Differentially expressed proteins identified by TMT proteomics analysis in children with verrucous epidermal naevi.

BACKGROUND: Verrucous epidermal naevi (VEN) are benign skin tumours, considered keratinocytic epidermal naevi, that appear at birth or early childhood. VEN may display a range of appearances, depending on patient age. Although the number of studies regarding VEN is increasing, the exact mechanism of VEN is still unknown. OBJECTIVES: The aim of this study was to analyse the changes in the expression of protein factors in lesions of VEN children by TMT labelling-based quantitative proteomics. METHODS: A total of 8 children with VEN (5 for experiment and 3 for validation) and 8 healthy children (5 for experiment and 3 for validation) presented to the Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Boao Super Hospital, between January 2019 and November 2019. The lesions and lesion-adjacent tissues from children with VEN and naevus-adjacent normal skin tissues from children with pigmented naevi were defined as the VEN group, VENC group and C group, respectively. We performed a proteomics analysis to screen for differentially expressed proteins in the lesions of these individuals. We further performed Western blotting to validate the relative expression levels of nine targeted proteins in the validation group. RESULTS: According to the proteomics results, a total of 4970 proteins were identified, and 4770 proteins were quantified. Among these proteins, 586 proteins were up- or downregulated at least 1.3-fold with a P-value < 0.05 (upregulated: 399, downregulated: 187) in lesions between the VEN group and the C group. These proteins played important roles in multiple biological functions, such as cornification, epidermal cell differentiation and neutrophil activation, and formed a complicated protein-protein interaction network. Of the 586 up- or downregulated proteins, nine were selected for further validation. According to Western blotting analysis results, the relative expression levels of Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A (Cytokeratin 6A), BRAF, Filaggrin, S100A7 and Desmocollin-3 were significantly upregulated in VEN children and may be associated with skin barrier dysfunction, epidermal cell overgrowth and differentiation, inflammation and immune and oxidative phosphorylation, which are involved in the pathogenesis of VEN. CONCLUSIONS: According to TMT-based proteomics and Western blotting results, we identified eight noteworthy proteins, Involucrin, NDUFA4, Loricrin, Keratin type II cytoskeletal 6A, BRAF, Filaggrin, S100A7 and Desmocollin-3, that were upregulated in the lesions of VEN children and may be associated with the pathogenesis of VEN. Our findings provide new starting points for identifying precise pathogenic mechanisms or therapeutic targets for VEN.

CircABCB10 promotes the proliferation and migration of lung cancer cells through down-regulating microRNA-217 expression.

OBJECTIVE: We aimed at studying the role and molecular mechanism of circular RNA circABCB10 in the progression of lung cancer (LCa). PATIENTS AND METHODS: We collected LCa tissues using quantitative real-time polymerase chain reaction (qRT-PCR) technology to determine circABCB10 expression and performed survival analysis based on the clinical data of LCa patients. At the same time, the specific effects of circABCB10 on the biological function of LCa cell lines were determined by certain cell function experiments, including cell counting kit-8 (CCK-8) test, plate cloning experiment, transwell and cell wound healing assays. The downstream key gene microRNA-217 of circABCB10 was predicted through bioinformatics analysis and the potential regulation between them was confirmed by luciferase assay. microRNA-217 was knocked down in LCa cell lines to verify its important role in the progression of LCa. RESULTS: CircABCB10 showed abnormally high expression in LCa tissues and cell lines and was related to the poor prognosis of patients. In vitro cell experiments demonstrated that knocking down circABCB10 remarkably suppressed the proliferation and migration ability of LCa cells. In addition, circABCB10 can specifically bind to microRNA-217 and negatively regulate its expression of microRNA-217 in LCa cells. Finally, cell functional experiments showed that microRNA-217 is a key downstream gene that mediates the regulation of circABCB10 on LCa cell function. CONCLUSIONS: CircABCB10, abnormally highly expressed in LCa tissues, is able to induce the malignant progression of this cancer.

Longitudinal changes in prostate volume in a community-based cohort study of middle-aged and elderly men in rural China.

BACKGROUND: Prostate volume (PV) and its change rate are important for the progression of prostate disease, but studies on their estimates are inconsistent. OBJECTIVES: To investigate whether age, prostate-specific antigen (PSA), and other specific characteristics are associated with PV and its change rate. MATERIALS AND METHODS: A community-based cohort study was conducted in a rural area of China among male residents aged 40-80 years. PV was estimated at baseline and at 4 years of follow-up by trans-abdominal ultrasound. Annual PV change rate (PVCR) was calculated as change in volume divided by time interval. Baseline characteristics, including age, serum PSA, and hormones, were evaluated. And their relationships with PV or PVCR were assessed with Pearson correlation and multivariate linear regression analyses. RESULTS: Totally, 462 participants completed the follow-up with baseline PV (PV0 ) of 15.6 ± 5.5 ml. PV0 was highly correlated with age and PSA in pairwise correlations (Pearson r = 0.35 and 0.34, respectively, p < 0.01). Multivariate linear regression showed similar associations that PV0 tended to increase with age and PSA. The average PVCR was 0.7 ± 1.8 ml/year. In pairwise correlations, PVCR was inversely correlated with PV0 and positively correlated with PSA, while it was not significantly related to baseline age. Linear regression of PVCR on age and PSA in groups classified by PV0 quartile showed that age was not a significant estimator of PVCR, whereas PSA was. In each PV0 group, PVCR tended to increase with PSA. DISCUSSION AND CONCLUSION: PV was positively associated with age and PSA, and it tended to grow faster in men with smaller baseline PV and higher PSA. PSA can be a valuable parameter for estimating both the size and the growth speed of prostate. Although age is associated with prostate enlargement, it does not appear to be related to the longitudinal change rate of PV.

The involvement of miR-155 in blood pressure regulation in pregnant hypertension rat via targeting FOXO3a.

OBJECTIVE: Pathogenesis factor of pregnant hypertension is still unclear and lacks of effective treatment. MiR-155 is a recently discovered miRNA molecule with differential expression in pregnant hypertension, which participates in the disease regulation. As a downstream target gene of miR-155, FOXO3a is correlated with blood pressure regulation. We investigated the regulatory role and mechanism of miR-155 in pregnant hypertension. MATERIALS AND METHODS: We established a pregnant hypertension rat model, on which miR-155 inhibitor or FOXO3a siRNA was applied, followed by HE staining, 24 h urea protein, blood pressure and serum creatine assay to evaluate disease severity. RESULTS: MiR-155 expression was significantly elevated in model rats, accompanied by a reduction of the FOXO3a level. MiR-155 inhibitor suppressed miR-155 expression, increased FOXO3a level and placental tissue morphology by HE staining, and depressed blood pressure as well as serum creatine level. Downregulation of FOXO3a by specific siRNA resulted in opposite effects. These results illustrated the miR-155 mediated FOXO3a expression in pregnant hypertension. CONCLUSIONS: The inhibition of miR-155 improves the damage of pregnant hypertension via the upregulation of FOXO3a, which provides academic leads for the future therapy of pregnant hypertension.

Allergy is associated with reduced risk of glioma: A meta-analysis

Background: Increasing evidences suggest that allergy may reduce the risk of glioma, so it is necessary to perform an up-to-data literature search and investigate this relationship by meta-analysis. Methods: We identified the included studies by searching PubMed and Web of Science and excluding irrelevant or ineligible articles. Nineteen studies from 15 articles, including 8435 cases and 118,719 controls, were selected for data extraction and synthesis. Results: Pooled outcomes showed that there was an inverse association between allergy and risk of glioma (OR = 0.64, 95% CI = 0.52-0.78, P < 0.001). Meanwhile, asthma and eczema would reduce the risk of glioma by 33% and 23% (OR = 0.67, 95% CI = 0.59-0.75, P < 0.001; OR = 0.77, 95% CI = 0.68-0.86, P < 0.001), respectively. Sensitivity analyses confirmed the stability of these findings. Besides, no publication biases were detected regarding all the investigations. Conclusions: Overall or specific allergy is protective against glioma. More prospective cohort studies or molecular laboratory experiments are warranted to elucidate the causation and key mechanism (AU)

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Allergy is associated with reduced risk of glioma: A meta-analysis.

BACKGROUND: Increasing evidences suggest that allergy may reduce the risk of glioma, so it is necessary to perform an up-to-data literature search and investigate this relationship by meta-analysis. METHODS: We identified the included studies by searching PubMed and Web of Science and excluding irrelevant or ineligible articles. Nineteen studies from 15 articles, including 8435 cases and 118,719 controls, were selected for data extraction and synthesis. RESULTS: Pooled outcomes showed that there was an inverse association between allergy and risk of glioma (OR=0.64, 95% CI=0.52-0.78, P<0.001). Meanwhile, asthma and eczema would reduce the risk of glioma by 33% and 23% (OR=0.67, 95% CI=0.59-0.75, P<0.001; OR=0.77, 95% CI=0.68-0.86, P<0.001), respectively. Sensitivity analyses confirmed the stability of these findings. Besides, no publication biases were detected regarding all the investigations. CONCLUSIONS: Overall or specific allergy is protective against glioma. More prospective cohort studies or molecular laboratory experiments are warranted to elucidate the causation and key mechanism.

N-acetylcysteine attenuates subcutaneous administration of bleomycin-induced skin fibrosis and oxidative stress in a mouse model of scleroderma.

BACKGROUND: Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of scleroderma, and thus antioxidant therapy may be useful for patients with an impaired oxidative defence mechanism. AIM: To examine the effect of N-acetylcysteine (NAC) on skin fibrosis and oxidative stress in a bleomycin (BLM)-induced mouse model of scleroderma. METHODS: We used this mouse model to evaluate the effect of NAC on skin fibrosis and oxidative stress. Skin fibrosis was evaluated by histopathological examination and hydroxyproline content. To measure lipid peroxidation, we used a thiobarbituric acid-reactive species, malondialdehyde (MDA). Oxidative protein damage (carbonyl content) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress in the skin tissue. RESULTS: Treatment with NAC attenuated the skin fibrosis induced by BLM, significantly reducing the MDA and protein carbonyl content in these mice. SOD activity in BLM-only mice and BLM plus NAC-treated mice was increased compared with control mice. However, there was no significant difference in skin SOD activity of mice treated with both BLM and NAC compared with those treated with BLM only. In addition, CAT activity was not altered in the BLM plus NAC mice. CONCLUSIONS: NAC treatment attenuates skin fibrosis in a BLM-induced mouse model of scleroderma, and this is associated with diminished oxidative stress. The results suggest that NAC may be a potential therapeutic agent for patients with scleroderma.

Protective effects of Ginkgo biloba leaf extracts on trichloroethylene-induced human keratinocyte cytotoxicity and apoptosis.

The objective of this study was to assess the protective effects of Ginkgo biloba leaf extracts (EGb) on trichloroethylene (TCE)-induced cytotoxicity and apoptosis in normal human epidermal keratinocytes (NHEK). Cytotoxicity was determined by neutral red uptake, and lipid peroxidation of the cells was assessed by malondialdehyde (MDA) and superoxide dismutase (SOD). Electron microscopy and flow cytometry were used to evaluate NHEK apoptosis. Treatment of NHEK with various concentrations of TCE caused a substantial decrease in cell viability. NR(50 )from the cytotoxicity assay was found to be 4.53 mM. TCE caused an increase in MDA, while an inhibition of SOD activity, in a concentration-dependent manner. Electron microscopic examination revealed typical morphologic changes of apoptosis in cells treated with TCE. Incubation of NHEK with TCE (0, 0.125, 0.5, 2.0 mM) for 4 h increased the proportion of apoptotic cells from control of 19.23% to nearly 44.35%. Pretreatment of EGb at 10-200 mg/l dose-dependently attenuated the cytotoxic effect of TCE, prevented TCE-induced elevation of lipid peroxidation and decline of antioxidant enzyme activities. Similar inhibition by EGb on TCE-mediated NHEK apoptosis was also observed. These results suggest that EGb can protect NHEK from TCE-induced cytotoxicity and apoptosis, which may be associated with the superoxide scavenging effect and enhancement of antioxidant enzyme activities.