Five-week music therapy improves overall symptoms in schizophrenia by modulating theta and gamma oscillations.

Introduction: Some clinical studies have shown that music therapy as an adjunctive therapy can improve overall symptoms in patients with schizophrenia. However, the neural mechanisms of this improvement remain unclear due to insufficient neuroimaging evidence. Methods: In this work, 17 patients with schizophrenia accepted a five-week music therapy (music group) that integrated listening, singing, and composing, and required patients to cooperate in a group to complete music therapy tasks. Meanwhile, 15 patients with schizophrenia received a five-week visual art intervention as the control group including handicraft and painting activities. We collected the Manchester Scale (MS) and Positive and Negative Symptom Scale (PANSS) scores and electroencephalography (EEG) data before and after intervention in two groups. Results: Behavioral results showed that both interventions mentioned above can effectively help patients with schizophrenia relieve their overall symptoms, while a trend-level effect was observed in favor of music therapy. The EEG results indicated that music therapy can improve abnormal neural oscillations in schizophrenia which is reflected by a decrease in theta oscillation in the parietal lobe and an increase in gamma oscillation in the prefrontal lobe. In addition, correlation analysis showed that in the music group, both reductions in theta oscillations in the parietal lobe and increases in gamma oscillations in the prefrontal lobe were positively correlated with the improvement of overall symptoms. Discussion: These findings help us to better understand the neural mechanisms by which music therapy improves overall symptoms in schizophrenia and provide more evidence for the application of music therapy in other psychiatric disorders.

Application of enzyme-assisted extraction of baicalin from Scutellaria baicalensis Georgi.

Endophytes may depend on degrading the plant cell wall with cellulases for their survival. Therefore, cellulase produced by endophytes may be useful in releasing the active ingredient of medicinal plants. Scutellaria baicalensis Georgi is a traditional Chinese medicinal plant widely used in China and baicalin is one of its main active ingredients. In this study, fresh S. baicalensis Georgi was used to isolate endophytes, Congo red staining was used to screen cellulase-producing strains, and HPLC was used to determine the content of baicalin in S. baicalensis Georgi. As a result, a highly active strain of endophyte capable of the extraction of high levels of baicalin was obtained. The strain was named HG-5 and identified as Bacillus sp. Scanning electron microscopy analysis confirmed that the enzyme better promotes the dissolution of plant active ingredients. After optimizing the enzyme production and extraction processes, we found that when compared with the traditional extraction method, the baicalin yield was increased 79.31% after extraction with the HG-5 enzyme. The current study provides a novel approach and method for the use of endophyte cellulase to improve the extraction of compounds from medicinal plants.

Diverse role of gut microbiota on reduction of ascites and intestinal injury in malignant ascites effusion rats treated with Euphorbia kansui stir-fried with vinegar.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia kansui (EK) is the dried root of Euphorbia kansui S.L.Liou ex S.B.Ho. Clinically, processing with vinegar is for reducing toxicity of EK, and EK stir-fried with vinegar (VEK) is used to treat ascites and edema. VEK has been confirmed to reduce ascites by accelerating the promotion of intestinal contents. AIM OF THE STUDY: The study aimed to investigate whether gut microbiota could affect the expelling water retention effects and the intestinal oxidative damage of EK and VEK on malignant ascites effusion (MAE) rats. MATERIALS AND METHODS: Pseudo-germ-free (PGF) MAE rats or probiotic intervented MAE rats were treated with EK/VEK. Related indicators such as serum, ascites, urine, feces, gastrointestinal tissues were analyzed, and the structure of the gut microbiota were also studied. The relationship between gut microbiota and the expelling water retention effects of EK/VEK where then further investigated. RESULTS: VEK reduce the volume of ascites by promoting urine and feces excretion, AQP8 protein and mRNA expression, when comparing with the MAE rats, also VEK could regulate the disordered gut microbiota in MAE rats. Mixed antibiotics could diminish VEK's expelling water retention effects in MAE rats, but increased oxidative damage in intestine. While existence of gut microbiota (especially probiotics) played an important role in the protection of intestines in VEK treated MAE rats. CONCLUSION: VEK had obvious pharmacological effect on MAE and could regulate gut microbiota, but gut microbiota was not a necessary condition for its pharmacological effects. The probiotics played a synergistic role with VEK in the effects of expelling water retention and intestinal protection.

Toxicity reduction and water expelling effect preservation of Shizaotang after its toxic members processing with vinegar on rats with malignant pleural effusions.

ETHNOPHARMACOLOGICAL RELEVANCE: Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG，fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown. AIM OF THE STUDY: We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT. MATERIALS AND METHODS: Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity. RESULTS: Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na+, K+ and Cl-) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats. CONCLUSION: SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT.

Effects of Qizhukangxian granules on idiopathic pulmonary fibrosis: a randomized, double blind, placebo-controlled and multicenter clinical pilot trial.

OBJECTIVE: To evaluate the effects of Qizhukangxian granules (QG) on idiopathic pulmonary fibrosis (IPF). METHODS: This is a randomized, double blind, placebo-controlled and multicenter clinical pilot trial. Six medical centers in Tianjin, China, participated in the study. A total of 120 IPF patients were enrolled and randomized into two groups, with 60 patients in each group. The treatment group was treated with QG, while the control group received a Qizhukangxian placebo. The pharmacological treatment lasted for 48 weeks from the enrollment date. The indexes of patients were recorded on the admission day and at the end of the 24th and 48th weeks. Data were analyzed to study the effects of QG; forced vital capacity, change in forced vital capacity and maximal 6-min walk test (6MWT) distance were the primary endpoints. Secondary endpoints were percentage of patients with episodes of acute exacerbation of IPF, pulmonary function, changes in pulse oxygen saturation during the 6MWT, dyspnea score, St. George's respiratory questionnaire score, arterial blood gas analyses and the total Traditional Chinese Medicine symptom pattern score. RESULTS: After 24 weeks of treatment, QG showed greater efficacy than the placebo in certain parameters, including the dyspnea score, Traditional Chinese Medicine symptom pattern score and some indicators in the St. George's respiratory questionnaire score. Analysis of the indexes obtained from all patients at the end of the 48th week showed that the therapeutic effects in the treatment group were significantly better than those in the control group because remarkable differences were observed in most of the primary and secondary endpoints between the two groups, except for the maximal distance of the 6MWT and arterial blood gas analyses. No adverse reaction was observed in either group during the 48-week trial treatment period. CONCLUSION: QG could effectively treat IPF patients by ameliorating pulmonary function, improving the quality of life and lowering the percentage of acute exacerbations.

Comparison of the short-chain fatty acids in normal rat faeces after the treatment of Euphorbia kansui, a traditional Chinese medicine for edoema.

Context: As a toxic traditional Chinese medicine for edoema, Euphorbia kansui S.L. Liou ex S.B. Ho (Euphorbiaceae) (EK) stir-fried with vinegar for detoxification was associated with alterations of gut microbiota. However, the evidence of correlation between short-chain fatty acids (SCFAs) and toxicity of EK has not been confirmed.Objective: In order to study the biological basis of detoxification of EK stir-fried with vinegar (VEK), a rapid, sensitive and validated GC-MS method was developed to determine SCFAs in normal rat faeces after given EK and VEK.Materials and methods: Sprague Dawley rats were orally administered 0.5% CMC-Na (control group), EK (EK-treated group) and VEK powder (VEK-treated group) at 680 mg/kg for six consecutive days (eight rats each group). Fresh faeces samples were promptly collected, derivatized and then analyzed by GC-MS.Results: The ranges of LOD and LOQ were within 0.13-1.79 and 0.45-5.95 µg/mL, respectively. The RSD values of intra-day and inter-day precisions were less than 15%. Four SCFAs were generally stable under four storage conditions. The extraction recoveries were ranged from 53.5% to 97.3% with RSD values lower than 15%. The concentrations of four SCFAs in EK and VEK were decreased significantly compared with those not administered (EK-treated, p < 0.01; VEK-treated, p < 0.05 and p < 0.01). After being stir-fried with vinegar, the concentrations were all increased (p < 0.05 and p < 0.01).Discussion and conclusions: The negative correlation between SCFAs and toxicity of EK may provide evidence for biological mechanism and toxic Chinese medicine.

Predicting final lesion characteristics during MR-guided focused ultrasound pallidotomy for treatment of Parkinson's disease.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the globus pallidus interna (GPi) is being investigated for the treatment of advanced Parkinson's disease symptoms. However, GPi lesioning presents unique challenges due to the off-midline location of the target. Furthermore, it remains uncertain whether intraprocedural MR thermometry data can predict final lesion characteristics. METHODS: The authors first performed temperature simulations of GPi pallidotomy and compared the results with those of actual cases and the results of ventral intermediate nucleus (VIM) thalamotomy performed for essential tremor treatment. Next, thermometry data from 13 MRgFUS pallidotomy procedures performed at their institution were analyzed using 46°C, 48°C, 50°C, and 52°C temperature thresholds. The resulting thermal models were compared with resulting GPi lesions noted on postprocedure days 1 and 30. Finally, the treatment efficiency (energy per temperature rise) of pallidotomy was evaluated. RESULTS: The authors' modeled acoustic intensity maps correctly demonstrate the elongated, ellipsoid lesions noted during GPi pallidotomy. In treated patients, the 48°C temperature threshold maps most accurately predicted postprocedure day 1 lesion size, while no correlation was found for day 30 lesions. The average energy/temperature rise of pallidotomy was higher (612 J/°C) than what had been noted for VIM thalamotomy and varied with the patients' skull density ratios (SDRs). CONCLUSIONS: The authors' acoustic simulations accurately depicted the characteristics of thermal lesions encountered following MRgFUS pallidotomy. MR thermometry data can predict postprocedure day 1 GPi lesion characteristics using a 48°C threshold model. Finally, the lower treatment efficiency of pallidotomy may make GPi lesioning challenging in patients with a low SDR.

[Effect of chemical ingredients B and C in Kansui stir-baked with vinegar on fecal metabolomics in rats].

To reveal the toxic mechanism of Kansui stir-baked with vinegar(VEK), conducta comparative study on the metabolites of fecal samples of rats before and after being treated with chemical constituents group B and C(VEKB/VEKC) extracted from VEK by metabolomics approach. The fecal samples of each group were analyzed using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UFLC-Q-TOF-MS). Then the data was processed by principal component analysis(PCA) and partial least square discriminant analysis(OPLS-DA) to screen and identify biomarkers relating to the toxicity of VEK. Besides, t-test was adopted for univariate statistical analysis, so as to study the changes of these biomarkers in drug groups before and after being treated with VEKB/VEKC and explore the effect of VEKB/VEKC on the metabolism of rat feces. Furthermore, the toxic mechanism of VEKB/VEKC was explored based on the results of the metabolic pathway analysis. The results displayed that compared with control group, the metabolism of fecal samples of VEKB and VEKC treated groups show obvious changes, and the VEKB treated group show more significant changes. A total of 16 potential biomarkers and 5 metabolic pathways relating to the toxicity of VEK were found and identified. And the toxicity of VEK might be associated with the disorder of such metabolic pathways as tryptophan metabolism, primary bile acid biosynthesis, amino sugar and nucleotide sugar metabolism, purine metabolism, and degradation of valine, leucine and isoleucine. This study provides a scientific basis for the clinical safety application of VEK.

A new mixed inhibitor of adenosine deaminase produced by endophytic Cochliobolus sp. from medicinal plant seeds.

Medicinal plants have been studied for potential endophytic interactions and numerous studies have provided evidence that seeds harbor diverse microbial communities, not only on their surfaces but also within the embryo. Adenosine deaminase (ADA) is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Therefore, in this study, 20 types of medicinal plant seeds were used to screen endophytic fungi with tissue homogenate and streak. In addition, 128 morphologically distinct endophyte strains were isolated and their ADA inhibitory activity determined by a spectrophotometric assay. The strain with the highest inhibitory activity was identified as Cochliobolus sp. Seven compounds were isolated from the strain using a chromatography method. Compound 3 showed the highest ADA inhibitory activity and was identified as 5-hydroxy-2-hydroxymethyl-4H-pyran-4-one, based on the results of 1H and 13C NMR spectroscopy. The results of molecular docking suggested that compound 3 binds to the active site and the nonspecific binding site of the ADA. Furthermore, we found that compound 3 is a mixed ADA inhibitor. These results indicate that endophytic strains are a promising source of ADA inhibitors and that compound 3 may be a superior source for use in the preparation of biologically active ADA inhibitor compounds used to treat cancer.

Reynoutria Japonica from Traditional Chinese Medicine: A Source of Competitive Adenosine Deaminase Inhibitors for Anticancer.

BACKGROUND: Adenosine deaminase (ADA) is an important enzyme in purine metabolism and is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Traditional Chinese Herbal Medicine (TCHM) is widely used alone or in combination with chemotherapy to treat cancer, due to its ability to deliver a broad variety of bioactive secondary metabolites as promising sources of novel organic natural agents. OBJECTIVE: In the present study, 29 varieties of medicinal plants were screened for the presence of ADA inhibitors. RESULTS: Extracts from Reynoutria japonica, Glycyrrhiza uralensis, Lithospermum erythrorhizon, Magnolia officinalis, Gardenia jasminoides, Stephania tetrandra, Commiphora myrrha, Raphanus sativus and Corydalis yanhusuo demonstrated strong ADA inhibition with rates greater than 50%. However, Reynoutria japonica possessed the highest ADA inhibitory activity at 95.26% and so was used in our study for isolating the ADA inhibitor to be further studied. Eight compounds were obtained and their structures were identified. The compound H1 had strong ADA inhibitory activity and was deduced to be emodin by 1H and 13C-NMR spectroscopic analysis with an IC50 of 0.629 mM. The molecular docking data showed that emodin could bind tightly to the active site of ADA. Our results demonstrated that emodin displayed a new biological activity which is ADA inhibitory activity with high cytotoxic activity against K562 leukemia cells. The bioactivity of cordycepin was significantly increased when used in combination with emodin. CONCLUSION: Emodin may represent a good candidate anti-cancer therapy and adenosine protective agent.

Euphorbia kansui fry-baked with vinegar modulates gut microbiota and reduces intestinal toxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia kansui (EK), a kind of toxic traditional Chinese medicine (TCM), is used in the treatment of edema, ascites and asthma. EK fry-baked with vinegar (VEK) is regularly used to reduce the toxicity in TCM. Previous studies have confirmed that fry-baking with vinegar could significantly reduce the significant gastrointestinal toxicity of EK. The toxic side-effects of EK are closely associated with intestinal tract, but existing research results could not provide practical measures for detoxification in terms of the biological effects of EK fry-baked with vinegar. AIM OF THE STUDY: This study aimed to investigate the gastrointestinal toxicity of EK and detoxification of VEK through the regulation of gut microbiota. Thirty male Sprague Dawley (SD) rats were randomly divided equally into 3 groups and received by oral gavage 0.5% CMC-Na (C group), EK (EKC group) or VEK (VEKC group) powder at 680 mg/kg for seven consecutive days. RESULTS: The ten toxic components in VEK were reduced significantly compared with those in EK. After fry-baked with vinegar, those side effects associated with VEK were significantly relieved in terms of histopathology and inflammatory injury indices of intestinal tissues, liver function and oxidative damage indices. The toxicity of EK might be highly correlated with Lactobacillus and Blautia genera. In addition, EK fry-baked with vinegar increased the production of short-chain fatty acids (SCFAs), which are regulated by gut microbiota. CONCLUSIONS: The proportion of main probiotics increased and potentially pathogenic bacteria decreased after EK was fry-baked with vinegar. It turned out that effective detoxification could be achieved by fry-baking with vinegar.

[Changes of the microcirculatory blood perfusion at "Feishu" (BL 13) in the COPD rats].

OBJECTIVE: To observe the change of the specificity of the microcirculatory blood perfusion at the area of "Feishu" (BL 13) in the rats of chronic obstructive pulmonary disease (COPD). METHODS: According to the random number table, 60 Wistar rats were divided into a 29 d model No. 1 group (C1 group), a 29 d normal control No.1 group (N1 group), a 89 d model No.2 group (C2 group) and a 89 d normal control No. 2 group (N2 group), 15 rats in each one. In the C1 and C2 groups, the smoking and intratracheal drops of endotoxin were used in combination to prepare COPD model. The rats were fed normally in the N1 and N2 groups. "Feishu" (BL 13), "Xinshu" (BL 15), the lateral site of "Feishu" (BL 13) and the lateral site of "Xinshu" (BL 15) were selected as the monitoring points. The pericam perfusion speckle imager (PeriCam PSI System) was adopted to monitor the microcirculatory perfusion unit (PU) at the monitoring points before and in 29 d and 89 d after modeling separately. RESULTS: Before modeling, the differences in PU were not significant at each monitoring point in comparison among the 4 groups and the differences were not significant among "Feishu" (BL 13) and "Xinshu" (BL 15) as well as their lateral sites (all P>0.05). After modeling, PU was increased at each monitoring point in the C1 and C2 groups (all P<0.05). PU in the C1 group was higher than the N1 group and that in the C2 group was lower than the N2 group, PU at each monitoring point in the C1 group were higher than the C2 group, indicating the significant differences (all P<0.05). In the C1 and C2 groups, the specific change occurred, in which PU at "Feishu" (BL 13) was higher than its lateral site. But such specific change did not happen in the N1 and N2 groups. CONCLUSION: PU at "Feishu" (BL 13) presents the specific change relevant with the sickness duration in the COPD rats.

Effect of bufei granule on stable chronic obstructive pulmonary disease: a randomized, double blinded, placebo-controlled, and multicenter clinical study.

OBJECTIVE: To study the therapeutic effect Bufei granule, which is a traditional Chinese drug that can enhance the immune function of the lung, on patients with stable chronic obstructive pulmonary disease (COPD). METHODS: This is a randomized, double blinded, placebo-controlled, and multicenter clinical study. Three medical centers in Tianjin, China, participated in the trial. A total of 140 patients with stable COPD were enrolled and randomized into two groups, with 70 patients in each. The treatment group was treated with Bufei granule, while the control group received Bufei placebo. The pharmacological treatment lasted for 12 weeks from the date of enrollment. Then, the indexes of patients were observed. Data were analyzed to study the effect of Bufei granule, with the frequency of acute exacerbation as the primary outcome. Traditional Chinese Medicine syndromes, Modified British Medical Research Council dyspnea scale score, St. George's respiratory questionnaire scores, pulmonary function, and serum inflammatory marker levels [including interleukin-6 (IL-6), interleukin-8, tumor necrosis factor-alpha, and transformation growth factor-beta1] were the secondary outcomes. RESULTS: During the 12-week treatment, treatment and control groups had no adverse reactions. The analysis of the indexes obtained from all patients showed that the therapeutic effect in the treatment group was significantly better than that in the control group because most of the similar probabilities of primary and secondary outcomes were less than 0.05, except for the level of IL-6. CONCLUSION: Bufei granule can treat patients with stable COPD by lowering the frequency of acute exacerbation, improving the quality of life, and alleviating the severity of inflammation.