GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.

G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.

A parallel-group study of near-infrared spectroscopy-neurofeedback in children with attention deficit hyperactivity disorder.

The present study aimed to assess the efficacy of Near-infrared spectroscopy (NIRS) real-time neurofeedback (NF) vs. atomoxetine (AT) in children with attention deficit hyperactivity disorder (ADHD). A parallel-group study was conducted to enroll children with ADHD between 8 and 12 years of age. Participants were assigned into the NIRS group and AT group as their wish. Subjects in the NIRS group received 12 sessions of NF training within 6 weeks, and subjects in the AT group were given oral medication. Changes in Swanson, Nolan, and Pelham-V rating scales (SNAP-IV), and performance of Go/No-Go and N-back working memory tasks at week 3, 6 and 8 were evaluated. Forty-nine patients completed the study, including 18 ADHD in the NIRS group and 31 in the AT group. Total scores of SNAP-IV significantly decreased from baseline to week 3, week 6, and week 8 in both groups. Patients in the NIRS group showed significant lower scores on the inattention subscale of SNAP-IV at week 3 and week 6, compared to the AT group. NIRS group had a shorter reaction time during the Go/No-Go task at week 6 and fewer errors during 2-back than the AT group at week 3. The findings revealed that NIRS real-time NF is more efficacious relative to AT in improving behavioral performance, highlighting its potential role and advantages in treating patients with ADHD.

Effects of chitooligosaccharide-zinc on the ovarian function of mice with premature ovarian failure via the SESN2/NRF2 signaling pathway.

Chitooligosaccharide-zinc (COS·Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg·kg-1·d-1 COS·Zn), a treatment group (300 mg·kg-1·d-1 COS·Zn), a prevention group, two control groups and two CY/BUS groups. COS·Zn (150, 300 mg·kg-1·d-1) and COS·Zn (300 mg·kg-1·d-1) were therapeutically and preventatively administered to POF mice in the treatment and prevention studies, respectively. All the groups were administered for 21 days. Fewer primary and secondary follicles were observed in the COS·Zn-treated groups (including the treatment and prevention groups) than those of the control groups. Meanwhile, the ovarian index and the levels of FSH and LH notably increased in the treatment and prevention groups compared with those in the CY/BUS group. The levels of MVH, OCT4 and PCNA in the treatment group (300·kg-1·d-1 COS·Zn) and MVH in the prevention group remarkably increased compared with those in the CY/BUS groups. Meanwhile, the levels of P53 and P16 protein were down-regulated in the treatment and prevention groups compared with those in the CY/BUS groups. Additionally, the amounts of Sestrin2 (SESN2) and SOD2 protein were obviously higher in the treatment group (150 mg·kg-1·d-1 COS·Zn) than those in the CY/BUS groups. Similarly, the amounts of NRF2 and SESN2 protein were up-regulated in the prevention group. Besides, an increased GSH level was observed in the two treatment groups, compared with that in the CY/BUS groups, and the same trend was also present in the prevention group. Taken together, COS·Zn improves the ovarian and follicular development through regulating the SESN2/NRF2 signaling pathway. These results suggest the role of COS·Zn as a novel agent for the treatment and prevention of POF.

A comparison between Zhishi Xiaopiwan and cisapride in treatment of functional dyspepsia.

AIM:To compare the therapeutic effect of the herbal medicine Zhishi Xiaopi with that of Cisapride in the treatment of functional dyspepsia (FD).METHODS:Fifty-one FD patients were randomized into Herbal group (n =27) and Cisapride group (n =24). Two two groups were given a four-week treatment of Zhishi Xiaopi 100ml, tid, a.c. and Cisapride 5mg, tid, a.c. respectively. Patients' symptoms were assessed and 39 patients'(22 of Herbal group and 17 of Cisapride group) gastric liquid emptying times were measured with ultrasonography before and after the treatment.RESULTS:The therapeutic effective rates of Herbal group and Cisapride group were 81.49% and 87.50% (P> 0.05). The half gastric emptying time (GET50) and gastric emptying time (GET) of healthy controls and FD patients were 36.12min ± 10.22min vs 52.95min ± 13.49min and 87.07min ± 21.11min vs 120.74min ± 23.08min (P < 0.001).The GET(50) and GET of Herbal group before and after the treatment were 51.63min ± 13.15min vs 45.62min ± 10.82min and 117.34min ± 23.29min vs 103.26min ± 22.19min (P < 0.01). The results of Cisapride group were 54.66min ± 14.14min vs 40.95min ± 11.29min and 125.12min ± 24.47minvs 95.49min ± 22.31min (P < 0.01). The differences in values (median) of GET(50) and GET for Herbal group and Cisapride group before and after treatment were 5.75min vs 17.18min and 13.22min vs 33.54min (P < 0.05). CONCLUSION:Delayed gastric emptying is one of the pathogenesis of FD. Both Zhishi Xiaopi pills and Cisapride can effectively alleviate the symptoms of FD and accelerate gastric liquid emptying.The effect of Zhishi Xiaopiwan on enhancing gastric motility is comparable with but less than that of Cisapride.