Association between atherogenic index of plasma and gestational diabetes mellitus: a prospective cohort study based on the Korean population.

BACKGROUND: Atherogenic index of plasma (AIP) is a non-traditional lipid parameter that can reflect the burden of atherosclerosis. A lipid profile resembling atherosclerosis emerged during pregnancy. Although lipid metabolism is pivotal in diabetes pathogenesis, there is no evidence linking AIP to gestational diabetes mellitus (GDM). Therefore, our objective was to explore the relationship between AIP and GDM and assess AIP's predictive capability for GDM. METHODS: This was a secondary analysis based on data from a prospective cohort study in Korea involving 585 single pregnant women. AIP was calculated as log10 (TG/HDL). We examined the relationship between AIP and GDM using logistic regression models, curve fitting, sensitivity analyses, and subgroup analyses. Receiver operating characteristic (ROC) analysis was also used to determine the ability of AIP to predict GDM. RESULTS: The average age of the participants was 32.06 ± 3.76 years. The AIP was 0.24 ± 0.20 on average. The GDM incidence was 6.15%. After adjustment for potentially confounding variables, AIP showed a positive linear relationship with GDM (P for non-linearity: 0.801, OR 1.58, 95% CI 1.27-1.97). The robustness of the connection between AIP and GDM was demonstrated by sensitivity analyses and subgroup analyses. An area under the ROC curve of 0.7879 (95% CI 0.7087-0.8671) indicates that AIP is an excellent predictor of GDM. With a specificity of 75.41% and sensitivity of 72.22%, the ideal AIP cut-off value for identifying GDM was 0.3557. CONCLUSIONS: This study revealed that the AIP at 10-14 weeks of gestation was independently and positively correlated with GDM risk. AIP could serve as an early screening and monitoring tool for pregnant women at high risk of GDM, thereby optimizing GDM prevention strategies. TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT02276144.

Flavokawain B Weakens Gastric Cancer Progression via the TGF-ß1/SMAD4 Pathway and Attenuates M2 Macrophage Polarization.

This study was designed to observe the treatment effects of flavokawain B (FKB) on gastric cancer both in SGC-7901 cells and nude mice. When SGC-7901 cells were exposed to 10 µg/mL FKB, cellular proliferative and apoptotic capacities and cell cycle were detected utilizing CCK-8 and flow cytometry assays. The results showed that FKB treatment induced cell apoptosis and G2/M arrest and suppressed cell proliferation for SGC-7901 cells. Western blot results showed that FKB upregulated proapoptotic proteins as well as downregulated antiapoptotic and cell cycle-related proteins in SGC-7901 cells. SMAD4, TGF-ß1, and TSPAN12 proteins were tested in FKB-induced SGC-7901 cells. Following exposure to FKB, SMAD4, TGF-ß1, and TSPAN12 expression was augmented in SGC-7901 cells. si-SMAD4 transfection weakened cell apoptosis and accelerated cell proliferation. Furthermore, FKB reversed the change in apoptotic and cell cycle-related proteins induced by si-SMAD4. A nude mouse tumorigenesis model was constructed, which was treated by FKB. In the nude mouse tumorigenesis model, FKB activated the TSPAN12 expression and TGF-ß1/SMAD4 pathway. Also, FKB treatment prolonged the survival time of nude mice and lowered tumor weight. iNOS and CD86 expression was significantly enhanced, and Arg-1 and CD206 expression was significantly decreased in THP-1 cells cultured in conditioned media from FKB-treated SGC-7901 cells. Additionally, FKB-treated SGC-7901 cells weakened macrophage migration. Collectively, this evidence suggested that FKB accelerated apoptosis and suppressed the proliferation of gastric cancer cells and attenuated M2 macrophage polarization, thereby exerting an anticancer effect on gastric cancer.

Role of kinesin family member 14 in disease monitoring and prognosis in patients with gastrointestinal cancer.

Kinesin family member 14 (KIF14) is not only involved in numerous essential biological activities, such as cytokinesis and myelination, but also regulates several malignant behaviors and progression of cancer. However, its role in gastrointestinal cancer is rarely reported. Therefore, the present study aimed to investigate the association of KIF14 expression with disease-free survival (DFS) and overall survival (OS) times in patients with gastrointestinal cancer. A total of 101 patients with gastrointestinal cancer (36 patients with gastric cancer and 65 patients with colorectal cancer) were retrospectively reviewed, and their cancer samples were collected to detect the protein and mRNA expression levels of KIF14 using immunohistochemistry and reverse transcription-quantitative PCR, respectively. KIF14 protein expression was increased in cancer tissues compared with adjacent tissues (all P<0.001). The protein expression levels of KIF14 were positively associated with T stage (P<0.001), distant metastases (P=0.007) and TNM stage (P<0.001), while KIF14 mRNA expression was positively associated with T stage (P<0.001), lymph node metastasis (P=0.004), distant metastases (P=0.001) and TNM stage (P<0.001). High protein and mRNA expression levels of KIF14 were associated with worse DFS (P<0.001) and OS (P=0.016) times. In addition, high KIF14 protein expression independently predicted unfavorable DFS times (P=0.007). Subgroup analysis revealed that in patients with gastric cancer, KIF14 expression was associated with DFS and OS times, while in patients with colorectal cancer, KIF14 expression was only associated with DFS time, but not with OS time. In conclusion, KIF14 expression was not only associated with advanced pathological differentiation and TNM stage but was also associated with poor survival time in patients with gastrointestinal cancer. These results indicate the potential of KIF14 as a biomarker for gastrointestinal cancer prognosis.

miR-1247-5p functions as a tumor suppressor in human hepatocellular carcinoma by targeting Wnt3.

Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR­1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis in vitro, and suppressed the growth of transplanted tumors in vivo. Wnt3 was found to be a potential target of miR-1247-5p and overexpression of miR-1247-5p was able to significantly downregulate the expression of Wnt3 by directly targeting the 3'UTR of this gene, which was verified by luciferase reporter assay and western blotting. Furthermore, we found that the miR-1247-5p gene was hypermethylated in HepG2 cells, and the transcript of miR-1247-5p was increased significantly after treatment with the demethylation drug 5-azacytidine. These findings demonstrated that miR-1247-5p functions as a tumor suppressor in human HCC by targeting Wnt3 and that the expression of miR-1247-5p can be regulated by DNA methylation, which indicates that miR-1247-5p has the potential to be a therapeutic target as well as a diagnostic marker of HCC.

[Construction of miR-508-5P lentiviral vector and its targeted effect on S-phase kinase-associated protein-2 gene].

OBJECTIVE: To construct a lentiviral vector overexpressing miR-508-5p and verify its targeted regulating effect on S-phase kinase-associated protein-2 (SKP2) gene. METHODS: The stem-loop structure RNA of miR-508-5p was obtained by chemical synthesis and cloned into the linearized pSicoR plasmid. The positive recombinants, which had been identified by restriction enzyme digestion and DNA sequencing method, were transfected into HEK293T cells. Meanwhile, the potential target gene of SKP2-3'UTR, which was complementary with miR-508-5p, was obtained and cloned into the linearized pMIR-Report plasmid. The targeted effect of miR-508-5p on SKP2 gene was verified by the relative luciferase activity measurement, Western blotting and real-time PCR. RESULTS: The PCR, restriction enzyme digestion and DNA sequencing analysis demonstrated that the recombinant plasmids of pSicoR-miR-508-5p and pMIR-Report-SKP2 3'-UTR were constructed successfully. And it was showed that over-expression of miR-508-5p suppressed the mRNA and protein expression level of SKP2 significantly (P<0.05); and suppression of miR-508-5p expression increased the mRNA and protein expression level of SKP2 significantly (P<0.05). CONCLUSION: We have successfully constructed the lentiviral vector containing miR-508-5p gene. MiR-508-5p can suppress SKP2 gene expression by targeting the specific sequence of SKP2-3'UTR.