Intercellular Interactions Mediated by HGF And TGF-Β Promote the 3D Spherical and Xenograft Growth of Liver Cancer Cells.

BACKGROUND: Recently, the importance of the interactions between liver cancer cells and fibroblasts has been increasingly recognized; however, many details remain to be explored. METHODS: In this work, we first studied their intercellular interactions using conditioned medium from mouse embryonic fibroblasts (MEFs), then through a previously established coculture model. RESULTS: Culturing in a conditioned medium from MEFs could significantly increase the growth, migration, and invasion of liver cancer cells. The coculture model further demonstrated that a positive feedback loop was formed between transforming growth factor-ß (TGF-ß) from HepG2 cells and mHGF (mouse hepatocyte growth factor) from MEFs during coculture. In this feedback loop, c-Met expression in HepG2 cells was significantly increased, and its downstream signaling pathways, such as Src/FAK, PI3K/AKT, and RAF/MEK/ERK, were activated. Moreover, the proportion of activated MEFs was also increased. More importantly, the growth-promoting effects caused by the interaction of these two cell types were validated in vitro by a 3D spheroid growth assay and in vivo by a xenograft mouse model. CONCLUSION: Collectively, these findings provide valuable insights into the interactions between fibroblasts and liver cancer cells, which may have therapeutic implications for the treatment of liver cancer.

Diagnostic Value of Serum DNASE1L3 in Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Deoxyribonuclease 1-like 3 (DNASE1L3) is an endonuclease associated with many autoimmune diseases and tumors. However, the serum DNASE1L3 level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unreported. Thus, this study compared the diagnostic value of DNASE1L3 and alpha-feto-protein (AFP) individually and in combination in HBV-related HCC. METHODS: The study population consisted of 88 patients with HBV-related HCC, 80 patients with HBV-related liver cirrhosis (LC) and 88 control subjects. The serum DNASE1L3 levels were measured using an enzyme-linked immunosorbent assay. The serum AFP was also assayed. RESULTS: Our data showed that the serum DNASE1L3 levels were significantly higher in patients with HBV-related HCC than in the healthy controls and patients with LC. When the two biomarkers were analyzed individually, the receiver operating characteristic curve analysis showed that the areas under the curve of DNASE1L3 and AFP were 0.898 and 0.866, respectively. When DNASE1L3 and AFP were combined, the area under the curve was 0.951. The sensitivities of DNASE1L3 and AFP were 72.73% and 74.81%, respectively, and the specificities were 93.18% and 92.05%, respectively, in the diagnosis of HBV-related HCC. The sensitivity of the two combined could be improved to 89.77%. However, no correlation was found between serum DNASE1L3 and AFP in HBV-related HCC patients (r = 0.005, p = 0.734). CONCLUSIONS: Serum DNASE1L3 has high sensitivity and specificity in the diagnosis of HCC. DNASE1L3 combined with AFP has higher sensitivity and can improve the diagnostic efficiency of HBV-related HCC.

Serum Deoxyribonuclease 1-like 3 is a potential biomarker for diagnosis of ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease with high disability rate, and it is sometimes difficult to distinguish from generalized osteoarthritis (GOA). Deoxyribonuclease 1-like 3 (DNASE1L3) was associated with a variety of autoimmune diseases. However, the serum DNASE1L3 level in AS and GOA remain unreported. Herein, this study was designed to gauge serum DNASE1L3 level in patients with AS and GOA, and to discern the utility of serum DNASE1L3 as a biomarker for assessing the severity of patients with AS. METHODS: The study population consisted of 60 patients with AS, 60 patients with GOA and 60 control subjects. Serum DNASE1L3 levels were measured using enzyme-linked immunosorbent assay (ELISA) assay. Disease activity were assessed with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS patients. RESULTS: Our data showed that serum DNASE1L3 levels were significantly higher in patients with AS than that of the healthy controls and patients with GOA. Serum DNASE1L3 levels in patients with AS were positively correlated with BASDAI scores, C3 and C-reactive protein (CRP). Furthermore, serum DNASE1L3 showed higher discriminatory accuracy in the diagnosis of AS from GOA (AUC = 0.851, sensitivity = 78.33% and specificity = 81.67%). CONCLUSIONS: Elevated Serum DNASE1L3 levels in patients with AS were significantly associated with the clinic features and disease activity. DNASE1L3 could be a serum biomarker with a positive diagnostic value in patients with AS, and which could be used as a differential diagnostic indicator for GOA and AS.

Serum Amyloid A is a Novel Inflammatory Biomarker in Polycystic Ovary Syndrome.

BACKGROUND: Serum amyloid A (SAA) is considered a biomarker of inflammation; however, the SAA levels in polycystic ovary syndrome (PCOS) are still uncertain. METHODS: In this study, SAA, glucose, insulin, C-reactive protein (CRP), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone concentrations were measured in 82 women with PCOS and 60 healthy controls. RESULTS: The median concentration of SAA was 5.000 mg/L (IQR: 2.825 - 5.400) in women with PCOS, which was significantly higher than that of controls (3.700 mg/L, IQR: 2.825 - 5.400, p = 0.025). SAA was only positively associated with the CRP (r = 0.303, p = 0.006). No significant association was observed between SAA and body mass index (BMI), total testosterone, or insulin resistance (IR). CONCLUSIONS: SAA levels were increased in women with PCOS, and SAA may be a potential inflammatory biomarker for PCOS.

Decreased Serum Kruppel-Like Factor 7 Level is Positively Associated with Low-Density Lipoprotein Cholesterol Level in Women with Polycystic Ovary Syndrome.

BACKGROUND: Kruppel-like factor 7 (KLF7) is associated with type 2 diabetes and obesity; however, at present the KLF7 level in polycystic ovary syndrome (PCOS) remains unreported. METHODS: In this study, serum KLF7, glucose, insulin, C-reactive protein (CRP), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone concentrations were measured in 65 women with PCOS and 61 healthy controls. RESULTS: Body mass index (BMI) in PCOS and the control group were all < 25 kg/m2. The median concentration of KLF7 was 3.630 ng/mL [interquartile range (IQR): 1.547 - 7.172] in women with PCOS, which was significantly lower than that of controls (5.282 ng/mL, IQR: 3.128 - 11.263, p = 0.003). The KLF7 level was positively correlated with low-density lipoprotein cholesterol (LDL-C) (r = 0.261, p = 0.018). No significant association was observed between KLF7 and the BMI, total testosterone, and insulin resistance (IR). CONCLUSIONS: The KLF7 level decreased in women with PCOS. KLF7 may represent a new therapeutic target in the treatment of PCOS.