Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

Sirtuin 3, an NAD+-dependent deacetylase, whose expression is considered a marker in life extension, is downregulated with age and in various diseases. Sirtuin 3 is predominantly localized to the mitochondria and considered a fidelity protein for the integrity and function of this organelle. Some studies report its localization in the nucleus to regulate the expression of stress response–related genes and that reduced expression of SIRT3 produces a cellular milieu permissive for human pathologies. Since the expression and activity of Sirtuin 3 are important for the regulation of antioxidant defense, metabolism, and apoptosis initiation, the expression of SIRT3 is also important in the context of age-associated illnesses. A variety of small molecules are being developed to modulate the expression or activity of Sirtuin 3 and are potentially a valuable strategy to change mitochondrial acetylome to treat several diseases. The AMPK-PGC1α-SIRT3 axis plays a critical role in preserving mitochondrial biogenesis and function. Here, we summarize how changes in Sirtuin 3 expression are regulated in cancer and dysfunctions in cardiovascular diseases. The potential therapeutic strategies by targeting Sirtuin 3 expression to improve mitochondrial function in cancer and cardiovascular diseases are summarized

Phenolic content and biological activities of Lycium barbarum L (Solanaceae) fruits (Goji berries) cultivated in Konya, Turkey

Purpose: To evaluate the phenolic content and biological activities of Lycium barbarum fruits cultivated in Turkey.Methods: Phenolic compounds in the water and methanol extracts of the fruits were determined by liquid chromatography-mass spectrometry (LC-MS/MS). 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging activities and ferric-reducing antioxidant power (FRAP) assays were used to evaluate the antioxidant potential of the fruits. The  acetylcholinesterase (AChE) inhibitory activity of the fruits was evaluated by Ellman assay.Results: LC-MS/MS results showed that all the extracts contained phenolic compounds including flavonoids, phenolic acids, anthocyanins and  polyphenols. Some anthocyanins, namely, cyanidin-3-Oglucoside, cyanidin chloride, pelargonin chloride, pelargonidin chloride, and pelargonidin-3-0-glucoside were identified in the fruits for the first time. Pelargonidin-3-O-glucoside and cyanidin-3-O-glucoside were the main anthocyanins in the water extract with levels of 119.60 ± 12.04 and 1112.25 ± 125.40 mg/kg, respectively. The results indicated that the extracts possessed good radical scavenging and ferric-reducing activities.Conclusion: The results show that Lycium barbarum cultivated in Konya is a good source of the phenolic compounds, and thus may be exploited for commercial production of the antioxidants.Keywords: Lycium barbarum, Goji berries, Antioxidant activity, Acetylcholinesterase, Flavonoid

Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer.

BackgroundUnderstanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer.MethodMitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) -/- or wild type mice. Colon cancer cell lines (+/- SMAD4) were interrogated for ligand-induced PI3K and MEK/ERK pathway activation and downstream protein/phospho-isoform expression/association after knockdown and pharmacologic inhibition of pathway members. EMT was assessed using epithelial/mesenchymal markers and migration assays.ResultsIn primary colon cancers, loss of nuclear p21 correlated with upstream activation of activin/PI3K while nuclear p21 expression was associated with TGFβ/MEK/ERK pathway activation. Activin, but not TGFβ, led to PI3K activation via interaction of ACVR1B and p85 independent of SMAD4, resulting in p21 downregulation. In contrast, TGFβ increased p21 via MEK/ERK pathway through a SMAD4-dependent mechanism. While activin induced EMT via PI3K, TGFβ induced EMT via MEK/ERK activation. In vivo, loss of ACVR2A resulted in loss of pAkt, consistent with activin-dependent PI3K signaling.ConclusionAlthough activin and TGFβ share growth suppressive SMAD signaling in colon cancer, they diverge in their SMAD4-independent pro-migratory signaling utilizing distinct mitogenic signaling pathways that affect EMT. p21 localization in colon cancer may determine a dominant activin versus TGFβ ligand signaling phenotype warranting further validation as a therapeutic biomarker prior to targeting TGFβ family receptors

Diabetic Foot Due to Anaphylactic Shock: A Case Report

Introduction: Diabetic foot is a clinical disorder, which is commonly seen in patients with diabetes mellitus. It is also the major cause of below knee amputation in the world. There are many underlying causes such as neuropathic, ischemic, and infectious causes for diabetic foot. Local or systemic complications may develop after snake bite. Case Presentation: We reported a very rare case, involving a 78-year-old male admitted to the Emergency Department, who developed anaphylactic shock and diabetic foot after the snake bite. Conclusions: Reviewing the literature, this is the second reported case of snake bite associated with diabetic foot

Clarithromycin resistance prevalence and Icea gene status in Helicobacter pylori clinical isolates in Turkish patients with duodenal ulcer and functional dyspepsia

Clarithromycin resistance in Helicobacter pylori is a principal cause of failure of eradication therapies, and its prevalence varies geographically. The IceA gene is a virulence factor associated with clinical outcomes. The objective of this study was to determine the current state of clarithromycin resistance prevalence, and to investigate the role of iceA genotypes in 87 Turkish adult patients (65 with functional dyspepsia and 22 with duodenal ulcer). A2143G and A2144G point mutations were tested by PCR-RFLP for clarithromycin resistance. Among the patients in the study, 28 patients were tested by agar dilution as well. Allelic variants of the iceA gene were identified by PCR. A total of 24 (27.6%) strains evidenced one of the mutations, either A2143G or A2144G. IceA1 was found to be positive in 28 of the strains (32.2%), iceA2 was positive in 12 (13.8%) and, both iceA1 and iceA2 were positive in 22 (25.3%) strains. In conclusion, we discovered no relationships between iceA genotypes and functional dyspepsia or duodenal ulcer, nor between clarithromycin resistance and iceA genotypes. Clarithromycin resistance appears to be more prevalent in Turkish patients. Copyright © 2006, The Microbiological Society of Korea

The epidemiology and factors associated with nocturnal enuresis among boarding and daytime school children in southeast of Turkey: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Nocturnal enuresis is an important problem among young children living in Turkey. The purpose of this study was to determine the possible differences in the prevalence of enuresis between children in boarding school and daytime school and the association of enuresis with sociodemographic factors.</p> <p>Methods</p> <p>This was a cross-sectional survey. A total of 562 self-administered questionnaires were distrubuted to parents from two different types of schools. One of them was a day-time school and the other was a boarding school. To describe enuresis the ICD-10 definition of at least one wet night per month for three consecutive months was used. Chi-square test and a logistic regression model was used to identify significant predictive factors for enuresis.</p> <p>Results</p> <p>The overall prevalence of nocturnal enuresis was 14.9%. The prevalence of nocturnal enuresis declined with age. Of the 6 year old children 33.3% still wetted their beds, while the ratio was 2.6% for 15 years-olds. There was no significant difference in prevalence of nocturnal enuresis between boys and girls (14.3% versus 16. 8%). Enuresis was reported as 18.5% among children attending day time school and among those 11.5% attending boarding school (p < 0.05). Prevalence of enuresis was increased in children living in villages, with low income and with positive family history (p < 0.05). After multivariate analysis, history of urinary tract infection (OR = 2.02), age (OR = 1.28), low monthly income (OR = 2.86) and family history of enuresis (OR = 3.64) were factors associated with enuresis. 46.4% of parents and 57.1% of enuretic children were significantly concerned about the impact of enuresis.</p> <p>Conclusion</p> <p>Enuresis was more frequent among children attending daytime school when compared to boarding school. Our findings suggest that nocturnal enuresis is a common problem among school children, especially with low income, smaller age, family history of enuresis and history of urinary tract infection. Enuresis is a pediatric public health problem and efforts at all levels should be made such as preventive, etiological and curative.</p

Sirt3, Mitochondrial ROS, Ageing, and Carcinogenesis

One fundamental observation in cancer etiology is that the rate of malignancies in any mammalian population increases exponentially as a function of age, suggesting a mechanistic link between the cellular processes governing longevity and carcinogenesis. In addition, it is well established that aberrations in mitochondrial metabolism, as measured by increased reactive oxygen species (ROS), are observed in both aging and cancer. In this regard, genes that impact upon longevity have recently been characterized in S. cerevisiae and C. elegans, and the human homologs include the Sirtuin family of protein deacetylases. Interestingly, three of the seven sirtuin proteins are localized into the mitochondria suggesting a connection between the mitochondrial sirtuins, the free radical theory of aging, and carcinogenesis. Based on these results it has been hypothesized that Sirt3 functions as a mitochondrial fidelity protein whose function governs both aging and carcinogenesis by modulating ROS metabolism. Sirt3 has also now been identified as a genomically expressed, mitochondrial localized tumor suppressor and this review will outline potential relationships between mitochondrial ROS/superoxide levels, aging, and cell phenotypes permissive for estrogen and progesterone receptor positive breast carcinogenesis

Micro, macro mineral and proximate composition of Atlantic bonito and horse mackerel: a monthly differentiation

P>Atlantic Bonito and horse mackerel were investigated for proximate and elemental composition throughout the year. Two fish species were collected from the Istanbul local fish market from December (2006) to November (2007) during the fishing season. Highest protein values were found in the June for Atlantic Bonito, in July for horse mackerel. Highest fat value of Atlantic Bonito and horse mackerel were determined in November. Trace and potential toxic minerals (mercury, cadmium, lead, copper and zinc) exceeded the legislative limits in some months of the year. The highest concentration among the elements was obtained for sodium, potassium, calcium, magnesium, manganese, iron, zinc, iodine and selenium throughout the year