Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana

Artemisia roxburghiana is used in traditional medicine for treating various diseases including diabetes. The present study was designed to evaluate the antidiabetic potential of active constituents by using protein tyrosine phosphatase 1B (PTP1B) as a validated target for management of diabetes. Various compounds were isolated as active principles from the crude methanolic extract of aerial parts of A. roxburghiana. All compounds were screened for PTP1B inhibitory activity. Molecular docking simulations were performed to investigate the mechanism behind PTP1B inhibition of the isolated compound and positive control, ursolic acid. Betulinic acid, betulin and taraxeryl acetate were the active PTP1B principles with IC50 values 3.49 ± 0.02, 4.17 ± 0.03 and 87.52 ± 0.03 µM, respectively. Molecular docking studies showed significant molecular interactions of the triterpene inhibitors with Gly220, Cys215, Gly218 and Asp48 inside the active site of PTP1B. The antidiabetic activity of A. roxburghiana could be attributed due to PTP1B inhibition by its triterpene constituents, betulin, betulinic acid and taraxeryl acetate. Computational insights of this study revealed that the C-3 and C-17 positions of the compounds needs extensive optimization for the development of new lead compounds

Transcription Inhibition by DRB Potentiates Recombinational Repair of UV Lesions in Mammalian Cells

Homologous recombination (HR) is intricately associated with replication, transcription and DNA repair in all organisms studied. However, the interplay between all these processes occurring simultaneously on the same DNA molecule is still poorly understood. Here, we study the interplay between transcription and HR during ultraviolet light (UV)-induced DNA damage in mammalian cells. Our results show that inhibition of transcription with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) increases the number of UV-induced DNA lesions (γH2AX, 53BP1 foci formation), which correlates with a decrease in the survival of wild type or nucleotide excision repair defective cells. Furthermore, we observe an increase in RAD51 foci formation, suggesting HR is triggered in response to an increase in UV-induced DSBs, while inhibiting transcription. Unexpectedly, we observe that DRB fails to sensitise HR defective cells to UV treatment. Thus, increased RAD51 foci formation correlates with increased cell death, suggesting the existence of a futile HR repair of UV-induced DSBs which is linked to transcription inhibition

Evaluation of parametric models with estimating the prediction error by apparent loss method in analyzing survival of colorectal patients

Abstract Background: Colorectal cancer is the most common gastrointestinal cancer. Investigating the factors that predict survival time for these patients is important.The purpose of this study was comparison of parametric models by estimating the prediction error and also identifying the effective factors on predicted survival time of patients with colorectal cancer. Materials and Methods: This cohort study was conducted with 600 patients who were suffered from colorectal cancer in Taleghani Hospital of Tehran between 2001 to 2005 and they were followed up for at least 5 years. For identifying the effective factors on survival time, of the patients we analyzed the data by some parametric models such as Weibull, Exponential and Log logistic and compared these models with the estimation of prediction error by apparent loss method. Results: Among 600 patients there was 344 men (57.3%) and 256 wemon (47.7%). Of total, 151 patients were died that 62.3% of them were men. Univariate analysis showed that the effect of BMI, sex, staging of tumor, tumor site were significant but in multivariate model staging of tumor and BMI were significant. By the estimation of prediction error, the best model was Log logistic . Conclusion: With respect to the importance of survival time prediction, we found that we can use the prediction error to compare the parametric models. In addition, because of effectiveness of tumor stages and BMI in the patients’ survival time, survival time could be increased by an on-time diagnosis and an appropriate controled diet

Histochemical study of cellular mucopolysaccharides in esophageal and gastric carcinoma and its relation to tumor differentiation

Background and Objective: Change in the cell surface and extracellular matrix glycoconjugates has been reported in many cancers. Moreover, diagnostic and prognostic importance of these substances and also their roles in therapeutic modalities for cancerous patients has been emphasized. This study was designed to explore the histochemical study of cellular mucopolysaccharides in esophageal and gastric carcinoma and its relation to tumor differentiation. Materials and Methods: In this laboratory study tissue samples of 40 patients with esophageal squamous cell carcinoma and 40 patients with stomach adenocarcinoma in different grades of tumor were selected from pathology department of Emam Reza hospital in Mashhad, Iran. Tissue samples were stained with Alcian Blue (PH 1 and PH 2.5) for Sulfated and Carboxylated mucosubstances respectively, along with positive and negative controls. Results: Normal esophageal epithelium and carcinoma cells of different grades showed negative reactivity but normal and tumoral stromal cells depicted positive staining in both PHs. In PH 1, normal glandular and carcinoma cells of the stomach were negative but in PH 2 glandular cells were positive though carcinoma cells showed weakly staining. Normal and tumoral gastric stromal cells showed positive staining in PH 1 and PH 2.5. Conclusion: It is highly probable that in the process of cancerization of normal esophageal squamous cells, functional changes, from the perspective of producing Carboxylated and Sulfated mucosubstances, do not occur, whereas some changes in glandular cells of stomach which result in diminishing the production of Carboxylated mucosubstances during cancerization process are observable