Pallidum volume as a predictor for the effectiveness of mindfulness-based cognitive therapy and psycho-education in unmedicated patients with obsessive-compulsive disorder.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) has been documented to be effective in treating obsessive-compulsive disorder (OCD). However, the neurobiological basis of MBCT remains largely elusive, which makes it clinically challenging to predict which patients are more likely to respond poorly. Hence, identifying biomarkers for predicting treatment outcomes holds both scientific and clinical values. This prognostic study aims to investigate whether pre-treatment brain morphological metrics can predict the effectiveness of MBCT, compared with psycho-education (PE) as an active placebo, among patients with OCD. METHODS: A total of 32 patients with OCD were included in this prognostic study. They received magnetic resonance imaging (MRI) brain scans before treatment. Subsequently, 16 patients received 10 weeks of MBCT, while the other 16 patients underwent a 10-week PE program. The effectiveness of the treatments was primarily assessed by the reduction rate of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score before and after the treatment. We investigated whether several predefined OCD-associated brain morphological metrics, selected based on prior published studies by the ENIGMA Consortium, could predict the treatment effectiveness. RESULTS: Both the MBCT and PE groups exhibited substantial reductions in Y-BOCS scores over 10 weeks of treatment, with the MBCT group showing a larger reduction. Notably, the pallidum total volume was associated with treatment effectiveness, irrespective of the intervention group. Specifically, a linear regression model utilizing the pre-treatment pallidum volume to predict the treatment effectiveness suggested that a one-cubic-centimeter increase in pallidum volume corresponded to a 22.3% decrease in the Y-BOCS total score reduction rate. CONCLUSIONS: Pallidum volume may serve as a promising predictor for the effectiveness of MBCT and PE, and perhaps, other treatments with the shared mechanisms by MBCT and PE, among patients with OCD.

Effect of 12-week shen-based qigong exercise on the residual symptoms of schizophrenia: Study protocol for a single-centre randomised controlled trial.

Introduction: Negative symptoms and cognitive impairment are common residual symptoms of schizophrenia that seriously affect the quality of life and social function of patients. The intervention of residual symptoms is an important part of schizophrenia rehabilitation. Traditional Chinese exercise has been applied as a supplementary rehabilitation method for schizophrenia. However, research on its use and pertinence in the rehabilitation of residual symptoms remains lacking. In this study, we will verify the intervention effect of a new method, namely, shen-based qigong exercise, on the residual symptoms of schizophrenia, in the hopes of finding a safe and effective rehabilitation method for the residual symptoms of schizophrenia. Methods: This is a single-centre randomised controlled trial. A total of 60 schizophrenics who meet the criteria will be randomly divided into the control and intervention groups in accordance with the ratio of 1:1. Conventional drug treatment will remain unchanged in both groups. In this case, the control group will be given daily rehabilitation, whereas the intervention group will be given daily rehabilitation and shen-based qigong exercise intervention. The intervention period will be 12 weeks. The primary outcome will be negative symptoms assessed by the Scale for the Assessment of Negative Symptoms. The secondary outcome will be the global cognitive function assessed by the Repeatable Battery for the Assessment of Neuropsychological Status and event-related potential P300. Other outcomes will include specific cognitive domain (i.e. working memory), quality of life and social function. The results will be measured within 1 week before and after the intervention. Discussion: The results of this study will likely help find an economical and convenient rehabilitation method for the residual symptoms of schizophrenia and, at the same time, may promote the popularisation and application of traditional Chinese exercises and traditional Chinese medicine theories in the treatment of mental diseases. Trial registration: ClinicalTrials.gov registry number: NCT05310955.

Integrating animal experiments, mass spectrometry and network-based approach to reveal the sleep-improving effects of Ziziphi Spinosae Semen and γ-aminobutyric acid mixture.

BACKGROUND: Ziziphi Spinosae Semen (ZSS) is a plant widely used as medicine and food in Asian countries due to its numerous health benefits. γ-aminobutyric acid (GABA), a non-proteinaceous amino acid, is one of the major inhibitory neurotransmitters with a relaxant function. In this study, a system pharmacology approach was employed to assess the effects of a mixture composed of ZSS and GABA (ZSSG) on sleep improvement. METHODS: Mice were divided into five groups (n = 10) and received either no treatment, sodium pentobarbital, or sodium barbital with diazepam or ZSSG. The effects of ZSSG on sleep quality were evaluated in mice, and differential metabolites associated with sleep were identified among the control, ZSS, GABA, and ZSSG groups. Additionally, network-based ingredient-insomnia proximity analysis was applied to explore the major ingredients. RESULTS: ZSSG significantly improved sleep quality by decreasing sleep latency and prolonging sleep duration in sodium pentobarbital-induced sleeping mouse model (P < 0.05). ZSSG significantly enhanced the brain content of GABA in mice. Furthermore, ZSSG also significantly decreased sleep latency-induced by sodium barbital in mice (P < 0.05). Metabolic analysis revealed significant differences in 10 metabolites between ZSSG group and the groups administering ZSS or GABA. Lastly, using the network-based ingredient screening model, we discovered potential four active ingredients and three pairwise ingredient combinations with synergistic effect on insomnia from ZSSG among 85 ingredients identified by UPLC-Q/TOF-MS. Also, we have constructed an online computation platform. CONCLUSION: Our data demonstrated that ZSSG improved the sleeping quality of mice and helped to balance metabolic disorders-associated with sleep disorders. Moreover, based on the network-based prediction method, the four potential active ingredients in ZSSG could serve as quality markers-associated with insomnia. The network-based framework may open up a new avenue for the discovery of active ingredients of herbal medicine for treating complex chronic diseases or symptoms, such as insomnia.

Bioactivity-Guided High Performance Counter-Current Chromatography and Following Semi-Preparative Liquid Chromatography Method for Rapid Isolation of Anti-Inflammatory Lignins from Dai Medicinal Plant, Zanthoxylum acanthopodium var. timbor.

The development of Dai medicine is relatively slow, and Zanthoxylum has great economic and medicinal value. It is still difficult to obtain medicinal components from the low-polarity parts of Zanthoxylum belonging to Dai medicine. In this study, we introduced one simple and quick strategy of separating target compounds from the barks of Z. acanthopodium var. timbor by high-performance countercurrent chromatography (HPCCC) with an off-line anti-inflammatory activity screening mode. The development of this strategy was based on the TLC-based generally useful estimation of solvent systems (GUESS) method and HPCCC in combination. This paper presented a rapid method for obtaining target anti-inflammatory compounds. Three lignins were enriched by HPCCC with an off-line inhibition mode of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells, using petroleum ether-ethyl acetate-methanol-water (3:2:3:2) as the solvent system. The results showed that this method was simple and practical and could be applied to trace the anti-inflammatory components of the low-polarity part in Dai medicine.

Tanshinone IIA improves contextual fear- and anxiety-like behaviors in mice via the CREB/BDNF/TrkB signaling pathway.

Posttraumatic stress disorder (PTSD) is one of the most common psychiatric diseases, which is characterized by the typical symptoms such as re-experience, avoidance, and hyperarousal. However, there are few drugs for PTSD treatment. In this study, conditioned fear and single-prolonged stress were employed to establish PTSD mouse model, and we investigated the effects of Tanshinone IIA (TanIIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza, as well as the underlying mechanisms in mice. The results showed that the double stress exposure induced obvious PTSD-like symptoms, and TanIIA administration significantly decreased freezing time in contextual fear test and relieved anxiety-like behavior in open field and elevated plus maze tests. Moreover, TanIIA increased the spine density and upregulated synaptic plasticity-related proteins as well as activated CREB/BDNF/TrkB signaling pathway in the hippocampus. Blockage of CREB remarkably abolished the effects of TanIIA in PTSD model mice and reversed the upregulations of p-CREB, BDNF, TrkB, and synaptic plasticity-related protein induced by TanIIA. The molecular docking simulation indicated that TanIIA could interact with the CREB-binding protein. These findings indicate that TanIIA ameliorates PTSD-like behaviors in mice by activating the CREB/BDNF/TrkB pathway, which provides a basis for PTSD treatment.

Alpinia hainanensis Rhizome Extract Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis: Active Ingredient Investigation and Evaluation.

Alpinia hainanensis is an important food spice and ethnic medicine in Southwest China. In this study, we found that the EtOAc-soluble fraction (AHE) of the A. hainanensis rhizome ethanol extract could ameliorate dextran sulfate sodium-induced ulcerative colitis (UC). To explore active constituents, five pairs of previously unreported enantiomers (1-5), together with nine known ones (6-14), were obtained. Structural characterization was achieved by comprehensive spectroscopic methods. Compounds 1 and 2 were new curcumin-butyrovanillone hybrids featuring a rare structural fragment of 2,3-dihyrofuran. The anti-inflammatory activities of isolates were evaluated, and the results indicated that compounds (-)-1, (-)-3, 6, 9, 11, and 12 significantly inhibited the nuclear factor-κB signaling pathway. These findings indicate the major active fraction of the A. hainanensis rhizome ethanol extract enriched with diarylheptanoids, flavonoids, phenolics, and their hybrid mixtures, which could be developed as a nutritional and dietary supplement for treating UC.

Mindfulness-Based Cognitive Therapy for Unmedicated Obsessive-Compulsive Disorder: A Randomized Controlled Trial With 6-Month Follow-Up.

Background: This was the first randomized controlled trial (RCT) designed to compare the efficacy of mindfulness-based cognitive therapy (MBCT) on unmedicated obsessive-compulsive disorder with that of the first-line treatment for OCD (SSRIs) or a placebo, as well as to analyze the treatment acceptability and safety of MBCT. Methods: A total of 123 unmedicated OCD patients with mild to moderate symptoms were randomly assigned into selective serotonin reuptake inhibitors group (SSRIs group), MBCT group or psycho-education group (PE group), respectively. They were intervened for 10 weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) grade was the primary outcome, and Hamilton Depression Scale-24 (HAMD-24) and Hamilton Anxiety Scale (HAMA) grades were secondary outcomes to be measured at baseline, mid-intervention, post-intervention and 14, 22, and 34 weeks of follow-up. The Five Facet Mindfulness Questionnaire (FFMQ) and Sheehan Disability Scale (SDS) were used to assess mindfulness and social functions, respectively. In addition, treatment acceptability (dropout rate and frequency of occurrence) and safety [adverse event (AE)] of MBCT were investigated. Results: Significant differences were detected in the treatment responses among SSRIs group, MBCT group and PE group. Notably, treatment responses were significantly better in the former two groups than that of PE group (χ2 = 6.448, p = 0.04), although we did not identify significant differences between SSRIs group and MBCT group (χ2 = 1.220, p = 0.543). Observed until 6 months of follow-up, there were no significant differences in treatment response among three groups. No AE was recorded in MBCT group. Conclusion: MBCT is effective in the treatment of unmedicated OCD with mild to moderate symptoms comparable to that of SSRIs, which contributes to maintain the treatment outcomes at follow-up. Besides, MBCT is safe with a good clinical compliance.

Mindfulness-Based Cognitive Therapy in Major Depressive Disorder: A Study Protocol of a Randomized Control Trial and a Case-Control Study With Electroencephalogram.

Background: In this report, a study protocol for a randomized control trial is presented in an attempt to explore the efficacy of mindfulness-based cognitive therapy (MBCT) for major depressive disorder (MMD), and a case-control study is conducted to find the difference in electroencephalograms (EEGs) between MMD and normal controls. Design: Seventy Chinese patients with MMD will be chosen for random division in the MBCT group or medication group, with half of the participants receiving common medication treatment [selective serotonin reuptake inhibitors (SSRIs)] and half receiving MBCT as a supplement to the common medication treatment. All participants, namely, 70 MMD cases and 35 matched normal controls, will be tested by a range of scales and EEG at baseline (week 0), mid-intervention (weeks 2, 4, and 6), post-intervention (week 8), and 6-months follow-up (weeks 12, 20, and 32). Discussion: The findings of this study will provide a positive reference for the treatment of depression and future research on MBCT treatment mechanism. Trial Registration: NCT03558256. Registered: June 13, 2018-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03558256.

A novel use for an old drug: resistance reversal in Candida albicans by combining dihydroartemisinin with fluconazole.

Aim: To investigate the effects of dihydroartemisinin combined with fluconazole against C. albicans in vitro and to explore the underlying mechanisms. Materials & methods: Checkerboard microdilution assay and time-kill curve method were employed to evaluate the static and dynamic antifungal effects against C. albicans. Reactive oxygen species (ROS) was measured by a fluorescent probe. Results: Combination of dihydroartemisinin and fluconazole exerted potent synergy against planktonic cells and biofilms of fluconazole-resistant C. albicans, with the fractional inhibitory concentration index values less than 0.07. A potent fungistatic activity of this drug combination could still be observed after 18 h. The accumulation of ROS induced by the drug combination might contribute to the synergy. Conclusion: Dihydroartemisinin reversed the resistance of C. albicans to fluconazole.

Lay abstract Patients with weakened immune system often suffer from C. albicans infections. C. albicans is a common fungus. Fluconazole is a widely used antifungal drug owing to its low price and few side effects. Unfortunately, fluconazole is gradually losing its effect against C. albicans due to the constantly emerging resistance in C. albicans. Interestingly, in this study a combined use of fluconazole and an old antimalarial agent restored the effect of fluconazole against resistant C. albicans. The antimalarial drug we used is dihydroartemisinin, with low price, high safety and multiple biological activities, which originates from a traditional Chinese medicine. Our study also presented that this drug combination generated abundant reactive oxygen, which might account for the effect. The drug combination would be expected to be used for treating C. albicans infections.

Structure of human GABAB receptor in an inactive state.

The human GABAB receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction1. A unique GPCR that is known to require heterodimerization for function2-6, the GABAB receptor has two subunits, GABAB1 and GABAB2, that are structurally homologous but perform distinct and complementary functions. GABAB1 recognizes orthosteric ligands7,8, while GABAB2 couples with G proteins9-14. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail15. Although the VFT heterodimer structure has been resolved16, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABAB receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.

Mindfulness-based cognitive therapy for obsessive-compulsive disorder: Study protocol for a randomized controlled trial with functional magnetic resonance imaging and a 6-month follow-up.

This article presents a study protocol for a single-blind randomized controlled trial to test the efficacy and feasibility of mindfulness-based cognitive therapy. A total of 120 un-medicated Chinese obsessive-compulsive disorder patients will be randomized to the mindfulness-based cognitive therapy group, the selective serotonin reuptake inhibitor group or the psycho-education group for 11 sessions in 10 weeks. A range of scales for clinical symptoms and functional magnetic resonance imaging will be completed at baseline (week 0), mid-intervention (week 4), post-intervention (week 10) and the 6-month follow-up (weeks 14, 22 and 34). The study will have relevance to decisions about treatment options for un-medicated obsessive-compulsive disorder patients.

Microwave Ablation of Primary Malignant Pelvic Bone Tumors.

Background: En bloc tumor resection followed by reconstruction is a widely used surgical treatment for malignant pelvic bone tumors. High rates of complications and mechanical instability often contribute to poor postoperative results. We attempted en bloc microwave ablation (MWA) in situ to improve the outcome. Methods: From May 1995 to December 2015, 104 patients with primary pelvic malignancy received radical MWA in our department. After careful dissection of the tumor-bearing bone from surrounding normal tissues with safe margins, a microwave antenna array was inserted into the tumor mass to emit electromagnetic energy, inducing tumor cellular death via thermocoagulation. The loose, devitalized tumor tissues were removed by cutting or curettage, leaving a defective bone scaffold. Re-strengthening by autograft or allograft was needed in most patients. Results: The over 3 years survival rate was 51.5% for high-grade malignancies (among them, 26.9% were osteosarcoma) and 94.8% for low-grade malignancies (chondrosarcoma). In most of the living patients, cosmetic and useful limbs were preserved. The mean functional score (Musculoskeletal Tumor Society) was 27 or 90% (range: 25-30, 75-100%). Among the 56 patients who belonged to the excellent function group, 11 were followed up for more than 10 years. The local recurrence rate was 8.6%. Among the 9 patients with recurrence, 5 died from disease, 2 were treated by hemipelvic amputation, and 2 underwent revision surgery with MWA and gained local control. The deep infection rate was 5.6%. All six patients with infection were healed by irrigation, debridement, and systemic antibiotic administration. Conclusion: Local, microwave-induced hyperthermia for treating malignant pelvic bone tumors is an effective alternative method. The oncological and functional results are encouraging. The use of MWA should be continued to evaluate and improve this new therapeutic system.

Anticancer activity of 1,25-(OH)2D3 against human breast cancer cell lines by targeting Ras/MEK/ERK pathway.

PURPOSE: Breast cancer is the most common cancer among women with ~1.67 million cases diagnosed annually worldwide, and ~1 in 37 women succumbed to breast cancer. Over the past decades, new therapeutic strategy has substantially improved the curative effect for women with breast cancer. However, the currently available ER-targeted and HER-2-based therapies are not effective for triple-negative breast cancer patients, which account for ~15% of total breast cancer cases. MATERIALS AND METHODS: We reported that 1,25-(OH)2D3, a biologically active form of vitamin D3, exhibited a strong anticancer effects on the proliferation, migration, invasion, cell cycle arrest, and apoptosis of both ER-positive (MCF-7) and ER-negative breast cancer cells (MDA-MB-453). RESULTS: The anticancer effect of 1,25-(OH)2D3 was more potent compared to the classical chemotherapeutics tamoxifen in MDA-MB-453 cells. Furthermore, we also found that 1,25-(OH)2D3 decreased the expression of Ras and resulted in decrease of the phosphorylation of downstream proteins MEK and ERK1/2, indicating that 1,25-(OH)2D3 plays its anticancer roles through targeting the Ras/MEK/ERK signaling pathway. In addition, Ras overexpression abrogated 1,25-(OH)2D3-induced G0/G1 cell cycle arrest and apoptosis of breast cancer cells, as well as the suppression of proliferation, migration, and invasion. Our study suggested that 1,25-(OH)2D3 suppressed breast cancer tumorigenesis by targeting the Ras/MEK/ERK signaling pathway. CONCLUSION: 1,25-(OH)2D3 might serve as a promising supplement for breast cancer drug therapy, especially for the ER-negative breast cancer and drug-resistant breast cancer.

The right thalamic glutamate level correlates with functional connectivity with right dorsal anterior cingulate cortex/middle occipital gyrus in unmedicated obsessive-compulsive disorder: A combined fMRI and 1H-MRS study.

OBJECTIVE: The imbalance in neurotransmitter and neuronal metabolite concentration within cortico-striato-thalamo-cortical (CSTC) circuit contributes to obsessive-compulsive disorder's (OCD) onset. Previous studies showed that glutamate mediated upregulation of resting-state activity in healthy people. However, there have been few studies investigating the correlational features between functional and neurochemical alterations in OCD. METHODS: We utilize a combined resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) approach to investigate the altered functional connectivity (FC) in association with glutamatergic dysfunction in OCD pathophysiology. Three regions of interest are investigated, i.e., medial prefrontal cortex and bilateral thalamus, for seed-based whole-brain FC analysis as well as MRS data acquisition. There are 23 unmedicated adult OCD patients and 23 healthy controls recruited for brain FC analysis. Among them, 12 OCD and 8 controls are performed MRS data acquisition. RESULTS: Besides abnormal FC within CSTC circuit, we also find altered FCs in large-scale networks outside CSTC circuit, including occipital area and limbic and motor systems. The decreased FC between right thalamus and right middle occipital gyrus (MOG) is correlated with glutamatergic signal within right thalamus in OCD patients. Moreover, the FC between right thalamus and right dorsal anterior cingulate cortex (dACC) is associated with glutamate level in right thalamus, specifically in patient's group. Finally, the FC between right thalamus and right MOG is correlated with patient's Yale-Brown Obsessive Compulsive Scale (YBOCS) compulsion and total scores, while the right thalamic glutamatergic signal is associated with YBOCS-compulsion score. CONCLUSION: Our findings showed that the coupled intrinsic functional-biochemical alterations existed both within CSTC circuit and from CSTC to occipital lobe in OCD pathophysiology.

Anterior thalamic radiation structural and metabolic changes in obsessive-compulsive disorder: A combined DTI-MRS study.

Numerous studies indicate the cortico-striato-thalamo-cortical (CSTC) circuit plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD). The anterior thalamic radiation (ATR), as a major fiber in the fronto-thalamic circuitry, contributes to symptomology of OCD. However, the underlying biochemical mechanism in relation with its structural alteration remains not understood. This study investigated the structural abnormality of ATR and its correlation with thalamic metabolic alteration in OCD, using diffusion tensor image (DTI) and proton magnetic resonance spectroscopy (1H-MRS). Twenty-six unmedicated adult OCD patients and twenty-six matched healthy controls participated in DTI study. Thirteen OCD patients and thirteen healthy controls, a subset of DTI participants, took part in MRS study. The results showed that mean fiber length of right ATR negatively correlated with ipsilateral thalamic choline (Cho) level in OCD patients. Additionally, significantly higher Cho concentration was detected in right thalamus of OCD patients compared to healthy controls. Moreover, the mean fractional anisotropy (FA) value of right ATR positively correlated with patients Yale-Brown Obsessive Compulsive Scale (YBOCS) total score, as well as YBOCS compulsion score. These results suggested the coupling of structural and metabolic changes in right ATR, which might serve as a multi-modal biomarker contributing to the pathogenesis of OCD.

Divergent Structural Responses to Pharmacological Interventions in Orbitofronto-Striato-Thalamic and Premotor Circuits in Obsessive-Compulsive Disorder.

Prior efforts to dissect etiological and pharmacological modulations in brain morphology in obsessive-compulsive disorder (OCD) are often undermined by methodological and sampling constraints, yielding conflicting conclusions and no reliable neuromarkers. Here we evaluated alteration of regional gray matter volume including effect size (Cohen's d value) in 95 drug-naïve patients (age range: 18-55) compared to 95 healthy subjects (age: 18-63), then examined pharmacological effects in 65 medicated (age: 18-57) and 73 medication-free patients (age: 18-61). Robustness of statistical outcomes and effect sizes was rigorously tested with Monte Carlo cross-validation. Relative to controls, both drug-naïve and medication-free patients exhibited comparable volumetric increases mainly in the left thalamus (d=0.90, 0.82, respectively), left ventral striatum (d=0.88, 0.67), bilateral medial orbitofrontal cortex (d=0.86, 0.71; 0.90, 0.73), and left inferior temporal gyrus (d=0.83, 0.66), and decreased volumes in left premotor/presupplementary motor areas (d=-0.83, -0.71). Interestingly, abnormalities in the thalamus and medial orbitofrontal cortex were present in medicated patients whereas entirely absent in premotor and ventral striatum. It suggests that pharmacotherapy elicited divergent responses in orbitofronto-striato-thalamic and premotor circuits, which warrants the design of longitudinal studies investigating the potential of these neuromarkers in stratified treatments of OCD.

Chemical constituents and anti-inflammatory activities of Maqian (Zanthoxylum myriacanthum var. pubescens) bark extracts.

In this study, 44 compounds in the petroleum ether extract of Maqian (Zanthoxylum myriacanthum var. pubescens) bark, a traditional Dai herbal medicine, were identified by GC-MS. Major components included 3(2H)-benzofuranone, asarinin and (dimethoxymethyl)-3-methoxy-benzene. A total of 18 compounds were isolated from the ethyl acetate extracts of Maqian bark by column chromatography and identified by chemical and spectral analyses. Rhoifoline B, zanthoxyline dimethoxy derivative, N-nortidine, nitidine, decarine are the major alkaloids. Both the petroleum ether and ethyl acetate extracts showed significant inhibition on NO production, which imply anti-inflammatory activity, in lipopolysaccharide-induced RAW 264.7 cells without cell toxicity. Decarine is the major anti-inflammatory constituent with NO IC50 values of 48.43 µM on RAW264.7 cells. The petroleum ether extract, the ethyl acetate extract and decarine showed anti-inflammatory activities through inhibiting TNF-α and IL-1ß production in lipopolysaccharide-stimulated THP-1 cells without cell toxicity too. Decarine showed anti-inflammatory activity on human colon cells by reducing IL-6 and IL-8 production in TNF-α+IL-1ß-induced Caco-2 cells. These results support the use of Maqian bark as a remedy for enteritis and colitis recorded by Dai medicine in China, and elucidate the major pharmacological compounds in Maqian bark.

Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model.

The treatment of malignant tumors following surgery is important in preventing relapse. Among all the post-surgery treatments, immunomodulators have demonstrated satisfactory effects on preventing recurrence according to recent studies. Ginsenoside is a compound isolated from panax ginseng, which is a famous traditional Chinese medicine. Ginsenoside aids in killing tumor cells through numerous processes, including the antitumor processes of ginsenoside Rh2 and Rg1, and also affects the inflammatory processes of the immune system. However, the role that ginsenoside serves in antitumor immunological activity remains to be elucidated. Therefore, the present study aimed to analyze the effect of ginsenoside Rh2 on the antitumor immunological response. With a melanoma mice model, ginsenoside Rh2 was demonstrated to inhibit tumor growth and improved the survival time of the mice. Ginsenoside Rh2 enhanced T-lymphocyte infiltration in the tumor and triggered cytotoxicity in spleen lymphocytes. In addition, the immunological response triggered by ginsenoside Rh2 could be transferred to other mice. In conclusion, the present study provides evidence that ginsenoside Rh2 treatment enhanced the antitumor immunological response, which may be a potential therapy for melanoma.

Reversal of P-glycoprotein overexpression by Ginkgo biloba extract in the brains of pentylenetetrazole-kindled and phenytoin-treated mice.

The purpose of this study was to investigate the combined effects of Ginkgo biloba extract and phenytoin (PHT) sodium as a dose regimen simulating the clinical treatment of patients with epilepsy, on P-glycoprotein (P-GP) overexpression in a pentylenetetrazole-kindled mouse model of epilepsy. Epilepsy was induced by intraperitoneal administration of pentylenetetrazole (40 mg/kg) for 7 days followed by intragastric administration of PHT (40 mg/kg) for 14 days. Thirty mice that developed seizures were randomly divided into three groups and administered PHT as well as the following treatments: saline (negative control); verapamil (20 mg/kg, positive control); and G. biloba (30 mg/kg). Seizure severity was recorded 30 minutes after treatment on Day 4 of drug administration, after which the mice were euthanized, and their brains isolated. Western blots and immunohistochemistry were performed to analyze the expression of P-GP and caspase-3, respectively, in the brain tissue. High-performance liquid chromatography was used to measure the concentrations of PHT in the brains of the treated mice. After 4 consecutive days of treatment, the seizure severity in the mice in the G. biloba extract group was more significantly reduced than the seizure severity in the saline control group, and a significant difference was observed between the G. biloba extract and verapamil control groups (p < 0.05). P-GP expression in the brain more significantly decreased in the mice treated with G. biloba extract and verapamil than it did in the saline-treated control group (p < 0.05). Compared with the saline-treated control group, the mice treated with G. biloba extract and verapamil showed significantly increased brain PHT concentrations (p < 0.05). Furthermore, caspase-3 expression in the brain tissue of the G. biloba extract group was significantly lower than that in the vehicle control group (p < 0.05); this finding demonstrated the neuroprotective effects of G. biloba. Therefore, this study showed that treatment with G. biloba extract in combination with PHT prevented the upregulation of P-GP expression in mice. Moreover, G. biloba extract decreased seizure severity in pentylenetetrazole-kindled/PHT-treated mice through a mechanism that might be related to the reduction of P-GP expression in the brain.

Decreased thalamic glutamate level in unmedicated adult obsessive-compulsive disorder patients detected by proton magnetic resonance spectroscopy.

BACKGROUND: Previous neuroimaging studies implied that the dysfunction of cortico-striato-thalamo-cortical (CSTC) circuit served as the neural basis for the pathophysiology of obsessive-compulsive disorder (OCD). The imbalances in neuronal metabolite and neurotransmitter within CSTC circuit have been shown as the leading reasons of the OCD onset. The aim of this study is to investigate the metabolic alterations, especially the glutamatergic signal dysfunction within CSTC circuit, and the relationships between neural metabolites and the symptom severity of OCD patients. METHODS: Single voxel magnetic resonance spectroscopy (MRS) was conducted in medial prefrontal cortex (mPFC) and bilateral thalamus areas for thirteen unmedicated adult OCD patients with age-, gender-, and education-matched healthy controls. Quantification and multivariate analysis were performed to identify vital metabolic biomarkers for patients and healthy controls group differentiation. Moreover, we performed Spearman׳s rank correlation analysis for OCD patients to examine the relationship between the metabolite concentration level and OCD symptomatology. RESULTS: Patients with OCD showed significantly decreased glutamate level in mPFC (p=0.021) and right thalamus (p=0.039), and significantly increased choline compounds in left thalamus (p=0.044).The glutamate in right thalamus was shown as the most important metabolite for group separation from multivariate analysis (Q(2)=0.134) and was significantly correlated with the patients׳ compulsion scores (Spearman r=-0.674, p=0.016). LIMITATIONS: Limited sample size, the use of creatine and phosphocreatine (Cr) ratios rather than absolute concentrations and unresolved glutamine (Gln) are limitations of the present study. CONCLUSION: Our study results consolidated the hypothesis about glutamatergic signaling dysfunction in OCD. To our knowledge, it is the first finding about a reduced thalamic glutamate level in adult unmedicated OCD patients. The dysregulation of glutamate serves as a potential target for the OCD pharmacotherapy and the detailed mechanisms underlying the glutamate alterations within CSTC circuits merit further investigations.