Serum C1q/TNF-Related Protein-2 (CTRP2) Levels are Associated with Coronary Artery Disease.

Recent studies have shown that complement C1q tumor necrosis factor related proteins (CTRPs) such as adiponectin, have different regulatory roles on the cardiovascular system. CTRP2 is the most similar to adiponectin and one of the best characterized beneficial adipokines important in the regulation of whole body metabolism. However, there were no studies about the relationship between CTRP2 and Coronary artery disease (CAD). This study aimed to evaluate the serum CTRP2 levels in patient with Coronary artery disease. In this study, a total of 82 participants who underwent vascular angiography were included. All of subjects were male. According to their coronary angiography results, all participants were divided into CAD group (n = 42) and control group (n = 40). Serum CTRP2 levels were determined quantitatively with enzyme-linked immunosorbent assay (ELISA). Our study for the first time showed that the CTRP2 levels were higher in CAD patients (1.79 ± 1.46 ng/mL) compared to control subjects (1.08 ± 0.78 ng/mL; p = 0.001). The levels of CTRP2 also were positively correlated with severity of CAD (r = 0.356, p = 0.001). In addition, logistic regression analysis indicated that CTRP2 had an independent association with the risk of CAD (OR [CI] = 3.366 [1.605-7.060]; p = 0.001). Increased levels of CTRP2 in CAD patients were independently associated with the progression of the CAD, it might be regarded as a novel biomarker for assessing the risk of CAD; however, more study is required in this regard.

Hesperetin is a potent bioactivator that activates SIRT1-AMPK signaling pathway in HepG2 cells.

Sirtuin 1 (SIRT1) is a deacetylase enzyme that plays crucial roles in controlling many cellular processes and its downregulation has been implicated in different metabolic disorders. Recently, several polyphenols have been considered as the effective therapeutic approaches that appear to influence SIRT1. The main goal of this study was to evaluate the effect of hesperetin, a citrus polyphenolic flavonoid, on SIRT1 and AMP-activated kinase (AMPK). HepG2 cells were treated with hesperetin in the presence or absence of EX-527, a SIRT1 specific inhibitor, for 24 h. Resveratrol was used as a positive control. SIRT1 gene expression, protein level, and activity were measured by RT-PCR, Western blotting, and fluorometric assay, respectively. AMPK phosphorylation was also determined by Western blotting. Our results indicated a significant increase in SIRT1 protein level and activity as well as an induction of AMPK phosphorylation by hesperetin. These effects of hesperetin were abolished by EX-527. Furthermore, hesperetin reversed the EX-527 inhibitory effects on SIRT1 protein expression and AMPK phosphorylation. These findings suggest that hesperetin can be a novel SIRT1 activator, even stronger than resveratrol. Therefore, the current study may introduce hesperetin as a new strategy aimed at upregulation SIRT1-AMPK pathway resulting in various cellular processes regulation.

Down-Regulation of SIRT1 Expression by mir-23b Contributes to Lipid Accumulation in HepG2 Cells.

Non-alcoholic fatty liver disease is one of the main causes of chronic liver disease and therefore is currently considered a major public health problem. Sirtuin 1 (SIRT1) is an NAD-dependent deacetylase enzyme that contributes in the regulation of metabolic processes and protects against lipid accumulation in hepatocytes. Its expression is potentially regulated by microRNAs which attach to the 3' untranslated region (3'-UTR) of their target mRNA. HepG2 cells were incubated by glucose to induce lipid accumulation and were subsequently transfected with mir-23b mimic and inhibitor. Real-time PCR was used for measuring the expression of mir-23b and SIRT1 mRNA. Cell survival assay and intracellular triglyceride measurement were performed using colorimetric methods. Determination of SIRT1 protein level and activity were done by western blot and fluorometric analysis, respectively. The interaction of miR-23b with 3'-UTR of SIRT1 mRNA was confirmed by dual luciferase. miR-23b mimic inhibited gene and protein expression of SIRT1, while the inhibitor of miR-23b significantly elevated the expression levels of SIRT1 mRNA and protein. The results showed that the 3'-UTR of SIRT1 mRNA is a direct target for miR-23b. The intracellular triglyceride level was increased following the inhibition of SIRT1 in transfected HepG2 cell by miR-23b mimic. Cell viability was decreased in response to miR-23b upregulation compared to control cells. miR-23b reduces the expression and activity of SIRT1 and therefore may be a causative factor in the enhancement of lipid accumulation in HepG2 cells.

Evaluation the Anti-Cancer Effect of PEGylated Nano-Niosomal Gingerol, on Breast Cancer Cell lines (T47D), In-Vitro

Background: Cancer is a significant problem in modern medicine, also is the most common cause of death after cardiovascular diseases, and in need of targeted drug release. Although, chemotherapy is an important candidate in cancer treatment, but it has many side effects on healthy tissues of the body. Therefore, Nano technology is used for specific function, by the least side effects and damage to normal cells. Materials and method: In this study, the pharmacological properties of PEGylated Nano-niosomal Gingerol was examined. Noisome were prepared using reverse phase evaporation method, which contains specific proportion of cholesterol, span60 and polyethylene glycol. Then, PEGylated the prepared formulation by PEG6600. The amount of release and encapsulation of the drug was investigated. The percentage of remains of cancer cell line T47D treated with PEGylated niosomal Gingerol. Results: The average diameter of the nanoparticles, size distribution and zeta potential were reported for PEGylated niosomal sample 35.65 nm, 0.17 and 21 mv, and for PEGylated niosomal drug sample 256.9 nm, 0.23 and 28 mv, respectively. The amount of OD for encapsulated drug was 0.198, also the amount of concentration of the drug which is not encapsulated, was 0.77947 µl of the drug per ml. This value of encapsulated drug was 76.38 percent. Conclusion: The results showed that IC50 of the formulation of PEGylated nanoniosomal Gingerol is less than the standard drug. It seems, the cause of this phenomenon is due to the effect of Polyethylene glycol, in more stability and slower drug release, in the formulation of PEGylated niosome. Also, Polyethylene glycol makes increase in the drug dealing and its greater influence with the target cell. In this study, more than 76% of the Gingerol drug in PEGylated nanoniosomal formulation were enclose. Also, we could reduce the amount of drug release, as much as possible.

Enterolactone Reduces Telomerase Activity and The Level of Its Catalytic Subunit in Breast Cancer Cells.

OBJECTIVE: There is a positive correlation between higher serum phytoestrogen concentrations and lower risk of breast cancer. The activation of telomerase is crucial for the growth of cancer cells; therefore, the aim of this study was to examine the effects of enterolactone (ENL) and enterodiol (END) on this enzyme. MATERIALS AND METHODS: In this experimental study, we performed the viability assay to determine the effects of different concentrations of ENL and END on cell viability, and the effective concentrations of these two compounds on cell growth. We used western blot analysis to evaluate human telomerase reverse transcriptase catalytic subunit (hTERT) expression and polymerase chain reaction (PCR)-ELISA based on the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. RESULTS: Both ENL and END, at 100 µM concentrations, significantly (P<0.05) reduced cell viability. However, only the 100 µM concentration of ENL significantly (P<0.05) decreased hTERT protein levels and telomerase activity. Lower concentrations of ENL did not have any significant effects on telomerase activity and hTERT protein levels. CONCLUSION: High concentration of ENL decreased the viability of MCF-7 breast cancer cells and inhibited the expression and activity of telomerase in these cells. Although END could reduce breast cancer cell viability, it did not have any effect on telomerase expression and activity.

Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells.

BACKGROUND: Visfatin is a novel adipokine and proinflammatory cytokine which is implicated in breast cancer progression. The exact proliferative and anti-apoptotic mechanisms of visfatin are still under debate. In this study, the effect of extracellular visfatin on proliferation and apoptosis of breast cancer cells were investigated considering key regulatory molecules in these procedures. METHODS: BrdU (Bromodeoxyuridine) experiment was used to assess cell proliferation in response to visfatin treatment. Cell viability and apoptosis were assessed using MTT assay and flowcytometry, respectively. Phosphorylation levels of AKT and ERK1/2 as well as survivin levels and Poly ADP ribose polymerase (PARP) cleavage were investigated by western blot analysis. RESULTS: Visfatin induced proliferation of MCF-7 and MDA-MB-231 cells, an effect that was repressed by using AKT and ERK1/2 inhibitors, indicating involvement of these two signaling pathways in the proliferative effect of visfatin. Similarly, phosphorylation of AKT and ERK1/2 were elevated by visfatin treatment. On the other hand, visfatin improved cell viability and prevented TNF-α-induced apoptosis as well as PARP cleavage. Visfatin also exerted a protective effect on survivin. CONCLUSION: The results of this study suggest that visfatin induces breast cancer cell proliferation through AKT/PI3K and ERK/MAPK activation and protects against apoptosis in these cells. Thus increased visfatin levels may augment breast cancer development and attenuate treatment efficiency in breast cancer patients.