The pathogenic role of succinate-SUCNR1: a critical function that induces renal fibrosis via M2 macrophage.

BACKGROUND: Renal fibrosis significantly contributes to the progressive loss of kidney function in chronic kidney disease (CKD), with alternatively activated M2 macrophages playing a crucial role in this progression. The serum succinate level is consistently elevated in individuals with diabetes and obesity, both of which are critical factors contributing to CKD. However, it remains unclear whether elevated succinate levels can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis. METHODS: Male C57/BL6 mice were administered water supplemented with 4% succinate for 12 weeks to assess its impact on renal interstitial fibrosis. Additionally, the significance of macrophages was confirmed in vivo by using clodronate liposomes to deplete them. Furthermore, we employed RAW 264.7 and NRK-49F cells to investigate the underlying molecular mechanisms. RESULTS: Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3ß/ß-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells. CONCLUSIONS: The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages. Succinate-SUCNR1 played a role in activating p-Akt/p-GSK3ß/ß-catenin, CTGF expression, and facilitating crosstalk between macrophages and fibroblasts. Our findings suggest a promising strategy to prevent the progression of metabolic CKD by promoting the excretion of succinate in urine and/or using selective antagonists for SUCNR1.

Response of photosynthate distribution in potato plants to different LED spectra.

Although light is essential to photosynthesis, few studies have examined the effects of different LED spectra on photosynthate distribution in potato plants. Therefore, we exposed tuberising potato plants to white (W), red (R), blue (B) and green (G) LED treatments and compared tuber development and carbohydrate partitioning among the plants. R-treated plants had greater photosynthetic leaf area during tuber development compared with those under other treatments, thus enhancing assimilation. Although R-treated plants had higher 13C assimilation in the leaves, stems and roots than those under B treatment, there was no difference in partitioning of 13C assimilation and yield in the tubers of each plant between R and B treatments. For the tuber size, R-treated plants had a higher ratio of large tubers (>20 g) and a lower ratio of small (2-20 g) and medium-sized (10-20 g) tubers than those under W. B-treated plants had more medium-sized and large tubers than those under W. The reason may be that plants under R treatment distributed more assimilated 13C in their first tuber than those under other treatments. By contrast, plants under B balanced photosynthate distribution among their tubers. Leaves under G treatment had lower photosynthetic efficiency and ΦPSII than those under W, R or B treatment, which resulted in lower 13C photosynthate allocation in organs and lower tuber yield per plant than in R and B treatments. Overall, R treatment promoted 13C assimilation and led to more large tubers than other treatments. B-treated plants distributed more photosynthates into tubers rather than other organs and showed balanced tuber development.

Role of intracardiac ultrasound in interventional electrophysiology.

PURPOSE OF REVIEW: Interventional procedures in the electrophysiology and catheterization laboratory are rapidly advancing. Critical to the advancement of these procedures is accurate identification of critical anatomic landmarks and catheter position. Fluoroscopy remains the mainstay for general identification of anatomic landmarks but is inadequate for the precise imaging needed for complex procedures. Precise imaging of anatomic landmarks and catheter position is now possible during the procedure with the use of intracardiac echocardiography (ICE). This paper reviews the rapid development and utilization of ICE in interventional electrophysiology. RECENT FINDINGS: Several recent studies show ICE as a major contribution to providing a safer, more reliable, and more cost-effective means of accomplishing the tasks performed by existing techniques. In the electrophysiology laboratory, the dependence on this new technology has been due to the rapid development of catheter-based radiofrequency ablation of the pulmonary veins for treatment of atrial fibrillation. Since the initial use of ICE in facilitating ablation of atrial fibrillation, other uses for ICE are continuously being identified. SUMMARY: A comprehensive look is provided at the history and development of this new technology along with the most recent applications of ICE in interventional electrophysiology.