The possible anti-seizure properties of Klotho.

Recurrent seizures in epilepsy may lead to progressive neuronal damage, which can diminish health-related quality of life. Evaluation and control of pathological processes in the brain is valuable. It seems imperative that new markers and approaches for seizure alleviation be discovered. Klotho (Kl), an antiaging protein, has protective effects in the brain against neurological disorders. It may also have antiseizure effects by improving creatine transfer to the brain, upregulating excitatory amino acid transporters, and inhibiting insulin/insulin-like growth factor-1 (IGF-1), Wingless (Wnt), transforming growth factor-beta (TGF-ß), and retinoic-acid-inducible gene-I (RIG-I)/nuclear translocation of nuclear factor-κB (NF-κB) pathways. Stimulation and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and apoptosis signal-regulating kinase 1 (ASK1)/p38 mitogen­activated protein kinase (MAPK) signaling pathways could also be considered other possible antiseizure mechanisms of Kl. In the present review, the roles of Kl in the central nervous system as well as its possible anti-seizure properties are discussed for the first time.

The presence, severity, and onset of preeclampsia is associated with maternal interleukin-23 level: A case-control study.

Background: Scientific evidence support that imbalance between inflammatory and anti-inflammatory cytokines play a critical role in preeclampsia (PE). Objective: To investigate the relationship between the maternal serum level of interleukin (IL)-23, a pro-inflammatory cytokine, PE and its severity risk was investigated. Materials and Methods: The case-control study included a total of 145 women counting 75 PE cases, 35 healthy pregnant and 35 healthy non-pregnant controls from Zahedan, southeast of Iran. The maternal levels of IL-23 in circulation were determined via enzyme-linked immunosorbent assay. Results: The maternal serum levels of IL-23 were increased in PE and its 2 subgroups severe PE and mild PE, so that these increases were significant in PE and severe PE, but not in mild PE compared with the controls (p < 0.001 and p < 0.001, p = 0.08, respectively). Besides, the maternal IL-23 serum level was statically significant in the early onset PE, but not in the late onset-PE group compared to healthy pregnant controls (p < 0.001, p = 0.46 respectively). Conclusion: The results of our study showed a positive association between IL-23 level and PE, especially in severe type and early onset PE, which suggests that IL-23 may be involved in the pathogenesis of this systemic syndrome.

Silymarin inhibits Toll-like receptor 8 gene expression and apoptosis in Ramos cancer cell line.

OBJECTIVE: Silymarin is a herbal extract containing flavonolignans, and it has inhibitory effects against the growth of different cancer cell lines by inducing apoptosis. Toll-like receptors are suggested as a novel and attractive target to treat cancer. The current study aimed at examining the mechanism of silymarin-induced apoptosis in Ramos cells and investigating its effects on TLR8 expression. MATERIALS AND METHODS: The half maximal inhibitory concentration (IC50) of silymarin in Ramos cells was determined via MTT viability test while the type of cell death was tested by annexin V/propidium iodide (PI) double staining method. The activity of caspase-3 and expression of TLR8 were measured in a time-dependent manner (in IC50) by colorimetric assay and real-time polymerase chain reaction (RT-PCR), respectively. RESULTS: The results of MTT showed that IC50 of silymarin in Ramos cells was 100 µg/ml after 48 hr treatment (p<0.01). Flow cytometry by annexin V/PI, showed that silymarin induced early/late apoptosis in this cell line (p<0.05 to p<0.01). In addition, the caspase-3 colorimetric method showed that caspase-3 increased in the Ramos cell line after treatment (p<0.01). This treatment led to a reduction in TLR8 mRNA expression in a time-dependent manner (p<0.01). CONCLUSION: The results indicated a new mechanism in the anticancer activity of Toll-like receptor (TLR) signaling after silymarin treatment in Ramos cancer cell line. This plant could be used to develop anticancer agents inhibiting TLRs.

Common Variations in Perilipin rs1052700 and FTO rs3751812 Gene Variants, and Risk for Obesity and Type-2 Diabetes.

BACKGROUND: Perilipins are proteins that coat lipid globules in adipocytes, which are steroid-generating cells that play a central role in lipid storage and breakdown. The FTO gene is associated with type-2 diabetes (T2D) and increased fat mass. In this work the association of perilipin and FTO gene polymorphisms in T2D was investigated. METHODS: One hundred eighty-three Iranian men and women with T2D, and 174 healthy controls with no known metabolic diseases, participated in the study. The subjects were genotyped using tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) and their clinical traits were analyzed. RESULTS: A significant association was found between the perilipin rs1052700 polymorphism and T2D, and between the FTO rs3751812 polymorphism and obesity (P = 0.03 and 0.003, respectively); however, no significant relationship was found between rs3751812 and T2D. CONCLUSION: The FTO rs3751812 polymorphism is a major genetic determinant of obesity, but not T2D. The perilipin rs1052700 polymorphism is related to T2D but not obesity.