Emerging Targets to Relieve Fat Stress-Induced Liver Diseases: UDCA, Tocotrienol, omega-3 PUFAs, and IgY Targeted NPC1L1 Cholesterol Transporter
CURRENT PHARMACEUTICAL DESIGN
Authors: Cha, Ji-Young; Park, Jong-Min; Lee, Ho-Jae; Bae, Jin-Sik; Han, Young-Min; Oh, Byung-Chul; Ko, Kwang Hyun; Hahm, Ki-Baik
Abstract
Fat stress-induced liver disease is a hepatic manifestation of metabolic syndrome initiated by excess fat accumulation and encompasses a wide spectrum of diseases from non-alcoholic fatty liver disease to nonalcoholic steatohepatitis, a precursor lesion progressing to more aggressive liver cirrhosis and hepatocellular carcinoma. Although the incidence of these fat stress-induced liver diseases is rapidly increasing worldwide in parallel with the growing epidemics of obesity and metabolic diseases, its exact pathogenesis is not well defined. Although obesity, sedentary life-style, altered dietary pattern, insulin resistance, altered intestinal barrier function, inflammatory cytokines, and oxidative stress have been acknowledged as contributing factors because of the indefinite pathogenesis of metabolic diseases, the only reliable treatment is lifestyle intervention composed of restrictive diet and exercise. Additionally, some existing medications such as pioglitazone and antioxidants such as vitamin E were reported to be effective; in this review, several novel agents especifically targeting nonalcoholic fatty liver disease pathogenesis under clinical trial will be introduced. These include an NPC1L1 blocker (ezetimibe), which significantly improved histological and symptomatic scores associated with steatohepatitis and fibrosis; clofibrate, phentoxyfylline, ursodeoxycholic acid, and tocopherol, all of which are prescribed to relieve fat stress; and additional IgY targeted NPC1L1, tocotrienol, ursodeoxycholic acid, and omega-3 polyunsaturated fatty acids, which are actively under investigation to confirm the safety of long- term use.
Immunogenicity and protective efficacy of DHBV DNA vaccines expressing envelope and capsid fusion proteins in ducks delivered by attenuated Salmonella typhimurium
JOURNAL OF INTEGRATIVE AGRICULTURE
Authors: Liu Si-yang; Jia Ren-yong; Li Qing-qing; Feng Dai-shen; Shen Hao-yue; Yang Cui; Wang Ming-shu; Zhu De-kang; Chen Shun; Liu Ma-feng; Zhao Xin-xin; Yin Zhong-qiong; Jing Bo; Cheng An-chun
Abstract
Duck hepatitis B virus (DHBV) shares many basic characteristics with hepatitis B virus (HBV) and is an attractive model for vaccine development. In this study, DHBV DNA vaccines were designed to express envelope and capsid fusion proteins to enhance the breadth of immune response in ducks. Attenuated Salmonella typhimurium (SL7207) was used as a carrier and adjuvant to boost the magnitude of immune response. Based on this strategy, novel DNA vaccines (SL7207-pVAX1-LC and SL7207-pVAX1-SC) were generated. Growth kinetics, genetic stabilities and relative transcription levels of the L, S and C genes introduced by these vaccine strains were measured before inoculation to guarantee safety and efficacy. The relative transcript levels of the CD4 and CD8 T genes and the antibody levels (IgY) in ducks receiving the vaccines were higher than those in single gene delivered groups. Additionally, the copy number of covalently closed circular DNA in hepatocytes after DHBV challenge also provided evidence that our fusion vaccines could enhance the protective efficiency against DHBV infection in ducks.