Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males.

Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.

Macrophage depletion with clodronate-containing liposomes affects the incidence and development of rheumatoid arthritis.

OBJECTIVE: This study investigated the effect of macrophage depletion with clodronate-containing liposomes (Clo-lip) on the incidence and development of rheumatoid arthritis (RA). METHODS: The effect of macrophage depletion with Clo-lip in the spleen was assessed by HE (haematoxylin and eosin) staining and immunohistochemistry (IHC). Thirty BALB/c mice were randomly divided into three groups, which were administered PBS-lip, Clo-lip, or normal saline. RA model mice were then created and the appearance of the paws was observed. Expression of CD68 by macrophages was examined by immunofluorescence on the 49th day. Forty-five RA model mice were created and randomly divided into three groups. The experiment group was administered Clo-lip at different timepoints. The degree of arthritis score was recorded during the administration. Histological features were detected by HE staining on the 84th day. RESULTS: Compared to controls, horseshoe-shaped nuclei and multi-core large cells were reduced in the experimental group (HE stain; p < 0.05). Brown tag-CD68 and tag-CD80 macrophages were fewer in the experimental group than in the control group (immunohistochemistry; p < 0.05). Furthermore, the degree of arthritis score in the experimental group was significantly decreased (p < 0.05). HE staining showed that there was no or less inflammatory cell infiltration in the articular cavity in mice in the experimental group, and that the percentage of CD68+ macrophage cells in synovial cells was significantly lower than in the control group (p < 0.05). CONCLUSION: Macrophage depletion with Clo-lip can affect the incidence and development of RA.

Clinical Effects of CpG-Based Treatment on the Efficacy of Hepatocellular Carcinoma by Skewing Polarization Toward M1 Macrophage from M2.

OBJECTIVE: This study aims to explore the clinical efficacy of CpG-based therapy for treating hepatocellular carcinoma (HCC) by skewing polarization toward M1 macrophage from M2. METHODS: Pulmonary metastasis rate, overall survival time, and remission rate of 10 patients with HCC treated with transcatheter arterial chemoembolization (TACE) combined with CpG therapy and 10 age-, gender-, and TNM0-matched patients treated with TACE (control group) were compared. RESULTS: No pulmonary metastasis rate was 70% in the combined treatment group and 40% in the control group, respectively; and the differences between the two groups were statistically significant (p < 0.05). Median overall survival time was 22 months in the combined treatment group, compared with 6.65 months in the control group (p < 0.05). Remission rate in the combined treatment group (70%) was higher than in the control group (30%), but the differences between these two groups were not statistically significant (p > 0.05). CONCLUSION: Compared with TACE, CpG combined with TACE can decrease the pulmonary metastasis rate. This combined therapy can also improve the overall survival time of patients.

Inhibition of tribbles protein-1 attenuates radioresistance in human glioma cells.

Radiotherapy is one of the remedies in the treatment of glioma. The radioresistance is a major drawback, of which the mechanism is unclear. Tribble protein and histone deacetylase are involved in the cancer pathogenesis. This study aims to test a hypothesis that the histone deacetylase inhibitors attenuate the radioresistance in human glioma cells. In this study, human glioma cells were cultured. The cells were treated with irradiation with or without a histone deacetylase inhibitor, butyrate. Apoptosis of the glioma cells was assessed by flow cytometry. The results showed that human glioma cells expressed a low level of Trib1, which was significantly up regulated by exposure to small doses (2 Gy/day for 4 days) of irradiation. Trib1-deficient glioma cells showed an enhanced response to irradiation-induced apoptosis. Exposure to small doses of irradiation, Trib1 formed a complex with pHDAC1 (phosphor histone deacetylase-1) to inhibit p53 expression in glioma cells. The presence of HDAC1 inhibitor, butyrate or parthenolide, significantly enforced irradiation-induced glioma cell apoptosis. In conclusion, the Trib1 plays a critical role in the development of radioresistance of glioma cells. The data suggest that inhibition of Trib1 or HDAC1 has the potential to prevent or attenuate the radioresistance.

Neovibsanin B inhibits human malignant brain tumor cell line proliferation and induces apoptosis.

The present study was designed to examine the effect of neovibsanin B on glioma cell viability, apoptosis and on the survival time in mice bearing tumor xenografts. The results demonstrated that neovibsanin B significantly reduced the cell viability of GL261-NS and GL261-AC cells in a dose-dependent manner. However the inhibition of proliferation was more significant in GL261-NS cells. The IC50 value of neovibsanin B against GL261-NS and GL261-AC cells is 5 and 25 nM, respectively. The inhibitory effect of neovibsanin B on cell growth was more effective than that of vincristine (VCR) (P < 0.05). We also observed a significant decrease in sphere-forming ability of GL261-NS cells on treatment with neovibsanin B. The number of colonies formed by GL261-NS cells on treatment with neovibsanin B, VCR and DMSO were 3.34 ± 1.02, 12.53 ± 3.46 and 61.34 ± 9.89% respectively after 7 days. The flow cytometry revealed a marked increase in apoptotic cell death of GL261-NS cells on treatment with neovibsanin B. The western blots showed a significant decrease in the level of activated caspase-3 on treatment with neovibsanin B after 24 h. In addition, neovibsanin B increased the median survival time of glioma-bearing mice (P < 0.05). Therefore, neovibsanin B effectively inhibits glioma cell viability by inducing apoptosis, and can be a potent therapeutic agent for the treatment of malignant glioma.

Specific cellular immune response elicited by the necrotic tumor cell-stimulated macrophages.

OBJECTIVE: To determine whether the necrotic tumor cell-stimulated macrophages (NTCSM) could elicit specific immune response. METHODS: Mice were immunized with the necrotic H22 tumor cell lysate-stimulated macrophages and the specific immune responses against the same tumor challenge were examined. The morphologic characteristics were observed with the transmission electron microscope and scanning electron microscopy. The expression of CD14, CD68, CD80 and CD86 were detected with the flow cytometer. The cytotoxicity and cytokine production of splenocytes were measured with the MTT assay and ELISA assay respectively. RESULTS: Our research results reveal that NTCSMs are larger cells which generally generate spherical and elongated protrusions, folding membrane, and vesicles on their surface. Also, abundant lysosomes, secondary lysosomes, phagosomes, rough endoplasmic reticulum, and lipid bodies were found in their cytoplasm. The flow cytometry results show that the necrotic H22 tumor cell lysate could enhance the expression of CD14 and CD86 molecules and the NTCSM was characterized by the expression of CD14+/-CD68+CD80-CD86+. After the mice were vaccinated with NTCSMs, the tumor forming rate, tumor volume and weight of the NTCSM-vaccinated group were significantly lower than those of the sterile saline-injected group and untreated macrophage-vaccinated group (p<0.05). The cytotoxicity to H22 tumor cells of the splenocytes obtained from the NTCSM-immunized group was higher than that of the sterile saline-injected group and untreated macrophage-vaccinated group (p<0.05). Meanwhile, the levels of IL-2 and IFN-γ in the culture supernatant of the NTCSM-immunized group were higher significantly than those of the saline-injected group and untreated macrophage-vaccinated group. The level of IL-4 of the NTCSM-immunized group was significantly lower than those of the other two groups. CONCLUSION: Our results indicated that NTCSMs could elicit specific cellular immune responses in vivo.

Application of attention network test and demographic information to detect mild cognitive impairment via combining feature selection with support vector machine.

Mild cognitive impairment (MCI) is now thought as the prodromal phase of Alzheimer's disease (AD), and the usual method for diagnosing the disease would be a battery of neuropsychological assessment. The present study proposes to integrate a feature selection scheme with support vector machine (SVM) to identify patients with MCI by using attention network test (ANT) and demographic data. Forty-two patients with MCI and forty-five normal individuals underwent ANT recording, and the reaction time and accuracy of ANT and demographics (age, gender, and educational level) were selected as original features. To select features, we first introduced some random variables as probe features in the original data, then ranked all the features according to their influence on the support vector machine decision function, and finally selected those features that had an influence higher than that of the probes. Initially 18 different features were reduced to only four features by our method. SVM classifier created by using these four features gave an 85% classification accuracy with a sensitivity of 85% and a specificity of 86%. And the area under the curve obtained by receiver operating characteristics analysis was 0.918. The experimental results demonstrate that the proposed method is a good potential use to assist identifying patients with MCI objectively and efficiently.

[Oral glucose tolerance and insulin release test in 52 cases of obese and overweight children].

OBJECTIVE: To assess the state of glucose metabolism and beta-cell function in obese and overweight children. METHODS: Levels of glucose and insulin were detected during oral glucose tolerance test in 52 obese and overweight children aged 11.3 +/- 1.8 years with body mass index (BMI) 30.2 +/- 19.2 kg/m(2). Insulin resistance index (IR = FIN x FPG/22.5), insulin sensitivity index (IS = 1/FIN x FPG) and ratio of insulin increment to glucose increment at 30' (I(30)-I(0)/G(30)-G(0)) post oral glucose were measured. (FIN = fasting insulin. FPG = fasting plasma glucose). The IR, IS and the ratio post oral glucose were compared among groups with varying BMI and between groups of impaired glucose tolerance (IGT) and control. Serum triglyceride determination and B ultrasonography of liver were performed. RESULTS: (1) one patient with type 2 diabetes (1.9%) and 5 patients with IGT (9.6%) were found. (2) IR (> or = 2.8) was observed in 76.9% of the cases. (3) The IR, IS and their ratio showed no difference between the compared groups. (4) IR and IS did not show significant difference but there was significant difference in ratio between the IGT and control group. (5) Increased serum triglyceride and fatty liver were noted in 36.5% and 53.3% of the cases, respectively. CONCLUSION: The results indicated that insulin resistance and reduced insulin sensitivity in obese and overweight children are common, and these changes seemed not to correlated with the varying degree of BMI. Beta-cells function was obviously impaired in obese children with IGT and disorder of lipid metabolism exists in many obese and overweight children revealed.

[Prader-Willi syndrome and genomic imprinting].

OBJECTIVE: Prader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome. The purpose of this study was to show the molecular genetic defects and genomic imprinting basis in Chinese PWS patients and to evaluate the clinical applications of a differential diagnostic test for PWS. METHODS: Fluorescence in situ hybridization (FISH) and methylation-specific PCR (MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using three probes, including SNRPN probe for identification of the critical locus in PWS region, D15Z1 and PML control probes for identification of the 15p arm and 15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on sodium bisulfite treatment of DNA and PCR primers specific for the maternal and paternal allele. RESULTS: When hybridized with mixed probes, it was found in 2 patients that the central specific signal was absent, but both the flanking control signals were retained, indicating SNRPN gene deletion of chromosome 15q11-13. Bisulfite-modified DNA from all PWS children amplified with methylated allele-specific primer pair showed only maternal 131bp PCR product, indicating the maternal uniparental disomy (UPD15). CONCLUSION: Genomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other cyto-molecular tests and its results were consistent with the clinical diagnosis of PWS, so it seems to be a reliable diagnostic method for PWS patients who show abnormal methylation at SNRPN. The genetic differential tests for PWS are important in determining familial recurrence risk.