A novel mutation in the FGG gene causes hypofibrinogenemia in a Chinese family.

Congenital fibrinogen disorders are a group of coagulation deficiencies caused by fibrinogen defects and are divided into four types, including afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. In this study, we collected a family with hypofibrinogenemia, and genetics analysis identify a novel pathogenic variants (c.668G > C, p.Arg223Thr) in the FGG gene. And electron microscope observation revealed significant changes in the ultrastructure of fibrin of the proband. Our research expands the phenotypic and genetic spectrum associated with the FGG gene, which would facilitate in genetic counselling and prenatal genetic diagnosis.

Inhibition of miR-155, a therapeutic target for breast cancer, prevented in cancer stem cell formation.

BACKGROUND: Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. METHODS: The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR. The invasive cell line MDA-MB-231 was used to quantify the expression of miR-155 by tumor-sphere forming experiment. Soft agar colony formation assay and tumor xenografts was used to explore whether the inhibition of miR-155 could reduce proliferation of cancer cells in vivo and vitro. RESULTS: In the study, we found miR-155 was upregulated in BC. Soft agar colony formation assay and tumor xenografts showed inhibition of miR-155 could significantly reduce proliferation of cancer cells in vivo and vitro, which confirmed that miR-155 is an effective therapeutic target of breast cancer. Sphere-forming experiment showed that overexpression of miR-155 significantly correlated with stem-like properties. Expressions of ABCG2, CD44 and CD90 were repressed by inhibition of miR-155, but CD24 was promoted. Interestingly, inhibition of miR-155 rendered MDA-MB-231 cells more sensitive to Doxorubicinol, which resulted in an increase of inhibition rate from 20.23% to 68.72%. Expression of miR-155 not only was a therapeutic target but also was associated with cancer stem cell formation and Doxorubicinol sensitivity. CONCLUSIONS: Our results underscore the importance of miR-155 as a therapeutic target and combination of Doxorubicinol and miR-155-silencing would be a potential way to cure breast cancer.

Identification of circulating long non-coding RNA GAS5 as a potential biomarker for non-small cell lung cancer diagnosisnon-small cell lung cancer, long non-coding RNA, plasma, GAS5, biomarker.

Non-small cell lung cancer (NSCLC) is one of the most malignant cancers in the world. Early diagnosis of NSCLC has become especially important for patient treatment and prognosis. Increasing evidence suggest that long non-coding RNA GAS5 plays vital roles in cancer proliferation and differentiation in NSCLC. However, its clinical value in the diagnosis of NSCLC is unclear. The objective of this study was to evaluate the importance of circulating GAS5 as a biomarker for NSCLC diagnosis. In our study, quantitative real-time PCR (QRT-PCR) was applied to detect the GAS5 expression level in 80 pairs of cancer tissues and 57 pairs of plasma samples of NSCLC patients. Further analysis was performed to study the differential expression of circulating GAS5 in 111 NSCLC patients and 78 healthy controls in our study. The results showed that GAS5 decreased in NSCLC tissues compared to noncancerous tissues (P<0.001). Furthermore, the GAS5 expression level was statistically declined in early stage of NSCLC before surgery compared with healthy controls (P<0.05) and sharply increased in postoperative groups (P=0.026). ROC curve analysis for early stage of NSCLC with the combination of GAS5, CEA and CA199 showed that the area under the ROC curve (AUC) was 0.734 (95% CI, 0.628­0.839; P<0.0005). In conclusion, circulating GAS5 could be functioned as a potential combined biomarker for screening NSCLC and patient monitoring after surgical treatment.

Plasma miR-92a-2 as a biomarker for small cell lung cancer.

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in the carcinogenesis and progression of cancers. Aberrant expression of miRNAs in tissue and plasma has been found in various solid tumors. Our research aims to determine whether the abnormal plasma miRNA expression patterns can be used as a predictive marker for the diagnosis and prognosis of small cell lung cancer (SCLC). Fifty SCLC patients and 30 healthy controls annotated with clinical characteristics and specific questionnaire survey for smoking history were available. Quantification of several miRNAs (miR-20a-5p, miR-92a-2-5p and miR-17-5p) was performed using quantitative real-time polymerase chain reaction (qRT-PCR), and results were analyzed using SPSS statistics 17.0. Plasma miR-92a-2 level was significantly higher in the SCLC patients group compared with healthy control (P< 0.0001), the receiver operating characteristic (ROC) curve analysis showed that the specificity and sensitivity were at 100% and 56% for diagnosis of SCLC, area under the ROC curve (AUC) was 0.761. No other statistically significant differences were found in the expression level of plasma miR-92a-2 among survival analysis in SCLC. Detection of miR-92a-2 levels in plasma could be a potential and noninvasive method for the diagnosis of SCLC.

Diagnostic Potential of Differentially Expressed Homer1 and Homer2 in Ischemic Stroke.

BACKGROUND: Ischemic stroke (IS) is an extremely heterogeneous disease with variable pathogenesis. Due to the lack of early diagnostic marker, the mortality rate of IS remains high worldwide. The family of Homer plays an important role in the pathology of atherosclerotic plaque. In this study, we have investigated its expression pattern and clinical significance in IS. METHODS: RT-qPCR was performed to detect the expression of Homer1, Homer2, and Homer3. RESULTS: We found that the mRNA levels of Homer1 (p<0.001) and Homer2 (p<0.001), but not Homer3, in large-artery atherosclerosis (LAA) strokes were significantly upregulated than those in non-LAA strokes and controls. Multinomial logistic regression analyses showed that, although none of the Homer was associated with non-LAA strokes, higher Homer1 (adjusted OR=1.337, 95% CI: 1.227-1.458) and Homer2 (adjusted OR=1.099, 95% CI: 1.062-1.138) levels showed significant associations with increased odds of having LAA stroke, compared with the controls. The receiver operating characteristic (ROC) curves showed that the combination of Homer1 and Homer2 had a better diagnostic accuracy to differentiate LAA strokes from non-LAA strokes and controls, and the sensitivity and specificity ratios were 80.5%/90.4% and 98.0%/70.3%, respectively. CONCLUSION: Our data suggested that Homer1 and Homer2 might be considered as novel diagnostic biomarkers for LAA stroke.

KAEMPFEROL, A FLAVONOID COMPOUND FROM GYNURA MEDICA INDUCED APOPTOSIS AND GROWTH INHIBITION IN MCF-7 BREAST CANCER CELL.

BACKGROUND: Kaempferol, a natural flavonoid, has been shown to induce cancer cell apoptosis and cell growth inhibition in several tumors. Previously we have conducted a full investigation on the chemical constituents of Gynura medica, kaempferol and its glycosides are the major constituents of G. medica. Here we investigated the growth inhibition and apoptosis induction effect of kaempferol extracted from G. medica. MATERIALS AND METHODS: The inhibition effects of kaempferol were evaluated by MTS assay and soft agar colony formation assay. Fluorescence staining and western blotting were be used to study the apoptosis. The structure was identified by 1H- NMR), 13C-NMR and ESI-MS analyses. RESULTS: Our results showed that kaempferol's inhibition of MCF-7 breast cancer cell growth may through inducing apoptosis and downregulation of Bcl2 expression. CONCLUSION: Kaempferol is a promising cancer preventive and therapeutic agent for breast cancer. List of non-standard abbreviations: MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, HPLC: High-performance liquid chromatography, NMR: Nuclear Magnetic Resonance, ESI-MS Electrospray Ionization Mass Spectral, PARP: Poly ADP-ribose polymerase.

[Effect of Auricularia auricula polysaccharide on PBMCs proliferation and cytokine expression in vitro].

OBJECTIVE: To investigate the proliferation and cytokine expression of Auricularia auricula polysaccharide (AAP) on peripheral blood monnuclear cells (PBMCs) in vitro. METHODS: AAP was obtained by water extraction and alcohol precipitation, and purified by DEAE-cellulose chromatogram. PBMCs were treated with AAP at different levels. The Cell Counting Kit-8 (CCK-8) was used to determine the proliferation of PBMCs. The concentration of TNF-alpha and TFN-gamma in supernatant were investigated by ELISA. RESULTS: The three fractions of AAP could stimulate PBMCs proliferation at the range of 100--800 microg/ml, and AAP2 enhanced significantly the level of TNF-alpha and IFN-gamma in supernatant of PBMCs (P < 0.05, P < 0.01). CONCLUSION: AAP is an immunomodulator and can enhance the immunomodulatory activity through TNF-alpha and TFN-gamma.