No Genetic Causality between Tobacco Smoking and Venous Thromboembolism: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Given the current debate in clinical research about the relationship between tobacco smoking and the risk of venous thromboembolism (VTE), a Mendelian randomization (MR) study was conducted aimed at elucidating the causal associations of current and past tobacco smoking with the risk of VTE, from the perspective of genetics. METHODS: Two-sample univariate and multivariable MR analyses were designed, using summary-level data from large genome-wide association studies involving European individuals. Causality was primarily assessed using multiplicative fixed-effects or random-effects model and inverse variance weighting, supplemented by MR-Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out for sensitivity analysis to test the reliability of the results. RESULTS: In the univariate MR analysis, no significant causal effects were found between current tobacco smoking and the risk of VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE). Similarly, no significant causal effects were found between past smoking and VTE, DVT, and PE. As for the multivariable MR analysis, results were consistent with univariate MR analysis, with no significant causal effect of either current or past tobacco smoking on the risk of VTE, DVT, and PE. CONCLUSION: Evidence from both univariate and multivariable MR analyses demonstrated no significant causal relationships between current and past tobacco smoking and VTE, DVT, and PE. This contradicts positive correlations reported in some previous observational studies, which may be explained by other confounding factors. This provided genetic evidence for the conclusion reported in other observational studies that smoking did not affect VTE risk.

Expression of Vimentin and Ki-67 Proteins in Cervical Squamous Cell Carcinoma and their Relationships with Clinicopathological Features.

OBJECTIVES: To investigate the expression of vimentin and Ki-67 proteins in cervical squamous cell carcinoma (CSCC) and their relationships with patient clinicopathological features. MATERIALS AND METHODS: Fifty-seven CSCC samples archived in Department of Pathology in the First Affiliated Hospital of Wenzhou Medical University were selected. The expression of vimentin and Ki-67 proteins in CSCC tissue were detected using immunohistochemical SP method, and correlations between them and their relationships with clinicopathological features were analyzed. RESULTS: Among 57 CSCC tissues, there were 43 with positive expression of Vimentin, and the positive rate was 75.4%; there were 57 cases with positive expression of Ki-67, and the positive rate came up to 100.0%. The results of Pearson correlation analysis displayed that the expression of vimentin had a significantly-positive correlation with Ki-67 in CSCC tissue (r=0.984, co0.000). The expression of both Ki-67 and vimentin was intimately associated with the presence or absence of local invasion and lymph node metastasis as well as differentiated degrees of the tumor (P=0.003, 0.017, 0.000; P=0.001, 0.008, 0.003) instead of the age, tumor size and clinical staging (P>0.05). CONCLUSIONS: Epithelial-mesenchymal transition (EMT) tends to appear in poorly-differentiated CSCC tissue, and the up-regulation of vimentin expression is accompanied by high expression of Ki-67, suggesting that invasion and metastasis readily occur in these tumor cells.

miR-34a inhibits migration and invasion of tongue squamous cell carcinoma via targeting MMP9 and MMP14.

BACKGROUND: miR-34a is an important tumor suppressor gene in various cancer types. But little is known about the dysregulation of miR-34a in tongue squamous cell carcinoma (TSCC). In this study, we investigate the expression and potential role of miR-34a in TSCC. METHODS: We evaluated miR-34a expression and its relationship with clinicopathological characters in 75 pairs of TSCC samples, and confirmed the role of miR-34a for predicting lymph node metastases from a further 15 pairs of paraffin-embedded TSCC specimens with stringent clinicopathological recruitment criteria using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of miR-34a on cell proliferation, migration and invasion were examined in TSCC cell lines using Cell Counting Kit-8 assay, wound healing assay and transwell assay, respectively. The effects of miR-34a on the expression of matrix metalloproteinase (MMP) 9 and 14 were detected by luciferase reporter assays and Western blot analysis. The expression of miR-34a, MMP9 and MMP14 were also confirmed in TSCC samples by in situ hybridization and immunohistochemistry. RESULTS: miR-34a expression in tumor tissues from TSCC patients with positive lymph node metastases was significantly lower than that with negative lymph node metastases. Overexpression of miR-34a significantly suppressed migration and invasion in TSCC cells and simultaneously inhibited the expression of MMP9 and MMP14 through targeting the coding region and the 3'untranslated region, respectively. Moreover, miR-34a expression in TSCC was inversely correlated with protein expression of MMP9 and MMP14 in the TSCC samples. CONCLUSIONS: miR-34a plays an important role in lymph node metastases of TSCC through targeting MMP9 and MMP14 and may have potential applications in prognosis prediction and gene therapy for lymph node metastases of TSCC patients.

miR-29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through PTEN-AKT signaling pathway by targeting Sp1.

OBJECTIVES: miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression. MATERIALS AND METHODS: The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures. RESULTS: miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens. CONCLUSION: miR-29b functions as a tumor suppressor in TSCC, and the miR-29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention.

[Effect of recombinant human S100A8 on the proliferation and migration of periodontal ligament cells].

OBJECTIVE: To investigate the effect of S100A8 on the proliferation and migration of periodontal ligament cells (PDLCs), and to learn the role of S100A8 in the development of periodontitis. METHODS: PDLCs were treated with S100A8 in vitro before MTT and flow cytometry assays were performed. Transwell assay and wound assay were conducted to test the migratory activity of the PDLCs as well. RESULTS: In the study, 10⁻7-10⁻5 mol/L recombined human S100A8 suppressed the proliferation of the PDLCs, while their proliferation was significantly inhibited with 10⁻5 mol/L S100A8 treatment for 48 h. And 10⁻9-10⁻7 mol/L S100A8 enhanced the migratory activity of the PDLCs while the effect of 10⁻9 mol/L S100A8 was statistically significant. CONCLUSION: Increased level of S100A8 in periodontitis could lead to the inhibition of cell proliferation and apoptosis of PDLCs, but S100A8 could promote the migration of PDLCs when its concentration decreased after treatment.

Central giant cell granuloma of the jaws: clinical and radiological evaluation of 22 cases.

OBJECTIVE: The objective was to investigate the clinical and radiological characteristics of central giant cell granulomas (CGCGs) of the jaws. METHODS: A retrospective analysis of a 20-year database was performed regarding both clinical and radiological features of 22 patients affected with CGCGs of the jaws. RESULTS: Fourteen women and 8 men were included with the age range of 7-81 years (mean 31.7 years). Among the 22 lesions, 16 were located in the mandible and 6 in the maxilla. Painless swelling was the most common clinical feature in 18 of all cases. Limited mouth opening was noted in 2 patients where the lesions involved the condyle. Radiographically, 13 lesions were homogeneously osteolytic and 9 lesions were trabeculated. Fifteen lesions were unilocular and 14 lesions presented with well-defined but not sclerotic margins. CT images in 5 patients clearly showed the trabeculation within the lesions. The follow-up ranged from 1.5 to 11 years with a mean period of 5 years. Three out of 9 aggressive and 1 out of 13 nonaggressive lesions developed recurrence. CONCLUSIONS: Diagnosis of CGCGs of the jaws depends on both correct interpretation of clinical, radiographic and pathological data. Differentiation between aggressive and nonaggressive CGCGs should be considered to improve individual treatment planning.