Liver X receptor (LXR) is a ligand-activated transcription factor that plays important roles in cholesterol and lipid homeostasis. However, ligand-induced posttranslational modification of LXR is largely unknown. Here, we show that ligand-free LXRalpha is rapidly degraded by ubiquitination. Without ligand, LXRalpha interacts with an ubiquitin E3-ligase protein complex containing breast and ovarian cancer susceptibility 1 (BRCA1)-associated RING domain 1 (BARD1). Interestingly, LXR ligand represses ubiquitination and degradation of LXRalpha, and the interaction between LXRalpha and BARD1 is inhibited by LXR ligand. Consistently, T0901317, a synthetic LXR ligand, increased the level of LXRalpha protein in liver. Moreover, overexpression of BARD1/BRCA1 promoted the ubiquitination of LXRalpha and reduced the recruitment of LXRalpha to the target gene promoters, whereas BARD1 knockdown reversed such effects. Taken together, these data suggest that LXR ligand prevents LXRalpha from ubiquitination and degradation by detaching BARD1/BRCA1, which might be critical for the early step of transcriptional activation of ligand-stimulated LXRalpha through a stable binding of LXRalpha to the promoters of target genes.
Objectives/Hypothesis: We compared the scar quality when different protocols were applied, and eventually aim to find the optimal scar management protocol.Study Design: We conducted a prospective, randomized, and blinded comparison of different scar management protocols in a single center.Methods: We allocated 126 patients who underwent thyroidectomy via collar neck incision randomly into three groups. Patients in group A were treated with tissue adhesive only. Patients in group B were treated by means of subcuticular suturing and early scar management with a non-ablative fractional laser (NAFL) and intralesional triamcinolone injection (ILI). Patients in group C had skin closure with tissue adhesive and early scar management. At 6 months after the operation, the Patient and Observer Scar Assessment Scale (POSAS) and the width of the final scar were compared.Results: Comparing the sum of PSAS, groups B and C showed significant higher satisfaction than did group A (22.81 ± 11.66 in group A, 10.9 ± 5.14 in group B, and 15.19 ± 9.98 in group C). In the sum of OSAS, group B also showed a significant difference than did groups A and C (17.74 ± 6.75 in group A, 10.26 ± 3.60 in group B, and 14.52 ± 6.48 in group C). Also, group B showed a narrower scar width than did groups A and C.Conclusions: Our finding suggests that subcuticular suturing using barbed suture material and early treatment with a combination therapy using NAFL and ILI showed a favorable aesthetic outcome for both patients and operators. Based on our algorithmic approach for thyroidectomy scar, we anticipate an optimal aesthetic outcome.
Background/Aims: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy, arising from the peripheral intrahepatic bile duct epithelium. Hepatitis B virus (HBV) or hepatitis C virus (HCV) may be involved in the development of ICC. We explored the prognostic value of hepatitis virus infection, as well as other prognostic factors affecting survival in patients with ICC. Methods: A retrospective chart review was performed for patients diagnosed with ICC between August 2005 and December 2018 at Konkuk University Medical Center. We identified a total of 131 patients with ICC. Overall survival rates of patients with and without hepatitis were determined. Univariate and multivariate analyses were used to estimate factors influencing survival outcomes. Results: A total of 17.6% (23/131) of patients were positive for HBV or HCV. Hepatitis B positive ICC patients were significantly younger with higher albumin and higher α-fetoprotein than those without hepatitis viral infections. The median survival of hepatitis-positive and hepatitis-negative groups was 280 and 213 days, respectively. Survival rates were not significantly different between the two groups (p = 0.279). Multivariate analyses indicated that lower serum carbohydrate antigen 19-9 (CA 19-9) (p < 0.001), lower T stage (p = 0.042), the absence of lymph-node metastasis (p = 0.043), and receiving curative surgery (p = 0.033) were independent predictors of better outcomes. Conclusions: While hepatitis influenced a number of clinical features in ICC patients, it did not affect survival rate. Prognostic factors influencing survival outcomes with ICC were CA 19-9 level, T stage, the presence of lymph node metastasis, and curative surgery.
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