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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.

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.

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.

The interleukin (IL)-1β-511 C/T polymorphism has been shown to be functional and to contribute to the risk of gastric cancer. However, the relationship between the IL-1β-511 C/T polymorphism and gastric carcinogenesis remains inconclusive. A systematical electronic search was conducted of the MEDLINE, EMBASE, and CENTRAL databases. A random and a fixed effects model were exploited to estimate summary odds ratios and 95 % confidence intervals. Subgroup and sensitivity analyses were carried out with respect to ethnicity, quality assessment scores, control sources, genotyping methods, cancer histopathology and location, and Helicobacter pylori (H. pylori) infection. A total of 45 studies containing 9,066 cases of gastric cancer and 11,192 control subjects satisfied the inclusion criteria. The IL-1β-511 C/T polymorphism was found to enhance the risk of stomach cancer for overall and HWE-satisfying studies. Asians showed a positive relationship in both the overall and HWE-satisfying groups, whereas Caucasians did not. Based on subgroup analysis, H. pylori infection and genotype analysis using PCR-RFLP methods increase the association between IL-1β-511 T allele carrier and risk of stomach cancer. A positive relationship was found between the IL-1β-511 C/T SNP and stomach carcinoma susceptibility, and the results suggest that Asian ethnicity, H. pylori infection and methodologically, PCR-RFLP genotyping strengthen this relationship. Reflecting on prevalence of H. pylori in Asian countries, additional studies on the IL-1β-511 C/T SNP in the context of ethnicity and H. pylori infection may provide key insights into the mechanism underlying gastric cancer carcinogenesis. It was found PCR-RFLP is the most reliable genotyping method, and thus, it is recommendable to adopt it to determine the presence of the IL-1β-511 C/T SNP.

MPXI is higher in sepsis than in non-infectious SIRS. However, there is currently no evidence that the MPXI adds any additional benefit to differentiate sepsis from non-infectious SIRS in the ED. Therefore, further study will be needed.

Herein, we report a concise synthesis of the proposed structure of sibiriaester B, a novel antioxidant phenyl caffeate derivative isolated from the leaves of Armeniaca sibirica. Proposed sibiriaester B was obtained via simple esterification between the known TBS‐protected caffeic acid and the commercially available methyl 4‐hydroxybenzoate, and subsequent deprotection. However, the NMR spectral data of the synthesized sibiriaester B were not consistent with those in previous reports. The structure of the synthesized sibiriaester B was confirmed using combined 2D‐NMR analysis, including COSY, HSQC, and HMBC. The synthesized sibiriaester B was observed to exhibit more potent immunomodulatory activity in murine epidermal T cells than p‐hydroxyphenyl caffeate, an immunomodulatory natural caffeate derivative, as treatment with sibiriaester B significantly reduced the production of interleukin 13 by murine epidermal T cells at lower concentrations than p‐hydroxyphenyl caffeate.