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BACKGROUND@#: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.@*METHODS@#: TS mice model (TSMO) (n = 80) were established with 3,3'-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.@*RESULTS@#: A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.@*CONCLUSIONS@#: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.
Subject(s)
Animals , Mice , Disease Models, Animal , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/physiology , RNA, Ribosomal, 16S/genetics , Serotonin , Tics , Tourette Syndrome/therapyABSTRACT
Objective To investigate the effect of Ningdong granule on 5-hydroxytryptamine metabolism and 5-HT2AR of Tourette’s Syndrome(TS) rat models. Methods 32 SD rats were divided into 4 groups randomly, the control group, the model (Apo) group, the low dosage NDG (NGL) group, and the high dosage (NGH) group. TS rat models were induced by intraperitoneal injection (i.p.) with Apo (2 mg/kg) in the experimental groups last 4 weeks. Rats in the control group were injected with normal saline (0.9%) (3 ml/kg, i.p.). Then, the rats were treated by intragastric administration (i.g.) with ND granular at 1.8g/(kg?d)in NGL group, with ND granular at 3.6 g/(kg?d)in NGH group, with distilled water at equal Volume in Control group and Apo group respectively for 12 successive weeks. Analysis the striatum 5-HT2AR protein expression by Immunohistochemical method;Determination of the content of 5-HT and 5-HIAA in striatum by Enzyme linked immunosorbent assay (ELISA). Results The level of 5-HT and 5-HT2AR protein expression in the model group [(1.98±0.14)ng/ml and(143.10±8.01)], compared with the control group[(1.78±0.10)ng/ml and(127.43±6.72)], was up-regulated (P<0.01 or 0.05). The levels of 5-HT and 5-HT2AR protein expression in NGH group[(2.20±0.14)ng/ml and(166.33±9.21)ng/ml] were further up-regulated, and the levels of 5-HIAA in NDH group [(0.58±0.08) ng/ml] became lower, compared with the control group(P<0.01 or 0.05). Conclusion Activity of 5-HT system enhanced in Apo-induced TS rat model. However, the enhanced activity may still be relatively insufficient. The mechanism of ND granulear treating TS was associated with depression of the 5-HT metabolism, up-regulation expression of 5-HT2AR, and improving the activity insufficient of 5-HT system.
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Objective To investigate the efficacy and safety of Ningdong granule on Obsessive-compulsive disorder (OCD) associated with Tourette's syndrome (TS).Methods Thirty-six patients with OCD associated with TS were randomly divided into 2 groups.18 patients in the treatment group were treated with ND granule,and 18 patients in the control group were treated with fluoxetine,the initial dose of fluoxetine was 10 mg/d,and maximum dose was 60 mg/d.All of the participants with history of medication had to be medication-free for≥ 1 weeks prior to the study.The severity of tics and OCD were evaluated at baseline and at end point (8 w),with Yale Global Tic Severity Scale (YGTSS)and Yale-Brown Obsessive Compulsive Scale (Y-BOCS),the contents of 5-HT in serum were measured by ELISA.Side-effects were evaluated according to an adverse event chart produced by this study team.Results The effective rate of treating tics in treatment group was 88.89％ (16/18),and in control group was 77.78％ (14/18).The effective rate of treating OCD in treatment group was 83.33％ (15/18),and in control group was 88.89％ (16/18).The differences in the aspects between treatment group and control group were not significant (P＞0.05).Compared with YGTSS scores [the treatment group was (27.28 ± 8.10),the control group was (29.17 ± 7.53)] and Y-BOCS scores [the treatment group was (22.72 ± 6.75),the control group was (23.17 ± 6.12)] at baseline,the scores YGTSS scores [the treatment group was (12.72±5.20),the control group was (15.50±5.39)] and Y-BOCS scores [the treatment group was (1250± 4.38),the control group was (12.22±4.31)] of both two groups at end point reduced significantly (P＜0.01),but the difference between the two groups was not significant (P＞0.05).The contents of serum 5-HT in the two groups were significantly raised after treatment [the treatment group was (86.05±24.26 vs 66.00±19.63) ng/ml,P=0.01),the control group was (91.16±26.07 vs 67.52±21.18) ng/ml,P＜0.01].Only one subject reported adverse reactions in the treatment group,while 6 subjects experienced adverse reactions in the control group,but no difference was shown in comparison of the aspect between the treatment group and the control group (P＞0.05).Conclusion ND granule with tiapride could improve the syndrome of tics and OCD associated with TS.ND granule with tiapride and fluoxetine with tiapride showed similar efficacy and safety for OCD with TS.
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To investigate the apoptosis-inducing effect of cinobufacini (Huachansu) on human hepatoma cell line HepG2 and its possible mechanism of action, HepG2 cells were treated with different concentrations of cinobufacini. Cell proliferation was measured by methylthiazolyl tetrazolium (MTT) assay. The morphological changes of apoptosis were observed by Hoechst 33258 staining. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry (FCM). Quantitative real-time RT-PCR and Western blotting analysis were used to detect the mRNA and protein expressions of apoptosis related factors Bcl-2, Bax and p53. The results indicated that cinobufacini could inhibit the proliferation of HepG2 cells in a dose and time dependent manner. Remarkable morphological changes of apoptosis including cytoplasmic and nuclear condensation and partition of cytoplasm were observed by Hoechst 33258 staining. According to FCM analysis, HepG2 cells were arrested in G2/M phase and the apoptotic rate increased with the increase of the concentration of cinobufacini. Both the mRNA and protein expressions of Bax and p53 were up-regulated while Bcl-2 expression down-regulated. Thus, cinobufacini could inhibit the proliferation and induce apoptosis of human hepatoma cell line HepG2. Furthermore, up regulation of Bax and p53 as well as down regulation of Bcl-2 expressions may be one of the important apoptotic inducing mechanisms.
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Objective To investigate the effect of the Pingshen Tongluo Jiangya granula on the blood pressure and RAS of spontaneously hypertensive rat (SHR). Methods SHR were randomly divided into model group, high dosage group, lower dosage group and captopril group, with normal Wistar rats as control group. Different dosage of Pingshen Tongluo Jiangya granula, captopril and water wes given orally to the rats at the same time of a day for 8 weeks. Blood pressure, AngⅠ, AngⅡ and ALD were determined respectively before treatment and 1, 2, 4, 6, 8 week. Results After eight weeks, the blood pressure of high dosage of Pingshen Tongluo Jiangya granula group had stepped down obviously (P 0.05). It shows that the granula could decrease blood pressure, inhibit the activity of RAS caused by high blood pressure. Conclusion The granula can decrease blood pressure smoothly and steadily, as well as reverse early stage of renal damage caused by high blood pressure.
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Objective To investigate the characteristics of TCM syndromes of Tourette syndrome (TS) to find out the basis for its TCM treatment. Methods Based on the preliminary studies,the TCM syndrome scale of TS is designed to investigate the general data,main symptoms and syndromes of 126 cases of TS children to find out the frequency of each syndrome. Results Of the 126 TS cases,97 were males,accounting for 77%; the average age was 8.31 years; and 32 had a positive family history,accountting for 25.4%. In the tic behavior,the facial twitching and limb twitching occupied 91.6% of the muscular stereotyped tic. In the vocal behavior,the throat and nasal sound occupied 42.1%. In the accompanied symptoms,the inattention occupied 69.8%. In the personality offset,the willfulness occupied 49.2%,irritable hyperactivity occupied 78.6%,and silence occupied 7.1%. More than 50% of the patients had red or dark red tongue with thick or sticky coating. Nearly 70% of them had string-taut or rolling pulse. As for the syndromes,heart-liver deficiency with deficiency wind stirred up,and liver-kidney yin deficiency with yang hyperactivity stirring up wind were common,being 41.3% and 34.1% respectively. Conclusion TS takes the heart-liver deficiency with deficiency wind stirred up and liver-kidney yin deficiency with yang hyperactivity stirring up wind as the common syndromes. The basic treating principle is enriching yin and reducing yang,and smoothing the liver to stop wind. At the same time,reinforcing the spleen and nourishing the heart,and dissolving phlegm and enlightening the brain should be applied for treatment.
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Objective To observe the therapeutic effect of Ningxin Granule Heart-Quieting Granule for pediatric viral myocarditis.Methods Totally 60 cases of pediatric viral myocarditis were randomly divided into treatment group (n=30) and control group (n=30).There was no significant difference between two groups in sexuality,age and pathogenetic condition.Patients in treatment group took Ningxin Granule,while ATP,CoA,Vit C,Inosine and Ribavirin were given to control group by intravenous drip.Results The treatment group was superior to control group in relieving symptoms,reducing the bearing premature,CK-MB,cTnI and LVEDD,and increasing LVEF.Conclusion Ningxin Granule can obviously relieve symptoms and signs,reduce the bearing premature,decrease the level of myocardial enzyme and improve the cardiac function.