The copper transporter, SLC31A1, transcriptionally activated by ELF3, imbalances copper homeostasis to exacerbate cisplatin-induced acute kidney injury through mitochondrial dysfunction.

Acute kidney injury (AKI) is a common complication of cisplatin chemotherapy, which greatly limits its clinical effect and application. This study explored the function of solute Carrier Family 31 Member 1 (SLC31A1) in cisplatin-induced AKI and its possible mechanism. Mice and HK-2 cells were exposed to cisplatin to establish the in vivo and in vitro AKI models. Cell viability was detected by CCK-8. Mitochondrial and oxidative damage was determined by Mito-Tracker Green staining, mtROS level, ATP production, mitochondrial membrane potential, MDA content and CAT activity. AKI was evaluated by renal function and histopathological changes. Apoptosis was detected by TUNEL and caspase-3 expression. Molecule expression was measured by RT-qPCR, Western blotting, and immunohistochemistry. Molecular mechanism was studied by luciferase reporter assay and ChIP. SLC31A1 level was predominantly increased by cisplatin exposure in AKI models. Notably, copper ion (Cu+) level was enhanced by cisplatin challenge. Moreover, Cu+ supplementation intensified cisplatin-induced cell death, mitochondrial dysfunction, and oxidative stress in HK-2 cells, indicating the involvement of cuproptosis in cisplatin-induced AKI, whereas these changes were partially counteracted by SLC31A1 knockdown. E74 like ETS transcription factor 3 (ELF3) could directly bind to SLC31A1 promoter and promote its transcription. ELF3 was up-regulated and positively correlated with SLC31A1 expression upon cisplatin-induced AKI. SLC31A1 silencing restored renal function, alleviated mitochondrial dysfunction, and apoptosis in cisplatin-induced AKI mice. ELF3 transcriptionally activated SLC31A1 to trigger cuproptosis that drove cisplatin-induced AKI through mitochondrial dysfunction, indicating that SLC31A1 might be a promising therapeutic target to mitigate AKI during cisplatin chemotherapy.

Effects of dural puncture epidural technique with different drug delivery methods for labor analgesia: A randomized controlled clinical trial.

This study aimed to investigate the effect of dural puncture epidural (DPE) combined with small-dose lidocaine for labor analgesia. Parturients were randomly divided into epidural anesthesia (EA), DPE1, and DPE2 groups. In the EA group, 5 mL of 1% lidocaine was administered via conventional L2-L3 puncture catheterization; in the DPE1 group, epidural drug was administered after catheterization using the DPE technique; in the DPE2 group, epidural puncture drug was administered through the epidural puncture needle before catheterization using the DPE technique. The primary outcome was the onset time of analgesia. The secondary outcomes included the numerical rating scale (NRS) scores during uterine contraction before bolus injection of experimental dose (T0) and the second time (T1), the fifth time (T2) and the tenth time (T3) after bolus injection of experimental dose; NRS scores at the second stage of labor (T4) and during perineal suture (T5); operation time of anesthesia; puncture related complications; anesthesia related complications; delivery outcome; use of local anesthesia during vaginal suture; and Apgar score of the neonates. There were 115 women included. The onset time in the DPE2 group was markedly shorter than in the EA and DPE1 groups (P < .001). The NRS scores in the DEP2 group at T1 and T4 were significantly lower than in the EA and DEP1 groups (P < .001). The overall incidence of puncture related complications in the DEP1 and DEP2 groups was markedly higher than in the EA group (P < .05). In dural puncture epidural analgesia, when the experimental dose was injected directly through the epidural puncture needle, the onset time was shorter and the analgesic effect was better as compared to the injection of test dose after inserting the epidural catheter.

[Effects and mechanisms of Xiao-Ai-Ping injection on angiogenesis].

This study was designed to investigate the effect of Xiao-Ai-Ping injection on cancer angiogenesis. CCK8 assay and Brd U incorporation immunofluorescence assay were used to detect the effect of Xiao-Ai-Ping injection on HUVECs proliferation; wound healing assay and transwell assay were employed to test the effect of Xiao-Ai-Ping injection on HUVECs migration. The anti-angiogenic effect of Xiao-Ai-Ping injection was examined by tube formation assay, rat aortic ring assay and chicken chorioallantoic membrane(CAM) assay. ELISA assay was used to measure the secretion of vascular endothelial growth factor(VEGF); and the activation of vascular endothelial growth factor receptor 2(VEGFR2) protein and its downstream signaling pathways were examined by Western blot. Our data demonstrated that Xiao-Ai-Ping injection inhibited HUVECs proliferation in a time- and dose-dependent manner, and the IC(50) (mg·m L(-1)) values for 24, 48 and 72 h were 48.7 ± 7.14, 29.1 ±2.25 and 22.0 ± 4.53, individually. Xiao-Ai-Ping injection inhibited HUVECs DNA synthesis and migration. Xiao-Ai-Ping injection suppressed HUVECs tube formation, and reduced microvessel sprouting from rat aortic rings and vessel growth in CAMs. Furthermore, Xiao-Ai-Ping injection attenuated the secretion of VEGF, and inhibited the expression of p-VEGFR2 and phosphorylation of protein kinase B(p-AKT). We conclude that Xiao-Ai-Ping injection inhibits angiogenesis by down-regulation of VEGF signaling and AKT pathway.