Management of anastomotic biliary stricture through utilizing percutaneous transhepatic cholangioscopy.

AIM: Occurrence of anastomotic biliary stricture (AS) remains an essential issue following hepatobiliary surgeries, and percutaneous transhepatic cholangioscopy (PTCS) has great therapeutic significance in handling refractory AS for patients with altered gastrointestinal anatomy after cholangio-jejunostomy. This present study aimed to investigate feasibility of PTCS procedures in AS patients for therapeutic indications. MATERIALS AND METHODS: This study was a single-center, retrospective cohort study with a total number of 124 consecutive patients who received therapeutic PTCS due to AS. Clinical success rate, required number, and adverse events of therapeutic PTCS procedures as well as patients survival state were reviewed. RESULTS: These 124 patients previously underwent choledochojejunostomy or hepatico-jejunostomy, and there was post-surgical altered gastrointestinal anatomy. Overall, 366 therapeutic PTCS procedures were performed for these patients through applying rigid choledochoscope, and the median time of PTCS procedures was 3 (1-11). Among these patients, there were 34 cases (27.32%) accompanied by biliary strictures and 100 cases (80.65%) were also combined with biliary calculi. After therapeutic PTCS, most patients presented with relieved clinical manifestations and improved liver functions. The median time of follow-up was 26 months (2-86 months), and AS was successfully managed through PTCS procedures in 104 patients (83.87%). During the follow-up period, adverse events occurred in 81 cases (65.32%), most of which were tackled through supportive treatment. CONCLUSION: PTCS was a feasible, safe and effective therapeutic modality for refractory AS, which may be a promising alternative approach in clinical cases where the gastrointestinal anatomy was changed after cholangio-jejunostomy.

Exosomes derived from TGF-ß1-pretreated mesenchymal stem cells alleviate biliary ischemia-reperfusion injury through Jagged1/Notch1/SOX9 pathway.

BACKGROUND: This study aimed to evaluate the efficacy of exosomes (EXO) derived from TGF-ß1-pretreated mesenchymal stem cells (MSCs) on biliary ischemia reperfusion injury (IRI) and further reveal the possible mechanisms. METHODS: Bone marrow-derived MSCs were treated with exogenous TGF-ß1, Jagged1/Notch1/SOX9 pathway inhibitor LY450139, or their combination. Then, EXO were isolated from the culture supernatants and further characterized. After establishing IRI model of biliary epithelial cells (EpiCs), EXO derived from differently-treated MSCs were applied to detect their protective effects on EpiCs, and LY450139 was applied in EpiCs to detect the possible mechanisms after treatment with MSCs-EXO. EXO derived from differently-treated MSCs were further injected into the hepatic artery immediately after establishment of intrahepatic biliary IRI for animal studies. RESULTS: Pretreatment with TGF-ß1 significantly enhanced MSCs-EXO production and elevated the levels of massive miRNAs associated with anti-apoptosis and tissue repair, which were evidently decreased after TGF-ß1 plus LY450139 cotreatment. Notable improvement was observed in EpiCs after MSCs-EXO treatment, evidenced by reduced cellular apoptosis, increased cellular proliferation and declined oxidative stress, which were more evident in EpiCs that were treated with EXO derived from TGF-ß1-pretreated MSCs. However, application of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs reversely enhanced cellular apoptosis, decreased cellular proliferation and anti-oxidants production. Interestingly, LY450139 application in EpiCs after treatment with MSCs-EXO also reversed the declined cellular apoptosis and enhanced oxidative stress induced by TGF-ß1 pretreatment. In animal studies, administration of EXO derived from TGF-ß1-pretreated MSCs more effectively attenuated biliary IRI through reducing oxidative stress, apoptosis, inflammation and enhancing the expression levels of TGF-ß1 and Jagged1/Notch1/SOX9 pathway-related markers, which were reversed after administration of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs. CONCLUSION: Our results provided a vital insight that TGF-ß1 pretreatment endowed MSCs-EXO with stronger protective effects to improve biliary IRI via Jagged1/Notch1/SOX9 pathway.

Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco.

Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins.