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Introduction: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and is considered to be a sterile inflammatory disease. Increasing evidence suggest that pyroptosis and subsequent inflammatory response play a key role in the pathogenesis of DN. However, the underlying cellular and molecular mechanisms responsible for pyroptosis in DN are largely unknown. Methods: The rat models of DN were successfully established by single 65 mg/kg streptozotocin treatment. Glomerular mesangial cells were exposed to 30 mmol/L high glucose media for 48 h to mimic the DN environment in vitro. Gene and protein expressions were determined by quantitative real-time PCR and Western blot. Cell viability and pyroptosis were measured by MTT assay and flow cytometry analysis, respectively. The relationship between lncRNA NEAT1, miR-34c, and Nod-like receptor protein-3 (NLRP3) was confirmed by luciferase reporter assay. Results: We found that upregulation of NEAT1 was associated with the increase of pyroptosis in DN models. miR-34c, as a target gene of NEAT1, mediated the effect of NEAT1 on pyroptosis in DN by regulating the expression of NLRP3 as well as the expressions of caspase-1 and interleukin-1β. Either miR-34c inhibition or NLRP3 overexpression could reverse the accentuation of pyroptosis and inflammation by sh-NEAT1 transfection in the in vitro model of DN. Conclusions: Our findings suggested NEAT1 and its target gene miR-34c regulated cell pyroptosis via mediating NLRP3 in DN, providing new insights into understanding the molecular mechanisms of pyroptosis in the pathogenesis of DN.

Background Accumulation of iron is associated with oxidative stress, inflammation, and regulated cell death processes that contribute to the development of acute kidney injury (AKI). We aimed to investigate the association between serum iron levels and prognosis in intensive care unit (ICU) patients with AKI. Methods A total of 483 patients with AKI defined as per the Kidney Disease: Improving Global Guidelines were included in this retrospective study. The data was extracted from the single-centre Medical Information Mart for Intensive Care III database. AKI patients with serum iron parameters measured upon ICU admission were included and divided into two groups (low group and high group). The prognostic value of serum iron was analysed using univariate and multivariate Cox regression analysis. Results The optimal cut-off value for serum iron was calculated to be 60 μg/dl. Univariable Cox regression analysis showed that serum iron levels were significantly correlated with prognosis of AKI patients. After adjusting for possible confounding variables, serum iron levels higher than 60 μg/dl were associated with increases in 28-day (hazard [HR] 1.832; P P Conclusions High serum iron levels were associated with increased short- and long-term mortality in ICU patients with AKI. Serum iron levels measured upon admission may be used for predicting prognosis in AKI patients.

This study aimed to investigate the differences in shoot and root traits, and water use and water use efficiency (WUE) in drought tolerant (DT) maize (Zea mays L.) hybrids under full and deficit irrigated conditions. A two-year greenhouse study was conducted with four hybrids (one conventional hybrid, 33D53AM, two commercial DT hybrids, P1151AM, N75H, and an experimental hybrid, ExpHB) grown under two water regimes (I100 and I50, referring to 100 and 50% of evapotranspiration requirements). Under water stress, the hybids P1151AM, N75, and ExpHB showed more drought tolerance and had either greater shoot dry weight or less dry weight reduction than the conventional hybrid (33D53AM). However, these three hybrids responded to water stress using different mechanisms. Compared with the conventional hybrid, the two commercial DT hybrids (P1151AM and N75H) had a smaller leaf area, shoot dry weight, and root system per plant. As a result, these hybrids used less water but had a higher WUE compared with the conventional hybrid. In contrast, the experimental hybrid (ExpHB) produced more shoot biomass by silking stage at both irrigation levels than all other hybrids, but it had relatively lower WUE. The hybrids demonstrated different drought response mechanisms that may require different irrigation management strategies. More investigation and validation are needed under field conditions and in different soil types.

Background Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder of the lungs and is associated with oxidative damage. However, red blood cell distribution width (RDW), as an indicator of body response to inflammation and oxidative stress, has not been studied for its relationship with ARDS as diagnosed by the Berlin definition. Objectives To examine the value of RDW in predicting the prognosis of in patients with ARDS. Methods This is a retrospective study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Berlin-defined ARDS patients using mechanical ventilation for more than 48 hours were selected using structured query language. The primary statistical methods were propensity score matching and sensitivity analysis, including an inverse probability weighting model to ensure the robustness of our findings. Results A total of 529 intensive care unit (ICU) patients with ARDS according to the Berlin definition were enrolled in the study. The adjusted OR showed an adverse effect between the higher RDW group and 30-day mortality [OR 2.33, 95% CI (1.15–4.75), P=0.019]. However, we found that length of ICU stay was not related to RDW (P=0.167), and in the anaemia group, RDW was poorly predictive of 30-day mortality (P=0.307). Conclusion In unselected ARDS patients, higher RDW was associated with higher 30-day mortality rate. Further investigation is required to validate this relationship with prospectively collected data.

Diabetic nephropathy (DN) is one of the most common and serious complication in diabetes patients. However, the evidences of gene regulation mechanism and epigenetic modification with DN remain unclear. Therefore, it is necessary to search regulating genes for early diagnosis on DN. We identified tissue specific genes through mining the gene expression omnibus (GEO) public database, enriched function by gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) analysis, and further compared tissue-specific network. Meanwhile, combining with differentially methylated sites, we explored the association epigenetic modification with the pathogenesis of DN. Glomeruli (Glom) may be the main tissue of signal recognition and tubulointerstitium (Tub) is mainly associated with energy metabolism in the occurrence of DN. By comparing tissue-specific networks between Glom and Tub, we screened 319 genes, which played an important role in multiple tissue on kidney. Among them, ANXA2, UBE2L6, MME, IQGAP, SLC7A7, and PLG played a key role in regulating the incidence of DN. Besides, we also identified 1 up-regulated gene (PIK3C2B) and 39 down-regulated genes (POLR2G, DDB1, and ZNF230, etc.) in the methylated data of Glom specific genes. In the Tub specific expressed genes, we identified two hypo-methylated genes (PPARA and GLS). Tub mainly caused abnormal energy metabolism, and Glom caused the changes in cell connections and histone modification. By analyzing differentially methylated sites and tissue-specific expressed genes, we found the change of methylated status about the core regulating genes may be a potential factor in the pathogenesis of DN.

To explore the significance of WIF-1 gene promoter methylation and the expression of β-catenin in acute leukemia (AL) patients.The method of methylation specific polymerase chain reaction was employed to detect the status of WIF-1 gene methylation in 55 acute leukemia patients and normal controls from January 2009 to June 2010 in our hospital. The expression of β-catenin was measured by flow cytometry.The methylation of WIF-1 gene promoter was found in 32.7% (18/55) AL patients. And the percentage was significantly higher than that of the controls (0). The patients with the methylation of WIF-1 gene had a lower complete remission rate (38.9%, 7/18) for the first chemotherapy than those without (81.1%, 30/37) (P0.05). The expressions of β-catenin in methylation AL patients and those with non-methylation were 17.5% ± 3.3% and 15.4% ± 3.6% respectively. And they were significantly higher than the controls (10.5% ± 1.5%, P0.05). The expression of β-catenin was higher in positive methylation patients than those negative ones (P0.05).The methylation of WIF-1 gene promoter and β-catenin may be involved in the abnormal activation of Wnt/β-catenin signal in acute leukemia.

To investigate the role of Apaf-1 gene promoter methylation and apoptosis inhibitor protein Apollon in pathogenesis of acute leukemia (AL) and their clinical significance.Methylation specific PCR (MSP) was used to detect the methylation status of Apaf-1 gene promoter in 53 AL patients (28 AML, 10 ALL and 15 relapsed) and 10 healthy or nonmalignant blood diseases patients as control. RT-PCR was used to detect the expression levels of Apaf-1 mRNA and immunocytochemistry to detect the expression levels of Apollon protein.The abnromal methylation of Apaf-1 gene promotor in AL was 18/53(33.9%). No Apaf-1 mRNA was detected in methylation positive patients. Only one case in healthy and nonmalignant individuals was deletion of Apaf-1 mRNA expression without abnormal methylation. The positive methylation rate in AL bone marrow mononuclear cells was significantly higher than that in controls (P0.05). The expressin levels of Apollon protein in AL patients was higher than that in control (P0.05). The positive methylation ratio and Apollon protein level were higher in white blood cell count10 × 10(9)/L than in ≤ 10 × 10(9)/L (P0.05). There is a positive correlaiton between positive methylation ratio and Apollon protein expression in AL patients.Abnormal methylation of Apaf-1 gene promotor and high expression of Apollon might involved in leukemogenesis.

To investigate the frequency of aborted AMI and clinical characteristics of the patients received prompt fibrinolytic therapy.1120 patients with AMI were divided into two groups, true AMI group and aborted AMI group. Aborted AMI was defined as maximal creatine kinase-MBor = 2 x upper limit of normal coupled with the presence of resolution of chest pain and 50% of ST-segment deviation within 2 hours after onset of therapy. We compared some characteristic of two groups such as the fibrinolytic time after symptom onset and the frequency of aborted AMI.The reopening ratio of infarct was 80.5%. 7.1% of the patients escaped myocardial necrosis. Aborted AMI was highest frequency within the first hour (22.0%) than other time groups (P0.01); There were no significant differences in the frequency of Aborted AMI in UK group, SK group and rt-PA group (7.0%, 6.7%, 7.1%, P0.05); The rate of Killip III/IV, major arrhythmias, angina pectoris and mortality at 30 day in aborted AMI patients compared with those who had true AMI was 3.9% versus 17.1%, 18.0% versus 30.0%, 1.3% versus 8.0%, 0 versus 6.0%, respectively (P0.01).Prompt fibrinolytic therapy improved the likelihood of aborted AMI and clinical outcomes. The frequency of aborted AMI has no relationship with fibrinolytic drug, but closely related to the starting time of treatment from symptom onset.