Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo

BACKGROUND: To evaluate whether PI3K/Akt pathway could effect on apoptosis and its mechanism in nasopharyngeal carcinoma cells. METHODS: The activation of the PI3K/Akt and its effect on CNE-2Z cells in vivo and in vitro was investigated by MTT assay, flow cytometry, western blot, ELISA, terminal deoxyribonucleotide transferase-mediated nick-end labeling assays (TUNEL), and immunohistochemical analyses, using PI3K inhibitor, LY294002. RESULTS: The results showed that LY294002 inhibited the phosphorylating of Akt (S473), cell proliferation, and induced apoptosis in CNE-2Z cells. However, our experiment results also demonstrated that apoptosis-induced LY294002 was directly regulated by caspase-9 activation pathway. CONCLUSION: These data suggested that PI3K inhibitor, LY294002, induced apoptosis by caspase-9 activation pathway and might be as a potentially useful target for therapeutic intervention in nasopharyngeal carcinoma patients

Interaction Effects of Life Events and Hair Cortisol on Perceived Stress, Anxiety, and Depressive Symptoms Among Chinese Adolescents: Testing the Differential Susceptibility and Diathesis-Stress Models

The differential susceptibility model and the diathesis-stress model on the interaction effect between the individuals’ traits and environmental factors will be conducive to understand in depth whether the psychophysiological traits are the risk factors of child development. However, there is no study focusing on the activity of the hypothalamic-pituitary-adrenal (HPA) axis. We examined whether the HPA activity serves as a physiological marker of the differential susceptibility model or the diathesis-stress model by exploring the interactive effect of life events and hair cortisol on perceived stress, anxiety, and depressive symptoms among Chinese adolescents. The participants were 324 students in senior high school. They reported their psychological states with questionnaires in their first semester after a 3-month adaptation period; 2 weeks later, they provided 1-cm hair segments closest to the scalp. We measured hair cortisol concentration as a biomarker of HPA activity using high-performance liquid chromatography–tandem mass spectrometry. There was a significant interaction effect of academic events and hair cortisol on adolescents’ perceived stress, anxiety, and depression symptoms. We also observed a significant interaction between interpersonal events and hair cortisol on adolescents’ anxiety symptoms. Looking at the region of significance, proportion of interaction index, and proportion affected index, we found that adolescents with higher cortisol levels had a tendency to experience higher perceived stress and anxiety symptoms when they had high academic events scores, but lower perceived stress and anxiety symptoms when they had lower academic events scores. By contrast, adolescents with higher cortisol levels had a greater risk of experiencing high depressive symptoms only when they had higher academic events scores. Adolescents with higher cortisol levels also tended to have lower anxiety symptoms when they had higher interpersonal events scores, but greater anxiety symptoms when they had lower interpersonal events scores. These results suggested that HPA activity might serve as a biomarker of the differential susceptibility model for perceived stress and anxiety symptoms, while for depressive symptoms, it might serve as a marker of the diathesis-stress model

Abnormal Plasma Levels of Steroids and Their Ratios in Patients With Prurigo Nodularis: A Pilot Study

Background: It has been suggested that cortisol levels are abnormal in chronic urticaria and atopic dermatitis, but other steroids, such as dehydroepiandrosterone (DHEA) and testosterone, are still unknown, and whether these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. Limited data are available on steroid levels in prurigo nodularis (PN)-related research, and no study has examined the association between pruritus severity and steroid levels in PN patients.Aims: This pilot study aimed to investigate the differences in the levels of five steroids combined with their ratios in plasma between PN patients and controls and to examine the associations between the biomarkers and pruritus severity.Methods: Plasma concentrations of five steroids, including cortisol, cortisone, testosterone, progesterone, and dehydroepiandrosterone (DHEA), in 36 patients with PN were compared with concentrations in thirty-six and matched healthy controls. The concentrations of steroids were quantitated using liquid chromatography-tandem mass spectrometry. The PN symptoms, including pruritus severity, pain, and life quality, were assessed with the use of the visual analog scale, prurigo score index, numerical rating scale, and verbal rating scale and dermatology life quality index scores.Results: In comparison with controls, PN patients had lower levels of plasma cortisol and cortisone, which negatively correlated with PN symptoms. PN patients had higher levels of cortisone and testosterone to cortisol, which positively correlated with pruritus severity. Additionally, there were no significant differences in plasma concentrations of DHEA and testosterone between the two groups. We found no correlation between plasma concentrations of DHEA and testosterone and pruritus severity.Conclusion: This pilot study suggests that there may be abnormalities in peripheral blood levels of cortisol, and cortisone and the ratios of cortisone and testosterone to cortisol in patients with PN, and they are related to pruritus severity. The plasma concentrations of testosterone and DHEA may be not abnormal in PN patients and may not be associated with pruritus severity

Hair Measurements of Cortisol, Dhea, and Dhea to Cortisol Ratio as Biomarkers of Chronic Stress Among People Living With HIV in China: Known-Group Validation

Background Existing literature suggests that endocrine measures, including the steroid hormones of cortisol and Dehydroepiandrosterone (DHEA), as well as the DHEA to cortisol ratio in the human hair can be used as promising biomarkers of chronic stress among humans. However, data are limited regarding the validity of these measures as biomarkers of chronic stress among people living with HIV (PLWH), whose endocrine system or hypothalamic pituitary adrenal (HPA) axis may be affected by HIV infection and/or antiretroviral therapy (ART) medications. Method Using hair sample data and self-reported survey from 60 PLWH in China, we examined the validity of three endocrine measures among Chinese PLWH using a known-groups validation strategy. High-stress group (n = 30) and low-stress group (n = 30) of PLWH were recruited through individual assessment interviews by a local licensed psychologist. The endocrine measures in hair were extracted and assessed by LC-APCI-MS/MS method. Both bivariate and multivariate analyses were conducted to examine the associations between the endocrine measures and the stress level, and to investigate if the associations differ by ART status. Results The levels of endocrine measures among Chinese PLWH were consistent with existing studies among PLWH. Generally, this pilot study confirmed the association between endocrine measures and chronic stress. The high stress group showed higher level hair cortisol and lower DHEA to cortisol ratio. The higher stress group also reported higher scores of stressful life events, perceived stress, anxiety and depression. Hair cortisol level was positively related to anxiety; DHEA was negatively associated with stressful life events; and the DHEA to cortisol ratio was positively related to stressful life events and perceived stress. ART did not affect the associations between the endocrine measures and stress level. Conclusions Our findings suggest that hair cortisol and DHEA to cortisol ratio can be used as promising biomarkers of chronic stress among PLWH. Clarifying the role of steroid hormones in the psychoimmunology of PLWH may yield important implications for clinical practice and psychological intervention

LC-MS/MS Quantification of Nevirapine and Its Metabolites in Hair for Assessing Long-Term Adherence

The adherence assessment based on the combination of nevirapine (NVP) and its two metabolites (2-hydroxynevirapine and 3-hydroxynevirapine) would more comprehensively and accurately reflect long-term adherence than that of a single prototype. This study aimed to develop a specific, sensitive and selective method for simultaneous detection of the three compounds in hair and explore whether there was consistency among the three compounds in assessing long-term adherence. Furthermore, 75 HIV-positive patients who were taking the NVP drug were randomly recruited and divided into two groups (high-and low-adherence group). All participants self-reported their days of oral drug administration per month and provided their hair strands closest to the scalp at the region of posterior vertex. The concentrations of three compounds in the hair were determined using a developed LC-MS/MS method in multiple reaction monitoring. This method showed good performances in limit of quantification and accuracy with the recoveries from 85 to 115% and in precision with the intra-day and inter-day coefficients of variation within 15% for the three compounds. The population analysis revealed that patients with high-adherence showed significantly higher concentrations than those with low-adherence for all three compounds. There were significantly moderate correlations of nevirapine with 2-hydroxynevirapine and 3-hydroxynevirapin and high correlation between 2-hydroxynevirapine and 3-hydroxynevirapin. The two NVP’s metabolites showed high consistency with NVP in evaluating long-term adherence

Epigenetic Modification of TLRs in Leukocytes Is Associated with Increased Susceptibility to Salmonella enteritidis in Chickens

Toll-like receptors (TLRs) signaling pathways are the first lines in defense against Salmonella enteritidis (S. enteritidis) infection but the molecular mechanism underlying susceptibility to S. enteritidis infection in chicken remains unclear. SPF chickens injected with S. enteritidis were partitioned into two groups, one consisted of those from Salmonella-susceptible chickens (died within 5 d after injection, n = 6), the other consisted of six Salmonella-resistant chickens that survived for 15 d after injection. The present study shows that the bacterial load in susceptible chickens was significantly higher than that in resistant chickens and TLR4, TLR2-1 and TLR21 expression was strongly diminished in the leukocytes of susceptible chickens compared with those of resistant chickens. The induction of expression of pro-inflammatory cytokine genes, IL-6 and IFN-β, was greatly enhanced in the resistant but not in susceptible chickens. Contrasting with the reduced expression of TLR genes, those of the zinc finger protein 493 (ZNF493) gene and Toll-interacting protein (TOLLIP) gene were enhanced in the susceptible chickens. Finally, the expression of TLR4 in peripheral blood mononuclear cells (PBMCs) infected in vitro with S. enteritidis increased significantly as a result of treatment with 5-Aza-2-deoxycytidine (5-Aza-dc) while either 5-Aza-dc or trichostatin A was effective in up-regulating the expression of TLR21 and TLR2-1. DNA methylation, in the predicted promoter region of TLR4 and TLR21 genes, and an exonic CpG island of the TLR2-1 gene was significantly higher in the susceptible chickens than in resistant chickens. Taken together, the results demonstrate that ZNF493-related epigenetic modification in leukocytes probably accounts for increased susceptibility to S. enteritidis in chickens by diminishing the expression and response of TLR4, TLR21 and TLR2-1

Psychometric properties of the Chinese version of adjustment disorder new module-20 in breast cancer patients

BACKGROUND: After the new definition of adjustment disorder (AjD) by the International Classification of Diseases-11(ICD-11), AjD has attracted more and more attention. Adjustment disorder new module-20 (ADNM-20), which is used to diagnose AjD, has been verified in some countries, but it has not been verified in China. As a result, the purpose of this study was to investigate the validity and reliability of the Chinese version of the Adjustment disorder new module-20 (ADNM-20) in female breast cancer patients. METHODS: The ADNM-20 translated into Chinese employed the translation and back translation technique. Three hundred fifty four newly diagnosed (< 1 year) female breast cancer patients were recruited from Tongji Hospital and Hubei Cancer Hospital in Hubei, China. The patients completed the self-report questionnaire including demographic characteristics and the scale ADNM-20. Data on psychometric properties were evaluated in terms of internal consistency, item-total correlations, test-retest reliability, and factorial validity. RESULTS: ADNM-20 core symptoms included 8 items and two factors, which were extracted by using exploratory factor analysis (EFA). It could explain 61.74% of the total variance. ADNM-20 accessory symptoms including 12 items and four factors, which were extracted by using EFA. It could explain 68.34% of the total variance. Cronbach's α coefficient for ADNM-20 was 0.93, split-half reliability was 0.87, and the test-retest correlation coefficient was 0.74. The correlation coefficient between each subscale was ranged from 0.53 to 0.71 (P < 0.01), while the correlation coefficient between the subscales and total scale was ranged from 0.79 to 0.89 (P < 0.01). CONCLUSIONS: The study verified the validity and reliability of the Chinese version of ADNM-20. It is applicable to measure the prevalence of adjustment disorder in the breast cancer population

Testosterone administration increases social discounting in healthy males

Although testosterone is thought to induce antisocial and aggressive behavior, research on social economic interactions has associated it with prosocial and affiliative behavior. Here, we investigated the effects of testosterone on social distance-dependent generosity in an economic discounting task where participants chose between selfish and generous alternatives. We administered testosterone gel or placebo to men in a double-blind, randomized design and measured how willing they were to share rewards with close and distant others. Across two studies (total n = 174), testosterone administration consistently increased social discounting, that is participants became more selfish, particularly with regard to distant others (vs. close others). This effect was not explained by testosterone-induced increases in social distance perception. Our findings provide causal evidence that-testosterone reduces generosity in human economic decision-making. Moreover, they suggest that the valuation and the perception of social distance are independently affected by testosterone

Simultaneous HPLC-APCI-MS/MS quantification of endogenous cannabinoids and glucocorticoids in hair

Hair matrix could retrospectively record association of endogenous cannabinoids (e.g. 2-arachidonoyl glycerol, 2-AG and N-arachidonoyl-ethanolamine, AEA) and glucocorticoids (e.g. cortisol and cortisone) in a myriad of physiological functions. However, depending on the extraction conditions, the spontaneous isomerization of 2-AG to 1-arachidonoylglycerol (1-AG) and the possible rearrangement of O-arachidonoyl ethanolamine (OAEA) to AEA in various sample matrices could be major obstacles encountered in the detection of both 2-AG and AEA. This study aimed to develop a novel method for simultaneous quantification of 2-AG, AEA, cortisol and cortisone in hair. Methanol was used as the incubation solution and an acidic mixture of deionized water and methanol were utilized as mobile phase in order to avert possible rearrangements of both OAEA and 2-AG. The analyses were performed on a high-performance liquid chromatography tandem mass spectrometer with atmosphere pressure chemical ionization in positive mode. The method showed good linearity in the range of 3.0-250 pg/mg for AEA, 15.0-1250 pg/mg for 2-AG and 1-250 pg/mg for cortisol and cortisone. Limit of detection was 1.5 pg/mg for AEA, 6.0 pg/mg for 2-AG and 0.5 pg/mg for cortisol and cortisone. For all four analytes, intra and inter-day coefficients of variation were less than 20% and recovery above 90%. Population analyses in 473 hair samples established that 2-AG was significantly correlated with AEA. 2-AG was significantly and positively correlated with cortisol and cortisone. There was a significant positive correlation of AEA with cortisol, but not with cortisone. Obese participants showed a significantly higher concentration of cortisone and 2-AG. Males showed significantly higher 2-AG and cortisone levels but significantly lower AEA levels than females. (C) 2016 Elsevier B.V. All rights reserved

Intraindividual stability of cortisol and cortisone and the ratio of cortisol to cortisone in saliva, urine and hair

Background: Cortisol, cortisone and the ratio of cortisol to cortisone in saliva, urine and hair are acute, short-term and long-term biomarkers to reliably assess the activity of hypothalamic-pituitaryadrenal (HPA) axis and 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). One key issue is whether these biomarkers have intraindividual relative stability. Salivary, urinary and hair cortisol was proven to show considerable long-term intraindividual relative stability. However, currently unknown is whether cortisone and the ratio in saliva, urine and hair show intraindividual relative stability.</p