1Broncho-Vaxom (OM85-BV) is an extract mixture from 8 strains of Gram + and Gram -bacteria and plays an important role in anti-infection immune response by regulating macrophage activity and cytokine productions. However, the mechanism by which OM85-BV enhances the cytokine expression is still obscure. In this study, we evaluated the effects of OM85-BV on the productions of interleukin (IL)-1b, IL-6, and tumor necrosis factor-a (TNF-a) in RAW264.7 murine macrophages. Exposure of RAW264.7 cells to 100 mg/mL OM85-BV upregulated the expression of IL-1b, IL-6, and TNF-a at the mRNA and protein levels in a time-and dosedependent manner. In addition, OM85-BV induced extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor-kappa B (NF-kB) phosphorylation. Pretreatment with U0126 or Bay11-7082, respectively, could decrease IL-1b, IL-6, and TNF-a productions induced by OM85-BV. Application of Toll-like receptor (TLR) 4 or TLR2 small-interfering RNA (siRNA) into RAW264.7 cells could inhibit the productions of cytokines and ERK1/2 and NF-kB phosphorylation induced by OM85-BV. Consistent with this, downregulating either myeloid differentiation factor 88 (MyD88) or TRIF-related adaptor molecule (TRAM) gene with MyD88-siRNA or TRAM-siRNA separately could reduce the productions of cytokines and ERK1/2 and NF-kB phosphorylation induced by OM85-BV. Our study demonstrated that the productions of IL-1b, IL-6, and TNF-a induced by OM85-BV in RAW264.7 cells were through TLR4 and TLR2 signaling pathway-mediated activation of ERK1/2 and NF-kB.

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4(+)Tim-3(+) T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

The role of inflammation and the correlation between inflammatory markers and type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) have been studied. In clinical work, a large number of T2DM patients complicated with CKD, but the cause of CKD was not clear. Our study aimed to evaluate the relationship between monocyte-to-lymphocyte ratio (MLR) and mortality in T2DM patients with CKD. The data from Medical Information Mart for Intensive Care III was analyzed. The primary outcome was 90-day all-cause mortality; the secondary outcomes were the length of ICU stay, hospital mortality and 30-day all-cause mortality. Cox regression was used to evaluate the association between MLR and 90-day mortality. We performed subgroup analyses to determine the consistency of this association, and used Kaplan–Meier survival curve to analysis the survival of different levels of MLR. A total of 1830 patients were included in study retrospectively. The length of ICU stay, 30-day all-cause mortality, and 90-day all-cause mortality in the MLR > 0.71 group were significantly higher than those in the MLR < 0.28 and 0.28 ≤ MLR ≤ 0.71 group. In Cox regression analysis, high MLR level was significantly associated with increased greater risk of 90-day all-cause mortality. The adjusted HR (95%CIs) for the model 1, model 2, and model 3 were 2.429 (1.905–3.098), 2.070 (1.619–2.647), and 1.898 (1.478–2.437), respectively. Subgroup analyses also showed the consistency of association between MLR and 90-day all-cause mortality. The Kaplan–Meier survival curve analysis revealed that MLR > 0.71 had worst prognosis. In T2DM patients with CKD in the intensive care unit, high MLR was significantly associated with increased risk 90-day all-cause mortality.

Stainless steel with high surface quality is required in many industries and chemical mechanical polishing can achieve both local and global planarization of the substrate surface. However, it is difficult to realize both high material removal rate and high surface quality by a single step polishing. In this regard, a two-step polishing process, coarse polishing with α-Al2O3 abrasives first and then fine polishing with silica abrasives, was proposed to solve the trade-off between material removal and surface quality. The effects of pH (1~12) and H2O2 (0~0.5wt%) on the polishing of 304 stainless steel disk (area ~6.7 cm2) were systematically studied and CMP mechanism of stainless steel was discussed. The results indicated that, at pH 4, with the addition of 0.01wt% H2O2, the surface roughness of stainless steel was successfully reduced from 0.702 μm to 44.6 nm (the first step using α-Al2O3 abrasives) and 1.61 nm (the second step using silica abrasives). Finally, an ultra-smooth surface was obtained with decent material removal rate.