eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective To investigate the effect of C peptide on tubulointerstitial oxidative stress injury in rats with diabetic nephropathy (DN) induced by streptozotocin (STZ). Methods Wistar rats with DN induced by STZ were randomly divided into control group and C peptide group. All rats were treated via intraperitoneal micro-osmotic pump. Normal Wistar rats at the same age were used as the normal group. Blood glucose and24 h urinary albumin were measured before treatment and every 4 weeks during treatment period. After 12 weeks of treatment, the expression of transforming growth factor - β1 (TGF - β1) in renal tubulointerstitium was detected by immunohistochemical staining. Fresh tubulointerstitial tissue homogenate was harvested and the activity of superoxide dismutase (SOD) was detected in WST-1 method, the content of malondialdehyde (MDA) was detected in TBA method, and the expression of protein kinase A (PKA) mRNA was detected by Real-time PCR. Results Levels of blood glucose, 24 h urinary albumin, MDA content and the expression of TGF-β1 were higher in the control group than those in the normal group, while SOD activity decreased and PKA mRNA was downregulated. C peptide treatment did not change blood glucose level but slowed down the increasing of 24 h urinary albumin, reduced the tubulointerstitial TGF-β1 expression and MDA content, increased the SOD activity and upregulated the PKA mRNA expression. Conclusions C-peptide can decrease the tubulointerstitial oxidative stress in DN rats by activating PKA pathway and then improve tubulointerstitial fibrosis and attenuate proteinuria.

Objective To evaluate the effect of single CVVH and HDF on endothelial system. Methods Group CVVH:20 patients with multiple organ dysfunction syndrome ( MODS) underwent CVVH for 12h.Vascular access was through two-lumen catheter in femoral vein;Group HDF:Twenty patients with end stage renal disease (ESRD) on maintenance hemodialysis underwent HDF for 4h.Vascular access was through internal arteriovenous fistula.Group control:Healthy people were examined at our hospital.The se-rum levels of sVCAM-1, sICAM-1, vWF and MMP-9 were measured by enzyme-linked immunosorbent assay ( ELISA) after centrifugation in treatment group before and after treatment.Four cytokines were also meas-ured in fasting healthy subjects in the morning.Results The levels of serum sVCAM-1, sICAM-1, vWF, MMP-9 were significantly higher in Group CVVH and HDF than control group before and after treatment( P<0.05).Group CVVH:The serum levels of sICAM-1 and sVCAM-1 were significantly lower in post-treat-ment than pre-treatment, But the serum levels of vWF and MMP-9 showed no obvious changes after CVVH;Group HDF:the levels of four cytokines showed no obvious changes after single HDF.Conclusions Endo-thelium becomes impaired in MODS and ESRD patients, Endothelium may be protected by CVVH through the partial removal of cytokines harmful to endothelium in MODS patients.Single HDF therapy does not pro-tect endothelial function obviously in MHD patients.