LncRNA MAYA promotes iron overload and hepatocyte senescence through inhibition of YAP in non-alcoholic fatty liver disease.

Although recent evidence has shown that hepatocyte senescence plays a crucial role in the pathogenesis and development of non-alcoholic fatty liver disease (NAFLD), the mechanism is still not clear. The purpose of this study was to investigate the signal transduction pathways involved in the senescence of hepatocyte, in order to provide a potential strategy for blocking the process of NAFLD. The results confirmed that hepatocyte senescence occurred in HFD-fed Golden hamsters and PA-treated LO2 cells as manifested by increased levels of senescence marker SA-ß-gal, p16 and p21, heterochromatin marker H3K9me3, DNA damage marker γ-H2AX and decreased activity of telomerase. Further studies demonstrated that iron overload could promote the senescence of hepatocyte, whereas the overexpression of Yes-associated protein (YAP) could blunt iron overload and alleviate the senescence of hepatocyte. Of importance, depression of lncRNA MAYA (MAYA) reduced iron overload and cellular senescence via promotion of YAP in PA-treated hepatocytes. These effects were further supported by in vivo experiments. In conclusion, these data suggested that inhibition of MAYA could up-regulate YAP, which might repress hepatocyte senescence through modulating iron overload. In addition, these findings provided a promising option for heading off the development of NAFLD by abrogating hepatocyte senescence.

Implications of the changes in serum neutrophil gelatinase-associated lipocalin and cystatin C in patients with chronic kidney disease.

AIM: Early intervention in patients with chronic kidney disease (CKD) significantly improves the prognosis. The present widely used markers of renal function, such as serum creatinine (sCr), fail to reflect early renal damage and predict the progression of disease. The authors aimed to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD. METHODS: We identified 92 patients with stage 2-4 CKD caused by primary chronic glomerulonephritis. The patients were followed for 2 years, the changes in NGAL levels in the progressive and non-progressive groups were compared. RESULTS: First, the serum NGAL levels of patients with stage 2-4 CKD were significantly increased compared with the control group. Second, based on Pearson correlation analysis, positive correlations existed between NGAL and cystatin C levels and between NGAL and sCr levels. Third, bounded by the progress of renal function, the area under the curve of serum NGAL was 0.872 (95% confidence interval, 0.786-0.933), which suggests a blood NGAL cut-off level of 246 ng/mL (sensitivity 85.19%, specificity 81.54%). Fourth, Kaplan-Meier survival curve analysis showed that the serum NGAL level was closely related to the end-point of renal function in patients with CKD. Fifth, Cox multivariate regression analysis showed that the estimated glomerular filtration rate and blood NGAL are associated with progression of CKD. CONCLUSION: Serum NGAL is an effective biomarker for detecting early-stage renal damage in CKD patients. Serum NGAL was significantly correlated with the severity of renal damage and the progression of renal function deterioration.

2-Chloro-5-nitro-pyridin-4-amine.

The title mol-ecule, C(5)H(4)ClN(3)O(2), possesses mirror symmetry, with all of the atoms lying in the mirror plane. There is an intra-molecular N-H⋯O hydrogen bond involving the adjacent -NO(2) and -NH(2) groups. A short C-H⋯O inter-action is also observed. In the crystal, adjacent mol-ecules are linked via N-H⋯Cl and N-H⋯N hydrogen bonds, forming chains propagating along [100].

4-Meth-oxy-3-(trifluoro-meth-yl)aniline.

In title compound, C(8)H(8)F(3)NO, the meth-oxy group is inclined at 8.7 (4)° to the benzene ring plane. The crystal structure is stabilized by inter-molecular N-H⋯F, N-H⋯N and C-H⋯F hydrogen-bonding inter-actions.

Levels of serum ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) predicts severity of abdominal aortic calcification in end-stage renal disease patients receiving regular dialysis.

OBJECTIVE: To investigate the correlation between serum ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) level and severity of abdominal vascular calcification in end-stage renal disease (ESRD) patients receiving dialysis. METHODS: A total of 124 patients were consecutively enrolled into the study in our local institution. Based on the Kidney Disease Improving Global Outcomes (KDIGO) guidelines and recommendations, abdomen lateral X-ray was used to determine abdominal aortic calcification score (AACS) for each patient at enrollment. Patients were divided into three groups based on AACS: no or mild calcification group, moderate calcification group, and severe calcification group. The relationships between ENPP1 levels and AACS were assessed by Spearman analysis and the value of ENPP1 in predicting severity of abdominal aortic calcification was evaluated by receiver operating characteristic (ROC). RESULTS: The level of ENPP1 in dialysis patients was (7.68 ± 1.67) ng/ml. There was no significant difference in serum ENPP1 level between peritoneal dialysis patients and hemodialysis patients (p > 0.05). The AACS of dialysis patients was negatively correlated with ENPP1 value (r = -0.70). Compared to no/mild calcification patients, the levels of serum ENPP1 in patients with moderate/severe calcification were decreased significantly (p < 0.01). The severity of vascular calcification was correlated with serum ENPP1 value, the severer the vascular calcification, the lower the serum ENPP1 level, and the difference was statistically significant (all p < 0.05). The area under ROC curve of ENPP1 was 0.90, the corresponding sensitivity was 0.86, and the specificity was 0.87. CONCLUSION: Levels of serum ENPP1 in non-diabetic ESRD patients are negatively related to the severity of abdominal aortic vascular calcification.

Quantitative determination of isorhamnetin, quercetin and kaempferol in rat plasma by liquid chromatography with electrospray ionization tandem mass spectrometry and its application to the pharmacokinetic study of isorhamnetin.

A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of quercetin, kaempferol and isorhamnetin in rat plasma. After being treated with beta-glucuronidase and sulfatase, the analytes were extracted by liquid/liquid extraction with the internal standard (IS; baicalein). The chromatographic separation was performed on a Diamonsil C(18) column with a mobile phase consisting of 2% formic acid/methanol (10:90, v/v) at a flow rate of 1.00 mL/min, with a split of 200 microL to the mass spectrometer. Validation results indicated that the lower limit of quantification (LLOQ) was 1 ng . mL(-1). The assay exhibited a linear range of 1-200 ng . mL(-1) and gave a correlation coefficient of 0.9980 or better for each analyte. Quality control samples (1, 5, 20 and 100 ng . mL(-1)) in six replicates from each of three different runs demonstrated an intra-assay precision (RSD) of 1.1-8.9%, an inter-assay precision of 1.6-10.8%, and an overall accuracy (bias) of <13.4%. The extraction recovery of each analyte and internal standard was 70-80%. In the present study, we have investigated the pharmacokinetic profiles of isorhamnetin after oral application in rats equipped with a jugular catheter. After oral dosing of isorhamnetin, the mean values (n = 10) of C(max) were 57.8, 64.8 and 75.2 ng . mL(-1) which were achieved at a T(max) of 8.0, 6.4 and 7.2 h for oral doses of 0.25, 0.5 and 1.0 mg . kg(-1) body weight, respectively. The corresponding mean values for isorhamnetin area under the curver (AUC) from 0 to 60 h were 838.2, 1262.8, 1623.4 ng . h . mL(-1). Our results further demonstrated that the samples analyzed showed isorhamnetin could not be transformed into quercetin or kaempferol in rats, indicating that the demethylation of the 3'-oxymethyl group of isorhamnetin does not occur in Wistar rats.