Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly

Background: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly.

Methods: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined.

Results: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P?>?0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P?=?0.007). The median serum PON level was 101?±?63.36?U/l in the case group and 63?±?60.50?U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P?=?0.004, r?=?0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P?=?0.607 and P?=?0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P?=?0.385), nor between those with PON1 L55M and Q192R polymorphisms (P?=?0.161 and P?=?0.336, respectively).

Conclusions: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.     

Association with Leptin Gene c.-2548 G>A Polymorphism,Serum Leptin Levels,and Body Mass Index in Turkish Obese Patients

Leptin is a protein hormone which plays a critical role in the regulation of both body-weight through reducing food intake and stimulating energy expenditure. Several polymorphisms in leptin gene (LEP), which encodes for leptin, have been described. However, its association with obesity is still controversial. Therefore, in the present study, we aimed to investigate whether LEP c.-2548 G>A polymorphism was associated with serum leptin levels, lipid parameters, and body mass index in Turkish obese patients. Forty-seven obese patients and 48 healthy individuals were included in the study. Blood samples were collected for DNA extraction. LEP c.-2548 G>A polymorphism were detected using polymerase chain reaction–restriction fragment length polymorphism technique. Serum leptin levels and lipid parameters were measured by ELISA and enzyme colorimetric assay techniques, respectively. GA or AA genotypes and A allele carrier frequencies of the c.-2548 G>A polymorphism in the LEP were higher in obese (38.3, 34.0 and 72.3 %) when compared with controls (14.6, 12.5, and 27.1 %; p = 0.011, 0.016, and 0.002, respectively). On the other hand, AA or AG genotypes were also related to increased serum leptin levels (p < 0.001) and body mass index (p < 0.0001). All these consequences showed that LEP -2548 AA or AG genotypes are important predictors for increased levels of leptin and BMI in Turkish obese patients and it may be a useful marker for obesity risk in our population.     

Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment

Abstract

Small interfering RNA (siRNA)-based gene silencing strategy has high potential on suppressing specific molecular targets, involved in cancer progression. However, the lack of an effective nanocarrier system that safely delivers siRNA to its target still limits the clinical applications of siRNA. This study aimed to develop albumin-sericin nanoparticles (Alb-Ser NPs) as a novel siRNA delivery system for laryngeal cancer treatment. Nanoparticle formulations composed of albumin and sericin at different ratios (1:1, 2:1, 1:2 w/w) were synthesized by desolvation method. The nanoparticles were modified with poly-L-lysine (PLL) for siRNA binding and decorated with hyaluronic acid (HA) to target laryngeal cancer cell line, Hep-2. HA/PLL/Alb-Ser NPs were individually loaded with siRNAs for casein kinase 2 (CK2), Absent, Small, or Homeotic-Like (ASH2L), and Cyclin D1 genes, which are overexpressed in Hep-2 cells. Downregulation of genes was confirmed by real-time PCR (RT-PCR). Size, morphological, and thermogravimetric characterizations revealed that Alb-Ser NPs having 2:1 (w/w) ratio are the most optimized formulation. Between 36.8 and 61.3% of siRNA entrapment efficiencies were achieved. HA/PLL-siRNA/Alb-Ser (2:1) NPs-mediated gene silencing resulted in a significant inhibition of cell growth and induction of apoptosis in cells. Our findings showed that HA/PLL/Alb-Ser (2:1) NPs were promising as a siRNA carrier.     

Evalution of toxicity of abcisic acid and gibberellic acid in rats: 50 days drinking water study

In the present study, the influence of subchronic effects of two plant growth regulators (PGRs) [Abcisic acid (ABA) and Gibberellic acid (GA₃)] on antioxidant defense systems [reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation level (malondialdehyde = MDA) in various tissues of the rat were investigated during treatment as a drinking water model. 75 ppm of ABA and GA₃ in drinking water were continuously administered orally to rats (Sprague-Dawley albino) ad libitum for 50 days. The PGRs treatments caused different effects on the antioxidant defense systems and MDA content of dosed rats compared to controls. The lipid peroxidation end product MDA significantly increased in the lungs, heart and kidney of rats treated with GA₃ without significant change in the spleen. ABA caused also a significant increase in MDA content in the spleen, lungs, heart and kidney. The GSH levels were significantly depleted in the spleen, lungs and stomach of rats treated with ABA without any change in the tissues of rats treated with GA₃ except the kidney where it increased. Antioxidant enzyme activities such as SOD significantly increased in the lungs and stomach and decreased in the spleen and heart tissues of rats treated with GA₃. Meanwhile, SOD significantly decreased in the spleen, heart and kidney and increased in the lungs of rats treated with ABA. While CAT activity significantly decreased in the lungs of rats treated with GA₃, a significant increase occurred in the heart of rats treated with both PGRs. On the other hand, the ancillary enzyme GR activity in the tissues were either significantly depleted or not changed with PGRs treatment. The drug metabolizing enzyme GST activity significantly decreased in the lungs of rats treated with ABA but increased in the stomach of rats treated with both PGRs.

As a conclusion, the rats resisted oxidative stress via the antioxidant mechanism. But the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat's tissues. This data, along with changes, suggests that PGRs produced substantial systemic organ toxicity in the spleen, lungs, stomach, heart and kidney during a 50-day period of subchronic exposure.     

Sonic hedgehog signaling is associated with resistance to zoledronic acid in CD133high/CD44high prostate cancer stem cells

Molecular Biology Reports - Cancer stem cells (CSCs) are a unique population that has been linked to drug resistance and metastasis and recurrence of prostate cancer. The sonic hedgehog (SHH)...     

Slow oocyte freezing and thawing in couples with no sperm or an insufficient number of sperm on the day of <Emphasis Type="Italic">in vitro</Emphasis>fertilization

Background  

The clinical results of in vitro fertilization of slowly frozen-thawed oocytes are known to be significantly worse than those obtained by fresh oocytes. Little is known about the factors affecting the clinical outcome of frozen-thawed oocytes. The aim of this retrospective study was to explore the role of oocyte cryopreservation in the group of patients with no available sperm on the day of in vitro fertilization. Additionally, the effects of the female serum FSH level and sperm quality on the clinical outcome of frozen-thawed oocytes were evaluated.     

Phytochemical constituents and inhibitory activity towards methicillin-resistant Staphylococcus aureus strains of Eryngium species (Apiaceae)

The chemical composition of the essential oils of Eryngium campestre, E. thorifolium, and E. creticum (Apiaceae), growing in the Aegean region of Turkey (Mount Sandras, Denizli), was determined by direct thermal desorption (DTD)-GC/MS analyses. A total of 49 components were identified in the oils, α-pinene and hexanal being the major compounds. The three essential oils were also tested for their inhibitory activity of nine different methicillin-resistant Staphylococcus aureus (MRSA) strains by the agar disc diffusion method. The anti-MRSA activity of E. thorifolium oil, the most active of the three oils, was comparable with those of the reference antibiotic vancomycin and oregano oil, although somewhat lower.     

Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation

Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/-) macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/-) macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing.     

Protein-Protein Interaction Domains of Bacillus subtilis DivIVA

DivIVA proteins are curvature-sensitive membrane binding proteins that recruit other proteins to the poles and the division septum. They consist of a conserved N-terminal lipid binding domain fused to a less conserved C-terminal domain. DivIVA homologues interact with different proteins involved in cell division, chromosome segregation, genetic competence, or cell wall synthesis. It is unknown how DivIVA interacts with these proteins, and we used the interaction of Bacillus subtilis DivIVA with MinJ and RacA to investigate this. MinJ is a transmembrane protein controlling division site selection, and the DNA-binding protein RacA is crucial for chromosome segregation during sporulation. Initial bacterial two-hybrid experiments revealed that the C terminus of DivIVA appears to be important for recruiting both proteins. However, the interpretation of these results is limited since it appeared that C-terminal truncations also interfere with DivIVA oligomerization. Therefore, a chimera approach was followed, making use of the fact that Listeria monocytogenes DivIVA shows normal polar localization but is not biologically active when expressed in B. subtilis. Complementation experiments with different chimeras of B. subtilis and L. monocytogenes DivIVA suggest that MinJ and RacA bind to separate DivIVA domains. Fluorescence microscopy of green fluorescent protein-tagged RacA and MinJ corroborated this conclusion and suggests that MinJ recruitment operates via the N-terminal lipid binding domain, whereas RacA interacts with the C-terminal domain. We speculate that this difference is related to the cellular compartments in which MinJ and RacA are active: the cell membrane and the cytoplasm, respectively.     

HER2 Ile655Val and PTEN IVS4 polymorphisms in patients with breast cancer

Although HER2/PTEN pathway is commonly disrupted in cancer, association of HER2 and PTEN polymorphisms with breast cancer (BC) remains controversial. We investigated the HER2 Ile655 Val and PTEN IVS4 polymorphisms in patients with BC in Turkish population. HER2 Ile655Val (rs 1136201) and PTEN IVS4 (rs 3830675) polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism (PCR–RFLP) in blood samples of 118 BC patients and 118 age-matched healthy controls. We found that the frequency of the Ile/Val genotype of HER2 Ile655Val gene was significantly higher in BC patients (p < 0.009; OR: 1,983 95 % CI: 1.181—3.328). The presence of ATCTT insertion (+/+) genotype at downstream of exon 4 in intron 4 of PTEN IVS4 gene was also associated with 1.83 fold decreased risk of BC development (p < 0.033; OR: 1.83, 95 % CI: 1.11—3.03). Analysis on clinico-pathological parameters showed neither HER2 Ile655Val nor PTEN IVS4 genotypes were not associated with any of the variables (p > 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population.