Ascorbate uptake enables tubular mitophagy to prevent septic AKI by PINK1-PARK2 axis.

Ascorbate (Vitamin C) has been proposed as a promising therapeutic agent against sepsis in clinical trials, but there is little experimental evidence on its anti-septic efficacy. We report that Toll-like receptor 4 (TLR4) activation by LPS stimuli augments ascorbate uptake in murine and human tubular cells through upregulation of two ascorbate transporters SVCT-1 and -2 mediated by Fn14/SCFFbxw7α cascade. Ascorbate restriction, or knockout of SVCT-1 and -2, the circumstance reminiscent to blockade of ascorbate uptake, endows tubular cells more vulnerable to the LPS-inducible apoptosis, whereas exogenous administration of ascorbate overrides the ruin execution, for which the PINK1-PARK2, rather than BNIP3-NIX axis is required. Ascorbate increases, while SVCT-1 and -2 knockout or ascorbate restriction dampens tubular mitophagy upon LPS stimuli. Treatment of endotoxemic mice with high-dose ascorbate confers mitophagy and substantial protection against mortality and septic acute kidney injury (AKI). Our work provides a rationale for clinical management of septic AKI with high doses of ascorbate.

[Operative treatment of upper lumbar disc herniation with modified transforaminal lumbar interbody fusion].

OBJECTIVE: To investigate the surgical methods and clinical results of modified transforaminal lumbar interbody fusion and internal fixation for the treatment of upper lumbar disc herniation. METHODS: Clinical data of 32 cases of upper lumbar disc herniation in our department from June 2005 to June 2009 were retrospectively analyzed. There were 21 males and 11 females, the age from 24 to 59 years with an average of 38.5 years. All the cases were treated by the use of nucleus pulposus removed, modified transforaminal lumbar interbody fusion (TLIF) and internal fixation with pedicle screw system. All patients were followed up with an average of 9 months (from 3 to 18 months), according to Japanese Orthopedic Association (JOA) scores and visual analogue scores (VAS) to evaluate clinical effects. RESULTS: All the cases were followed up from 3 to 18 months with an average of 9 months and the fusion rate was 100%. The JOA sores before and after operation were 10.5 +/- 2.1, 26.2 +/- 2.4 respectively, and the improvement rate was 84.9%. The VAS before and after operation was 7.2 +/- 1.3 and 1.4 +/- 1.1 respectively, and the rate of catabatic pain was 80.6%. Lumbar rigidity and unwell had 4 cases, obviously leg pain had 2 cases after operation, but the systems vanished gradually at 1-8 weeks after non-operative treatment. CONCLUSION: Modified transforaminal lumbar interbody fusion has the advantages of simple, safe operation and thoroughly decompression, and it is a therapeutic method for upper lumbar disc herniation.