Low dose cadmium inhibits syndecan-4 expression in glycocalyx of glomerular endothelial cells.

Cadmium (Cd) is one of the most polluting heavy metal in the environment. Cd exposure has been elucidated to cause dysfunction of the glomerular filtration barrier (GFB). However, the underlying mechanism remains unclear. C57BL/6J male mice were administered with 2.28 mg/kg cadmium chloride (CdCl2) dissolved in distilled water by oral gavage for 14 days. The expression of SDC4 in the kidney tissues was detected. Human renal glomerular endothelial cells (HRGECs) were exposed to varying concentrations of CdCl2 for 24 h. The mRNA levels of SDC4, along with matrix metalloproteinase (MMP)-2 and 9, were analyzed by quantitative PCR. Additionally, the protein expression levels of SDC4, MMP-2/9, and both total and phosphorylated forms of Smad2/3 (P-Smad2/3) were detected by western blot. The extravasation rate of fluorescein isothiocyanate-dextran through the Transwell was used to evaluate the permeability of HRGECs. SB431542 was used as an inhibitor of transforming growth factor (TGF)-ß signaling pathway to further investigate the role of TGF-ß. Cd reduced SDC4 expression in both mouse kidney tissues and HRGECs. In addition, Cd exposure increased permeability and upregulated P-Smad2/3 levels in HRGECs. SB431542 treatment inhibited the phosphorylation of Smad2/3, Cd-induced SDC4 downregulation, and hyperpermeability. MMP-2/9 levels increased by Cd exposure was also blocked by SB431542, demonstrating the involvement of TGF-ß/Smad pathway in low-dose Cd-induced SDC4 reduction in HRGECs. Given that SDC4 is an essential component of glycocalyx, protection or repair of endothelial glycocalyx is a potential strategy for preventing or treating kidney diseases associated with environmental Cd exposure.

[Feasibility of Preheating at 41 ℃ to Correct Red Blood Cell Parameters in the Presence of High-titer Cold Agglutinins].

Objective To explore the feasibility of preheating in 41 ℃ water bath for 30 minutes to correct the red blood cell parameters in the specimens containing high-titer cold agglutinins(CAs). Methods Two specimens containing high-titer CAs were selected during work,and the parameters of complete blood count at room temperature or after preheating in 37 ℃ or 41 ℃ water bath were compared.The smears were stained,and the distribution of red blood cells was observed with a microscope.Further,74 specimens without CAs were collected for complete blood count,and then the test results at room temperature and after preheating at 41 ℃ were compared. Results At room temperature,the specimens containing high-titer CAs showed significantly reduced red blood cell count(RBC)and hematocrit(HCT),abnormally increased mean corpuscular hemoglobin(MCH)and mean cell hemoglobin concentration(MCHC),abnormal percents of hemoglobin(HGB)and RBC,and aggregation of a large number of red blood cells.After being preheated at 37 ℃ for a certain time,the specimens demonstrated obviously improved parameters while still aggregation of a small number of red blood cells.After being preheated at 41 ℃ for 30 minutes,the specimens showed significantly increased RBC,normal HCT,MCH,and MCHC,and evenly distributed red blood cells.The 74 specimens without CAs showed the comparability was ≥80% between room temperature and preheating at 41 ℃ for 30 minutes or 60 minutes. Conclusion We can preheat the specimens containing high-titer CAs in a water bath at 41 ℃ to obtain accurate red blood cell parameters.

Evaluation of anthracycline-induced subclinical LV dysfunction by using myocardial composite index and two-dimension speckle tracking echocardiography technique.

Objective: To obtain various myocardial strain parameters by using two-dimension speckle tracking echocardiography (2D-STE) technique, calculate the myocardial composite index (MCI) which combines the global longitudinal strain (GLS) of left ventricle and the left ventricular twist (LVtw), and evaluate their diagnostic efficacies for subclinical left ventricular (LV) dysfunction in patients undergoing anthracycline chemotherapy. Methods: A total of 35 female breast cancer patients, who underwent postoperative chemotherapy in the Department of Thyroid and Breast Surgery of Nantong Third People's Hospital from September 2018 to December 2019 and had successful follow-up, were included into the chemotherapy group, and the patients were evaluated respectively at baseline and in early, interim and later chemotherapy stages according to the course of chemotherapy; in addition, 30 healthy women undergoing physical examination during the same period were included into the control group. In different chemotherapy stages, the data such as left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and left ventricular ejection fraction (LVEF) were collected by using conventional echocardiography, and various myocardial strain parameters such as GLS, global radial strain (GRS), global circumferential strain(GCS) and LVtw were measured using 2D-STE, and then MCI was calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the application values of various parameters in the diagnosis of early cardiotoxicity. Results: There was a difference in MCI between patients at baseline and in the early chemotherapy stage; there were differences in GLS, LVtw and MCI between patients at baseline and in the interim chemotherapy stage; there were differences in four parameters such as MCI, GLS, LVtw and GCS between patients at baseline and in the later chemotherapy stage; The AUC of MCI was 0.915, when the cutoff value was -210.89 (%×°), the sensitivity and specificity were 84.37% and 90.41%, respectively. Conclusion: MCI combines the longitudinal and torsional motions of myocardium, and thus has a better diagnostic value for early detection of subclinical LV dysfunction caused by anthracycline chemotherapy drugs compared with strain parameters in a single direction.

Multi-Omics Interpretation of Anti-Aging Mechanisms for ω-3 Fatty Acids.

Aging is one of the hottest topics in biomedicine. Previous research suggested that ω-3 fatty acids have preventive effects on aging. However, most of previous studies on the anti-aging effects of ω-3 fatty acids are focused on clinical observations, and the anti-aging mechanisms of ω-3 fatty acids have not been fully elucidated. This stimulated our interest to use multi-omics data related to ω-3 fatty acids in order to interpret the anti-aging mechanisms of ω-3 fatty acids. First, we found that ω-3 fatty acids can affect methylation levels and expression levels of genes associated with age-related diseases or pathways in humans. Then, a Mendelian randomization analysis was conducted to determine whether there is a causal relationship between the effect of ω-3 fatty acids on blood lipid levels and variation in the gut microbiome. Our results indicate that the impact of ω-3 fatty acids on aging is partially mediated by the gut microbiome (including Actinobacteria, Bifidobacteria and Streptococcus). In conclusion, this study provides deeper insights into the anti-aging mechanisms of ω-3 fatty acids and supports the dietary supplementation of ω-3 fatty acids in aging prevention.