[Mechanisms of liver-soothing and mind-regulating acupuncture mediating opioid receptor participated in the treatment of migraine].

OBJECTIVE: To observe the effect of "Shugan Tiaoshen"(liver-soothing and mind-regulating) acupuncture on behavior reactions, opioid receptor expressions in the anterior cingulate cortex tissue and inflammatory factors in the serum in migraine rats, in order to explore its mechanism underlying improvement of migraine. METHODS: In the first part of this study, forty male Wistar rats were randomized into control, model, routine acupuncture and "Shugan Tiaoshen" acupuncture groups (n=10/group), and in the second part, other 40 more male Wistar rats were randomized into low, medium and high dosage of blocker of µopioid receptor (OPRM）CTOP5 and PBS groups (n=10/group, for validating the involvement of opioid receptor in the effect of "Shugan Tiaoshen"). The migraine model was established by subcutaneous injection of glyceryl trinitrate. Routine acupuncture was applied to "Baihui" (GV20) and bilateral"Fengchi" (GB20), and "Shugan Tiaoshen" acupuncture applied to GV20, and bila-teral GB20, "Neiguan" (PC6) and "Taichong" (LR3), with the needles retained for 30 min. Behavior responses (head scratching, tail biting, cage climbing and number of going there and back) were scaled. Serum IL-1ß, IL-6 and TNF-α were detected by ELISA, and the expression levels of opioid receptor µ, δ and κ (OPRM, OPRD, OPRK) mRNAs and proteins in the anterior cingulate cortex were detected by fluorescence quantitative PCR and Western blot separately. In the second part of this study, CTOP solution (5µL at concentrations of 20µg/µL,10µg/µL and 5µg/µL) or PBS was injected into the bilateral rostral portions of anterior cingulate cortex 30 min before every "Shugan Tiaoshen" acupuncture intervention, followed by observing the behavioral changes and assaying the contents of serum IL-1ß, IL-6 and TNF-α. RESULTS: After modeling, the behavioral score, serum IL-1ß, IL-6 and TNF-α contents were significantly increased in the model group relevant to the control group (P<0.05), and the beha-vioral score had no significant difference among the model and two acupuncture groups before intervention (P>0.05). Whereas the expression levels of OPRM, OPRD and OPRK mRNAs and proteins had a slight increase in the model group (P>0.05). After the intervention, the behavioral score, serum IL-1ß, IL-6 and TNF-α contents were significantly decreased and the expression levels of OPRM, OPRD and OPRK mRNAs (2.150, 1.066 and 0.805 folds in the "Shugan Tiaoshen" group) and proteins (2.273, 0.901 and 0.893 folds in the "Shugan Tiaoshen" group) notably up-regulated in both "Shugan Tiaoshen" and routine acupuncture groups relevant to the model group (P<0.01, P<0.05), showing that the biggest up-regulation of mRNA expression was OPRM. Comparison between two acupuncture groups showed that the behavioral score, and serum IL-1ß, IL-6 and TNF-α contents were significantly lower, and the expression levels of OPRM, OPRD and OPRK mRNAs and proteins obviously higher in the "Shugan Tiaoshen" group than those in the routine acupuncture group (P<0.01,P<0.05). Results of the second part of this study showed that after injection of antagonist CTOP of OPRM, the therapeutic effect of "Shugan Tiaoshen" acupuncture was weakened in the reduction of behavioral score and serum IL-1ß, IL-6 and TNF-α contents, being minimal, moderate and maximum in the high, medium and low dose of antagonist relevant to PBS in sequence (P<0.05, P<0.01). CONCLUSION: "Shugan Tiaoshen" acupuncture can mitigate pain in migraine rats, which may be associated with its function in up-regulating the expressions of opioid receptors (especially OPRM), and in inhibiting inflammatory reaction in the anterior cingulate cortex.

Association Between Exposure to Outdoor Artificial Light at Night and Sleep Disorders Among Children in China.

Importance: Healthy sleep has an important role in the physical and mental health of children. However, few studies have investigated the association between outdoor artificial light at night (ALAN) and sleep disorders in children. Objective: To explore the associations between outdoor ALAN exposure and sleep disorders in children. Design, Setting, and Participants: This population-based cross-sectional study, part of the National Chinese Children Health Study, was conducted from April 1, 2012, to June 30, 2013, in the first stage and from May 1, 2016, to May 31, 2018, in the second stage in 55 districts of 14 cities in China. This analysis included 201 994 children and adolescents aged 2 to 18 years. Data were analyzed from February 20 to March 21, 2022. Exposures: Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's residential address obtained from the satellite imagery data, with a resolution of approximately 500 m. Main Outcomes and Measures: Sleep disorders were measured by the Chinese version of the Sleep Disturbance Scale for Children. Generalized linear mixed models were used to estimate the associations of outdoor ALAN with sleep scores and sleep disorders. Results: The study included 201 994 children and adolescents (mean [SD] age, 11.3 [3.2] years; 106 378 boys [52.7%]), 7166 (3.5%) of whom had sleep disorder symptoms. Outdoor ALAN exposure of study participants ranged from 0.02 to 113.48 nW/cm2/sr. Compared with the lowest quintile (Q1) of outdoor ALAN exposure, higher quintiles of exposure (Q2-Q5) were associated with an increase in total sleep scores of 0.81 (95% CI, 0.66-0.96) in Q2, 0.83 (95% CI, 0.68-0.97) in Q3, 0.62 (95% CI, 0.46-0.77) in Q4, and 0.53 (95% CI, 0.36-0.70) in Q5. Higher quintiles of exposure were also associated with odds ratios for sleep disorder of 1.34 (95% CI, 1.23-1.45) in Q2, 1.43 (95% CI, 1.32-1.55) in Q3, 1.31 (95% CI, 1.21-1.43) in Q4, and 1.25 (95% CI, 1.14-1.38) in Q5. Similar associations were observed for sleep disorder subtypes. In addition, greater effect estimates were found among children younger than 12 years. Conclusions and Relevance: The findings of this cross-sectional study suggest that sleep disorders are more prevalent among children residing in areas with high levels of outdoor ALAN and the associations are generally stronger in children younger than 12 years. These findings further suggest that effective control of outdoor ALAN may be an important measure for improving the quality of children's sleep.

Discovery of novel indole derivatives that inhibit NEDDylation and MAPK pathways against gastric cancer MGC803 cells.

A series of novel indole derivatives were synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (MGC803, EC-109 and PC-3). Among these analogues, 2-(5-methoxy-1H-indol-1-yl)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (V7) showed the best inhibitory activity against MGC803 cells with an IC50 value of 1.59 µM. Cellular mechanisms elucidated that V7 inhibited colony formation, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, indole analogue V7 inhibited NEDDylation pathway and MAPK pathway against MGC803 cells.