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BackgroundInduction of pro-inflammatory factors is one of the characteristics of microglia activation and can be regulated by numerous active components of Chinese traditional herbs. Suppression of pro-inflammatory factors is beneficial to alleviate microglia-mediated cell injury. The present study aims to investigate the effect and possible mechanism of 2,3,4’,5-tetrahydroxystilbene 2-O-β-D-glucoside (TSG) on LPS-mediated induction of pro-inflammatory factors in microglia.MethodsWestern blot, ELISA, and Hoechst 33258 were used to measure the protein expression, TNF-α/IL-6 content, and apoptotic nuclei, respectively. The mRNA level was measured by real time-PCR. Nitric oxide (NO) content, lactate dehydrogenase (LDH) content, and NF-κB binding activity were assayed by commercial kits.ResultsTSG reduced iNOS protein expression as well as TNF-α, IL-6, and NO content in LPS-stimulated BV-2 cells. TSG attenuated the increase in apoptotic nuclei, caspase-3 cleavage, and LDH content induced by BV-2 cell-derived conditioned medium in primary hippocampal neurons. Mechanistic studies showed that TSG reduced the mRNA level of iNOS, TNF-α, and IL-6. TSG failed to suppress IκB-α degradation, NF-κB phosphorylation and nuclear translocation, and ERK1/2, JNK, and p38 phosphorylation. TSG, however, markedly reduced the binding of NF-κB to its DNA element. Chromatin immunoprecipitation (ChIP) assays confirmed that TSG reduced NF-κB binding to the iNOS promoter. These findings were ascertained in primary microglia where the LPS-induced increase in iNOS expression, NO content, apoptotic nuclei, and NF-κB binding to its DNA element were diminished by TSG.ConclusionsThese studies demonstrate that TSG attenuates LPS-mediated induction of pro-inflammatory factors in microglia through reducing the binding activity of NF-κB. This might help us to further understand the pharmacological role of TSG in inflammatory response in the central nervous system.

Background: Marijuana is the most commonly used illicit drug in the United States. More and more states legalized medical and recreational marijuana use. Adolescents and emerging adults are at high risk for marijuana use. This ecological study aims to examine historical trends in marijuana use among youth along with marijuana legalization. Method: Data (n = 749,152) were from the 31-wave National Survey on Drug Use and Health (NSDUH), 1979-2016. Current marijuana use, if use marijuana in the past 30 days, was used as outcome variable. Age was measured as the chronological age self-reported by the participants, period was the year when the survey was conducted, and cohort was estimated as period subtracted age. Rate of current marijuana use was decomposed into independent age, period and cohort effects using the hierarchical age-period-cohort (HAPC) model.Results: After controlling for age, cohort and other covariates, the estimated period effect indicated declines in marijuana use in 1979-1992 and 2001-2006, and increases in 1992-2001 and 2006-2016. The period effect was positively and significantly associated with the proportion of people covered by Medical Marijuana Laws (MML) (correlation coefficients: 0.89 for total sample, 0.81 for males and 0.93 for females, all three p values < 0.01), but was not significantly associated with the Recreational Marijuana Laws (RML). The estimated cohort effect showed a historical decline in marijuana use in those who were born in 1954-1972, a sudden increase in 1972-1984, followed by a decline in 1984-2003. Conclusion: The model derived trends in marijuana use were coincident with the laws and regulations on marijuana and other drugs in the United States since the 1950s. With more states legalizing marijuana use in the United States, emphasizing responsible use would be essential to protect youth from using marijuana.

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Background:Current antidepressants are clinically effective only after several weeks of administration. Tetramethylpyrazine (TMP) is an identified component of Ligusticum wallichii with neuroprotective effects. Here, we investigated the antidepressant effects of TMP in mice models of depression.Methods:Antidepressant effects of TMP were first detected in the forced swim test (FST) and tail suspension test (TST), and further assessed in the chronic social defeat stress (CSDS) model. Changes in the brain-derived neurotrophic factor (BDNF) signaling pathway and in hippocampal neurogenesis after CSDS and TMP treatment were then investigated. A tryptophan hydroxylase inhibitor and BDNF signaling inhibitors were also used to determine the mechanisms of TMP.Results:TMP exhibited potent antidepressant effects in the FST and TST without affecting locomotor activity. TMP also prevented the CSDS-induced symptoms. Moreover, TMP completely restored the CSDS-induced decrease of BDNF signaling pathway and hippocampal neurogenesis. Furthermore, a blockade of the BDNF signaling pathway prevented the antidepressant effects of TMP, while TMP produced no influence on the monoaminergic system.Conclusions:In conclusion, these data provide the first evidence that TMP has antidepressant effects, and this was mediated by promoting the BDNF signaling pathway.

Chinese gay men are preferentially vulnerable to mental health problems because of deep-rooted, traditional social influence that overemphasizes heterosexual marriage, fertility, and filial piety. A cross-sectional survey was conducted from November to December 2017 using the Chinese version of the Symptom Checklist-90-R (SCL-90-R) to assess the status of, and factors associated with the mental health of Chinese gay men. Unadjusted associations between demographic factors and the total score of SCL-90-R were examined using t/F tests or person correlation analysis. The main factors that were most predictive of the aggregate score of SCL-90-R were identified by multiple linear regressions. A total of 367 gay men participated in this survey with an average score of SCL-90-R of 180.78 ± 79.58. The scores of seven dimensions (OCS, INTS, DEPR, ANX, HOS, PHOA, PARI) for Chinese gay men were found to be significantly higher than the national norm (all p < 0.001). Age (B = −1.088, SE = 0.478, p = 0.023), educational level (B = −14.053, SE = 5.270, p = 0.008), and degree of coming out publicly (B = −23.750, SE = 4.690, p < 0.001) were protective factors for participants’ mental health status. A gay man who is the only child in his family was more likely to obtain a higher total score of SCL-90-R in China (B = 59.321, SE = 7.798, p < 0.001). Our study reveals the worrying mental health status of Chinese gay men. Shifts in familial, governmental, and societal normas are suggested to improve the current social acceptance towards sexual minority men, as well as to reduce detrimental health effects.