Diagnosis and Treatment of Liver Disease: Current Trends and Future Directions.

This narrative review delves into the intricate landscape of liver diseases, providing a comprehensive background of the diverse conditions that afflict this vital organ. Liver diseases, ranging from viral hepatitis and non-alcoholic fatty liver disease (NAFLD) to cirrhosis and hepatocellular carcinoma (HCC), pose significant global health challenges. Understanding these diseases' multifaceted origins and progression is pivotal for developing effective diagnostic and therapeutic strategies. The epidemiology and etiology of liver diseases emphasize the global impact of viral hepatitis, with hepatitis B and C as significant contributors. Concurrently, the rising prevalence of NAFLD, linked to lifestyle factors and metabolic syndrome, underscores the intricate relationship between modern living and liver health. Chronic liver diseases often evolve insidiously, progressing from inflammation to fibrosis and, ultimately, to cirrhosis - a stage characterized by irreversible scarring and compromised function. The heightened risk of HCC in advanced liver disease stages further underscores the urgency of effective diagnostic and therapeutic interventions. The evolving landscape of non-invasive diagnostic tools is explored for their role in enabling early detection and accurate staging of liver diseases. In the realm of treatment, there is a continuous transition toward personalized medicine, customized to suit the unique profiles of individual patients. This shift encompasses a broad spectrum, ranging from personalized pharmacological interventions to lifestyle modifications and surgical options. Delving into innovative therapies, such as gene editing and immunomodulation, offers a glimpse into the promising future directions that have the potential to redefine the landscape of liver disease diagnosis and treatment.

Alantolactone induces apoptosis in HepG2 cells through GSH depletion, inhibition of STAT3 activation, and mitochondrial dysfunction.

Signal transducer and activator of transcription 3 (STAT3) constitutively expresses in human liver cancer cells and has been implicated in apoptosis resistance and tumorigenesis. Alantolactone, a sesquiterpene lactone, has been shown to possess anticancer activities in various cancer cell lines. In our previous report, we showed that alantolactone induced apoptosis in U87 glioblastoma cells via GSH depletion and ROS generation. However, the molecular mechanism of GSH depletion remained unexplored. The present study was conducted to envisage the molecular mechanism of alantolactone-induced apoptosis in HepG2 cells by focusing on the molecular mechanism of GSH depletion and its effect on STAT3 activation. We found that alantolactone induced apoptosis in HepG2 cells in a dose-dependent manner. This alantolactone-induced apoptosis was found to be associated with GSH depletion, inhibition of STAT3 activation, ROS generation, mitochondrial transmembrane potential dissipation, and increased Bax/Bcl-2 ratio and caspase-3 activation. This alantolactone-induced apoptosis and GSH depletion were effectively inhibited or abrogated by a thiol antioxidant, N-acetyl-L-cysteine (NAC). The data demonstrate clearly that intracellular GSH plays a central role in alantolactone-induced apoptosis in HepG2 cells. Thus, alantolactone may become a lead chemotherapeutic candidate for the treatment of liver cancer.