Healthy orthorexia, orthorexia nervosa, and personality traits in a community sample in Turkey.

OBJECTIVE: Orthorexia nervosa is an eating disorder characterized by a rigid preoccupation with a perceived healthy diet. However, little is known about healthy orthorexia compared to orthorexia nervosa. The current study examined the relationship between healthy orthorexia and orthorexia nervosa and personality traits in a Turkish sample. METHODS: Three hundred fifty participants from a community sample aged 18-65 were included in the study. Participants completed a sociodemographic data collection form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Teruel Orthorexia Scale (TOS), and the 10-Item Personality Inventory (TIPI). RESULTS: The frequency of healthy orthorexia was 32.3% and orthorexia nervosa was 10.2%. There were no differences between genders regarding healthy orthorexia and orthorexia nervosa scores. Healthy orthorexia symptoms were negatively correlated with depression and anxiety (r = -0.11 and r = -0.20, respectively, P < .05), while they were positively correlated with agreeableness (r = 0.17), conscientiousness (r = 0.14), and extraversion (r = 0.15). Orthorexia nervosa symptoms were positively associated with anxiety (r = 0.12), depression (r = 0.10), and healthy orthorexia (r = 0.55). Hierarchical regression analyses demonstrated that depression was negatively associated with healthy orthorexia symptoms, explaining 4% of the variance. The agreeableness trait was positively associated with healthy orthorexia symptoms, explaining 4% of the variance. However, no specific personality trait was associated with orthorexia nervosa symptoms. CONCLUSION: To our knowledge, the present study is the first to examine the relationships between personality traits, healthy orthorexia, and orthorexia nervosa symptoms in a Turkish sample. Sociocultural factors may be important for understanding orthorexia nervosa and healthy eating behaviors in this population.

Altered Polarization and Impaired Phagocytic Activity of Lung Macrophages in People With Human Immunodeficiency Virus and Chronic Obstructive Pulmonary Disease.

BACKGROUND: People with human immunodeficiency virus (PWH) have an increased risk of developing chronic obstructive pulmonary disease (COPD). METHODS: We phenotyped lung macrophages in 4 subgroups-M1 (CD40+CD163-), M2 (CD40-CD163+), double positives (CD40+CD163+), and double negatives and (CD40-CD163-)-and we determined their phagocytic capacity in PWH with and without COPD. RESULTS: People with human immunodeficiency virus with COPD have more double-negative macrophages (84.1%) versus PWH without (54.3%) versus controls (23.9%) (P=.004) and reduced phagocytosis (P=.012). Double-negative macrophages had the worst phagocytic capacity (P<.001). CONCLUSIONS: People with human immunodeficiency virus with COPD have an abundance of nonpolarized macrophages, which have poor phagocytic capacity and therefore predispose PWH to increased risk of disease progression.

Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis.

Objective- Smooth muscle cells (SMCs) are the most abundant cells in human atherosclerotic lesions and are suggested to contribute at least 50% of atheroma foam cells. In mice, SMCs contribute fewer total lesional cells. The purpose of this study was to determine the contribution of SMCs to total foam cells in apolipoprotein E-deficient (ApoE-/-) mice, and the utility of these mice to model human SMC foam cell biology and interventions. Approach and Results- Using flow cytometry, foam cells in the aortic arch of ApoE-/- mice were characterized based on the expression of leukocyte-specific markers. Nonleukocyte foam cells increased from 37% of total foam cells in 27-week-old to 75% in 57-week-old male ApoE-/- mice fed a chow diet and were ≈70% in male and female ApoE-/- mice following 6 weeks of Western diet feeding. A similar contribution to total foam cells by SMCs was found using SMC-lineage tracing ApoE-/- mice fed the Western diet for 6 or 12 weeks. Nonleukocyte foam cells contributed a similar percentage of total atheroma cholesterol and exhibited lower expression of the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1) when compared with leukocyte-derived foam cells. Conclusions- Consistent with previous studies of human atheromas, we present evidence that SMCs contribute the majority of atheroma foam cells in ApoE-/- mice fed a Western diet and a chow diet for longer periods. Reduced expression of ABCA1, also seen in human intimal SMCs, suggests a common mechanism for formation of SMC foam cells across species, and represents a novel target to enhance atherosclerosis regression.

Determining the factors influencing the intimate relationship between sexual satisfaction and dyadic adjustment in postmenopausal women.

INTRODUCTION: Identifying and characterizing sexual dysfunction is crucial in order to improve the quality of the marital relationship in postmenopausal women. Regarding this, the present study aimed to determine the association of menopausal characteristics with sexual satisfaction and marital adjustment. MATERIAL AND METHODS: This cross-sectional study was conducted on 89 postmenopausal women chosen using an improbable randomized sampling method. A questionnaire that collects demographic characteristics, the Dyadic Adjustment Scale (DAS) and The Golombok Rust Inventory of Sexual Satisfaction (GRISS) index were used to collect relevant data during the survey. RESULTS: The mean age of postmenopausal women recruited to the present study was 54.6 ±6.7. The overall mean GRISS score and DAS score were 5.6 ±1.7 and 92.1 ±11.2 respectively. The mean GRISS scores were found to significantly increase as the ages of the women increased (p = 0.044). Mean DAS scores were lower in postmenopausal women that have menopause duration longer than 10 years (p = 0.035). Higher education level of the spouse is associated with lower GRISS scores (p = 0.024). No correlation was observed between marital adjustment and sexual satisfaction. CONCLUSIONS: Although sexual satisfaction and marital adjustment levels are decreased in the postmenopausal period, these two parameters do not seem to be related to each other. Multidimensional factors must be taken into account when evaluating sexual and marital satisfaction in postmenopausal women.

Increased serum G72 protein levels in patients with schizophrenia: a potential candidate biomarker.

OBJECTIVE: The product of the G72 gene is an activator of d-amino acid oxidase and has been suggested to play a role in the pathogenesis of schizophrenia. Increased G72 protein levels may be associated with disturbed glutamatergic transmission and increased reactive oxygen species. Only one pilot study by Lin et al. has investigated the potential role of serum G72 protein levels as a biomarker for schizophrenia. In this study, we aimed to compare serum G72 protein levels between patients with schizophrenia and healthy controls, and to retest the results of the previous pilot study. Materials and methods In total, 107 patients with a diagnosis of schizophrenia according to the inclusion and exclusion criteria and 60 age-sex-matched healthy controls were included in the study. The groups were compared regarding serum G72 protein levels. RESULTS: The mean serum G72 protein values were 495.90±152.03 pg/ml in the schizophrenia group and 346.10±102.08 pg/ml in the healthy control group. The mean serum G72 protein level was significantly increased in the schizophrenia group compared with the healthy control group (t=-3.89, p<0.001). A receiver operating characteristics analysis was performed to compare the schizophrenia and healthy control groups. It was determined that the cut-off value was 141.51 pg/ml with a sensitivity of 0.991 and a specificity of 0.821. CONCLUSION: We suggest that serum G72 protein levels may represent a candidate biomarker for schizophrenia and have confirmed the results of the previous preliminary study. Additional studies with larger sample sizes and the inclusion of first episode schizophrenia patients are required to clarify the reliability and validity of serum G72 protein levels as a biomarker for schizophrenia.

The effect of music therapy during shockwave lithotripsy on patient relaxation, anxiety, and pain perception.

OBJECTIVES: To research the effect of listening to music during shock wave lithotripsy (SWL) on the patient's pain control, anxiety levels, and satisfaction. PATIENTS AND METHODS: The study comprised 400 patients from three hospitals. Half of patients listened to music during their first SWL session but not during their second session. The other half had no music for the first session but the second session was accompanied by music. During all sessions, with and without music, pulse rates, blood pressure, State-Trait Anxiety Inventory-State Anxiety scores (STAI-SA), Visual Analog Scale (VAS scores for pain), willingness to repeat procedure (0 = never to 4 happily), and patient satisfaction rates (0 = poor to 4 = excellent) were assessed. RESULTS: There was no statistical difference between the two groups in terms of blood pressure and pulse rates. In both groups, the STAI-SA and VAS pain scores were lower in the session when music was listened to (p < 0.001). The patients requested more SWL treatment be completed while listening to music and their satisfaction was greater. CONCLUSION: Music lowered the anxiety and pain scores of patients during SWL and provided greater satisfaction with treatment. Completing this procedure while the patient listens to music increases patient compliance greatly and reduces analgesic requirements.

CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.

The role of culture and self-construal in autobiographical memories of US and Turkish college students.

This study examined memory variables both cross-culturally and across four cultural self-construal types. US (N=240) and Turkish (N=174) college students described their earliest childhood memory, and another significant childhood memory, and completed the Balanced Integration-Differentiation (BID) Scale (Imamoglu, 1998; 2003), which measured relatedness and individuation, and allowed for the classification of students into four different self-construal types (Related-Individuated, Separated-Individuated, Related-Patterning, Separated-Patterning). At the cultural level US students' earliest memories were dated approximately 6 months earlier, had greater volume, and were more positive. US students also reported memories as more important. Turkish students' memories had more detail, a higher proportion of propositions, self-, other- and we-related words, and higher other-self ratios, and they were clearer than those of US students. Turkish students also reported greater ease in describing their earliest memory in words. At the level of self-construal the primary differences were between students high in both relatedness and individuation and those low in both. The culture by BID interaction was significant in only 1 of the more than 24 analyses.

Circulating cytokine levels in systemic sclerosis related interstitial lung disease and idiopathic pulmonary fibrosis.

Exploration of cytokine levels in systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is needed to find common and diverse biomolecular pathways. Circulating levels of 87 cytokines were compared amongst 19 healthy controls and consecutive patients with SSc-ILD (n = 39), SSc without ILD (n = 29), and IPF (n = 17) recruited from a Canadian centre using a log-linear model adjusted for age, sex, baseline forced vital capacity (FVC), and immunosuppressive or anti-fibrotic treatment at time of sampling. Also examined was annualized change in FVC. Four cytokines had Holm's corrected p-values less than 0.05. Eotaxin-1 levels were increased approximately two-fold in all patient categories compared to healthy controls. Interleukin-6 levels were eight-fold higher in all ILD categories compared to healthy controls. MIG/CXCL9 levels increased two-fold more in all but one patient category compared to healthy controls. Levels of a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, (ADAMTS13) were lower for all categories of patients compared to controls. No substantial association was found for any of the cytokines with FVC change. Observed cytokine differences suggest both common and diverse pathways leading to pulmonary fibrosis. Further studies evaluating longitudinal change of these molecules would be informative.

Macrophages with reduced expressions of classical M1 and M2 surface markers in human bronchoalveolar lavage fluid exhibit pro-inflammatory gene signatures.

The classical M1/M2 polarity of macrophages may not be applicable to inflammatory lung diseases including chronic obstructive pulmonary disease (COPD) due to the complex microenvironment in lungs and the plasticity of macrophages. We examined macrophage sub-phenotypes in bronchoalveolar lavage (BAL) fluid in 25 participants with CD40 (a M1 marker) and CD163 (a M2 marker). Of these, we performed RNA-sequencing on each subtype in 10 patients using the Illumina NextSeq 500. Approximately 25% of the macrophages did not harbor classical M1 or M2 surface markers (double negative, DN), and these cells were significantly enriched in COPD patients compared with non-COPD patients (46.7% vs. 14.5%, p < 0.001). 1886 genes were differentially expressed in the DN subtype compared with  all other subtypes at a 10% false discovery rate. The 602 up-regulated genes included 15 mitochondrial genes and were enriched in 86 gene ontology (GO) biological processes including inflammatory responses. Modules associated with cellular functions including oxidative phosphorylation were significantly down-regulated in the DN subtype. Macrophages in the human BAL fluid, which were negative for both M1/M2 surface markers, harbored a gene signature that was pro-inflammatory and suggested dysfunction in cellular homeostasis. These macrophages may contribute to the pathogenesis and manifestations of inflammatory lung diseases such as COPD.

Abundance of Non-Polarized Lung Macrophages with Poor Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD).

Lung macrophages are the key immune effector cells in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Several studies have shown an increase in their numbers in bronchoalveolar lavage fluid (BAL) of subjects with COPD compared to controls, suggesting a pathogenic role in disease initiation and progression. Although reduced lung macrophage phagocytic ability has been previously shown in COPD, the relationship between lung macrophages' phenotypic characteristics and functional properties in COPD is still unclear. (1) Methods: Macrophages harvested from bronchoalveolar lavage (BAL) fluid of subjects with and without COPD (GOLD grades, I-III) were immuno-phenotyped, and their function and gene expression profiles were assessed using targeted assays. (2) Results: BAL macrophages from 18 COPD and 10 (non-COPD) control subjects were evaluated. The majority of macrophages from COPD subjects were non-polarized (negative for both M1 and M2 markers; 77.9%) in contrast to controls (23.9%; p < 0.001). The percentages of these non-polarized macrophages strongly correlated with the severity of COPD (p = 0.006) and current smoking status (p = 0.008). Non-polarized macrophages demonstrated poor phagocytic function in both the control (p = 0.02) and COPD (p < 0.001) subjects. Non-polarized macrophages demonstrated impaired ability to phagocytose Staphylococcus aureus (p < 0.001). They also demonstrated reduced gene expression for CD163, CD40, CCL13 and C1QA&B, which are involved in pathogen recognition and processing and showed an increased gene expression for CXCR4, RAF1, amphiregulin and MAP3K5, which are all involved in promoting the inflammatory response. (3) Conclusions: COPD is associated with an abundance of non-polarized airway macrophages that is related to the severity of COPD. These non-polarized macrophages are predominantly responsible for the poor phagocytic capacity of lung macrophages in COPD, having reduced capacity for pathogen recognition and processing. This could be a key risk factor for COPD exacerbation and could contribute to disease progression.

Chitinase-3-like protein 1 levels in bipolar disorder.

OBJECTIVES: To evaluate the relationship between the expression level and biologic role of YKL-40 in bipolar disorder (BD). METHODS: This case-control study was conducted in the Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, Turkey in 2015. One hundred and four patients diagnosed as having bipolar disorder (DSM5 criteria), and 96 participants were included as healthy controls in this study. A human YKL-40 enzyme-linked immunosorbent assay (ELISA) kit was used to measure the serum YKL-40 levels. As independent variables, we collected data on C-reactive protein (CRP), demographic variables, and medications. Results: The mean YLK-40 levels for the BD was 2723.5±543.8 pg/ml and control groups was 2132.5±576.3 pg/ml (t=7.42, p less than 0.001). The mean CRP levels for the BD was 0.4±0.6 mg/dl and control groups was 0.4±0.7 mg/dl (t=0.02, p=0.985). The receiver operating characteristics (ROC) analysis revealed an area under the curve (AUC) of YKL-40 in the diagnosis of BD as 0.79 (95% confidence interval [CI]: 0.72-0.85) with a sensitivity of 82.7% and specificity of 68.1% at a cutoff level of 2307.1 pg/ml. The use of antidepressants, antipsychotics, mood modifiers, and the presence of any comorbidity was not related to the YKL-40 levels (p greater than 0.05). Conclusion: With acceptable sensitivity and specificity levels, the YKL-40 can be utilized as a marker in the diagnosis and follow-up of BD.

Whole blood vs PBMC: compartmental differences in gene expression profiling exemplified in asthma.

BACKGROUND: Blood has proven to be a useful resource for molecular analysis in numerous biomedical studies, with peripheral blood mononuclear cells (PBMCs) and whole blood being the major specimen types. However, comparative analyses between these two major compartments (PBMCs and whole blood) are few and far between. In this study, we compared gene expression profiles of PBMCs and whole blood samples obtained from research subjects with or without mild allergic asthma. METHODS: Whole blood (PAXgene) and PBMC samples were obtained from 5 mild allergic asthmatics and 5 healthy controls. RNA from both sample types was measured for expression of 730 immune-related genes using the NanoString nCounter platform. RESULTS: We identified 64 uniquely expressed transcripts in whole blood that reflected a variety of innate, humoral, and adaptive immune processes, and 13 uniquely expressed transcripts in PBMCs which were representative of T-cell and monocyte-mediated processes. Furthermore, analysis of mild allergic asthmatics versus non-asthmatics revealed 47 differentially expressed transcripts in whole blood compared to 1 differentially expressed transcript in PBMCs (FDR < 0.25). Finally, through simultaneous measurement of PBMC proteins on the nCounter assay, we identified CD28 and OX40 (TNFRSF4), both of which are critical co-stimulatory molecules during T-cell activation, as significantly upregulated in asthmatics. CONCLUSIONS: Whole blood RNA preserved in PAXgene tubes is excellent for producing gene expression data with minimal variability and good sensitivity, suggesting its utility in multi-centre studies requiring measurement of blood gene expression.

Effect of Nausea and Vomiting on Anxiety and Depression Levels in Early Pregnancy.

OBJECTIVE: Nausea and vomiting of pregnancy (NVP) have been reported to be associated with distinct physiological responses to psychosocial stress. In this study, we aimed to evaluate the impact of nausea and vomiting on anxiety and depression during pregnancy. MATERIALS AND METHODS: Eighty-three pregnant women with nausea and vomiting and 83 healthy pregnant women were included. All participants completed the demography- and pregnancy-related questionnaire, including Rhodes Index of Nausea and Vomiting, Beck Anxiety Inventory (BAI), and Edinburgh Postnatal Depression Scale (EPDS). RESULTS: The median BAI and EPDS levels were 13 (min-max: 0-43) and 7 (min-max: 0-20) for the study group and 4 (min-max: 0-26) and 4 (min-max: 0-16) for control group, respectively. A univariate analysis revealed a statistically significant increase in terms of BAI levels (p<0.001) between the groups, but no significant difference was observed in terms of EPDS. In a logistic regression analysis, both anxiety (p=0.018) and depression (p=0.022) were found to be affected by NVP. The BAI levels of the NVP group correlated with the severity of NVP. CONCLUSION: According to the results of the present study, women with severe NVP experienced a higher level of anxiety and depression, which necessitates an extra awareness from healthcare professionals in order to be able to contribute effectively.

Metabolic syndrome and vaspin in patients with bipolar disorder.

Metabolic disorders and abnormal levels of circulating adipokines have been reported in patients with bipolar disorder (BD). The aim of this study was to investigate the differences in the correlations of vaspin plasma levels and metabolic parameters between two groups: patients with BD and mentally healthy persons. We measured plasma levels of vaspin, metabolic parameters, and metabolic syndrome (MS) in 101 patients with BD and 90 healthy control (HC) subjects. Patients with BD were evaluated with the Young Mania Rating Scale (YMRS) to assess manic symptoms and the Hamilton Depression Scale (HDS) to assess depressive symptoms. The Global Assessment of Functioning (GAF) was used to evaluate the general functions of the patients. Body mass index (BMI), weight, waist circumference (WC), fasting glucose, and triglyceride levels of the study group were statistically higher than those of the healthy controls (p = 0.001, p < 0.001, p < 0.001, p = 0.027, and p = 0.001 respectively). Plasma levels of vaspin were 0.978 ng/ml in patients with BD and 0.292 in the HC group (p < 0.001). Our study revealed associations between metabolic parameters/metabolic syndrome and vaspin plasma concentrations in patients with BD. Vaspin can play a specific role in the pathogenesis of metabolic disorders in these subjects and can be a specific indicator substance in BD.

An assessment of marital adjustment in patients with rheumatoid arthritis.

Aim To investigate marital adjustment in patients with rheumatoid arthritis and factors affecting this. Methods A total of 32 patients diagnosed with Steinbrocker class 1-2 rheumatoid arthritis and 32 healthy individuals from a similar age group were included. Sociodemographic characteristics, the Beck Depression Inventory (BDI), short-form 36(SF-36) and the dyadic adjustment scale (DAS) were evaluated in both groups. A visual analogue scale (VAS), the disease activity score 28(DAS28) and a health assessment questionnaire (HAQ) were also investigated in the patient group. Results Mean ages were 46.5±9.2 years in the patient group and 47.7±8.1 in the control group (p=0.5). No significant difference was determined between the two groups in terms of sociodemographic characteristics. No statistically significant correlation was observed between erythrocyte sedimentation rate (ESR), patient and physician global VAS, DAS28, HAQ and morning stiffness and DAS total score. Comparison of DAS subunits revealed a significant difference in dyadic satisfaction and affectional expression in the patient and control groups (p=0.046 and p=0.037). A statistically significant negative correlation was observed between duration of the disease and marital adjustment (p=0.01;r= -0.58). Conclusion Due to its progressive and prolonged course rheumatoid arthritis can also affect individuals' social relationships besides restricted daily living activities. Activation of rheumatoid arthritis did not affect marital adjustment in this study, but adjustment decreased with duration of the disease.

Increased childhood abuse in patients with premenstrual dysphoric disorder in a Turkish sample: a cross-sectional study.

OBJECTIVE: Abuse is considered to have a place in the etiology of various psychiatric disorders. Premenstrual dysphoric disorder (PMDD) is one of the psychiatric disorders for which abuse could be an etiologic factor; however, few studies have investigated the relationship between abuse and PMDD. In this study, our aim was to investigate childhood abuse in patients with PMDD and compare them with healthy female subjects. METHOD: This cross-sectional study included 70 women with PMDD (DSM-IV-TR criteria) who were admitted to the outpatient psychiatry clinic of Ankara Yenimahalle State Hospital, Ankara, Turkey, between December 2012 and December 2013. Additionally, 78 healthy controls were included in the study. Sociodemographic, familial, and reproductive period characteristics of the women were recorded. All subjects were administered the Premenstrual Syndrome Scale (PMSS) and the Childhood Trauma Questionnaire (CTQ). RESULTS: Among the sociodemographic characteristics, being a university graduate (76.9%) and being a public servant (70.5%) were significantly higher in the healthy control group (P = .01 and P = .01, respectively). A family history of PMDD (31.4%), a history of postpartum psychiatric disorders (11.4%), and a history of attempted suicide (7.1%) were higher in the PMDD group compared with the healthy control group (P = .001, P = .003, and P = .024, respectively). Significant differences were also found between PMDD and healthy controls in PMSS score (P ≤ .001), CTQ total scores (P = .002), and subscale scores including emotional abuse and emotional neglect (P = .004), physical abuse (P = .009), and sexual abuse (P = .012). CONCLUSIONS: To our knowledge, the present study is the first to investigate associations between PMDD and childhood abuse from Turkey. More comprehensive studies on this topic with larger sample sizes are required to enrich the literature and enable practitioners to be more effective in clinical practice.

siRNA therapy in cutaneous T-cell lymphoma cells using polymeric carriers.

Cutaneous T-cell lymphomas (CTCLs) arise from specific molecular aberrations that lead to uncontrolled cell proliferation. RNA interference (RNAi) with short interfering RNAs (siRNAs) is a feasible approach to interrupt aberrant signal processing in CTCL cells, but functional biomaterial carriers are needed to effectively deliver siRNAs intracellularly. Towards this goal, we explored the utility of lipid-substituted polyethylenimines (PEI) carriers in a cell model of CTCL. Using caprylic and linoleic acid substituted 2 kDa PEI (PEI-CA and PEI-LA, respectively), we showed effective delivery of siRNA to T-lymphocyte Hut78 and Jurkat cells, but silencing of a model protein (Green Fluorescent Protein, GFP) was possible only in the Hut78 cells. To enhance siRNA delivery to Hut78 cells, a high siRNA: carrier ratio used to assemble the complexes and centrifugation of cells in the presence of complexes were found effective. The toxicities of PEI-CA and PEI-LA were significantly lower than other commercial carriers, 25 kDa PEI and Lipofectamine(®) RNAiMAX. This might have contributed to reduced siRNA delivery efficiency of the latter carriers. Screening several endogenous targets led us to identify phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and cyclin-dependent kinase 18 (CDK18) as viable targets to induce siRNA-mediated cell growth inhibition. The results of this study identified promising polymeric carriers and molecular targets that could control proliferation of CTCL cells based on RNAi therapy.

Effect of Laurus nobilis L. Essential Oil and its Main Components on α-glucosidase and Reactive Oxygen Species Scavenging Activity.

The present study was designed to determine the effects of the essential oil of Laurus nobilis L. (Lauraceae) and its three main components on α-glucosidase and reactive oxygen species scavenging activity. The chemical composition of the essential oil from Laurus nobilis L. leaves was analyzed by GC/GC-MS and resulted in the identification of 29 compounds, representing 99.18% of the total oil. 1,8-cineole (68.82%), 1-(S)-α-pinene (6.94%), and R-(+)- limonene (3.04%) were determined to be the main components. The antioxidant features of the essential oil and its three main components were evaluated using inhibition of 2,2-diphenyl-1- picrylhydrazyl, hydroxyl, and superoxide radicals, inhibition of hydrogen peroxide and lipid peroxidation assays. The results show that the DPPH, hydroxyl, and superoxide radical as well as hydrogen peroxide scavenging activities of the essential oil are greater than the positive controls and the three main components of the oil when tested independently. The inhibition of lipid peroxidation by the oil occurred less frequently than with 1,8-cineole and R-(+)- limonene alone, but the effects were more pronounced than those seen with 1-(S)-α-pinene and the positive controls. An α-glucosidase inhibition assay was applied to evaluate the in-vitro antidiabetic activity of the essential oil. IC50-values were obtained for laurel essential oil, 1, 8-cineole, 1-(S)-α-pinene, and R-(+)-limonene: 1.748 µL/mL, 1.118 µL/mL, 1.420 µL/mL and 1.300 µL/mL, respectively. We also found that laurel essential oil and 1, 8-cineole inhibited the α-glucosidase competitively while 1-(S)-α-pinene and R-(+)-limonene were uncompetitive inhibitors.