A molecular and computational study of galbanic acid as a regulator of Sirtuin1 pathway in inhibiting lipid accumulation in HepG2 cells.

INTRODUCTION: Sirtuin1 (SIRT1) plays a crucial role in the pathophysiology of non-alcoholic fatty liver disease. We investigated the mechanistic role of galbanic acid (Gal) as a regulator of SIRT1 in silico and in vitro. METHODS: HepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns. RESULTS: The semi-quantitative results of Oil red (p < .03) and TG level (p < .009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p < .05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar. CONCLUSION: Computational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells.

Predictive value of body mass index (BMI) and determination of optimum cut-off point in the diagnosis of endometrial hyperplasia in pre-menopausal women with abnormal uterine bleeding.

Background: The suitable BMI cut-off point in persons with endometrial cancer or hyperplasia with abnormal uterine bleeding was investigated in this study. Methods: This case-control research was conducted on 1470 women with abnormal uterine bleeding in Ayatollah Rouhani Hospital,Babol between 2010 and 2012, with 312 participants included in the study. In terms of uterine biopsy results, patients were split into six groups: simple hyperplasia without atypia, simple hyperplasia with atypia, complicated hyperplasia with atypia, complex hyperplasia without atypia, endometrial cancer, and normal persons. Results: The mean age and BMI of patients in these three groups were not significantly different (P equal to 0.081 and 0.435, respectively). The kind of disease exhibited a strong relationship with menstruation (P 0.001). The body mass index (BMI) values ​​did not have significant levels under the curve to determine the appropriate cut-off point in the diagnosis of hyperplasia plus endometrial cancer and endometrial cancer alone (P 0.380 and 0.124, respectively) and hyperplasia alone (P = 0.920). Based on logistic regression, age 50 years and older and irregular menstruation were significant with OR equal to 2.36 and 2.09 (P = 0.011) and HTN with OR equal to 0.44 (P = 0.026), respectively. Conclusion: BMI has little predictive value in the detection of endometrial cancer or hyperplasia, according to the findings, and other diagnostic and screening modalities should be utilized instead. The findings backed up the theory that old age and irregular menstruation are linked to an increased risk of endometrial cancer.