Role of FSCN1 in the tumor microenvironment of lung squamous cell carcinoma.

Tumor microenvironment (TME) regulated the development of the Lung squamous cell carcinoma (LUSC). To know more about the LUSC, this study tried to figure the role of fscin actin-bundling protein 1 (FSCN1) in the TME. We identified the FSCN1 as the hub immune gene in LUSC, with the use of weighted gene co-expression network analysis (WGCNA) and the Human Protein Atlas. Furthermore, we verified the higher expression of FSCN1 in LUSC compared with the normal tissues by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry. We then explored the associations among FSCN1, immune infiltrations, and inflammatory factors with the use of Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor IMmune Estimation Resource (TIMER). As a result, the expressions of FSCN1 was negatively related to the immune infiltrations, and positively related to the expressions of IL1A, IL1B, TGFB1 and TGFA. Moreover, we used the single-cell RNA-sequencing (scRNA-seq) data of LUSC to figure out the expressions level of FSCN1, IL1A, IL1B, TGFB1 and TGFA in the different cell type's of the TME. Finally, through the cytological experiments, we found that FSCN1 affected by TGFB1 contributes to the proliferation, anti-apoptotic effect, migration and invasion of the LUSC cells. In summary, this study Identified FSCN1 as the potential therapeutic target of LUSC, and reveals a complicated immune and inflammatory net in the TME.

Host defense against Salmonella and rotaviral gastroenteritis: a serial study of transcriptional factors and cytokines.

BACKGROUND AND PURPOSE: Common etiologies of acute enterocolitis in childhood include the intracellular pathogens Salmonella and rotavirus, along with extracellular pathogens. In order to elucidate differentiating immunologic parameters in patients with acute gastroenteritis of different etiologies, we investigated interferon (IFN)-gamma, interleukin (IL)-12, and T-bet of T-helper type 1 subsets, and IL-4 and GATA-3 of T-helper type 2 subsets. METHODS: From June 1, 2003 to December 31, 2003, 32 patients with acute gastroenteritis were enrolled. Sequential heparinized blood samples were obtained on the day of presentation (day 1) and on day 3 of hospitalization. Using reverse transcriptase-polymerase chain reaction, the mean ratios of IFN-gamma, T-bet and IL-12 mRNA levels relative to beta-actin were determined. RESULTS: Salmonella infections induced stronger IFN-gamma and T-bet responses than either rotavirus infection or other enterocolitis (p<0.05). However, poor IL-12 response in Salmonella infections implied failed T-helper type 1 immunity, and probably accounted for the prolonged clinical course. In contrast, by day 3 of hospitalization, most patients with rotavirus enterocolitis were symptom-free. CONCLUSIONS: IL-12 is the key factor in determining host response against and, hence, disease activity of Salmonella infections.

Daily urinary interleukin-11 excretion correlated with proteinuria in IgA nephropathy and lupus nephritis.

Interleukin-11 (IL-11) is a multifunctional cytokine with both thrombopoietic and anti-inflammatory effects. In an animal study IL-11 was shown to reduce proteinuria in mice with necrotizing glomerulonephritis. The purpose of this current study is to explore the role of IL-11 in human glomerulonephritis. Subjects of this study were patients with proteinuria (daily urine protein excretion >40 mg/m2 per hour) and underlying pathology of IgA nephropathy (IgAN) (n=20), lupus nephritis (LN) (n=40), and idiopathic nephrotic syndrome (INS) (n=68). Daily urinary IL-11 level was measured by enzyme-linked immunosorbent assay (ELISA). Correlation between urinary IL-11 and urinary protein was determined by Pearson's correlation coefficient. Another five patients with serial data of urinary protein, IL-11 and IL-11 messenger RNA (mRNA) expression in urine sediment are presented. The correlation between urinary IL-11 and daily urinary protein was significant for patients with IgAN (r=0.596, P=0.006) and LN (r=0.630, P<0.001), but not for patients with INS (r=0.030, P=0.812). Serial data revealed the same correlation. Furthermore, the peak of urinary IL-11 mRNA preceded that of urinary IL-11. We conclude that daily urinary IL-11 excretion is correlated with urinary protein loss in nephritis having local T helper (Th)1 predominant immune response, such as IgAN and LN. Local IL-11 production may serve as a counter cytokine against Th1-mediated inflammation.