Proteasome Modulator 9 Gene rs14259 Polymorphism in Patients with Diabetic Polyneuropathy.

INTRODUCTION: Diabetic polyneuropathy (DPN) is a major chronic neurological complication of diabetes mellitus (DM) and typically presents as diabetic sensory polyneuropathy (DSPN). Whereas some patients with similar risk factors develop polyneuropathy, others don't, which suggests that genetics plays an important role in the progression of disease. The proteasome modulator 9 gene (PSMD9) is a transcriptional regulator of the insulin gene and its variants cause beta-cell dysfunction that devastates insulin transcription. The aim of this study was to determine the correlation between PSMD9 rs14259 polymorphism and the risk of DSPN in Turkish DM patients with DPN. METHODS: The study included 31 DM patients with DSPN and 29 healthy controls. All participants underwent electrophysiological investigation. In addition, DNA was isolated from peripheral blood samples for the genotyping of PSMD9 rs14259 polymorphism. RESULTS: Mean age in the DSPN and control groups was 58.03±9.59 years and 57.62±12.32 years, respectively. There were significant differences between the DSPN and controls groups in the frequencies of the genotype for AA (n=9 and n=12, respectively), AG (n=10 and n=15, respectively), and GG (n=12 and n=2, respectively). According to the distribution of PSMD9 rs14259 polymorphism, 45.2% (n=28) of the patients and 67.2% (n=39) of the controls had the A allele, and 54.8% (n=34) of the patients and 32.8% (n=19) of the controls had the G allele, whereas the frequency of the G allele of rs14259 was significantly higher in the DSPN group (X2=1.059, P=0.015) than in the control group (OR: 2.49; 95% CI: 1.18-5.23). CONCLUSION: The present findings show that the GG genotype and G allele of PSMD9 rs14259 polymorphism may be associated with an increased risk of DSPN in Turkish DM patients.

Resin extract obtained from Cilician fir (Abies Cilicica) inhibits glucose dependent inflammation in vitro.

OBJECTIVE: The potential anti-inflammatory efficacy of resin extract of Abies cilicica in glucose dependent inflammation and tumor necrosis factor alpha (TNF-a) induced inflammation models was investigated. Its effects on monocyte adhesion, gene expression levels of P-selectin, ICAM-1, VCAM1 and transendothelial migration for the two in vitro models were measured. Also, total flavonoid and total phenolic contents of the extract were determined. OBJECTIVE: Monocyte adhesion tests showed that the extract increased 100% inflammatory effect of TNF-a induced inflammation. On the other hand, it did not change number of adherent monocytes in glucose dependent inflammation model. Although the extract has trigger effect on monocyte adhesion, it did not change migration of leukocytes across ECV304 cells after administration of TNFa on ECV304 cells. The number of migrated monocytes was similar with only TNFa incubation experiment results. However, it significantly decreased monocyte migration in glucose dependent inflammation model. In our both experimental inflammation model, ICAM-1 expression significantly decreased. Although it is known that triggering effect of TNF-a on ICAM-1 expression, the content of of resin extract of A. cilicica prevented this effect. Phenolic antioxidant capacity of the extract are higher than its flavonoid contents.This study provides the first evidence that the extract inhibits glucose dependent inflammation. It may serve as an anti-inflammatory agent in the treatment of chronic inflammation caused by diabetes.

Apoptotic Effect of Nigella sativa on Human Lymphoma U937 Cells.

OBJECTIVE: Nigella sativa is from botanical Ranunculaceae family and commonly known as black seed. Apoptotic effect of N. sativa and its apoptotic signaling pathways on U937 lymphoma cells are unknown. MATERIALS AND METHODS: In this study, we investigated selective cytotoxic and apoptotic effects of N. sativa extract and its apoptotic mechanisms on U937 cells. In addition, we also studied selective cytotoxic activity of thymoquinone that is the most active essential oil of N. sativa. RESULTS: Our results showed that N. sativa extract has selective cytotoxicity and apoptotic effects on U937 cells but not ECV304 control cells. However, thymoquinone had no significant cytotoxicity against on both cells. N. sativa extract increased significantly caspase-3, BAD, and p53 gene expressions in U937 cells. CONCLUSIONS: N. sativa may have anticancer drug potential and trigger p53-induced apoptosis in U937 lymphoma cells. SUMMARY: This is the first study showing the apoptotic effect of Nigella sativa extract on U937 cells. Abbreviations used: CI: Cytotoxicity index, DMEM: Dulbecco's Modified Eagle Medium, HL: Hodgkin's lymphoma, MTT: 3-(4,5-dimethy lthiazol-2yl)-2,5-diphenyl tetrazolium bromide, RPMI: Roswell Park Memorial Institute medium.

Recently emerging signaling landscape of ataxia-telangiectasia mutated (ATM) kinase.

Research over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells.

Decreased IFN-γ and IL-12 levels in panic disorder.

OBJECTIVE: The aim of this study is to assess the measures of proinflammatory cytokines in patients with panic disorder in comparison with the healthy subjects. METHODS: Twenty three patients with panic disorder with or without agoraphobia and twenty three controls were recruited for the study. Plasma samples of all subjects were analyzed for TNF-α, IFN-γ, IL-1ß, IL-2, IL-6, and IL-12 concentrations and NK-cell activity is measured in the peripheral blood samples of the subjects. RESULTS: We found significant differences on the mean values of IL-12 (p=0.01) and IFN-γ (p=0.02) between the panic disorder and control groups. In a logistic regression analysis, IFN-γ values were significant statistical predictors of the presence of panic disorder (B=-0.07, SE=0.03, p=0.04). CONCLUSION: The most important implication of our results is to suggest a relation between panic disorder and low levels of IFN-γ, compatible with the results of the animal studies showing that IFN-γ plays a role by acting to regulate the development of anxiety-like behaviors.