Int J Med Sci
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Type 2 diabetes mellitus (T2DM) is associated with chronic inflammation, suggesting the metabolic abnormalities are originated from or exacerbated by cytokine overproduction. Cytokines and counter-regulatory molecules are crucial in keeping the balance of immune responses and, therefore, are potential candidates involved in T2DM etiology, development and complications. Our previous reports identify several significant associations between the genotypes of cytokine genes and T2DM and/or the clinical lipid parameters, which strongly suggest the participation of immune-regulatory molecules in lipid metabolism. ⋯ Intriguingly, CTLA-4 -318 genotype was associated with circulatory triglycerides in T2DM subjects (P=0.019) although no significant association between CTLA-4 -318 (P=0.119) and +49 (P=0.2) genotypes with T2DM was identified. In addition, CTLA-4 +49 genotype was significantly associated with the ratio between total cholesterol and high-density lipoprotein (P=0.004) in control subjects. Our results suggest that CTLA-4 may be involved in lipid metabolism and affect T2DM disease progression and/or the development of diabetic complications although this gene does not represent a major risk factor for T2DM.
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Objectives: To provide insight into the biological effects of activated Yes-associated protein (YAP) on the proliferation, apoptosis, and senescence of human periodontal ligament stem cells (h-PDLSCs). Methods: h-PDLSCs were isolated by the limiting dilution method, and their surface markers were quantified by flow cytometry. Enhanced green fluorescence protein (EGFP)-labeled lentiviral vector was used to activate YAP in h-PDLSCs, then qRT-PCR and Western blotting were used to evaluate the expression level of YAP. ⋯ When YAP was overexpressed in h-PDLSCs, proliferation activity was improved; early and late apoptosis rates decreased (P<0.05); the proportion of cells in G2/M phases increased (P<0.05), while that in G0/G1 phase decreased (P<0.05); cellular senescence was delayed (P<0.01); the expression of P-MEK, P-ERK, P-P90RSK and P-Msk increased, while the expression of Bcl-2 family members (Bak, Bid and Bik) decreased. Conclusions: Activated YAP promotes proliferation, inhibits apoptosis, and delays senescence of h-PDLSCs. The Hippo-YAP signaling pathway can influence ERK and Bcl-2 signaling pathways.
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Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer mortality worldwide. AURKA (aurora kinase A) is a mitotic serine/threonine kinase that functions as an oncogene and plays a critical role in hepatocarcinogenesis. We report on the association between 4 single nucleotide polymorphisms (SNPs) of the AURKA gene (rs1047972, rs2273535, rs2064836, and rs6024836) and HCC susceptibility as well as clinical outcomes in 312 patients with HCC and in 624 cancer-free controls. ⋯ Moreover, carriers of at least one A allele in rs2273535 were less likely to progress to stage III/IV disease, develop large tumors or be classified into Child-Pugh class B or C. Individuals with at least one G allele at AURKA SNP rs2064863 were at lower risk of developing large tumors or progressing to Child-Pugh grade B or C. Our results indicate that genetic variations in the AURKA gene may serve as an important predictor of early-stage HCC and be a reliable biomarker for the development of HCC.
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Background: α-Mangostin (αMG) is extracted from Garcinia mangostana Linn and exerts antiproliferative activities. Although several researches on αMG were performed using cell monolayers, the in vitro pharmacological effects on 3D cancer models have never been investigated. Aim of the present study was to find new anticancer properties of αMG by evaluating the changes that this compound provokes in multicellular tumour spheroids (MCTSs). ⋯ Finally, doses higher than 5 μg/ml caused a progressive impairment in cell migration from the edge of MDA-MB-231 MCTSs. Conclusion: After exposure at doses of αMG just above IC50, MDA-MB-231 spheroids showed a significant reduction in cell adhesion that did not stimulate cell migration but, on the contrary, blunted cell motility. These findings suggest a novel anticancer feature of αMG that could be taken into consideration to improve conventional drug penetration into the tumour bulk.
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Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. ⋯ The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.