The effect of encomir-93 mimic transfection on the expression of miR-93 and PSA and androgen receptor in prostate cancer LNcap cell line.

OBJECTIVES: Prostate cancer (PCa) is one of the most common cancers in men with high mortality rate which is a major concern for men's health. However, the molecular mechanisms remain poorly understood. miR-93 is an important oncogene which may have important function in prostate cancer.So, this study aimed to predict that encomir-93 mimic transfection on the expression of miR-93 and PSA and AR in prostate cancer LNcap cell line. METHODS: Lymph node carcinoma of the prostate (LNCaP) was cultured and then miR-93 mimics was designed, synthesized and the transfected to LNCaP. The expression level of prostate-specific antigen (PSA) and androgen receptor (AR) was determined via Real-time PCR after treated with 15 pmol of miR-93 mimics. RESULTS: miR-93 mimic transfection led to significant increase in PSA and AR expression in comparison with control group (p≤0.05). CONCLUSIONS: The miR-93 and its target genes has important role in PCa progression via enhancement in PSA and AR expression. Further research on the function of the miR-93 and its target genes in tumorgenesis and progression PCa could be helpful for the treatment of prostate cancer.

NF-κB and NLRP3 gene expression changes during warm hepatic ischemia-reperfusion in rats with and without silibinin.

AIM: This research examined silibinin's anti-inflammatory outcomes on the NOD-like receptor protein-3 (NLRP3) and NF-κB gene expression, which plays a notable role in inciting inflammatory pathways. BACKGROUND: Hepatic ischemia-reperfusion (I/R) is a common phenomenon in many clinical cases, including liver surgery and transplantation. Inflammatory mediators are vital contributors to the expansion of hepatic damage after I/R injury (I/RI), and therefore, targeting inflammation is a considerable candidate for the management of hepatic I/RI and its complications. METHODS: Thirty-two male Wistar rats were divided equally into four groups: 1) Control (Vehicle) group, in which rats underwent laparotomy and received normal saline; 2) SILI group, in which rats underwent laparotomy, and 30 mg/kg silibinin was injected intraperitoneal (IP); 3) I/R group, in which rats underwent I/R and received normal saline; and 4) I/R + SILI group, who encountered I/R after laparotomy and received silibinin. After one hour of ischemia and three hours of reperfusion, blood and liver tissue samples were assembled for future biochemical, histological, and gene expression studies. RESULTS: In vivo analysis attested that serum AST and ALT activities were significantly lessened by silibinin in the SILI + I/R group (p <0.001). Silibinin ameliorated inflammatory liver tissue injuries, including neutrophil and macrophage infiltration, hepatocyte degeneration, cytoplasmic vacuolation, vascular endothelial damages, and sinusoid dilation observed in the I/R group. During I/R, NLRP3 and NF-κB gene expression showed a significant increment compared to the control group (p <0.001), which could be alleviated by silibinin (p <0.01). CONCLUSION: The results evidence that adjusting the expression of NLRP3 and NF-κB genes during I/R is probably one of the mechanisms of the anti-inflammatory effects of silibinin.

Importance of paraoxonase 1 (PON1) as an antioxidant and antiatherogenic enzyme in the cardiovascular complications of type 2 diabetes: Genotypic and phenotypic evaluation.

Oxidant-antioxidant imbalance is involved in the etiology of different diseases, including cardiovascular diseases (CVDs), liver disorders, kidney diseases, cancers and diabetes mellitus. Antioxidant enzymes play a key role in striking an oxidant-antioxidant balance. Moreover, paraoxonase 1 (PON1) is an antioxidant enzyme that binds with high-density lipoprotein (HDL) in the circulation, and antioxidant and antiaterogenic properties of this lipoprotein are significantly associated with PON1. Research suggests PON1 contributes to the pathogenesis of certain human diseases such as type 2 diabetes (T2D). The association between PON1 and T2D appear to be reciprocal so that the disease significantly decreases PON1 levels and in turn, the genetics of PON1 may have a role the risk of susceptibility to T2D. Several factors that reduce the activity and concentration of PON1 in patients with T2D include increased glycation and loss-of-function polymorphisms. The genotypic and phenotypic evaluations of PON1 are therefore crucial for assessing the risk of cardiovascular complications in these patients, and strategies for increasing or restoring PON1 levels are useful for reducing or preventing their cardiovascular complications as their main cause of mortality. The present review aimed at discussing and emphasizing the key role of PON1 in T2D as a silent and dangerous disease.

Effects of quercetin on microRNAs: A mechanistic review.

MicroRNA (miRNA)-dependent pathways are one of the newest gene regulation mechanisms in various diseases, particularly in cancers. miRNAs are endogenous noncoding RNAs with about 18 to 25 nucleotide length, which can regulate the expression of at least 60% of human total genome posttranscriptionally. Quercetin is the most abundant flavonoid in a variety of fruits, flowers, and medical herbs, known as a strong free radical scavenger that could show antioxidant, anti-inflammatory, and antitumor activities. Recent studies also reported its strong impact on various miRNA expressions in different abnormalities. In this review, we aimed to summarize the studies focused on the effects of quercetin on different miRNA expressions to more clear the main possible mechanisms of quercetin influences and introduce it as a beneficial agent for regulation of miRNAs in various biological directions.

Effects of silibinin on hepatic warm ischemia-reperfusion injury in the rat model.

OBJECTIVES: Liver ischemia-reperfusion injuries (I/RI) are typically the main causes of liver dysfunction after various types of liver surgery especially liver transplantation. Radical components are the major causes of such direct injuries. We aimed to determine the beneficial effects of silibinin, a potent radical scavenger on liver I/RI. MATERIALS AND METHODS: Thirty-two rats were divided into 4 groups. Group I: VEHICLE, the rats underwent laparotomy and received DMSO, group II: SILI, laparotomy was done and silibinin was administered. Group III: I/R, the rats received DMSO and were subjected to a liver I/R procedure and group IV: I/R+SILI, the animals underwent the I/R procedure and received silibinin. After 1 hr of ischemia followed by 3 hr reperfusion, blood was collected to evaluate the serum marker of liver injuries. Hepatic tissue was harvested to investigate glycogen content, histological changes, and vasoregulatory gene expression. RESULTS: Results showed that serum AST, ALT, LDH, GGT, ALP, and hyaluronic acid (HA) increased significantly in I/R group compared with the VEHICLE group. Silibinin reduced this elevation except for GGT. Silibinin inhibited hepatocyte vacuolization and degeneration, endothelium damages, sinusoidal congestion and inflammation, and glycogen depletion during I/R. ET-1 mRNA was overproduced in the I/R group compared with the VEHICLE group which was decreased by silibinin. KLF2 and eNOS expression was reduced during I/R compared with the VEHICLE group. Silibinin elevated KLF2 expression but had no meaningful effect on eNOS expression. CONCLUSION: Silibinin protected the liver from I/RI. Silibinin could improve liver circulation by preventing sinusoidal congestion, inflammation, and perhaps modification of the vasoregulatory gene expression.