5 research outputs found

    Supplementary Material for: VEGF-A Inhibition Ameliorates Podocyte Apoptosis via Repression of Activating Protein 1 in Diabetes

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    <b><i>Background/Aims:</i></b> Vascular endothelial growth factor-A (VEGF-A) upregulation and podocyte apoptosis have been documented in diabetes. This study was designed to investigate whether inhibiting VEGF-A could ameliorate podocyte apoptosis in diabetes and the underlying mechanisms. <b><i>Methods:</i></b> In vitro, small interfering RNAs (siRNAs) of VEGF-A and activator protein 1 (AP-1, c-fos and c-jun), bevacizumab (VEGF-A inhibitor) and SP600125 (AP-1 inhibitor) were added to high glucose (30 mM) induced podocytes. Luciferase reporter assay was used to investigate whether AP-1 was a direct target of VEGF-A. In vivo, bevacizumab and SP600125 were administered to 12-week-old streptozotocin-induced male Sprague Dawley rats. The level of VEGF-A, c-fos, c-jun and bcl-2 were examined using immunostaining and Western blot analysis. Podocyte apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay, electron microscopy and flow cytometry. <b><i>Results:</i></b> Silencing VEGF-A or AP-1 upregulated bcl-2 and ameliorated podocyte apoptosis. Silencing VEGF-A decreased the level of c-fos and c-jun and bevacizumab and SP600125 treatment attenuated podocyte apoptosis. Luciferase reporter activity of VEGF-A-3′-UTR constructs was significantly provoked when stimulated with TGF-β1. In diabetic rat kidneys, VEGF-A co-localized with bcl-2 in podocytes. With bevacizumab and SP600125 treatment, the level of VEGF-A and AP-1 decreased while bcl-2 increased. Podocyte apoptotic rate was reduced with condensed podocyte nuclei less frequently observed. The urine albumin excretion rate (UAER) and albumin/creatinine were improved. <b><i>Conclusion:</i></b> This study demonstrates VEGF-A inhibition ameliorates podocyte apoptosis by regulating AP-1 and bcl-2 signaling. AP-1 is a direct target of VEGF-A and a novel player in podocyte apoptosis

    Supplementary Material for: Prevalence and Determinants of Parathyroid Dysfunction in Elderly Patients on Hemodialysis

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    <b><i>Background:</i></b> The goal of this study was to investigate underlying factors of parathyroid dysfunction in elderly patients undergoing maintenance hemodialysis. <b><i>Methods:</i></b> A total of 286 patients on maintenance hemodialysis were included. Hemoglobin, serum creatinine (Scr), blood urea nitrogen (BUN), serum calcium, serum phosphorus (P), intact parathyroid hormone (iPTH), and serum albumin (Alb) were measured and analyzed both before and after dialysis. <b><i>Results:</i></b> A higher incidence of low iPTH level (<150 pg/l) was observed in the elderly group than that in the non-elderly group (55.8 vs. 36.7%, p < 0.05). Elderly patients had a shorter dialysis duration, lighter dry weight, lower concentrations of BUN, Scr, P, iPTH, Alb and standard protein nitrogen present rate (nPNA) compared to that of non-elderly group patients (p < 0.05). <b><i>Conclusions:</i></b> Low iPTH level occurs more frequently in elderly hemodialysis patients. Furthermore, age, serum P, serum Alb and nPNA were independently associated with a low iPTH level

    Supplementary Material for: Identification of Subpathway Signatures For Ovarian Cancer Prognosis by Integrated Analyses of High-Throughput miRNA and mRNA Expression

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    <b><i>Background/Aims:</i></b> Ovarian cancer (OC) causes more death and serious conditions than any other female reproductive cancers, and many expression signatures have been identified for OC prognoses. However, no significant overlap is found among signatures from different studies, indicating the necessity of signature identifications at the functional level. <b><i>Methods:</i></b> We performed an integrated analyses of miRNA and gene expressions to identify OC prognostic subpathways (pathway regions). Using The Cancer Genome Atlas data set, we identified core prognostic subpathways, and calculated subpathway risk scores using both miRNA and gene components. Finally, we performed global risk impact analyses to optimize core subpathways using the random walk algorithm. <b><i>Results:</i></b> Subpathway-level analyses displayed more robust results than the gene- and miRNA-level analyses. Moreover, we verified the advantage of core subpathways over the entire pathway-based results and their prognostic performance in two independent validation data sets. Based on the global impact score, 13 subpathway signatures were selected and a combined subpathway-based risk score was further calculated for OC patient prognoses. <b><i>Conclusions:</i></b> Overall, it was possible to systematically perform integrated analyses of the expression levels of miRNAs and genes to identify prognostic subpathways and infer subpathway risk scores for use in OC clinical applications

    Supplementary Material for: Impact of Age on the Management of Primary Melanoma Patients

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    <b><i>Objectives:</i></b> Age is an understudied factor when considering treatment options for melanoma. Here, we examine the impact of age on primary melanoma treatment in a prospective cohort of patients. <b><i>Methods:</i></b> We used logistic regression models to examine the associations between age and initial treatment, using recurrence and melanoma-specific survival as endpoints. <b><i>Results:</i></b> 444 primary melanoma patients were categorized into three groups by age at diagnosis: 19-45 years (24.3%), 46-70 (50.2%), and 71-95 (25.5%). In multivariate models, older patients experienced a higher risk of recurrence (hazard ratio 3.34, 95% confidence interval, CI, 1.53-7.25; p < 0.01). No significant differences were observed in positive biopsy margin rates or extent of surgical margins across age groups. Patients in the middle age group were more likely to receive adjuvant therapy than those in the older group (odds ratio 2.78, 95% CI 1.19-6.45; p = 0.02) and showed a trend to longer disease-free survival when receiving adjuvant therapy (p = 0.09). <b><i>Conclusion:</i></b> Our data support age as an independent negative prognostic factor in melanoma. Our data suggest that age does not affect primary surgical treatment but may affect decisions of whether or not patients receive postoperative treatment(s). Further work is needed to better understand the biological variables affecting treatment decisions and efficacy in older patients

    Supplementary Material for: Mild renal function impairment and long-term outcomes in patients with three-vessel coronary artery disease: a cohort study

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    Background: Limited data are available on the long-term impact of mild renal dysfunction (eGFR 60-89 ml/min/1.73m2) in patients with three-vessel coronary disease (3VD). Methods: A total of 5,272 patients with 3VD undergoing revascularization were included and were categorized into 3 groups: normal renal function (eGFR ≥90 ml/min/1.73m2, n=2352), mild renal dysfunction (eGFR 60-89, n=2501) and moderate renal dysfunction (eGFR 30-59, n=419). Primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction and stroke. Results During the median 7.6-year follow-up period, 555 (10.5%) deaths occurred. After multivariable adjustment, patients with mild and moderate renal dysfunction had significantly higher risks of all-cause death (adjusted HR: 1.36, 95% CI 1.07-1.70; adjusted HR 2.06, 95% CI 1.53-2.78, respectively) compared with patients with normal renal function. patients after coronary artery bypass grafting (CABG) had a lower rate of all-cause death and MACCE than those undergoing percutaneous coronary intervention (PCI) in the normal and mild renal dysfunction group, but not in the moderate renal dysfunction group. Results were similar after propensity score matching. Conclusions In patients with 3VD, even mild renal impairment was significantly associated with a higher risk of all-cause death. The superiority of CABG over PCI diminished in those with moderate renal dysfunction. Our study alerts clinicians to the early screening of mild renal impairment in patients with 3VD and provides real-world evidence on the optimal revascularization strategy in patients with renal impairment
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