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Chronic kidney diseases are characterized by renal fibrosis with excessive matrix deposition, leading to a progressive loss of functional renal parenchyma and, eventually, renal failure. Renal microcirculation lesions, including the phenotypic conversion of vascular cells, contribute to renal fibrosis. Here, renal microcirculation lesions were established with monocrotaline (MCT, 60 mg/kg). Sitagliptin (40 mg/kg/d), a classical dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the renal microcirculation lesions by inhibiting glomerular tuft hypertrophy, glomerular mesangial expansion, and microvascular thrombosis. These effects of sitagliptin were mediated by glucagon-like peptide-1 receptor (GLP-1R), since they were blocked by the GLP-1R antagonist exendin-3 (Ex-3, 40 ug/kg/d). The GLP-1R agonist liraglutide showed a similar renal protective effect in a dose-independent manner. In addition, sitagliptin, as well as liraglutide, alleviated the MCT-induced apoptosis of renal cells by increasing the expression of survival factor glucose-regulated protein 78 (GRP78), which was abolished by the GLP-1R antagonist Ex-3. Sitagliptin and liraglutide also effectively ameliorated the conversion of vascular smooth muscle cells (SMCs) from a synthetic phenotype to contractile phenotype. Moreover, sitagliptin and liraglutide inhibited endothelial-mesenchymal transition (EndMT) via downregulating transforming growth factor-β1 (TGF-β1). Collectively, these findings suggest that DPP-4 inhibition can reduce microcirculation lesion-induced renal fibrosis in a GLP-1-dependent manner.
The Plackett-Burman design and support vector machine (SVM) were reported to be used on many fields such as some feature selections, protein structure prediction, or forecasting of other situations. Here, with suspension adapted Chinese hamster ovary (CHO) cells as the object of study, a serum-free medium for the culture of CHO cells in suspension was optimized by this method. Support vector machine based on genetic algorithm was used to predict the growth rate of CHO and prove the results from the trial designs. Experimental results indicated that ZnSO4, transferrin, and bovine serum albumin (BSA) were important ones. The same conclusion was arrived at when the support vector regression model analyzed the experimental results. With the methods mentioned, the influence of 7 medium supplements on the growth of CHO cells in suspension was evaluated efficiently.
This paper studied the alterations in arterial stiffness and hemodynamic responses during resting state and immediately following acute cycling intervention at different times across 12-week supervised exercise training. Twenty-six sedentary young males participated in the exercise training program at moderate intensity. Arterial stiffness and hemodynamic variables of the right common carotid artery were measured and computed during resting state and immediately following acute cycling intervention at weeks 0, 4, 8, and 12. Across the 12-week exercise training, carotid arterial stiffness was decreased at weeks 8 and 12 and hemodynamic variables were improved at week 12 during resting state. In response to acute cycling intervention, carotid arterial stiffness exhibited an acute increase foremost at 8 weeks, and arterial maximal and mean diameters showed acute decreases at weeks 0 and 4. Despite significant differences in arterial stiffness and hemodynamic variables between resting state and immediately after acute intervention for each time period, these differences presented a progressive decrease across the 12-week exercise training. In conclusion, long-term exercise training not only improved carotid arterial stiffness and hemodynamic alterations when at rest but also negated the acute responses of carotid arterial stiffness and hemodynamic variables to acute cycling intervention.
A large number of facts have shown that epigenetic modification and metabolic reprogramming represented by noncoding RNA play an important role in the invasion and metastasis of breast cancer, but the mechanism is not clear. The purpose of our study is to find a new biomarker of breast cancer and to provide a new perspective for regulating glucose metabolism and aerobic glycolysis of BC. In this paper, by downregulating C-myc protein, our team found that the expression of long-chain noncoding RNATSPAR-AS2 was significantly downregulated. However, the expression of long-chain noncoding RNASPAR-AS2 in BC is relatively high, and the prognosis is poor. TSPEAR-AS2 can promote the malignant phenotype of BC cells, including proliferation, apoptosis, invasion and metastasis, and glycolysis. At the same time, TSPEAR-AS2 can also upregulate the expression of GLUT1, an important regulator of glycolysis, thus promoting the metabolic reprogramming of BC. Molecular mechanism experiments show that TSPEAR-AS2 may promote the expression of GLUT1 by participating in IGF2BP2 modified by the GLUT1 gene. Our results suggest that the C-myc/TSPEAR-AS2/GLUT1 axis promotes the invasion and metastasis of BC by inducing glucose metabolism reprogramming. However, more phenotypic and molecular mechanism results need to be further verified.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children accounts for a small proportion of all infections and is usually mild or asymptomatic. There are few studies on the clinical characteristics of SARS-CoV-2 infection in children, and the causes of the low prevalence in children remain unclear. Herein, we compared the epidemiological and clinical characteristics of SARS-CoV-2 infection between adults and children. Fifty-two patients with Coronavirus Disease 2019 (COVID-19) were retrospectively analyzed, including 38 adults and 14 children. Their clinical information such as epidemiological exposure history, laboratory indicators, chest computed tomography (CT) performance, and number of SARS-CoV-2 positive days were analyzed and compared. In children, 5 (35.71%) had mild COVID-19 and 9 (64.29%) had common type, while, in adults, 9 (23.68%) cases were mild, and 29 (76.32%) were common COVID-19. Among them, family clustering infection accounted for 50% (7/14) of child cases and 23.68% (9/36) of adult cases. Epidemiological exposure history, clinical classification, clinical symptoms, chest CT manifestations, and number of SARS-CoV-2-positive days were not significantly different between children and adults. However, the percentage of neutrophils in adults was significantly higher than that in children (P < 0.05). The percentage and absolute value of lymphocytes, platelet counts, aspartate aminotransferase, and aspartate aminotransferase/alanine aminotransferase in adults were lower than those in children (P < 0.05). Conclusively, children infected with SARS-CoV-2 show the characteristics of family clustering, and the proportion of mild and asymptomatic infections is higher. For families with a history of epidemiological exposure, routine SARS-CoV-2 nucleic acid testing and chest CT examination should be performed in asymptomatic children to determine whether they are infected. Unlike adults, although the reduction of lymphocytes and platelets in children is not common, it is necessary to be alert to the increased risk of liver damage in children.
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