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1.
Mol Ther Nucleic Acids ; 17: 102-112, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31234008

RESUMO

Contrast-induced acute kidney injury (CI-AKI) is a severe complication of intravascular applied radial contrast media, and recent progress in interventional therapy and angiography has revived interest in explaining detailed mechanisms and developing effective treatment. Recent studies have indicated a potential link between CI-AKI and microRNA (miRNA). However, the potential non-coding RNA-associated-competing endogenous RNA (ceRNA) pairs involved in CI-AKI still remain unclear. In this study, we systematically explored the circRNA or lncRNA-associated-ceRNA mechanism in a new rat model of CI-AKI through deep RNA sequencing. The results revealed that the expression of 38 circRNAs, 12 lncRNAs, 13 miRNAs and 127 mRNAs were significantly dysregulated. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses for mRNAs with significantly different expression and then constructed comprehensive circRNA or lncRNA-associated ceRNA networks in kidney of CI-AKI rats. Thereafter, two constructed ceRNA regulatory pathways in this CI-AKI rat model-novel_circ_0004153/rno-miR-144-3p/Gpnmb or Naglu and LNC_000343/rno-miR-1956-5p/KCP-were validated by real-time qPCR. This study is the first one to provide a systematic dissection of non-coding RNA-associated ceRNA profiling in kidney of CI-AKI rats. The selected non-coding RNA-associated ceRNA networks provide new insight for the underlying mechanism and may profoundly affect the diagnosis and therapy of CI-AKI.

2.
Cancer Imaging ; 19(1): 38, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215488

RESUMO

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a major adverse effect caused by intravascular administration of iodinated contrast medium. Whether there is a difference in CI-AKI incidence between iso-osmolar (IOCM) and low-osmolar contrast media (LOCM) among diabetic patients is controversial. METHODS: Randomized controlled trials comparing the nephrotoxic effects between IOCM and LOCM in diabetic patients with or without CKD (eGFR< 60 ml/min/1.73 m2) were included in the analysis. The incidence of CI-AKI was defined as an initial increase in serum creatinine (SCr) concentration of at least 0.5 mg/dl or a rise in creatinine of 25% from baseline. RESULTS: A total of 2190 patients were included, among whom 1122 patients received IOCM and 1068 received LOCM. When compared to LOCM, IOCM had no significant benefit in preventing CI-AKI (OR = 1.66, [CI: 0.97-2.84], P = 0.06, I2 = 54%). However, the difference between IOCM and LOCM was found when CI-AKI was defined as an absolute SCr increase (≥0.5 mg/dl) rather than a relative SCr increase (≥25%). Further analysis showed that LOCM resulted in more adverse events. CONCLUSIONS: Whether there is a difference of CI-AKI incidence between IOCM and LOCM in diabetic patients was related to the selected diagnostic criteria. The incidence of adverse events was significantly lower with IOCM when compared with LOCM. Therefore, we suggest that IOCM may be used in diabetic and CKD (eGFR< 60 ml/min/1.73 m2) patients.


Assuntos
Lesão Renal Aguda/etiologia , Meios de Contraste/efeitos adversos , Diabetes Mellitus/epidemiologia , Lesão Renal Aguda/epidemiologia , Meios de Contraste/química , Feminino , Humanos , Masculino , Concentração Osmolar , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Am J Transl Res ; 10(7): 2115-2125, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30093948

RESUMO

OBJECTIVE: The isobaric tags for relative and absolute quantification (iTRAQ) technique for proteomic analysis was employed to identify diagnostic markers and therapeutic targets of Shenkangling intervention or prednisone tablets in rats with adriamycin nephropathy (AN). METHODS: Fifty healthy, clean-grade Sprague-Dawley rats were selected, with 10 rats in the normal group and the remaining 40 rats receiving a tail vein injection of 5.5 mg/kg of adriamycin (ADR) to induce AN. Treatment began 1 week later. The normal group received gastric administration of normal saline. Forty rats with induced AN were further randomly divided into the AN modeling group (n = 10), AN modeling + prednisone treatment group (n = 10), AN modeling + Shenkangling intervention group (n = 10), and AN modeling + prednisone + Shenkangling intervention group (n = 10). iTRAQ was employed in combination with mass spectrometry to analyze the differentially expressed proteins in the urine after 3 weeks of treatment (in the fourth week of the experiment). RESULTS: Compared with normal rats, AN rats had 6 down-regulated proteins and 1 upregulated protein. Compared with AN rats, prednisone rats had 2 down-regulated and 6 upregulated proteins. Compared with AN rats, combined treatment rats had 2 down-regulated and 8 upregulated proteins. Compared with the AN model group, the Shenkangling treatment group had 3 down-regulated and 9 upregulated proteins. Gro, Afamin, Cystatin-related protein 2, Afamin, and isoform CRA_a were considered diagnostic markers of primary nephrotic syndrome (PNS). Telomerase was considered the therapeutic target of prednisone. Urinary protein 2, Apolipoprotein A-II, 45 kDa calcium-binding protein, Vitronectin, and Osteopontin were the therapeutic targets of the Shenkangling intervention. Afamin, isoform CRA_a, Apolipoprotein A-IV, Coagulation factor XII, Prolactin-induced protein, and Coagulation factor XII were the therapeutic targets of the Shenkangling intervention combined with prednisone. CONCLUSION: The feasibility of urinary proteomics analysis in rats using a large number of proteins with finite molecular weights is controversial. The markers screened in this study may be of clinical value for the diagnosis and treatment of nephropathy. However, these findings should be confirmed in future cohort studies.

4.
Arch Toxicol ; 92(7): 2245-2257, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29860548

RESUMO

Recent progress in angiography and interventional therapy has revived interest in comparison of nephrotoxicity of low-or iso-osmolar contrast media, but detailed mechanisms and effective treatments of contrast-induced acute kidney injury (CI-AKI) remain elusive. We established a new model of CI-AKI and compared the nephrotoxicity of iohexol and iodixanol with a focus on renal oxidative stress, mitochondrial damage and mitophagy. Our results showed that 48-h dehydration plus furosemide injection before iohexol administration successfully induced CI-AKI in rats. Compared with iodixanol, iohexol induced a greater decrease in renal function, more severe morphological damage and mitochondrial ultrastructural changes, an increased number of apoptotic cells, decreased antioxidative enzymes with activation of NLRP3 inflammasome in renal tissue. Renal contrast media kinetics showed the immediate excretion of iohexol and the transient renal accumulation of iodixanol. Plasma mtDNA Tc numbers were positively correlated with markers of renal mitochondrial disruption but negatively correlated with the level of serum creatinine and the score of tubular injury. Of note, iodixanol appeared to induce a stronger activation of mitophagy than iohexol, evidenced by greater protein levels of LC3II and PINK1/Parkin in the renal tissue of iodixanol-treated rats. Taken together, our results indicate that iohexol induced more severe nephrotoxicity than iodixanol in vivo due to apoptosis, destruction of antioxidative defense machinery, activation of NLRP3 inflammasome, mitochondrial damage and mitophagy. Plasma mtDNA may serve as a biological marker for renal mitochondrial disruption and damage in CI-AKI. Antioxidative defense and mitophagy are involved in the process of CI-AKI and may be promising targets of therapies.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Meios de Contraste/toxicidade , Modelos Animais de Doenças , Iohexol/toxicidade , Mitocôndrias/efeitos dos fármacos , /efeitos dos fármacos , Ácidos Tri-Iodobenzoicos/toxicidade , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Testes de Função Renal , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/ultraestrutura , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
5.
Cell Physiol Biochem ; 46(3): 975-985, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29680838

RESUMO

BACKGROUND/AIMS: Contrast induced-acute kidney injury (CI-AKI) is one of the most common causes of acute kidney injury (AKI) in hospitalized patients. Mitophagy, the selective elimination of mitochondria via autophagy, is an important mechanism of mitochondrial quality control in physiological and pathological conditions. In this study, we aimed to determine effects of iohexol and iodixanol on mitochondrial reactive oxygen species (ROS), mitophagy and the potential role of mitophagy in CI-AKI cell models. METHODS: Cell viability was measured by cell counting kit-8. Cell apoptosis, mitochondrial ROS and mitochondrial membrane potential were detected by western blot, MitoSOX fluorescence and TMRE staining respectively. Mitophagy was detected by the colocalization of LC3-FITC with MitoTracker Red, western blot and electronic microscope. RESULTS: The results showed that mitophagy was induced in human renal tubular cells (HK-2 cells) under different concentrations of iodinated contrast media. Mitochondrial ROS displayed increased expression after the treatment. Rapamycin (Rap) enhanced mitophagy and alleviated contrast media induced HK-2 cells injury. In contrast, autophagy inhibitor 3-methyladenine (3-MA) down-regulated mitophagy and aggravated cells injury. CONCLUSIONS: Together, our finding indicates that iohexol and iodixanol contribute to the generation of mitochondrial ROS and mitophagy. The enhancement of mitophagy can effectively protect the kidney from iodinated contrast (iohexol)-induced renal tubular epithelial cells injury.


Assuntos
Meios de Contraste/toxicidade , /efeitos dos fármacos , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Adenina/análogos & derivados , Adenina/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Meios de Contraste/química , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Iodo/química , Iohexol/toxicidade , Túbulos Renais/citologia , Potencial da Membrana Mitocondrial , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirolimo/farmacologia , Ácidos Tri-Iodobenzoicos/toxicidade
6.
Sci Rep ; 7(1): 7862, 2017 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801674

RESUMO

Currently, little information is available to stratify the risks and predict acute kidney injury (AKI)-associated death. In this present cross-sectional study, a novel scoring model was established to predict the probability of death within 90 days in patients with AKI diagnosis. For establishment of predictive scoring model, clinical data of 1169 hospitalized patients with AKI were retrospectively collected, and 731 patients of them as the first group were analyzed by the method of multivariate logistic regression analysis to create a scoring model and further predict patient death. Then 438 patients of them as the second group were used for validating this prediction model according to the established scoring method. Our results showed that Patient's age, AKI types, respiratory failure, central nervous system failure, hypotension, and acute tubular necrosis-individual severity index (ATN-ISI) score are independent risk factors for predicting the death of AKI patients in the created scoring model. Moreover, our scoring model could accurately predict cumulative AKI and mortality rate in the second group. In conclusion, this study identified the risk factors of 90-day mortality for hospitalized AKI patients and established a scoring model for predicting 90-day prognosis, which could help to interfere in advance for improving the quality of life and reduce mortality rate of AKI patients.


Assuntos
Lesão Renal Aguda/mortalidade , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Modelos Teóricos , Lesão Renal Aguda/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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