Quercetin improves diabetic kidney disease by inhibiting ferroptosis and regulating the Nrf2 in streptozotocin-induced diabetic rats.

Diabetic kidney disease (DKD) is a leading factor in end-stage renal disease. The complexity of its pathogenesis, combined with the limited treatment efficacy, necessitates deeper insights into potential causes. Studies suggest that ferroptosis-driven renal tubular damage contributes to DKD's progression, making its counteraction a potential therapeutic strategy. Quercetin, a flavonoid found in numerous fruits and vegetables, has demonstrated DKD mitigation in mouse models, though its protective mechanism remains ambiguous. In this study, we delved into quercetin's potential anti-ferroptotic properties, employing a DKD rat model and high glucose (HG)-treated renal tubular epithelial cell models. Our findings revealed that HG prompted unusual ferroptosis activation in renal tubular epithelial cells. However, quercetin counteracted this by inhibiting ferroptosis and activating NFE2-related factor 2 (Nrf2) expression in both DKD rats and HG-treated HK-2 cells, indicating its renal protective role. Further experiments, both in vivo and in vitro, validated that quercetin stimulates Nrf2. Thus, our research underscores quercetin's potential in DKD treatment by modulating the ferroptosis process via activating Nrf2 in a distinct DKD rat model, offering a fresh perspective on quercetin's protective mechanisms.

Ultrasonographic and cytological characterization of ultrasound-guided fine-needle aspiration cytology of cervical lymph nodes for false-negative and false-positive diagnosis.

OBJECTIVES: The primary goal of this study was to examine the ultrasound and cytological characteristics of inconsistent cases (false negatives and false positives)of ultrasound-guided fine-needle aspiration cytology (US-FNAC) of cervical lymph nodes, to investigate factors influencing the diagnostic accuracy of fine-needle aspiration, and to improve diagnostic efficiency. METHODS: The results of US and FNAC of cervical lymph nodes in 562 cases treated at our institution from February 2019 to June 2021 were retrospectively analyzed. FNAC cytology results were compared with the final diagnostic results (242 surgical resections/core-needle biopsy, 320 cases followed up for more than 1 year), and the final diagnostic results were taken as the gold standard, and the ultrasound features and clinicopathology-related features were systematically retrospectively analyzed in cases of inconsistency. RESULTS: The overall diagnostic accuracy of US-FNAC for cervical lymph nodes was 94.9%, with a false-negative rate of 6.7% and a false-positive rate of 3.8%. Analyzing the cases, sampling error due to factors associated with ultrasound features, such as larger, more numerous nodes, non-solid, hypoechoic, inhomogeneous, and increased vascularity are the main causes of false-negative diagnosis, while smaller nodules, overlapping cytologic patterns, and overinterpretation by pathologists are associated with false-positive FNAC results. CONCLUSIONS: Proper interpretation of cytomorphologic and ultrasound features can improve diagnostic accuracy, and diagnostic misdiagnosis should be carefully observed, the identification of both features should be enhanced to reduce interpretation errors and sampling errors and to reduce the rate of misdiagnosis and missed diagnoses in fine needle aspiration of lymph nodes.

Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-κB pathway in diabetic kidney disease.

Inflammation and glomerular endothelial dysfunction promote diabetic kidney disease (DKD) progression, but the mechanisms are not fully understood. Allograft inflammatory factor-1 (AIF-1) is a protein that regulates inflammatory reactions and immune responses. This study aimed to explore the mechanism of AIF-1 in a DKD animal model and mouse renal glomerular endothelial cells (MRGECs). We injected AIF-1-shRNA into the tail vein to knockdown AIF-1 in db/db mice. Metabolic index, renal pathological changes and inflammatory factors were measured in each group. Lentiviral transfection was used to overexpress AIF-1 in MRGECs. Inflammatory factors, oxidative stress and nuclear factor-κB (NF-κB) pathway-related proteins were examined. AIF-1 expression was upregulated in glomerular endothelial cells in renal tissues of db/db mice. Knockdown of AIF-1 reversed kidney injury and renal inflammation in db/db mice. In a 30 mM high-glucose environment, overexpression of AIF-1 in MRGECs activated the NF-κB pathway and induced inflammation and oxidative stress. Moreover, this damage could be attenuated by the addition of an NF-κB inhibitor (BAY 11-7082). In conclusion, AIF-1 facilitates glomerular endothelial cell inflammation and oxidative stress in DKD via the NF-κB signaling pathway. Our results provide evidence for the molecular mechanism of DKD and may offer a potential target for DKD treatment.

Expression Level, Correlation, and Diagnostic Value of Serum miR-127 in Patients with Acute Respiratory Distress Syndrome.

OBJECTIVE: To analyze the expression of miR-127 in the serum of patients with acute respiratory distress syndrome (ARDS) and to explore its correlation with the severity of ARDS patients and its value as a molecular marker for diagnosis of ARDS. METHODS: 70 patients with ARDS admitted to our hospital from September 2017 to September 2019 were selected as the observation group, and 60 healthy persons with physical examination were collected as the control group. RT-PCR was used to detect the serum miR-127 levels of all subjects, and the serum miR-127 levels of the observation group and control group were compared. The oxygenation index (PaO2/FiO2) of ARDS patients was recorded and divided into three subgroups: mild group, moderate group, and severe group. Serum miR-127 levels of patients in the mild group, moderate group, and severe group were compared. Pearson correlation was used to analyze the relationship between serum miR-127 levels and the severity of ARDS patients. The receiver operating characteristic curve (ROC) was drawn, and the area under the ROC curve (AUC) was used to evaluate the diagnostic value of miR-127 in patients with ARDS. RESULTS: The serum level of miR-127 (10.15 ± 1.03) in the observation group was significantly higher than that in the control group (3.09 ± 0.62). And in the three subgroups of mild, moderate, and severe, the serum miR-127 level in the moderate group (10.43 ± 0.71) and the severe group miR-127 level (11.05 ± 1.26) were significantly higher than those in the mild group level (9.38 ± 1.24). Pearson correlation analysis showed that the serum miR-127 level was negatively correlated with PaO2/FiO2 (r = -0.715, P < 0.05), that is, the serum miR-127 level was positively correlated with the severity of ARDS patients. The area under the curve (AUC) of the diagnostic value of serum miR-127 for ARDS was 0.732 (95% CI 0.607-0.858). When the optimal cutoff value was 0.380, the sensitivity was 59.1% and the specificity was 78.6%, which suggested that miR-127 can be used as a marker for ARDS diagnosis. CONCLUSION: There is an increase in miR-127 levels in the serum of ARDS patients. The serum miR-127 level is positively correlated with the severity of ARDS. The higher the level of miR-127, the worse the condition of ARDS, which is positively correlated with the severity of the condition. It suggests that the serum miR-127 level is an important indicator for evaluating the severity of ARDS patients. It can be used as a molecular marker for clinical diagnosis of ARDS.