Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.

HACE1 is a member of the HECT domain-containing E3 ligases with 909 amino acid residues, containing N-terminal ankyrin-repeats (ANK) and C-terminal HECT domain. Previously, it was shown that HACE1 is inactive in human tumors and plays a crucial role in the initiation, progression, and invasion of malignant tumors. Recent studies indicated that HACE1 might be closely involved in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. HACE1 interacts with its substrates, including Ras-related C3 botulinum toxin substrate 1 (Rac1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumor necrosis factor receptor (TNFR), and optineurin (OPTN), through which participates in several pathophysiological processes, such as oxidative stress, autophagy and inflammation. Therefore, in this review, we elaborately describe the essential substrates of HACE1 and illuminate the pathophysiological processes by which HACE1 is involved in neurodegenerative diseases. We provide a new molecular target for neurodegenerative diseases.

[Study on liver damage caused by anti-TB drug intermittent treatment on patients with HBV-TB co-infection].

OBJECTIVE: To study the features of liver damage caused by anti-TB medicines among patients with TB-HBV co-infection, in order to complement and improve the implementation of DOTs strategy in the region. METHODS: A historical cohort study was conducted including the process of reviewing and analyzing files of the 781 naive TB patients hospitalized from June 2004 to October 2005. Cases were divided into HBsAg (+) group and HBsAg (-) group. RESULTS: The overall damage rate among the 781 investigation cases was 20.74%, including 121 cases (74.69%) in HBsAg (+) group and 41 cases (25.31%) in HBsAg (-) group. Data showed that liver damage rate and average value of ALT and AST of HBsAg (+) group were higher than those in HBsAg (-) group. First case with liver damage in HBsAg (+) group happened on the 7th day of the treatment, while the first liver damage case happened in HBsAg (-) group was on the 16th day. The average onset in HBsAg (+) group was earlier than HBsAg (-) group for 18.09 days. The average time of liver function recovery in HBsAg (+) group was 57.02 days and in HBsAg (-) group it was 27.56 days while the appearance among HBsAg (+) group was 29.46 days later than in HBsAg (-) group. CONCLUSION: The incidence rate of liver damage caused by anti-TB medicines was higher among HBV positive patients than those HBV negative patients. Patients co-infected with HBV infection appeared to be more serious, with higher incidence on liver damage and earlier onset, as well as with the degree of damage to the liver.