Bile-derived circulating extracellular mi R-30d-5p and mi R-92a-3p as potential biomarkers for cholangiocarcinoma

Background: Cholangiocarcinoma (CCA) is from cholangiocytes, and therefore bile is a potentially rich source of biomarkers for CCA. The aim of the study was to identify and validate microRNAs (miRNAs) in bile samples that are differentially expressed between benign biliary disease (BBD) and CCA. Methods: Bile samples from 106 patients with obstructive biliary disease were allocated consecutively to a discovery set (10 patients with BBD and 11 with CCA) and then a validation set (48 patients with BBD and 37 with CCA). An miRNA microarray platform was used to screen 1209 miRNAs in the discovery set. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the pro ling results in the discovery and validation sets. In addition, the levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were determined from patient serum samples. Results: Microarray pro ling showed that miR-30d-5p and miR-92a-3p were signi cantly upregulated in bile from the CCA group compared with those from the BBD group. qRT-PCR results indicated that the expression levels of miR-30d-5p and of miR-92a-3p were signi cantly upregulated in the CCA group compared to the BBD group, validating the miRNA microarray results. Pathway analysis suggested that putative target genes of miR-30d-5p and of miR-92a-3p were involved in CCA-associated signalling path- ways, such as Hippo, Wnt, p53, MAPK, and EGFR. Receiver operating curve analysis revealed that the areas under the curve for bile miR-30d-5p, miR-92a-3p, serum CA19-9, and CEA were 0.730, 0.652, 0.675, and 0.603, respectively, and bile miR-30d-5p showed the best diagnostic performance with a sensitivity of 81.1% and a speci city of 60.5%. Conclusions: The levels of extracellular miR-30d-5p and miR-92a-3p in bile were signi cantly higher in patients with CCA than those in patients with BBD. Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p are potential biomarkers for discriminating CCA from BBD.

Effect of Hoechunyangkyeok-San Extract on Melanogenesis

Forsythia fructus has been shown to have antioxidative, anti-inflammatory, antibacterial, anti-aging and whitening effects. Hoechunyangkyeok-san (Forsythia viridissima-prescription) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory disorders. This work was carried out to investigate the skin whitening effects of Forsythia viridissima-prescription extract (a hydrolyzed extract of Hoechunyangkyeok-san: SID White HYC) on skin. The effects of SID White HYC were assessed the melanin contents in B161 melanoma cells and the pigmented equivalent with HMB45 and Fontana Masson staining in 3D skin model. Then, we examined the expression of major pigment enzymes regulating melanin synthesis and melanosome transport related proteins in B16F1 cells. SID White HYC significantly inhibited the melanin synthesis (56.7% and 30.6% inhibition at 100 μg/mL, intracellular and secreted, respectively) in B16F1 cells and 3D skin model. In addition, western blotting analysis showed that SID White HYC reduced the expression of melanin synthesis and melanosome transport related proteins in B16F1 cells. In clinical trials, the cream containing 0.05% SID White HYC showed skin depigmentation effect without any irritation. These results suggest that SID White HYC may be useful inhibition of melanogenesis and melanosome transport. Therefore, SID White HYC may have potential as a skin-whitening ingredient in cosmetics.

Efficacy of early treatment with infliximab in pediatric Crohn’s disease

AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and maintenance therapy for the first year, and were treated with azathioprine after 1 year. All patients were followed for at least 24 mo. Efficacy was determined by the relapse rate using the pediatric Crohn’s disease activity index score in each group at 12 and 24 mo. RESULTS: At the 1 year follow-up, the relapse ratee, Mi Jin Kim, Hae Jeong Lee, Yon Ho Choe (23.1%, 3 of 13 patients) in group C was lower than that (61.5%, 8 of 13 patients) in group B (P = 0.047). At the 2 years follow-up, the relapse rate (38.5%, 5 of 13 patients) in group C was lower than that (76.9%, 10 of 13 patients) in group B (P = 0.047). Adverse events in group C were fewer than in groups A and B. CONCLUSION: Early induction with infliximab at diagnosis, known as "top-down" therapy, was effective for reducing the relapse rate compared to conventional therapies for at least 2 years.

How has the disease course of pediatric ulcerative colitis changed throughout the biologics era?A comparison with the IBSEN study

BACKGROUND In Korea,infliximab was approved for use in children with ulcerative colitis(UC)in October 2012.AIM To compare the clinical course of UC before and after the introduction of biological agents,and to compare with the IBSEN study.METHODS Patients under 18 years of age,who were diagnosed with UC and followed from January 2003 to October 2020,were included in the study.Group A(n=48)was followed for at least 2 years between January 2003 and October 2012,and Group B(n=62)was followed for at least 2 years between November 2012 and October 2020.We compared endoscopic remission,drug composition,relapse rate,steroidfree period,and the quality of life of each group.We plotted the clinical course of the included patients using the pediatric UC activity index score,and compared our patients with those in the IBSEN study.RESULTS After 2 years of treatment,colonoscopy evaluation revealed different outcomes in the two treatment groups.Remission was confirmed in 14 patients(29.2%)of Group A,and in 31 patients(50.0%)of Group B(P<0.012).The median cumulative corticosteroid-free period was 3.0 years in Group A and 4.4 years in Group B.Steroid-free period of Group B was significantly longer than that of Group A(P<0.001).There was a statistically significant difference between the two groups in evaluation of the relapse rate during the observation period(P<0.001).The plotted clinical course graphs of Group A showed similar proportions to the graphs in the IBSEN study.However,in Group B,the proportion of patients corresponding to curve 1(remission or mild severity after initial high activity)was high at 76%(47/62).CONCLUSION The incidence of relapse has decreased and the steroid-free period has increased after the introduction of the biological agent.The clinical course also showed a different pattern from that of IBSEN study.The active use of biological agents may change the long-term disease course in moderate to severe pediatric UC.

<i>Trapa japonica</i>Flerov Extract Attenuates Lipid Accumulation through Downregulation of Adipogenic Transcription Factors in 3T3-L1 Cells

Obesity is a major human health problem associated with various diseases, including cardiac injury and type 2 diabetes. Trapa japonica Flerov (TJF) has been used in traditional oriental medicine to treat diabetes. In this study, we evaluated the inhibitory effect of and the mechanism underlying the effect of TJF extract on adipogenesis in 3T3-L1 cells. The effects of TJF extract on cell viability were analyzed using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and the anti-adipogenic effect was measured by oil red O staining. The expression of peroxisomal proliferator activated receptor (PPAR)γ, CCAAT/enhancer-binding protein-α (C/EBP)α, adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), adiponectin, and fatty acid binding protein (FABP)4 involved in adipogenesis was determined by western blot analysis. TJF extract effectively inhibited lipid accumulation and the expression of PPARγ and C/EBPα in 3T3-L1 cells. TJF also increased the phosphorylation of AMPK and ACC, and decreased the expression of adiponectin and FABP4. These results indicate that TJF extract exerts its anti-obesity effect through the downregulation of adipogenic transcription factors and adipogenic marker genes.