Calcipotriol abrogates TGF-ß1/pSmad3-mediated collagen 1 synthesis in pancreatic stellate cells by downregulating RUNX1.

RUNX1 with CBFß functions as an activator or repressor of critical mediators regulating cellular function. The aims of this study were to clarify the role of RUNX1 on regulating TGF-ß1-induced COL1 synthesis and the mechanism of calcipotriol (Cal) on antagonizing COL1 synthesis in PSCs. RT-qPCR and Western Blot for determining the mRNAs and proteins of RUNX1 and COL1A1/1A2 in rat PSC line (RP-2 cell). Luciferase activities driven by RUNX1 or COL1A1 or COL1A2 promoter, co-immunoprecipitation and immunoblotting for pSmad3/RUNX1 or CBFß/RUNX1, and knockdown or upregulation of Smad3 and RUNX1 were used. RUNX1 production was regulated by TGF-ß1/pSmad3 signaling pathway in RP-2 cells. RUNX1 formed a coactivator with CBFß in TGF-ß1-treated RP-2 cells to regulate the transcriptions of COL1A1/1A2 mRNAs under a fashion of pSmad3/RUNX1/CBFß complex. However, Cal effectively abrogated the levels of COL1A1/1A2 transcripts in TGF-ß1-treated RP-2 cells by downregulating RUNX1 production and hindering the formation of pSmad3/RUNX1/CBFß complexes. This study suggests that RUNX1 may be a promising antifibrotic target for the treatment of chronic pancreatitis.

Graves' disease overlapping with chronic hepatitis B and methimazole-induced liver injury and autoimmune hepatitis: a case report.

BACKGROUND: Liver injury related to Graves' Disease (GD) includes hepatotoxicity of thyroid hormone excess, drug-induced liver injury, and changes resulting from concomitant liver disease. Methimazole (MMI) has been shown to induce several patterns of liver injury. However, the diagnosis and treatment of autoimmune hepatitis (AIH) overlapping with either GD or chronic hepatitis B are challenging. CASE PRESENTATION: A 35-year-old man from China presented with a two-year history of GD and a 10-day history of progressive jaundice. He had taken MMI for two months and discontinuing treatment due to liver toxicity 1 year ago and for another 6 days 20 days prior to hospitalization. The patient was diagnosed with GD overlapping with chronic hepatitis B and MMI-induced liver injury with early stage of acute-on-chronic liver failure on admission. However, the elevated aminotransferase and bilirubin levels could not be controlled after correction of liver failure and effective control of HBV replication and hyperthyroidism by daily oral entecavir and one-time oral administration of 131-iodine. The patient underwent liver biopsy on the 43rd day of hospitalization, showing HBsAg expression on the membrane of hepatocytes and typical histopathological characteristics of AIH. He was finally diagnosed with GD overlapping with chronic hepatitis B and MMI-induced liver injury and AIH. The elevated aminotransferase and bilirubin completely returned to normal by 3-month glucocorticoid therapy and continuous entecavir treatment and there was no recurrence during a 6-month follow-up, suggesting that AIH in this patient is different from classical AIH or GD-associated AIH. CONCLUSIONS: GD together with AIH is a complex and difficult subject. It needs to be clarified whether MMI or HBV can act as a trigger for AIH in this patient.

Ambroxol Chaperone Therapy for Gaucher Disease Type I-Associated Liver Cirrhosis and Portal Hypertension: A Case Report.

BACKGROUND: Gaucher Disease (GD) is a rare autosomal recessive inherited disease caused by the deficiency of glucocerebrosidase and characterized by a broad spectrum of clinical manifestations, including hepatosplenomegaly, bone infiltration, and cytopenia. Moreover, it is even involved in the central nervous system. GD is classified into three phenotypes on the ground of neurologic involvement: type 1 (GD1), the commonly adult-onset, non-neuropathic variant; type 2 (GD2), the acute neuropathic form; and type 3 (GD3), the severe chronic neuro-visceral form. Recently, several studies have shown a promising outcome of ambroxol chaperone therapy for the treatment of GD, but its therapeutic role in GD1-associated liver cirrhosis and portal hypertension was not verified. CASE PRESENTATION: A 36-year-old male patient was admitted for esophageal varices lasting for one year with a 34-year history of liver and spleen enlargement. The patient was diagnosed with GD1 with cirrhosis and portal hypertension based on the identification of Gaucher cells and advanced fibrosis in the liver biopsy tissue and two known pathogenic mutations on the glucocerebrosidase (GBA) gene. The patient received 660 mg/d of ambroxol for up to two years. At his six-month follow- up, the patient exhibited a remarkable increase in GBA activity (+35.5%) and decrease in liver stiffness (-19.5%) and portal vein diameter (-41.2%) as examined by ultrasound elastography and computer tomography, respectively. At two-year follow-up, the liver stiffness was further reduced (-55.5%) in comparison with untreated patients. CONCLUSION: This case report suggests that long-term treatment with high dose ambroxol may play a role in the reduction of hepatic fibrosis in GD1.

[The development and clinical application of the penetrater for stomach wall].

This paper introduces the design principles of a penetrator for stomach wall, and its operating method. All the experimental results show that it is a very practical, safe and is a useful medical device while used with the GF-I Model Anastomat in esophagogastro-anastomosis. It may prevent the anastotic stoma complication and may be of great importance in clinical applications.