Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion (CIR) injury is initiated by the generation of reactive oxygen species (ROS), which leads to the oxidation of cellular proteins, DNA, and lipids as an initial event. The reperfusion process impairs critical cascades that support cell survival, including mitochondrial biogenesis and antioxidant enzyme activity. Failure to activate prosurvival signals may result in increased neuronal cell death and exacerbation of CIR damage. Melatonin, a hormone produced naturally in the body, has high concentrations in both the cerebrospinal fluid and the brain. However, melatonin production declines significantly with age, which may contribute to the development of age-related neurological disorders due to reduced levels. By activating various signaling pathways, melatonin can affect multiple aspects of human health due to its diverse range of activities. Therefore, understanding the underlying intracellular and molecular mechanisms is crucial before investigating the neuroprotective effects of melatonin in cerebral ischemia-reperfusion injury.

Impaired expression of Drosha in breast cancer.

BACKGROUND: Impaired miRNAs processing pathway is one interesting scenario for global downregulation of the miRNAome in various types of malignancy. We previously reported that DGCR8 and Dicer genes dysregulated in patients with breast cancer. OBJECTIVE: To evaluate the expression pattern of Drosha in patients with breast cancer. METHODS: We evaluated the mRNA expression level of Drosha in 70 fresh breast carcinomas and adjacent non-neoplastic tissue using quantitative real-time PCR and assessed the possible correlation between its expression and clinicopathological parameters. RESULTS: Our results revealed that mRNA expression level of Drosha was decreased in tumors when compared to adjacent non-neoplastic tissue. However, this difference is not statistically significant (P > 0.05). Downregulation of Drosha is related to older age at diagnosis, higher histological grade, higher tumor size and metastasis. However, there was no significant correlation between Drosha expression level and clinicopathological parameters (P > 0.05). We found that Drosha expression negatively correlated with DGCR8 (P = 0.043), whereas dysregulated expression levels of Drosha and Dicer are positively correlated with to each other (P < 0.0001). CONCLUSION: This study provides evidence that the expression of Drosha is impaired in breast cancer. However, the molecular basis of observed expression pattern have remained inexplicable and should be further investigated.

A comparison of the inhibitory effect of nano-encapsulated helenalin and free helenalin on telomerase gene expression in the breast cancer cell line, by real-time PCR.

BACKGROUND: The up-regulation of telomerase gene expression occurs in numerous cancers such as breast cancer. A recent study used the PLGA-PEG-helenalin complex, and free helenalin, to inhibit the expression of telomerase in the breast cancer cell line. The purpose of this study was to examine whether nano encapsulating helenalin improves the anti-cancer effect of free helenalin in the T47D breast cancer cell line. METHOD: The breast cancer cell line (T47D) was grown in the RPMI 1640 medium, supplemented with 10% FBS. The helenalin was encapsulated by the double emulsion method. Then, the drug loading was calculated and its morphology identified by SEM. Other properties of this copolymer were characterized by Fourier transform infrared (FTIR) spectroscopy and H nuclear magnetic resonance (H NMR) spectroscopy. The assessment of drug cytotoxicity on the growth of the breast cancer cell line was carried out through MTT assay. After treating the cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess the amount of telomerase gene expression, real-time PCR was performed. RESULTS: With regard to the amount of the drug loaded, IC50 value was significantly decreased in nanocapsulated (NC) helenalin, in comparison with that of free helenalin. This finding has been proved through the decrease of telomerase gene expression by real-time PCR. CONCLUSION: In this study, we demonstrated that the NC-helenalin complex is more effective than free helenalin in inhibiting the growth of breast cancer cells.

The effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of hemodialysis-related catheter infection.

Bacterial overgrowth in the inner layer of the catheter as a biofilm is highly encountered in routine medical care, and it may occur in a few days after inserting a catheter as an access in hemodialysis (HD) patients. Catheter-induced bacteremia is often due to the development of biofilms. Locking catheters with antimicrobial agents is an effective way of reducing the risk of catheter-related infection. In a controlled, randomized clinical trial, 64 chronic HD patients (32 men and 32 women with a mean age of 57.5 ± 15.6 years) were divided into case and control groups, with 32 patients in each group. The case group received systemic antibiotic and a lock of catheters with 60% ethanol and the control group received only systemic antibiotic. The results were evaluated after three weeks of treatment. The success rate of clearing infection in group A (29 patients) and group B (18 patients) was 90.6% and 56.2%, respectively (P = 0.002). We conclude that the significant difference in the success rate of clearing catheter infection in HD patients is due to the use of 60% ethanol-lock along with antibiotic therapy, and suggest this for routine use.

Inhibitory effects of ß-cyclodextrin-helenalin complexes on H-TERT gene expression in the T47D breast cancer cell line - results of real time quantitative PCR.

BACKGROUND: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in ß-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. ß-Cyclodextrin (ß-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. MATERIALS AND METHODS: To test our hypothesis, we prepared ß-cyclodextrin- helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. RESULTS: MTT assay showed that not only ß-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that ß-cyclodextrin- helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of ß-cyclodextrin-helenalin complexes increased. CONCLUSIONS: ß-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, ß-cyclodextrin could be superior carrier for this kind of hydrophobic agent.