal-transition-and-to-fibrosis
#12
Lea Landolt, Øystein Eikrem, Philipp Strauss, Andreas Scherer, David H Lovett, Christian Beisland, Kenneth Finne, Tarig Osman, Mohammad M Ibrahim, Gro Gausdal, Lavina Ahmed, James B Lorens, Jean Paul Thiery, Tuan Zea Tan, Miroslav Sekulic, Hans-Peter Marti
Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq(®) Access library preparation protocol and TruSeq Small RNA library preparation kit...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28460073/regulation-of-mir-29b-and-mir-30c-by-vitamin-d-receptor-activators-contributes-to-attenuate-uraemia-induced-cardiac-fibrosis
#13
Sara Panizo, Natalia Carrillo-López, Manuel Naves-Díaz, Guillermo Solache-Berrocal, Laura Martínez-Arias, Raúl R Rodrigues-Díez, Amalia Fernández-Vázquez, Carlos Martínez-Salgado, Marta Ruiz-Ortega, Adriana Dusso, Jorge B Cannata-Andía, Isabel Rodríguez
Background.: Uraemic cardiomyopathy, a process mainly associated with increased myocardial fibrosis, is the leading cause of death in chronic kidney disease patients and can be prevented by vitamin D receptor activators (VDRAs). Since some microRNAs (miRNAs) have emerged as regulators of the fibrotic process, we aimed to analyse the role of specific miRNAs in VDRA prevention of myocardial fibrosis as well as their potential use as biomarkers. Methods.: Wistar rats were nephrectomized and treated intraperitoneally with equivalent doses of two VDRAs: calcitriol and paricalcitol...
April 28, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28452949/generation-and-applications-of-a-dna-aptamer-against-gremlin-1
#14
Qian Li, Yongwei Huo, Yonghong Guo, Xiaoyan Zheng, Wengang Sun, Zhiming Hao
Gremlin-1, a highly conserved glycosylated and phosphorylated secretory protein, plays important roles in diverse biological processes including early embryonic development, fibrosis, tumorigenesis, and renal pathophysiology. Aptamers, which are RNA or DNA single-stranded oligonucleotides capable of binding specifically to different targets ranging from small organics to whole cells, have potential applications in targeted imaging, diagnosis and therapy. In this study, we obtained a DNA aptamer against Gremlin-1 (G-ap49) using in vitro Systematic Evolution of Ligands by Exponential Enrichment (SELEX)...
April 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28446517/a-novel-%C3%AE-calcitonin-gene-related-peptide-analogue-protects-against-end-organ-damage-in-experimental-hypertension-cardiac-hypertrophy-and-heart-failure
#15
Aisah A Aubdool, Pratish Thakore, Fulye Argunhan, Sarah-Jane Smillie, Moritz Schnelle, Salil Srivastava, Khadija M Alawi, Elena Wilde, Jennifer Mitchell, Keith Farrell-Dillon, Daniel A Richards, Giuseppe Maltese, Richard C Siow, Manasi Nandi, James E Clark, Ajay M Shah, Anette Sams, Susan D Brain
BACKGROUND: Research into the therapeutic potential of α-calcitonin gene-related peptide (α-CGRP) has been limited because of its peptide nature and short half-life. Here, we evaluate whether a novel potent and long-lasting (t½ ≥7 hours) acylated α-CGRP analogue (αAnalogue) could alleviate and reverse cardiovascular disease in 2 distinct murine models of hypertension and heart failure in vivo. METHODS: The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin by using a CGRP receptor antagonist...
July 25, 2017: Circulation
https://www.readbyqxmd.com/read/28414804/cyclosporine-a-alters-expression-of-renal-micrornas-new-insights-into-calcineurin-inhibitor-nephrotoxicity
#16
Jennifer L Gooch, Clayton King, Cynthia E Francis, Paul S Garcia, Yun Bai
Calcineurin inhibitors are powerful immunosuppressants that revolutionized organ transplantation. However, non-immune effects of the calcineurin inhibitor, such as cyclosporine A (CsA), have significantly hindered their use. Specifically, nephrotoxicity, which is associated with tubulointerstitial fibrosis, inflammation, and podocyte damage, affects up to half of all transplant patients. Calcineurin is involved in many aspects of kidney development and function; therefore, mechanisms of CsA-induced nephrotoxicity are complex and not yet fully understood...
2017: PloS One
https://www.readbyqxmd.com/read/28352334/long-non-coding-rna-asncmtrna-2-is-upregulated-in-diabetic-kidneys-and-high-glucose-treated-mesangial-cells
#17
Yan Gao, Zhao-Yu Chen, Yan Wang, Yan Liu, Jian-Xia Ma, Yu-Kun Li
Diabetic nephropathy (DN) is one of the most frequent complications associated with type I and II diabetes mellitus. Kidneys from patients with DN are characterized by mesangial matrix expansion and increased thickness of the glomerular basement membrane, which are induced by reactive oxygen species (ROS) production. Previous studies have been conducted to investigate this; however, the detailed mechanism of DN progression remains to be elucidated. The present study evaluated the expression of antisense mitochondrial non-coding RNA-2 (ASncmtRNA-2) in an experimental DN model and cultured human mesangial cells...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28339906/interstitial-fibrosis-scored-on-whole-slide-digital-imaging-of-kidney-biopsies-is-a-predictor-of-outcome-in-proteinuric-glomerulopathies
#18
Laura H Mariani, Sebastian Martini, Laura Barisoni, Pietro A Canetta, Jonathan P Troost, Jeffrey B Hodgin, Matthew Palmer, Avi Z Rosenberg, Kevin V Lemley, Hui-Ping Chien, Jarcy Zee, Abigail Smith, Gerald B Appel, Howard Trachtman, Stephen M Hewitt, Matthias Kretzler, Serena M Bagnasco
Background.: Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. Methods.: We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37)...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#19
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not exclusively established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
July 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28237649/protein-kinase-ck2%C3%AE-catalytic-subunit-ameliorates-diabetic-renal-inflammatory-fibrosis-via-nf-%C3%AE%C2%BAb-signaling-pathway
#20
Junying Huang, Zhiquan Chen, Jie Li, Qiuhong Chen, Jingyan Li, Wenyan Gong, Jiani Huang, Peiqing Liu, Heqing Huang
Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA)...
May 15, 2017: Biochemical Pharmacology
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