CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.

OBJECTIVE: Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. METHOD: Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1ß, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. RESULTS: CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1ß, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CONCLUSION: CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Atorvastatin reduces contrast media-induced pyroptosis of renal tubular epithelial cells by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure. However, there is no effective treatment of CI-AKI, and its mechanism is unknown. Interestingly, atorvastatin has been reported to be effective in renal injury. Therefore, the aim of this study was to explore the effect and possible molecular mechanism of atorvastatin in CI-AKI. METHODS: On the CI-AKI in vitro model, rat tubular epithelial cells (NRK-52E) were treated with 18 mg I/ml meglumine diatrizoate (MEG) and then pretreated with atorvastatin. pcDNA3.1-TLR4 treatment was performed to overexpress toll-like receptor 4 (TLR4) in NRK-52E cells. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) kits were used to detect NRK-52E cell viability as well as LDH release in each group, respectively; qRT-PCR to determine mRNA expression of TLR4 in cells; western blot to detect protein expression levels of pyroptosis-related proteins (NLRP3, caspase-1, ASC, and GSDMD) and TLR4/MyD88/NF-κB signaling pathway-related proteins (TLR4, MyD88, NF-κBp65, and p-NF-κB p65) in cells. RESULTS: MEG treatment significantly inhibited the viability of NRK-52E cells, increased pro-inflammatory factor levels and promoted pyroptosis, representing successful establishment of a rat tubular epithelial cell (NRK-52E) CI-AKI in vitro model. Notably, atorvastatin increased the activity of MEG-treated NRK-52E cells and alleviated cell injury in a concentration-dependent manner. In addition, atorvastatin significantly down-regulated the expression of TLR4 in MEG-treated NRK-52E cells. However, overexpression of TLR4 inhibited the effects of atorvastatin on increasing cell viability, alleviating cell injury, reducing pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) levels, and inhibiting apoptosis (by down-regulating the expression of NLRP3, caspase-1, ASC, and GSDMD). Furthermore, atorvastatin also inhibited the expression of TLR4/MyD88/NF-κB pathway-related proteins (TLR4, MyD88, and p-NF-κB p65). CONCLUSION: Atorvastatin can attenuate CI-AKI through increasing the activity of MEG-treated renal tubular epithelial cells, relieving cell injury, as well as inhibiting pyroptosis and inflammation. More importantly, the mechanism was achieved by inhibiting the TLR4//MyD88/NF-κB signaling pathway.

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

OBJECTIVES: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. RESULTS: After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p < .05) and ameliorated the contrast-induced acute kidney injury (p < .05) and significantly reduced Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (Myd88), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression and relative mRNA expression levels (p < .05) and significantly decreased expression levels of downstream inflammatory factors (p < .05). CONCLUSION: Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

Renal pathological implications in type 2 diabetes mellitus patients with renal involvement.

AIMS: To investigate the renal pathological implications in type 2 diabetes mellitus patients with renal involvement. METHODS: A total of 328 type 2 diabetes mellitus (T2DM) patients with renal involvement who underwent a renal biopsy and received follow-up for at least one year were recruited in our study. The patients were divided into the diabetic nephropathy (DN), non-diabetic renal disease (NDRD), and NDRD superimposed on DN groups based on the pathological diagnosis. Renal outcomes were defined by the initiation of renal replacement therapy or doubling of the serum creatinine. Kaplan-Meier analysis was used to compare renal survival, and Cox proportional hazard analysis was used to determine the predictors of renal outcomes in the DN group. RESULTS: Renal biopsy findings revealed that 188 patients (57.32%) had pure DN, 121 patients (36.89%) had NDRD alone, and 19 patients (5.79%) had NDRD superimposed on DN. The most frequent subclassification of NDRD was membranous nephropathy (MN). Compared with the NDRD and NDRD superimposed on DN groups, patients with pure DN had poorer renal function and lower renal survival rates. In the DN group, the five-year renal survival rates of glomerular classes of I, IIa, IIb, III and IV were 100%, 84.62%, 60%, 47.5% and 33.33%, respectively. Multivariate Cox proportional hazard analysis showed that the glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes, while interstitial fibrosis/inflammation and arteriolar hyalinosis were not independently associated with renal outcomes in the DN group. CONCLUSIONS: Making an accurate pathologic diagnosis by renal biopsy is crucial for diabetes mellitus (DM) patients with renal involvement. The findings of our present study indicated that patients with pure DN had poorer renal outcomes than patients with NDRD or NDRD superimposed on DN. The classification of glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes in the DN group. More studies with large samples and longer time follow-up are needed to evaluate the relationship between pathological changes and clinical characteristics in T2DM patients who have renal involvement.

Significance of Cystatin C for Early Diagnosis of Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography.

BACKGROUND Contrast-induced nephropathy is acute kidney injury caused by contrast medium exposure. Serum creatinine is the clinical diagnostic standard, but it does not yield quick results. The serum level of cystatin C is stable and it can reflect renal function sensitively. The study aimed to assess the usefulness of cystatin C for early diagnosis of contrast-induced nephropathy in patients undergoing coronary angiography. MATERIAL AND METHODS We included 300 patients who underwent CAG. According to the sCr at 48 h, patients were divided into 2 groups: CIN group and non-CIN group. Their demographics and basal renal function were recorded. Changes in sCr, Cys C, and e GFR were compared at the same time. ROC analysis was used to assess the sensitivity and specificity of Cys C in the early diagnosis of CIN. RESULTS Comparison of basal renal function and serum level of Cys C showed no significant differences between the 2 groups. Serum level of Cys C increased significantly at 24 h (p<0.001), and sCr increased significantly at 48 h. ROC analysis showed that the AUC of the change in Cys C between baseline and 24 h was 0.936 (95% CI: 0.879-0.992, p=0.000) and the optimum cut-off level was 0.26 mg/L (sensitivity=89.7% and specificity=95.6%). CONCLUSIONS The concentration change of Cys C is better than sCr as a biomarker in the early detection of CIN.

Atrial Fibrillation is Associated With Poor Outcomes in Thrombolyzed Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

The influence of atrial fibrillation (AF) on the clinical outcomes of patients with ischemic stroke (IS) has not been completely determined. We aimed to perform a systematic review and meta-analysis to assess the relationship between AF and adverse events in patients with acute IS treated with thrombolysis.PubMed, EMBASE, and the Cochrane Library were searched for relevant studies regarding the association between AF and the outcomes of patients with IS treated with thrombolysis. Random and fixed effect models were used for pooling data.Twelve cohort studies involving 14,801 patients with acute IS were included. Meta-analysis revealed that patients with AF were more likely to die within 90 days after thrombolysis (odds ratio [OR], 2.13; 95% confidence interval [CI]: 1.68-2.70, P < 0.001), whereas this association was not observed in hospitalized patients (OR, 1.50; 95% CI, 0.86-2.60; P = 0.150). AF was associated with a reduced incidence of favorable outcomes (modified Rankin Scale ≤ 2) (OR, 1.95; 95% CI: 1.33-2.85, P = 0.001) and an increased risk of symptomatic intracerebral hemorrhage (OR, 1.28; 95% CI: 1.08-1.52, P = 0.006). No evident publication bias was found by Begg's test or Egger's test.Comorbidity of AF may increase the risk of adverse outcomes for patients with IS undergoing thrombolysis. Further well-designed trials are warranted to confirm this association.

Effect of Mini-Tyrosyl-tRNA Synthetase/Mini-Tryptophanyl-tRNA Synthetase on Angiogenesis in Rhesus Monkeys after Acute Myocardial Infarction.

AIMS: The purpose of this study was to clarify the effect of mini-tyrosyl-tRNA synthetase/mini-tryptophanyl-tRNA synthetase (mini-TyrRS/mini-TrpRS) in ischemic angiogenesis in rhesus monkeys with acute myocardial infarction (AMI). METHODS: A 27-gauge needle was incorporated percutaneously into the left ventricular myocardium of rhesus monkeys with AMI. All monkeys were randomized to receive adenoviral vector mini-TyrRS/mini-TrpRS, which was administered as five injections into the infarcted myocardium, or saline or ad-null (control groups). The injections were guided by EnSite NavX left ventricular electroanatomical mapping. Mini-TyrRS/mini-TrpRS proteins were detected by Western blot and immunoprecipitation analyses. Microvessel density (MVD) per section was measured using immunostaining with a CD34 monoclonal antibody. Proliferating cardiomyocytes were identified through histological and immunohistochemical analyses. Myocardial perfusion and cardiac function were estimated by G-SPECT. Infarction size was also measured. RESULTS: Western blot analyses showed that compared to the normal zone, the expression level of mini-TyrRS/mini-TrpRS was significantly different in the infarction zone. G-SPECT analysis indicated that the mini-TyrRS group had better cardiac function and myocardial perfusion after the injection of ad-mini-TyrRS than before, while mini-TrpRS injection had a totally opposite effect. After mini-TyrRS was administered, there was less of an infarction zone and more proliferating cardiomyocytes and capillaries in the mini-TyrRS group compared to both of the control groups, and the ad-mini-TrpRS group had a totally opposite effect. CONCLUSION: These results indicated that angiogenesis could be either stimulated by mini-TyrRS or inhibited by mini-TrpRS.

New ideas for teaching electrocardiogram interpretation and improving classroom teaching content.

BACKGROUND: Interpreting an electrocardiogram (ECG) is not only one of the most important parts of diagnostics but also one of the most difficult areas to teach. Owing to the abstract nature of the basic theoretical knowledge of the ECG, its scattered characteristics, and tedious and difficult-to-remember subject matter, teaching how to interpret ECGs is as difficult for teachers to teach as it is for students to learn. In order to enable medical students to master basic knowledge of ECG interpretation skills in a limited teaching time, we modified the content used for traditional ECG teaching and now propose a new ECG teaching method called the "graphics-sequence memory method." METHODS: A prospective randomized controlled study was designed to measure the actual effectiveness of ECG learning by students. Two hundred students were randomly placed under a traditional teaching group and an innovative teaching group, with 100 participants in each group. The teachers in the traditional teaching group utilized the traditional teaching outline, whereas the teachers in the innovative teaching group received training in line with the proposed teaching method and syllabus. All the students took an examination in the final semester by analyzing 20 ECGs from real clinical cases and submitted their ECG reports. RESULTS: The average ECG reading time was 32 minutes for the traditional teaching group and 18 minutes for the innovative teaching group. The average ECG accuracy results were 43% for the traditional teaching group and 77% for the innovative teaching group. CONCLUSION: Learning to accurately interpret ECGs is an important skill in the cardiac discipline, but the ECG's mechanisms are intricate and the content is scattered. Textbooks tend to make the students feel confused owing to the restrictions of the length and the format of the syllabi, apart from many other limitations. The graphics-sequence memory method was found to be a useful method for ECG teaching.

[Continuous blood purification therapy on 16 patients with diabetic ketoacidosis and acute kidney injury].

OBJECTIVE: To determine the effectiveness of Continuous blood purification (CBP) therapy on diabetic ketoacidosis (DKA) and acute kidney injury (AKI) in diabetic nephropathy (DN) patients. METHODS: Sixteen DN patients who developed severe DKA and AKI between 2008 and 2011 in the West China Hospital were recruited. All of the recruited patients presented with severe metabolic acidosis, electrolyte disturbance and dehydration. In addition to routine treatments, continuous venovenous hemofiltration (CVVH) was performed for at least 48 h with Baxter Accura or B. Braun Diapact CRRT machine and B. Braun Diacap Acute M hemofilter. Hemofiltration was accomplished using predilution bicarbonate replacement fluid at the rate of 3000 mL/h and citrate or low-molecular weight heparin (LMWH) for anticoagulation, with blood flow rates of 180 to 250 mL/min. RESULTS: One patient died unexpectedly 10 h after admission to hospital. The other fifteen patients had significant improvements in metabolic acidosis index after 12 hours of CVVH therapy, such as an average increase of 7.21 +/- 0.07 carbon dioxide combining power (CO2CP)and improvement of arterial PH. The blood urea nitrogen (BUN), serum creatinine (SCr), serum glucose (Glu), serum potassium (K(+)) and bloodosmotic pressure of the 15 patients decreased significantly after 48 hours of CVVH therapy. Eleven cases entered into diuretic phase and had renal functions recovered (12 +/- 5) d and (18 +/- 12) d after admission to the hospital, respectively. CONCLUSION: CVVH therapy as an early intervention can bring significant benefits to DN patients with DKA and AKI. Early institution of CVVH therapy may be considered not only for treating uremia and fluid retention but also for correcting metabolic abnormalities like metabolic acidosis.

Preparation of Cu2+-loaded porous chitosan particles for immunoglobulin G adsorption.

Chitosan porous particles were prepared using a precipitation technique. The porous particles could bind Cu(2+), from which Cu(2+)-loaded porous particles were prepared. The Cu(2+)-loaded porous chitosan particles could remove immunoglobulin (Ig) G more selectively than albumin, IgA and IgM from aqueous solutions and human plasma. The effect of the volume ratio of plasma to particles on protein adsorption was studied, with the results indicating that a volume ratio of 3:1 might be a good choice for clinical use. The particles could be easily incorporated into a column. When human plasma was applied to the particle column, higher removal efficiency was obtained. These results suggested that Cu(2+)-loaded porous particles may be a potentially good sorbent for IgG removal from plasma.