New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats

Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.

Accuracy of Ultrasound and Magnetic Resonance Cholangiopancreatography Findings in the Diagnosis of Biliary System Stones

This study aimed to evaluate the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) and Ultrasound (US) images for the diagnosis of biliary system stones, as well as to assess the consistency between MRCP and US findings. The study sample included 200 cases (90 males and 110 females) with symptomatic biliary system stones between 14 and 82 years. All cases underwent both the US and MRCP imaging for biliary system diagnosis. The study revealed that the most prominent age group with symptoms of biliary system stones was the 33-60-year-old group. It also found that the accuracy of US and MRCP in detecting gallbladder (GB) stones compared with the final diagnosis was 94% and 91%, respectively, with moderate conformity between their results. The accuracy of US and MRCP images in detecting common bile duct (CBD) stones was 61% and 98%, respectively, with fair conformity between their results. In addition, there is a significant agreement between the MRCP and US results in detecting the GB and CBD stones with an agreed percentage of 74% and 71%, respectively. The study concluded that US is the preferred imaging technique for patients with symptomatic gallbladder stones, whereas MRCP is a trustworthy investigation for common bile duct stones.

Maternal regulation of biliary disease in neonates via gut microbial metabolites

Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn’s susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.

Challenges in treatment of a patient suffering from neuroendocrine tumor G1 of the hilar bile duct: a case report

Background Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are extremely rare in the biliary tract. Currently, there are no guidelines for the diagnosis and treatment of biliary NETs. We presented a case with NETs G1 of the hilar bile duct and the challenges for her treatment. Case presentation A 24-year-old woman was presented to our department with painless jaundice and pruritus, and the preoperative diagnosis was Bismuth type II hilar cholangiocarcinoma. She underwent Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy. Unexpectedly, postoperative pathological and immunohistochemical examination indicated a perihilar bile duct NETs G1 with the microscopic invasion of the resected right hepatic duct. Then the patient received 3 cycles of adjuvant chemotherapy (Gemcitabine and tegafur-gimeracil-oteracil potassium capsule). At present, this patient has been following up for 24 months without recurrence or disease progression. Conclusion We know little of biliary NETs because of its rarity. There are currently no guidelines for the diagnosis and treatment of biliary NETs. We reported a case of perihilar bile duct NETs G1 with R1 resection, as far as we know this is the first report. More information about biliary NETs should be registered.