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Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from long-term non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions. [ABSTRACT FROM AUTHOR]

Objective: To explore heterosexual and homosexual behaviors, and influencing factors, in those unmarried out-of-school young people aged 15 to 24 years, so as to provide the basis on the education and service of sexual and reproductive health for those young people. Methods: The questionnaire survey form was anonymously filled out by 1 113 unmarried out-of-school young people on six target spots in urban and rural areas of six provinces by the computer assisted self-interview (CASI) system. Results: The incidences of hetero-or homo- sexual behaviors in the 15 to 18 years male group and the 19 to 24 years male group were significantly higher than those in female groups (P < 0.05). 7.14% of the first heterosexual behaviors in the 15 to 18 years female group were forced. Sexual safety precautions were used in 66.67% of males and 40.00% of females in the 15 to 18 years group, and in 58.82% of males and 49.11% of females in the 19 to 24 years group. About 30.00% of males reported that they had partners' pregnancies, and 30% of females reported that they had pregnancies. The incidence of multiple sexual partners in the 19 to 24 years male group was significantly higher than that in the age-matched female group (P < 0.01). On homosexual behaviors, the average age of the first homosexual behaviors in the 15 to 18 years group was about 14 years, 15.79% of males in the 19 to 24 years group were forced to have, and 46.15% of males and 33.33% females reported that they had more than two sexual partners. Multivariate analyses showed that watching pornographic materials and being older were common risk factors of heterosexual behaviors for males (OR, 3.51 and 3.81 respectively) and females (OR, 6.41 and 3.85 respectively). Compared with those factors approving premarital sexual behaviors, the attitudes rejecting premarital sexual behaviors from respondents themselves (OR = 0.18) and their parents (OR = 0.37), and the neutral attitude from friends (OR =0.47), were protective factors in males, while the options that the female respondents thought it being not good but acceptable (OR =0.14) or opposed (OR = 0.06), and that friends thought it being unacceptable (OR = 0.16) or unknown (OR = 0.21), were protective factors and the neutral attitude from parents was risk factor (OR = 12.56) in females. Conclusions: The incidences of heterosexual and homosexual behaviors, and unsafe sexual behaviors, in those unmarried out-of-school young people were high, which were positively related to the pornographic material and the open attitudes from respondents themselves, parents and friends. [ABSTRACT FROM AUTHOR]

Sphingosine-1-phosphate (S1P) receptor subtype 1 (S1P1), a G-protein coupled receptor (GPCR), regulates many biological activities of endothelial cells (ECs). In this report, we show that S1P1 receptors are present in the nuclei of ECs by using various biochemical and microscopic techniques such as cellular fractionation, immunogold labeling, and confocal microscopic analysis. Live cell imaging showed that plasma membrane S1P1 receptors are rapidly internalized and subsequently translocated to nuclear compartment upon S1P stimulation. Utilizing membrane biotinylation technique further supports the notion that nuclear S1P1 receptors were internalized from plasma membrane S1P1 after ligand treatment. Moreover, nuclear S1P1 is able to regulate the transcription of Cyr61 and CTGF, two growth factors functionally important in the regulation of vasculature. Collectively, these data suggest a novel S1P–S1P1 signaling axis present in the nuclear compartment of endothelial cells, which may regulate biological responses of endothelium. [ABSTRACT FROM AUTHOR]