The effect of saraglitazar on TGF-ß-induced smad3 phosphorylation and expression of genes related to liver fibrosis in LX2 cell line.

BACKGROUND AND PURPOSE: Liver fibrosis is a reversible liver injury that occurs as a result of many chronic inflammatory diseases and can lead to cirrhosis, which is irreversible and fatal. So, we studied the anti-fibrotic effects of saroglitazar on LX-2 cell lines, as a dual PPARα/γ agonist. METHODS: Cells, after 80% confluence, were treated with TGF-ß (2 ng/mL) for 24 h. Then cells were treated with saroglitazar at different doses (2.5, 5, 10 µM) for 24 h. After same incubation, the cells of control group, TGF-ß group, and TGF-ß + saroglitazar group were harvested for RNA and protein extraction to determine the effects of saroglitazar. RT-PCR and western blot methods were used to express genes related to fibrosis. RESULTS: Our results show that the relative expression of α-SMA, collagen1α, N-cadherin, NOX (1, 2, and 4), and phosphorylated Smad3 protein was significantly higher in TGF-ß-treated cells compared with the normal group, and E-cadherin expression was decreased in TGF-ß-treated cells. After TGF-ß-treated cells were exposed to saroglitazar, the expression of these genes was significantly reversed (P < 0.05). CONCLUSIONS: Our results clearly show the short-term inhibitory role of saroglitazar in the expression of fibrotic factors using the TGF-ß/Smad signaling pathway. These results suggest that saroglitazar can be considered as a suitable therapeutic strategy for fibrotic patients. Although more studies are needed.

Molecular Insights into the Relationship Between Platelet Activation and Endothelial Dysfunction: Molecular Approaches and Clinical Practice.

Platelets are one of the coagulation cells. When platelet activation occurs, many mediators are released and affect endothelial cells (ECs) and lead to endothelial dysfunction (ED). ED plays an important role in the pathogenesis of many diseases, including cardiovascular disease (CVD). Platelet are of important factors in ED. The release of mediators by platelets causes the stimulation of inflammatory pathways, oxidative stress, and apoptosis, which ultimately result in ED.On the other hand, platelet activation in CVD patients can be associated with a bad prognosis. Platelet activation can increase the level of markers such as p-selectin in the serum. Also, in this study, we have discussed the role of platelet as a diagnostic factor, as well as its use as a treatment option. In addition, we discussed some of the molecular pathways that are used to target platelet activation.

Comparison of the effects of cholesterol, palmitic acid, and glucose on activation of human hepatic stellate cells to induce liver fibrosis.

Background: In hepatic damage, Hepatic stellate cells (HSCs) become active, proliferate, and change to myofibroblasts. Increasing the fibrogenic genes, such as Transforming growth factor-ß (TGF-ß), Alpha Smooth Muscle Actin (α-SMA), and Collagen1 α (COL 1α) show that the activation of HSCs can lead to hepatic fibrosis. Purpose: These days people consume much cholesterol, palmitic acid, and glucose which can have adverse effects on an individuals' health, but their influences on activating human HSCs and inducing liver fibrosis have not been assessed. Our purpose is to investigate the effects of these three main and abundant ingredients in the diet on the activation of human HSCs and inducing liver fibrosis. Methods: To measure cholesterol, palmitic acid, and glucose cytotoxic effects on the viability of the cells, the MTT technique was used. Then the treated cells were incubated in media containing cholesterol, palmitic acid, and glucose with different concentrations for 24 h. At last, the α-SMA, COL 1α, and TGF-ß, genes mRNA expression were measured by real-time PCR. Results and Conclusions: Our results demonstrated that high concentrations of cholesterol and palmitic acid can activate human HSCs that lead to an increase in the mRNA expressions of fibrogenic genes. Thus, controlling fat intaking and knowing its mechanism is crucial to prevent and attenuate hepatic fibrosis.

Assessing agreement between the three common clinical measurement methods of HbA1c.

Reliable measurement of hemoglobin A1c (HbA1c) has great importance in the diagnosis and monitoring of diabetes mellitus. The aim of the present study was to compare the performance parameters of the three common methods of HbA1c assay, including the Roche, Sebia and TOSOH G8 systems. We studied 120 patients referred to a clinical laboratory for HbA1c assay. The blood samples were analyzed with the Roche, Sebia and TOSOH G8 systems based on immunoassay, capillary electrophoresis, and ion-exchange chromatography techniques, respectively. The Spearman and the Passing-Bablok regression,as well as the Bland-Altman plots, were used to compare these methods. For each assay, the patients' classification was evaluated at the three cut-points of 6.5, 7, and 8% and the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the methods were estimated. Our results showed that there were good correlations and agreement between the methods. We found a mean difference of 0.07% for the TOSOH G8 vs. Roche, 0.06% for the TOSOH G8 vs. Sebia and - 0.01% for the Roche vs. Sebia. The methods represented very low bias, indicating the good accuracy of the results. The sensitivity and specificity of the methods were comparable as well. The three methods also performed similarly in the classification of patients at the proposed cut-off points. Based on our results, the Roche, Sebia and TOSOH G8 systems showed a very high level of agreement with comparable performance parameters and yielded similar and accurate classification of diabetic patients. Therefore, these methods can be used interchangeably.