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The hepatitis B virus (HBV) is a DNA virus that can cause chronic hepatitis B (CHB) in humans. Current therapies for CHB infection are limited in efficacy and do not target the pre-existing viral genomic DNA, which are present in the nucleus as a covalently closed circular DNA (cccDNA) form. The transcription activator-like (TAL) effector nucleases (TALENs) are newly developed enzymes that can cleave sequence-specific DNA targets. Here, TALENs targeting the conserved regions of the viral genomic DNA among different HBV genotypes were constructed. The expression of TALENs in Huh7 cells transfected with monomeric linear full-length HBV DNA significantly reduced the viral production of HBeAg, HBsAg, HBcAg, and pgRNA, resulted in a decreased cccDNA level and misrepaired cccDNAs without apparent cytotoxic effects. The anti-HBV effect of TALENs was further demonstrated in a hydrodynamic injection-based mouse model. In addition, an enhanced antiviral effect with combinations of TALENs and interferon-α (IFN-α) treatment was observed and expression of TALENs restored HBV suppressed IFN-stimulated response element-directed transcription. Taken together, these data indicate that TALENs can specifically target and successfully inactivate the HBV genome and are potently synergistic with IFN-α, thus providing a potential therapeutic strategy for treating CHB infection. [ABSTRACT FROM AUTHOR]

• 919 syrup (919 T J) can inhibit liver inflammation to provide hepatoprotection. • 919 T J can reduce weight and food intake in a NAFLD model. • 919 T J improves lipid metabolism and liver function abnormalities in a NAFLD model. • 919 T J increases PPARγ expression and inhibits IL-1β, TNF-α, and CXCL6 expression. • 919 T J downregulates the expression of NF-κB-related pro-inflammatory signaling. In many countries, nonalcoholic fatty liver disease (NAFLD) has risen to be the leading cause of liver disease, seriously threatening public health, while effective medical treatments are currently limited. 919 syrup (919 T J) is a Chinese herbal medicine, and both clinical and experimental studies have revealed that it can improve liver function. To study whether 919 T J shows a protective effect in a NAFLD rat model and explore its underlying mechanism, with a focus on the NF-κB pathway. Rats were randomly divided into three groups, including a control group, NAFLD group, and 919 T J group (n = 10 each). The control group received a standard diet, and the other two groups were fed a high-fat diet to establish the NAFLD model. From week 10, rats in the 919 T J group were intragastrically administered 919 T J for 4 weeks, and the NAFLD group was administered the same amount of saline. All rats were anesthetized at the beginning of week 14 to collect blood and liver specimens. Serum lipid levels, serum biochemical markers of liver function, and the gene expression levels of IL-1β, TNF-α, CXCL6, CXCR1, SREBP-1c, PPARγ, and NF-κB in the liver were measured. Oil Red O and hematoxylin and eosin staining of the liver was performed to observe pathological changes in the liver. Significant abnormalities in serum lipid levels and serum biochemical markers of liver function were found in the NAFLD group relative to those in the control group. In addition, serious abnormalities were noted in the expression levels of liver inflammatory factors and lipid metabolism-related genes. Treatment of NAFLD rats with 919 T J reduced body weight and food intake and ameliorated the abnormal blood lipid levels and liver function markers. By regulating the NF-κB pathway, 919 T J downregulated the NF-κB-related proinflammatory signals, ameliorating the expression of inflammatory (IL-1β, TNF-α, CXCL6, and CXCR1) and lipid metabolism-related (SREBP-1c) factors in the liver and improving the NAFLD-induced pathological changes in the liver. 919 T J reduces the liver injury, steatosis, and inflammation caused by NAFLD, thus reversing the disease process. [ABSTRACT FROM AUTHOR]