Long-term risk of primary liver cancers in entecavir versus tenofovir treatment for chronic hepatitis B.

It remains controversial whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) is associated with different clinical outcomes for chronic hepatitis B (CHB). This study aimed to compare the long-term risk of ETV versus TDF on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in CHB patients from a large multi-institutional database in Taiwan. From 2011 to 2018, a total of 21,222 CHB patients receiving ETV or TDF were screened for eligibility. Patients with coinfection, preexisting cancer and less than 6 months of follow-up were excluded. Finally, 7248 patients (5348 and 1900 in the ETV and TDF groups, respectively) were linked to the National Cancer Registry database for the development of HCC or ICC. Propensity score matching (PSM) (2:1) analysis was used to adjust for baseline differences. The HCC incidence between two groups was not different in the entire population (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.66-1.02, p = 0.078) and in the PSM population (HR 0.83; 95% CI 0.65-1.06, p = 0.129). Among decompensated cirrhotic patients, a lower risk of HCC was observed in TDF group than in ETV group (HR 0.54; 95% CI 0.30-0.98, p = 0.043, PSM model). There were no differences between ETV and TDF groups in the ICC incidence (HR 1.84; 95% CI 0.54-6.29, p = 0.330 in the entire population and HR 1.04; 95% CI 0.31-3.52, p = 0.954 in the PSM population, respectively). In conclusion, treatment with ETV and TDF showed a comparable long-term risk of HCC and ICC in CHB patients.

Effects of cadmium on structure and enzymatic activity of Cu,Zn-SOD and oxidative status in neural cells.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder disease. Ten percent of the ALS patients are congenital (familial ALS), and the other 90% are sporadic ALS (SALS). It has been shown that mutations found in the Cu,Zn-SOD cause 20% of the familial ALS due to its low enzyme activity. We hypothesized that heavy metals may interfere the structure of Cu,Zn-SOD protein to suppress its activity in some of the SALS. In this study, we expressed and characterized the recombinant human Cu,Zn-SOD under various concentrations of Cu(2+), Zn(2+), and Cd(2+). By atomic absorption spectrophotometry, we demonstrated that adding of cadmium significantly increased the content of cadmium ion, but reduced its Zn(2+) content and enzyme activity of the Cu,Zn-SOD protein. The data of circular dichroism spectra demonstrated that the secondary structure of Cu,Zn-SOD/Cd is different from Cu,Zn-SOD, but close to apo-SOD. In addition to the effect of cadmium on Cu,Zn-SOD, cadmium was also shown to induce neural cell apoptosis. To further investigate the mechanism of neural cell apoptosis induced by cadmium, we used proteomics to analyze the altered protein expressions in neural cells treated with cadmium. The altered proteins include cellular structural proteins, stress-related and chaperone proteins, proteins involved in reactive oxygen species (ROS), enzyme proteins, and proteins that mediated cell death and survival signaling. Taken together, in this paper, we demonstrate that cadmium decreases the content of Zn(2+), changes the conformation of Cu,Zn-SOD protein to decrease its enzyme activity, and causes oxidative stress-induced neural cell apoptosis.

The crystal structure of Ym1 at 1.31 A resolution.

Upon nematode infection, murine peritoneal macrophages synthesize and secrete large amounts of the Ym1 protein, which is a unique functional marker for alternatively activated macrophages in T(H)2-mediated inflammatory responses. Ym1 shares significant structural similarity to the family 18 chitinases. Previously, Ym1 has been studied with respect to its carbohydrate-binding ability and glycosyl hydrolysis activity and this has led to various inconclusive interpretations. Our present co-crystallization and soaking experiments with various glucosamine or N-acetylglucosamine oligomers yield only the uncomplexed Ym1. The refined Ym1 structure at 1.31A resolution clearly displays a water cluster forming an extensive hydrogen bond network with the "active-site" residues. This water cluster contributes notable electron density to lower resolution maps and this might have misled and given rise to a previous proposal for a monoglucosamine-binding site for Ym1. A structural comparison of family 18 glycosidase (-like) proteins reveals a lack of several conserved residues in Ym1, and illustrates the versatility of the divergent active sites. Therefore, Ym1 may lack N-acetylglucosamine-binding affinity, and this suggests that a new direction should be taken to unravel the function of Ym1.