MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups, namely: normal control (NC), diabetic control (DC), diabetic on 300 mg/kg b.w. MP, diabetic on 300 mg/kg b.w. metformin, and diabetic on MP and metformin combined therapy. Treatment was done orally for 4 weeks, and NC and DC groups received distilled water as vehicle.
KEY FINDINGS: Results showed increased fasting blood glucose and serum markers of hepatic lesion (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase and gamma-glutamyl transferase), increased hepatic lactate dehydrogenase activity, decreased hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities, increased immunoexpressions of nuclear factor kappa B, tumor necrosis factor-α, interleukin(IL)-1β and caspase-3, and decreased immunoexpressions of IL-10 and proliferating cell nuclear antigen in the liver of DC group. Histopathology of the liver revealed numerous hepatocytes with pyknotic nuclei and inflammatory infiltration, while periodic acid-schiff staining decreased in the liver of DC group. Treatment with MP attenuated these negative effects and was comparable to metformin. Furthermore, these effects were better attenuated in the combined therapy-treated diabetic rats.
SIGNIFICANCE: Malaysian propolis attenuates hepatic lesion in DM and exerts a synergistic protective effect with the anti-hyperglycemic medication, metformin.
CASE PRESENTATION: The liver progenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatic tumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number of liver progenitor cell under high magnification examination by stain of immunomarkers. This is the first in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.
Methods: This study included patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosed between November 2012 and October 2015. Serum cathepsin D levels were measured using the CatD enzyme-linked immunosorbent assay (USCN Life Science, Wuhan, China) using stored samples collected on the same day of the liver biopsy procedure. The performance of cathepsin D in the diagnosis and monitoring of NASH was evaluated using receiver operating characteristic analysis.
Results: Data for 216 liver biopsies and 34 healthy controls were analyzed. The mean cathepsin D level was not significantly different between NAFLD patients and controls; between NASH and non-NASH patients; and across the different steatosis, lobular inflammation, and hepatocyte ballooning grades. The area under receiver operating characteristic curve (AUROC) of cathepsin D for the diagnosis of NAFLD and NASH was 0.62 and 0.52, respectively. The AUROC of cathepsin D for the diagnosis of the different steatosis, lobular inflammation, and hepatocyte ballooning grades ranged from 0.51 to 0.58. Of the 216 liver biopsies, 152 were paired liver biopsies from 76 patients who had a repeat liver biopsy after 48 weeks. There was no significant change in the cathepsin D level at follow-up compared to baseline in patients who had histological improvement or worsening for steatosis, lobular inflammation, and hepatocyte ballooning grades. Cathepsin D was poor for predicting improvement or worsening of steatosis and hepatocyte ballooning, with AUROC ranging from 0.47 to 0.54. It was fair for predicting worsening (AUROC 0.73) but poor for predicting improvement (AUROC 0.54) of lobular inflammation.
Conclusion: Cathepsin D was a poor biomarker for the diagnosis and monitoring of NASH in our cohort of Asian patients, somewhat inconsistent with previous observations in Caucasian patients. Further studies in different cohorts are needed to verify our observation.