This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1

Background: Goslings in several Taiwanese farms experienced gosling feather loss disease (GFL) at 21–35 days and goose broke feather disease (GBF) at 42–60 days. The prevalence ranges from a few birds to 500 cases per field. It is estimated that about 12,000 geese have been infected, the morbidity is 70–80% and the mortality is 20–30%. Objectives: This study aims to investigate the pathogens that cause GFL and GBF. Focus on the study of the correlation between goose circovirus (GoCV) and goose parvovirus (GPV) with the goose feather loss in southern Taiwan. Furthermore, a phylogenetic tree was established to align the differences between southern and northern Taiwan and compare with virus strains from China and Europe. Methods: Samples were collected from animal hospitals. Molecular and microscopy diagnostics were used to examine 92 geese. Specific quantitative polymerase chain reaction (Q-PCR) assays are performed to evaluate GPV and GoCV viral loads and simultaneously evaluated the feather loss conditions in geese with the scoring method. Results: High prevalence of GoCV and GPV infection in geese showing signs of GFL and GBF. Inclusion body was detected in the feather follicles and Lieberkühn crypt epithelial cells. The Q-PCR showed the high correlation between feather loss and viruses during 3rd– 5th week. However, the infection was not detected using the same test in 60 healthy geese. Conclusions Thus, GFL and GBF appear to be significantly closely related to GoCV and GPV. The geese feathers showed increasing recovery after being quarantined and disinfected.

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.