A Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Tacrolimus and Corticosteroids in Combination With or Without Mycophenolate Mofetil in Liver Transplantation Recipients Infected With Hepatitis B Virus.

BACKGROUND: Mycophenolate mofetil exhibits pharmacologic mechanisms different from calcineurin inhibitors. Therefore, the dose of calcineurin inhibitors can be reduced along with side effects for effective immunosuppression. We aimed to evaluate the efficacy and safety of tacrolimus and corticosteroid in combination with or without mycophenolate mofetil in living donor liver transplantation (LDLT) recipients infected with hepatitis B virus (HBV). METHODS: A randomized, open-label, comparative, multicenter, phase IV study was conducted with 119 patients from January 2014 to September 2017. In the full analysis set population, 58 and 59 patients were included in the study group (triple-drug regimen: TacroBell + My-rept + corticosteroid) and the control group (dual-drug regimen: TacroBell + corticosteroid), respectively. In the per protocol set population, 49 and 42 patients were included in the study and control groups, respectively. RESULTS: In the full analysis set population, the incidence of biopsy-proven acute cellular rejection (rejection activity index score ≥4) was 3.4% in the study group; however, this finding was not observed in the control group (P = .468). Hepatitis B virus recurrence was observed in one patient in the control group. No cases of biopsy-proven acute cellular rejection and HBV recurrence were observed in the per protocol set population. The incidences of serious adverse events were 25.9% and 18.0% in the study and control groups, respectively; however, the difference between the groups was not statistically significant (P = .376). CONCLUSION: Although the study involved a small number of patients, the triple-drug regimen can be considered safe and effective for immunosuppression after living donor liver transplantation in patients infected with HBV.

Synthesis, carbonic anhydrase inhibition, anticancer activity, and molecular docking studies of 1,3,4-oxadiazole derivatives.

In this work, we have synthesized various organic compounds possessing 1,3,4-oxadiazole as a core structure and the structure of the newly synthesized target compounds has been revealed using different analytical approaches such as FT-IR, LCMS, and NMR (proton and carbon), respectively. The in vitro carbonic anhydrase potentials of these synthesized 17 different analogues were investigated. The result suggests that compound 7g, a 3-pyridine substituted analogue with an IC50 of 0.1 µM, was found to have the most potent carbonic inhibitory activity (11-fold more active) than the positive control (acetazolamide) with an IC50 of 1.1 ± 0.1 µM. Besides, among the series 7(a-q) approved in the identification of four potent carbonic anhydrase inhibitors with the IC50 standards varies from 0.1 to 1.0 ± 0.1 µM. Additionally, the non-competitive behaviour for potent compound 7g was analysed using the Lineweaver-Burk plot from the kinetic study. Furthermore, the anticancer activity of all the synthesized compounds screened against B16F10 melanoma cells using the MTT assay method. Additionally, the molecular docking studies revealed that 7g inhibitor shows good binding energy as well as good binding interaction pattern along with enzyme.

Schiff Base Functionalized 1,2,4-Triazole and Pyrene Derivative for Selective and Sensitive Detection of Cu2+ ion in the Mixed Organic- Aqueous Media.

We have prepared Schiff base functionalized 1,2,4-triazole and pyrene derivative for selective, sensitive, and naked eye colorimetric detection of Cu2+ in the mixed organic- aqueous media. Amongst the 18 different metal ions studied for absorption and fluorescence titration, only Cu2+ ion encourages the modification in spectral properties of Schiff base functionalized 1,2,4-Triazole and Pyrene Probe. The stoichiometric ratio of the TP-Cu2+ complex was determined to be 2:1 according to Job's plot. The lower detection limit estimated for Cu2+ is 0.234 nM which shows excellent sensitivity and selectivity of the present analytical method towards detection of Cu2+ ion in the mixed organic-aqueous media. The present approach has been successfully utilized for the quantitative determination of Cu2+ ion from environmental aqueous solution.

Novel 1,3,4-oxadiazole compounds inhibit the tyrosinase and melanin level: Synthesis, in-vitro, and in-silico studies.

In this research work, we have designed and synthesized some biologically useful of 1,3,4-Oxadiazoles. The structural interpretation of the synthesized compounds has been validated by using FT-IR, LC-MS, HRMS, 1H NMR and 13C NMR techniques. Moreover, the in-vitro mushroom tyrosinase inhibitory potential of the target compounds was assessed. The in-vitro study reveals that, all compounds demonstrate an excellent tyrosinase inhibitory activity. Especially, 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-ylthio)-N-phenylacetamide (IC50 = 0.003 ± 0.00 µM) confirms much more significant potent inhibition activity compared with standard drug kojic acid (IC50 = 16.83 ± 1.16 µM). Subsequently, the most potent five oxadiazole compounds were screened for cytotoxicity study against B16F10 melanoma cells using an MTT assay method. The survival rate for the most potent compound was more pleasant than other compounds. Furthermore, the western blot results proved that the most potent compound considerably decreased the expression level of tyrosinase at 50 µM (P < 0.05). The molecular docking investigation exposed that the utmost potent compound displayed the significant interactions pattern within the active region of the tyrosinase enzyme and which might be responsible for the decent inhibitory activity towards the enzyme. A molecular dynamic simulation experiment was presented to recognize the residual backbone stability of protein structure.

Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer.

PURPOSE: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer. METHODS: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell. RESULTS: The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC50 of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients. CONCLUSION: These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer.

Right side fixation of sigmoid colon with a hepato-sigmoidocolic fistula in patient with hepatocellular carcinoma and midgut malrotation.

The location of the sigmoid colon varies within the abdominal cavity, but its mesocolon is fixed to the left side. Right side fixation of the sigmoid colon is a very rare congenital positional anomaly. In addition, it has been reported that hepatocolic fistula is also a very rare disease that may present lower gastrointestinal bleeding. Here, the authors describe a case of a 71-year-old man who underwent surgery for hepato-sigmoidocolic fistula complicated by hepatocellular carcinoma and the right side fixation of the sigmoid colon.