[Screening of small molecule inhibitors of IL-15Rα using molecular docking and surface plasmon resonance technology].

The study aims to explore the active molecules of traditional Chinese medicine that specifically bind to interleukin-15 receptor α (IL-15Rα) using molecular docking and surface plasmon resonance (SPR) technology. AutoDock molecular docking software was used to perform simulated docking of more than 3 000 compounds from 48 traditional Chinese medicines at IL-15Rα and screen the specific binding compounds. Then Biocore T200 biomolecular interaction analysis system of SPR was used to confirm the binding specificity of the selected target compounds. Finally, the biological effects of the target compounds on IL-15Rα were verified by cell biological experiments. The results showed that neoprzewaquinone A (Neo) possessed the highest specific binding affinity among the active molecules from traditional Chinese medicine, and the dissociation constant (KD) value was (0.62 ± 0.20) µmol/L. The results of cell experiment showed that Neo significantly inhibited the proliferation of Mo7e cells induced by IL-15, and the IC50 was 1.075 µmol/L, approximately 1/120 of the IC50 of Cefazolin (IL-15 specific antagonist). These results suggest that Neo is a specific inhibitor of IL-15Rα and may be a potential active drug for the treatment of diseases related to the dysfunction of the IL-15Rα signaling.

The use of biochemical indexes in hair for clinical studies of psychiatric diseases: What can we learn about mental disease from hair?

Analysis of hair samples provides unique advantages, including non-invasive sampling, sample stability, and the possibility of additional optimization of high sensitivity detection methods. Hair sample analysis is often used in psychiatric disease research to evaluate previous periods of stress encountered by patients. Glucocorticoid analysis is the most frequently tested indicator of stress. Furthermore, the hypothalamus-pituitary-gonad axis and endocannabinoid system also are involved in the occurrence and development of mental disorders. The endocannabinoid and sex hormone levels in patients experiencing mental illness are considerably different from levels observed in healthy individuals. Nevertheless, due to the different methods used to assess the degree of disease and the range of analytical methods involved in clinical research, the trends in changes for these biomarkers are not uniform. The correlations between changes in biomarker concentrations and illness severity also are not clear. The observed alterations suggest these biochemical substances in hair have potential as biomarkers for diagnosis or predictive treatment. However, the variable results obtained thus far could hamper further development of hair samples for clinical assessment in psychiatric disorders. This article summarizes the published reports documenting the changes in the content of relevant substances in hair in individuals experiencing mental illness and the degree of correlation. In the discussion section, we proposed several issues that should be considered in future studies of hair samples obtained from patients with mental disorders to promote the use of hair sample assessment as an aid in diagnosis or predictive treatment.

Higher Serum C-Reactive Protein Levels in Catatonic Patients: A Comparison to Non-catatonic Patients and Healthy Controls.

Catatonia is a psychomotor syndrome defined by a constellation of predominantly motor symptoms. The aim of the present study was to determine whether recently admitted psychiatric patients with catatonia exhibited higher serum C-reactive protein (hs-CRP) levels compared to non-catatonic psychiatric patients and healthy controls (HCs). Recently admitted psychiatric patients were screened and evaluated for the catatonia syndrome using the Bush-Francis Catatonia Rating Scale and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The study sample was formed by 150 individuals (39 male and 111 female), including 51 catatonic patients, 55 non-catatonic patients, and 44 HCs. Serum hs-CRP levels were processed with the enzyme-linked immunosorbent assay. Serum levels of creatine kinase (CK), adrenocorticotropic hormone (ACTH), immunoglobulin G (IgG), complement component 3 (C3), and complement component 4 (C4) were also determined. There was a significantly higher percentage of patients with high inflammatory levels (hs-CRP > 3000ng/ml) in the catatonic (43.1%) than in the non-catatonic (14.5%) or HCs group (9.1%) (χ 2 =18.9, P < .001). Logistic regression showed that catatonic patients had significantly higher hs-CRP levels compared to non-catatonic patients even after controlling for other clinical and laboratory variables (OR = 3.52, P = .015, 95% CI 1.28-9.79). Multiple linear regression analysis revealed that log-transformed hs-CRP was independently predicted by body mass index and log-transformed C4, ACTH, and Cortisol in catatonic patients. Findings of the present study suggest that catatonia is specifically linked to a higher level of systemic inflammation, not merely attributable to the overall psychopathology, or alterations in the stress level and complement system.

The Role of Group II Metabotropic Glutamate Receptors in the Striatum in Electroacupuncture Treatment of Parkinsonian Rats.

AIMS: Glutamatergic transmission may play a critical role in the pathogenesis of Parkinson's disease (PD). Electroacupuncture (EA) has been demonstrated to effectively alleviate PD symptoms. In this study, a potential glutamate-dependent mechanism underlying the therapeutic action of EA was investigated. METHODS: The effects of EA stimulation on motor behaviors, dopamine contents, glutamate release, and group II metabotropic glutamate receptor (mGluR2/3) expression in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats were examined. RESULTS: Unilateral 6-OHDA lesions of the nigrostriatal system caused a marked increase in glutamate content in the ipsilateral cortex and striatum. mGluR2/3 protein expression and mGluR3 mRNA expression were reduced in the striatum. Noticeably, prolonged EA stimulation at 100 Hz significantly reversed these changes in the striatal glutamate system. Behaviorally, EA improved the motor deficits induced by 6-OHDA lesions. Intrastriatal infusion of an mGluR2/3 antagonist APICA blocked the improving effect of EA. CONCLUSIONS: These data collectively demonstrate that the group II mGluR-mediated glutamatergic transmission in the striatum is sensitive to dopamine depletion and may serve as a substrate of EA for mediating the therapeutic effect of EA in a rat model of PD.

Serum brain-derived neurotrophic factor levels associate with cognitive improvement in patients with schizophrenia treated with electroacupuncture.

Accumulating evidence supports that acupuncture has been successfully used for the treatment of neurological disorders to improve cognitive function. This study was set to evaluate the efficacy of electroacupuncture (EA, using two acupoints: Baihui and Shenting) on clinical symptoms, cognitive function and brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia. Sixty-one inpatients diagnosed schizophrenia with DSM-IV criteria were recruited. The participants were randomly divided into an experimental group (n=30) and a control group (n=31). The patients were evaluated using the Positive and Negative Symptom Scale (PANSS), the Wisconsin Card Sorting Test (WCST) and Wechsler Memory Scale (WMS) at baseline and after EA treatment. There were no significant differences in the PANSS scores and serum BDNF levels between the experimental group and the control group, either at baseline or at the end of the 4-week study period. However, the EA treatment appeared to have significant benefits on memory and moderate benefits on executive functions and problem solving. Significant positive correlation was observed between the increase of BDNF levels and memory improvement after EA treatment. Our results indicated that EA treatment could improve cognitive function, and the cognitive benefits positively associate with serum BDNF levels in patients with schizophrenia.

Therapeutic drug monitoring of psychotropic drugs in China: a nationwide survey.

OBJECTIVE: To understand the status of therapeutic drug monitoring (TDM) of psychotropic drugs in psychiatric facilities in mainland China and to lay the foundation for improvement of TDM in psychiatry. METHODS: A cross-sectional survey was conducted with a locally developed questionnaire among psychiatric facilities in which TDM of psychotropic drugs was available. The questionnaire included laboratory situations, implementation of TDM, equipment and analytical methods, internal quality control (IQC), and external quality assessment (EQA). RESULTS: Forty-seven of the 58 delivered questionnaires were collected from the psychiatric facilities involving 26 provinces in mainland China. The response rate was 81.0%. Among all facilities surveyed, lithium was the most common psychotropic drug (68.1% of the laboratories) monitored by TDM, followed by clozapine (44.7%), carbamazepine (25.5%), chlorpromazine (21.3%), norclozapine (19.1%), risperidone (19.1%), paliperidone (17.0%), valproic acid (14.9%), and quetiapine (10.6%). Only 10.2% of the laboratories had recommendations for dose adjustments based on their TDM reports. Others only provided drug concentration results with no clinical recommendations. The analytical methods used included high-performance liquid chromatography, liquid chromatography with tandem mass spectrometric detection, and immunoassay. For lithium, most hospitals used ion-selective electrode methods. IQC and EQA were still in their infancy. CONCLUSIONS: This first nationwide survey showed that TDM has been available in a considerable number of psychiatric hospitals across China. Though current equipment and analytical methods meet the TDM need, much improvement is needed, particularly in new analytical method development, interpretation of results, consultation services, and quality control, including IQC and EQA. Guidance or consensus guideline for TDM of psychotropic drugs in the Chinese language is also urgently required.

[High-frequency electro-acupuncture stimulation modulates intracerebral γ-aminobutyric acid content in rat model of Parkinson's disease].

The purpose of the present study is to observe the effect of electro-acupuncture (EA) stimulation on intracerebral neurotransmitters in a rat model of Parkinson's disease (PD), and explore the possible mechanism. We used 6-hydroxydopamine (6-OHDA) injection in medial forebrain bundle (MFB) in the right brain of Sprague Dawley (SD) rat to establish the parkinsonian rat model, and randomly divided the PD rats into model and 100 Hz EA stimulation groups (n =10 in each group). EA stimulation group received 4 courses of EA stimulation on Baihui (GV-20) and Dazhui (GV-14) acupuncture points. Moreover, ten rats were randomly selected as sham operation group, only receiving normal saline (NS) injection in MFB. Then apomorphine (APO)-induced rotational behavior in different groups was recorded, and the contents of γ-aminobutyric acid (GABA) in the brain were analyzed with high pressure/performance liquid chromatography-electrochemical detection (HPLC-ECD). The results showed that model group exhibited abnormal rotational behavior with APO treatment, suggesting the successful establishment of PD model. Compared with sham operation group, model group showed increased GABA contents in cortex and striatum, as well as decreased GABA content in ventral midbrain, on the lesioned side. EA stimulation could effectively ameliorate the abnormal rotational behavior of PD rat. Compared with the model group, EA stimulation decreased the ratio of GABA content on the lesioned side to that on unlesioned side in the cortex, while increased the ratios in the striatum and cerebellum. However, there was no difference of the ratio in the ventral midbrain among three groups. These results suggest high-frequency EA stimulation significantly improves the abnormal behavior of PD rats, which may exert through enhancing the inhibitory effect of cerebellum-basal ganglia-cortical loop on motor center.

Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.