Prognostic value of pretreatment prognostic nutritional index in non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND:: The pretreatment prognostic nutritional index has been considered a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC), but this remains controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of the prognostic nutritional index in patients with NSCLC. METHODS:: We systematically searched PubMed, EMBASE, Web of Science, and CNKI. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between the prognostic nutritional index and the oncological outcomes of patients with NSCLC, including overall survival, disease-free survival/recurrence-free survival, and progression-free survival. RESULTS:: Fifteen studies were included in this meta-analysis. Twelve of these studies explored the association between the prognostic nutritional index and the overall survival of patients with NSCLC. Our pooled analysis indicated that a low prognostic nutritional index was significantly related to adverse overall survival (HR 1.61; 95% CI 1.44, 1.81; P < 0.001). Our results also showed that the prognostic nutritional index was a negative predictor for disease-free survival/recurrence-free survival, and progression-free survival in patients with NSCLC. CONCLUSION:: Our meta-analysis demonstrated that there was a close association between the prognostic nutritional index value and prognosis in NSCLC patients and that the prognostic nutritional index may act as a useful prognostic biomarker in NSCLC patients.

The preparation and characterization of a novel sphingan WL from marine Sphingomonas sp. WG.

Sphingans, a group of structurally closely related bacterial exopolysaccharides produced by members of the genus Sphingomonas, can be applied in a variety of industries such as food, cement, and personal care applications due to their high viscosity. A high sphingan-producing-bacterium, Sphingomonas sp. WG can secret large quantity of sphingan designated as WL. To enhance the production of WL, a three-stage control strategy was applied and the highest WL production can reach 33.3 g/L. The rheological analysis showed that the aqueous solution of WL had high viscosity, typical shearing-thinning behavior and great stability to high temperature, a wide range of pH (1 to 14), and high salinity. WL was composed principally of carbohydrate with 6.52% O-acyl groups. The carbohydrate portion of WL contained about 13% glucuronic acid and some neutral sugars including mannose, glucose and rhamnose in the molar ratio of 1:2.28:2.12. Partial acid hydrolysis of WL produced a new oligosaccharide WL-1. Structural resolution revealed that WL-1 consisted of α-L-Rha-(1→4)-ß-L-Rha-(1→4)-ß-D-Glc-(1→3)-α-D-Glc with ß-D-Man substituent at the third glucose residue and carboxyl and O-acyl groups. These findings will broaden the applications of this novel sphingan in food, ink, oil and other industries.

Draft Genome Sequence of Sphingomonas sp. WG, a Welan Gum-Producing Strain.

We report the draft genome sequence of Sphingomonas sp. WG, a high welan gum-producing strain with a yield of 33 g/L. The core of wel cluster for welan gum biosynthesis contained 24 coding sequences in the genome, which will provide the genetic information on welan gum production.

Elevated follicular helper T cells and expression of IL-21 in thyroid tissues are involved in the pathogenesis of Graves' disease.

The follicular helper T cell (Tfh) and IL-21 have been shown to play an important role in many autoimmune diseases. However, less is known about their role in Graves' disease (GD). This study aimed to investigate the expression of Tfhs and related factors (IL-21, IL-21R, CXCR5, and CXCL13) in GD thyroid tissues and to explore the effect of IL-21 on thyroid follicular cells (TFCs). The expression of Tfh-related factors in GD and normal thyroid tissues was validated using immunohistochemistry, real-time polymerase chain reaction and Western blotting. Confocal microscopy confirmed the presence of Tfh and IL-21R on CD4(+)T-/CD19(+)B cell in GD thyroid tissues. Furthermore, the effect of IL-21 on cAMP production in TFCs upon thyroid-stimulating antibody (TSAb) stimulation was also examined by an in vitro bioassay. The increased expression of Tfh-related factors was observed in GD thyroid tissues compared to control subjects. Confocal microscopy further confirmed the presence of Tfhs and the expression of IL-21R on CD4(+)T cells and CD19(+)B cells in GD thyroid tissues. Moreover, the expression of IL-21mRNA in GD thyroid tissues was correlated with the levels of thyroid autoantibodies. Additionally, IL-21 could indirectly promote cAMP production upon TSAb stimulation in TFCs when cooperating with lymphocytes, and GD TFCs were more sensitive to IL-21 stimulation than normal TFCs. There is increased expression of Tfhs and related factors (IL-21, IL-21R, CXCR5, and CXCL13) in GD thyroid tissues, and the expression of IL-21mRNA in GD thyroid tissues was found to correlate with the serum levels of thyroid autoantibodies and thyroid hormones. Moreover, IL-21 could indirectly enhance the biological activity of TFCs upon TSAb stimulation when cooperating with lymphocytes in vitro, particularly in GD TFCs, suggesting that Tfh and IL-21 might be involved in the pathogenesis of GD.

Interleukin-21 is associated with disease activity in patients with Graves' disease.

Graves' disease (GD) is a common autoimmune disease mainly caused by thyroid-stimulating antibodies (TSAbs). Interleukin 21 (IL-21) has recently been reported to play a vital role in the production of pathogenic autoantibodies in several autoimmune diseases, but less is known about GD. This study aimed to investigate the serum levels of IL-21 in GD patients and to explore their association with disease activity. We performed a case-control association study of 152 patients with GD and 32 healthy controls. All patients were further classified into three subgroups: the GD-untreated group (n = 70), the GD-recurrence group (n = 41), and the GD-remission group (n = 41). Serum IL-21 levels were assayed with ELISA. TSAb activity was measured by an in vitro bioassay. Changes in serum IL-21 were also observed in 12 GD patients before and after treatment. Additionally, correlations among the serum IL-21 and free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), thyrotropin receptor antibody (TRAb), and TSAb were also analyzed. The serum IL-21 levels in all GD patients were significantly higher than those in the control group (P < 0.001), and specifically, both the GD-untreated and GD-recurrence groups had elevated serum IL-21 compared to the control group (P < 0.001). Moreover, serum IL-21 in newly diagnosed patients markedly decreased after treatment (P < 0.001). Additionally, the serum IL-21 levels in GD-goiter patients were higher than those of the GD-non-goiter patients (P < 0.001). However, no significant differences were found in the serum IL-21 levels in patients with or without Graves' ophthalmopathy. Importantly, serum IL-21 positively correlated with FT3, FT4, TPOAb, TGAb, and TRAb (r = 0.5053, r = 0.3266, r = 0.1792, r = 0.2445, and r = 0.4096, respectively; all P < 0.0001), and particularly with TSAb activity (r = 0.8171, P < 0.0001), negatively correlated with TSH (r = -0.2713, P < 0.0001). Serum IL-21 levels were significantly elevated in patients with GD and decreased after treatment; moreover, IL-21 may be associated with the clinical disease activity. These observations suggest that IL-21 may play an important role in the pathogenesis of GD.

Role of site-specific DNA demethylation in TNFα-induced MMP9 expression in keratinocytes.

Inappropriately high expression of matrix metalloproteinase 9 (MMP9) in the late stage of diabetic foot ulcers suppresses wound healing. The underlying mechanisms are not completely understood. Site-specific demethylation was reported to function in the regulation of genes, causing persistent high expression of target genes. Therefore, this study was designed to determine whether site-specific DNA demethylation was a key regulatory component of MMP9 expression in diabetic wound healing, and to further verify the crucial CpG site(s). Human keratinocyte cell line (HaCaT) cells were exposed to tumor necrosis factor a (TNFα), and changes in MMP9 expression and DNA methylation status were detected. We found TNFα treatment increased endogenous MMP9 expression in HaCaT cells and decreased the DNA methylation percentage at the -36 bp promoter site in a time-dependent manner. Bisulfite sequencing PCR revealed differentially demethylated CpG sites in the human MMP9 promoter region, but only the change at the -36 bp site was statistically significant. Dual-luciferase reporter assays showed that the promoter with only the -36 bp site demethylated had slightly higher transcriptional activity than the promoter with all other sites except the -36 bp site demethylated. Our results demonstrate that site-specific DNA demethylation plays an important role in MMP9 expression in TNFα-stimulated keratinocytes. The -36 bp site in the MMP9 gene promoter is crucial to this effect, but other CpG sites may exert synergistic effects. Collectively, these data may contribute to the future development of novel therapeutic strategies to treat diabetic foot ulcers and prevent gangrene and amputation.