Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKß/AMPK pathway.

OBJECTIVE: Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease. METHODS: Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 µg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin-eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKß)/AMPK signaling pathway activation. RESULTS: Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKß/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice. CONCLUSIONS: Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKß/AMPK signaling pathway in kidney tissue.

Classification of pleasantness of wind by electroencephalography.

Thermal comfort of humans depends on the surrounding environment and affects their productivity. Several environmental factors, such as air temperature, relative humidity, wind or airflow, and radiation, have considerable influence on the thermal comfort or pleasantness; hence, these are generally controlled by electrical devices. Lately, the development of objective measurement methods for thermal comfort or pleasantness using physiological signals is receiving attention to realize a personalized comfortable environment through the automatic control of electrical devices. In this study, we focused on electroencephalography (EEG) and investigated whether EEG signals contain information related to the pleasantness of ambient airflow reproducing natural wind fluctuations using machine learning methods. In a hot and humid artificial climate chamber, we measured EEG signals while the participants were exposed to airflow at four different velocities. Based on the reported pleasantness levels, we performed within-participant classification from the source activity of the EEG and obtained a classification accuracy higher than the chance level using both linear and nonlinear support vector machine classifiers as well as an artificial neural network. The results of this study showed that EEG is useful in identifying people's transient pleasantness when exposed to wind.

Sarcopenia predicts cardiovascular disease in chronic kidney disease at advanced stage and associated risks.

Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD), and sarcopenia is a new risk factor for CKD. However, whether sarcopenia predicts CVD in CKD remains to be determined. Sarcopenia would predict CVD in CKD at advanced stage. This analysis included 101 patients with CKD at stage 3 or over to determine the prevalence of sarcopenia and cardiovascular disease in patients with CKD at stage 3 or over in our center. The patients were further categorized into sarcopenia group (N = 19) and non-sarcopenia group (N = 82) according to the diagnostic criteria for sarcopenia. Data on demographics, laboratory tests, and measurements of extracardiac adipose tissue thickness (EAT) was collected. The prevalence of sarcopenia in patients with CKD at stage ≥ 3 was 19%. Compared with non-sarcopenia group, patients from the sarcopenia group were older (P = .005), and presented longer disease durations (P = .002). The serum level of albumin was significantly decreased, (P = .047), and high-sensitivity C-reactive protein level (CRP) was significantly increased (P = .003) in sarcopenia group. In addition, the EAT was thicker in the sarcopenia group compared with non-sarcopenia group (P = .032). Furthermore, the le-stratified atherosclerotic cardiovascular disease (ASCVD) risk scores were positively correlated with inflammation, nutrition, body mass index (BMI) and disease duration of CKD in sarcopenia group (P < .001). Patients with CKD are prone to have sacropenia, which is associated with inflammation and malnutrition. Presence of sarcopenia in CKD patients predicts the risk of ASCVD.

Low Blood Glucose Index Associated with Cardiovascular Events in Diabetic Hemodialysis Patients.

INTRODUCTION: Blood glucose monitoring was vitally important in diabetic kidney disease (DKD) patients for preventing complications and improving survival rates. The associations between glycemic variability and blood biochemical indicators were underestimated in patients with DKD undergoing hemodialysis. Therefore, we primarily aimed to investigate the glycemic variability and 1-year risk of cardiovascular disease events in diabetic hemodialysis patients. And we secondarily aimed to explore the association between glycemic variability and blood biochemical indicators. METHODS: In total, 27 patients were included in the final analysis. Continuous glucose monitoring (CGM) was used to evaluate glucose variability for 14 days. Patients were divided into two groups by the cutoff level of time in range (TIR; >70% or ≤70%). The three-point major adverse cardiovascular event (3P MACE) was recorded within 1 year. RESULTS: After 1 year of follow-up, 4 patients in the high-TIR group and 3 patients in the low-TIR group had 3p MACE. Higher low blood glucose index (LBGI) level in diabetic hemodialysis patients increased the risk of 3p MACE outcomes (HR = 2.37, p = 0.018). And the level of albumin was positively associated with LBGI (ß = 0.51, p = 0.036). The plasma levels of albumin, glycosylated hemoglobin, and hemoglobin were positively associated with other CGM parameters. CONCLUSION: LBGI during 14 days was positively associated with the risk of cardiovascular events in diabetic hemodialysis patients.

sPD-1 and sPD-L1 Levels in Serum and Urine of Patients with Primary Nephrotic Syndrome and their Clinical Significance.

BACKGROUND: Primary nephrotic syndrome (PNS), a clinically prevalent glomerular disease, mostly results in a large loss of plasma albumin, and its predominant clinical manifestations are proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Research has uncovered [9] that sPD-L1 and sPD-1 modulate the PD and PD-L1 pathway in the development of various autoimmune diseases. METHODS: We randomly selected 80 PNS patients treated for PNS in our institution from October 2017 to October 2018 as the case group and 78 healthy volunteers examined in our hospital during the same period as the control group. Not only sPD-1 but also sPD-L1 level in serum and urine was assayed via ELISA. We compared the distribution of T lymphocyte subsets in peripheral blood and mALB and NAG levels in urine. Pearson's correlation analysis was adopted for assessing the relationship of serum and urine sPD-1, sPD-L1 with T lymphocyte subsets and mALB. RESULTS: (1) In contrast to the control group, the case group harbored higher pretreatment serum and urine sPD-1 and sPD-L1 contents (p < 0.05). (2) Before treatment, sPD-1 in the serum and urine held a positive relationship with sPD-L1 level (r was 0.683 and 0.235, respectively, p < 0.05); serum sPD-1 harbored a positive link with urine sPD-1 (r = 0.287, p < 0.01), whereas no relationship was discovered in serum sPD-L1 and urine sPD-L1. (3) In contrast to the control group, the CD4+ level in the case group abated, CD8+ increased, the CD4+/CD8+ ratio assuaged, and mALB level in urine increased (all p < 0.05), whereas NAG harbored no statistical difference (p > 0.05). (4) In the case group, the CD4+/CD8+ ratio possessed positive association with serum sPD-1 (r = 0.384, p < 0.001), and the mALB had a positive relationship with urine sPD-1 (r = 0.704, p < 0.001). (5) After treatment, in comparison with the remission group, the serum sPD-1 level of the non-remission group was increased (p < 0.05), whereas sPD-L1 value was not statistically different (p > 0.05); the sPD-1 level in urine was not statistically significant (p > 0.05), while sPD-L1 content was elevated (p < 0.05). CONCLUSIONS: Serum and urine sPD-1/sPD-L1 levels of PNS patients change dynamically. Detecting sPD-L1 and sPD-1 has certain clinical value for the prognosis of PNS.