[ZEB2 Regulates the Migration and Invasion of PANC-1 Pancreatic Cancer Cells: An Experimental Study].

Objective: To investigate the effects and mechanisms of zinc finger E-box binding homeobox transcription factor-2 ( ZEB2) on the proliferation, colony formation, migration, and invasion abilities and the epithelial-mesenchymal transition (EMT) of PANC-1 cells, a human pancreatic cancer cell line. Methods: Data on the expression of ZEB2 in pancreatic cancer tissues and paracancerous tissues from The Cancer Genome Atlas (TCGA) database were analyzed. PANC-1 pancreatic cancer cells were divided into si-NC group, si- ZEB2 group, pcDNA3.1 group, and pcDNA3.1- ZEB2 group. qRT-PCR and Western blot were conducted to confirm the effectiveness of ZEB2 knockdown or overexpression. CCK-8, colony formation, wound healing, and Transwell assays were conducted to examine the effects of ZEB2 on the proliferation, colony formation, migration, and invasion of PANC-1 cells. qRT-PCR and immunofluorescence assays were performed to examine the expression of E-cadherin and vimentin, the EMT markers, in the cells. Prediction of proteins interacting with ZEB2 was made through the STRING database. Results: TCGA database analysis showed that the expression level of ZEB2 in pancreatic cancer tissues was significantly higher than that in adjacent tissues ( P<0.05). Compared with those of cells in the control group, the proliferation, colony formation, migration, and invasion of cells in the si- ZEB2 group were decreased ( P<0.05). Compared with those of cells in the pcDNA3.1 group, the proliferation, colony formation, migration and invasion of cells in the pcDNA3.1- ZEB2 group were increased (all P<0.05). According to the results of qRT-PCR and immunofluorescence assays, compared with those of the si-NC group, the expression of E-cadherin mRNA, an epithelial marker, in the si- ZEB2 group increased, while the expression of vimentin mRNA, an mesenchymal marker, and the protein decreased. Compared with those of the pcDNA3.1 group, the expression of E-cadherin mRNA in the PANC-1 cells of the pcDNA3.1- ZEB2 group decreased, while the expression of vimentin mRNA and the protein increased (all P<0.05). Analysis with the STRING database predicted that 10 proteins had close interaction with ZEB2. Conclusion: Overexpression of ZEB2 promotes the migration, invasion, and the EMT process of PANC-1 pancreatic cancer cells.

tBHQ attenuates podocyte injury in diabetic nephropathy by inhibiting NADPH oxidase-derived ROS generation via the Nrf2/HO-1 signalling pathway.

Aims: Oxidative stress plays a crucial role in podocyte injury in diabetic nephropathy (DN). tert-Butylhydroquinone (tBHQ) is an activator of Nrf2 that exerts protective effects in diabetic mice, but the underlying mechanism of tBHQ in the podocytes of DN is not fully understood. Materials and methods: A high glucose (HG)-induced HK2 cell model and streptozotocin-induced rat model of DN were established and treated with tBHQ or apocynin. The expression levels of Nrf2, HO-1, NOX2 and NOX4 were determined by Western blot or immunohistochemical staining. The level of oxidative stress in podocytes or kidney tissues was assessed using DCFH-DA or dihydroethidium (DHE) staining. Cell injury was assessed by F-actin staining and flow cytometry analysis. Key findings: We showed that HG treatment increased the expressions of NOX2 and NOX4 and enhanced ROS production in podocytes. Inhibition of NADPH oxidase activity by apocynin dramatically attenuated HG-induced ROS production and further alleviated cell injury and apoptosis in podocytes. Moreover, we found that HG inhibited the Nrf2/HO-1 signalling pathway in podocytes; however, tBHQ treatment significantly activated the Nrf2 signalling pathway, inhibited NADPH oxidase activity, and attenuated ROS production and cell injury in HG-treated podocytes. Furthermore, we observed that tBHQ treatment partially attenuated renal injury, activated the Nrf2 signalling pathway, inhibited NADPH oxidase activity and reduced ROS generation in the kidneys of STZ-induced diabetic rats. Significance: These results suggest that tBHQ exerts a protective role in hyperglycaemia-induced podocyte injury, and that the potential protective mechanism of tBHQ involves inhibiting NADPH oxidase-derived ROS generation by activating the Nrf2/HO-1 signalling pathway.

High expression of disabled homolog 2-interacting protein contributes to tumor development and proliferation in cutaneous squamous cell carcinoma.

BACKGROUND: Disabled homolog 2-interacting protein (DAB2IP), a Ras GTPase-activating protein, is downregulated in several cancers. Its depletion is involved in tumor cell proliferation, apoptosis, and metastasis, as well as epithelial-mesenchymal transition. The present study aimed to explore the potential role of DAB2IP in cutaneous squamous cell carcinoma (cSCC) and provide a theoretical basis for the diagnosis and targeted therapy of cSCC. METHODS: The clinicopathological features of DAB2IP expression in cSCC were analyzed by immunohistochemistry, and the effects of DAB2IP on SCL-1 cell behavior were determined via genetic interference in vitro. SCL-1 cell lines that exhibited reduced expression of DAB2IP and a scrambled shRNA control were constructed using a lentivirus vector-based shRNA technique. RNA extraction, reverse transcription-quantitative PCR (RT-qPCR), MTT assay, colony formation test, cell cycle analysis, apoptosis test, transwell assay, wound-healing assay, in vitro invasive assay were used in this study. RESULTS: The immunohistochemical results demonstrated that the expression of DAB2IP was higher in cSCC tissues than in soft fibroma. The level of DAB2IP expression was associated with the degree of malignancy and the depth of tumor infiltration; however, it had no association with patients' sex, tumor size, location, or phenotype. The results of the MTT, cell cycle, apoptosis, and invasion experiments demonstrated that knockdown of DAB2IP inhibited the viability and invasion of SCL-1 cells in vitro. CONCLUSIONS: High expression of DAB2IP may contribute to the development and proliferation of cSCC.

Incidence and types of HIV-1 drug resistance mutation among patients failing first-line antiretroviral therapy.

OBJECTIVE: This study aims to investigate the prevalence and types of drug resistance mutations among patients failing first-line antiretroviral therapy (ART). METHODS: Plasma samples from 112 patients with human immunodeficiency virus-1 (HIV-1) were collected for virus RNA extract and gene amplification. The mutations related to drug resistance were detected and the incidence was statistically analyzed, and the drug resistance rate against common drugs was also evaluated. RESULTS: 103 cases were successfully amplified, and the main drug resistance mutations in the reverse transcriptase (RT) region were M184V (50.49%), K103N (28.16%), Y181C (25.24%), and K65R (27.18%), while no drug main resistance mutation was found in the protease (PR) region. The incidence of drug resistance mutations was significantly different among patients with different ages, routes of infection, duration of treatment, initial ART regimens and viral load. The drug resistance rate to the common drugs was assessed, including Efavirenz (EFV, 71.84%), Nevirapine (NVP, 74.76%), Lamivudine (3TC, 66.02%), Zidovudine (AZT, 4.85%), Stavudine (D4T, 16.51%), and Tenofovir (TDF, 21.36%). CONCLUSION: The drug resistance mutations to NRTIs and NNRTIs are complex and highly prevalent, which was the leading cause of first-line ART failure. This study provides significant theoretical support for developing the second-line and third-line therapeutic schemes.

Matrix Metalloproteinase-3 -1171 5A/6A Polymorphism (rs35068180) is Associated with Risk of Periodontitis.

Matrix metalloproteinase-3 (MMP3) plays a key role in tissue degradation in periodontitis. The relationship between the MMP3 -1171 5A/6A polymorphism (rs35068180) and periodontitis has been widely studied. However, existing studies have yielded contradictory results. We therefore conducted a meta-analysis to comprehensively investigate these inconclusive findings. Several electronic databases were searched for eligible articles. Seven case-control studies from 6 articles were searched without any language restrictions. Pooled estimates indicated that MMP3 -1171 5A/6A polymorphism is associated with a decreased risk of periodontitis (allelic genetic model: OR = 0.70, 95% CI: 0.62-0.80, P(heterogeneity) = 0.315; heterozygous model: OR = 0.50, 95% CI: 0.39-0.65, P(heterogeneity) = 0.221; homozygous model: OR = 0.42, 95% CI: 0.25-0.69, P(heterogeneity) = 0.265; dominant model: OR = 0.49, 95% CI: 0.38-0.62, P(heterogeneity) = 0.238, respectively). Similar results were also found in chronic periodontitis (CP), Asian, Asian&CP, and non-smokers subgroups. Moreover, MMP3 rs35068180 polymorphism might be associated with a lower risk of aggressive periodontitis (AgP) in Asians (allelic genetic model: OR = 0.66, 95% CI: 0.48-0.91, P(heterogeneity) = 0.945), and CP in Caucasians and Brazilians. In conclusion, this meta-analysis demonstrates that MMP3 -1171 5A/6A polymorphism may be associated with decreased risk of both CP and AgP in Asians. Large independent studies to replicate these results are necessary to validate these associations in other populations.

Epidemiology of migraine in the She ethnic minority group in Fujian province, China.

OBJECTIVES: We examined the prevalence and risk factors of migraine among the She population. The prevalence of migraine among She Chinese in Fujian province is high. METHODS: This study is a cross-sectional survey. Subjects completed a questionnaire that collected demographic and clinical data related to migraine. Physical examination and clinical laboratory tests were performed. Data were analyzed by regression analysis. RESULTS: Of the 5519 subjects enrolled, 2377 were male (43·1%) and 3142 female (56·9%). Of these, 581 (10·53%) experienced migraine annually, including 6·18% of males and 13·82% of females. Highest prevalence rate was among those aged 40-49 years (11·28%). The 141 (24·3%) subjects who had migraine with aura had higher incidence of family history of headache than those without aura (38·5% vs 19·9%, P < 0·0001). CONCLUSION: Female gender and insomnia are possible risk factors for migraine in the She population.