Astragalus membranaceus treatment combined with caloric restriction may enhance genesis factors and decrease apoptosis in the hippocampus of rats.

Humans have been searching for ways of extending life span, and possible underlying molecular mechanisms behind it for many years. Traditional plants and their extracts are good candidates for finding anti-aging strategies. In addition to its usage in a variety of medical treatments such as inflammation, neural diseases and cancer, Astragalus membranaceus was used to extend lifespan of C. elegans. Therefore, we aimed to show the molecular mechanisms of the possible anti-aging effects of combination of A. membranaceus and caloric restriction. Herein, Wistar rats (n = 24) were divided into Control, A. membranaceus (A) (25 mg/kg A), Caloric restriction (CR) (20% restricted-diet), and CR+A (25 mg/kg A + 20% CR diet) groups. After 18 weeks, behavioral tests were applied to observe alterations on cognitive functions. After animals were decapitated, their hippocampi and livers were dissected for molecular analysis and telomerase activity. Eventually, CR increased learning performances of rats with an increase in the telomerase activity when combined with astragalus. There was a negative correlation between learning and apoptosis parameters. In the CR group, the apoptosis rate increased, and the pyramidal neuron numbers decreased which were reached to control levels with A treatment. The CR+A treatment significantly increased the BDNF level. The A also significantly increased GDNF level independent from CR. In the combination group, the neurogenesis and angiogenesis markers increased with an increase in the anti-senescence protein klotho land a decrease in the apoptosis. In conclusion, combination of caloric restriction with A. membranaceus would become a promising strategy for healthy cognitive aging.

The role of galectin-3 and its genetic variants in tumor risk and survival of patients with surgically resected early-stage non-small cell lung cancer.

BACKGROUND: The aim of this study was to investigate the possible relationship between galectin-3 gene variants, serum level, gene expression level, and the risks and survivals of resectable non-small cell lung cancer patients. METHODS: The rs4644 and rs4652 variants of galectin-3 were genotyped by TaqMan single nucleotide polymorphism assay using genomic deoxyribonucleic acid isolated from the peripheral blood of 65 (54 males, 11 females; mean age: 60.1±11.9 years; range, 34 to 83 years) with Stage IA-IIIA non-small cell lung cancer who underwent primary surgical treatment and 95 healthy individuals (48 males, 47 females; mean age: 53.9±13.5 years; range, 32 to 87 years) between March 2017 and September 2018. Circulating galectin-3 levels in serum samples of the patient and control groups were assessed by enzyme-linked immunosorbent assay. Messenger ribonucleic acid expression of galectin-3 in tumor and surrounding tissues of the patient group was examined by real-time quantitative polymerase chain reaction. Both predictive and prognostic significance of the results were analyzed. RESULTS: The presence of angiolymphatic invasion was significant in the patients with rs4652 AA genotype (p=0.04). Serum galectin-3 levels were significantly higher in the patients than the controls (p<0.0001). The patients with rs4644 CA/CC (p<0.0001 and p<0.0001) and rs4652 AA/AC (p=0.001 and p<0.0001) genotypes had higher serum galectin-3 levels than their corresponding controls. Serum galectin-3 levels increased in the presence of vascular invasion in patients with both rs4644 AC (p=0.03) and rs4652 AC (p=0.019) genotypes. The receiver operating characteristic curve suggested serum galectin-3 level as a strong predictive marker for the patient group with a cut-off value of 17.089 ng/mL (area under the curve: 0.910±0.04; 95% confidence interval: 0.832-0.988; p<0.001). Univariate analysis revealed the association of lower serum galectin-3 levels with better survival (p=0.048). Multivariate survival analysis showed that only high serum galectin-3 levels tended to be related to survival of the patients (hazard ratio: 5.106; 95% confidence interval: 0.956-27.267; p=0.056). CONCLUSION: The presence of galectin-3 gene variants may lead to histopathological differences among patients with non-small cell lung cancer. Serum galectin-3 level may be a valuable diagnostic biomarker and be associated with survival of these patients.

AnvirzelTMregulates cell death through inhibiting GSK-3 activity in human U87 glioma cells.

Objectives: Cardiac glycosides are used as potential anti-cancer agents due to their effects on the inhibition of proliferation and induction of apoptosis and/or autophagy in cancer cells. Herein, we aimed to study the potential signaling pathways taken role in differential cell-death properties of AnvirzelTM which is consisted of two toxic cardiac glycosides (oleandrin and oleandrigenin), in U87 human glioblastoma cells.Methods: The anti-proliferative and anti-migratory effects of AnvirzelTM were assessed in U87 cells by WST-1 assay and wound healing assay, respectively. After treatment of AnvirzelTMwith doses of 10, 25, 50, 100 and 250 µg/ml, expression levels of proteins related to cell death were investigated by Western blot.Results: Anvirzel™ markedly inhibited the growth of U87 cells in a time- and dose-dependent manner following 24 h and 48 h treatments (p < 0.05). In addition, it was found that Anvirzel™ inhibited GSK-3, NOS and HIF1-α expressions whereas activated ERK in U87 cells compared to vehicle (p < 0.05).Discussion: The results suggested that AnvirzelTM regulated cell death distinctly from apoptosis in human glioblastoma cells. Further studies are required for validation of mechanistic insights about the potential signaling pathways taken role in differential cell death properties of AnvirzelTM.

Achieving the balance: Biphasic effects of genistein on PC-3 cells.

This study examined the response of PC-3 cells to physiological (0.5, 2.5, 5, 10 µM) and pharmacological (50 µM) concentrations of genistein which is a main bioactive compound in soy. Following 48 hr genistein treatment, cell-based assays and genome-wide microarray were performed. It was evidenced that maximal physiologically achievable concentrations of genistein (0.5-10 µM) lead to significant increase in cell viability (p < 0.05) and decrease in migration at 0.5 µM (p = 0.000) and 10 µM (p = 0.001). The highest percentage of apoptotic cells was obtained at 50 µM. Microarray analysis gave the most critical pathways such as cell cycle regulation and proliferation, tumorigenesis, DNA damage and repair, stress response, and apoptosis. Physiological concentrations (≤10 µM) induced activation of CDKs, MAPKs, and RPSKs, while high concentrations of genistein (>10 µM) appeared to have a novel mechanism of action, specifically down-regulating TGF-ß by decreasing specifically SMAD 2/3,4 which are in the downstream TGF-ß signaling cascade. PRACTICAL APPLICATIONS: This study highlights for the first time that maximal physiologically achievable concentrations of genistein (0.5-10 µM) have proliferative effects evidenced by alterations in global gene expression patterns of PC-3 cells. Our results particularly represent a closer examination of dietary genistein consumption for the prevention and/or treatment of cancer that maximal physiologically achievable concentrations of genistein could have detrimental effects on individuals with prostate cancer. Further studies as in vivo would be necessary to remove shadows on the effect of genistein on prostate cancer progression.