A Preliminary Comparison of Plasma Tryptophan Metabolites and Medium- and Long-Chain Fatty Acids in Adult Patients with Major Depressive Disorder and Schizophrenia.

Background and Objectives: Disturbance of tryptophan (Trp) and fatty acid (FA) metabolism plays a role in the pathogenesis of psychiatric disorders. However, quantitative analysis and comparison of plasma Trp metabolites and medium- and long-chain fatty acids (MCFAs and LCFAs) in adult patients with major depressive disorder (MDD) and schizophrenia (SCH) are limited. Materials and Methods: Clinical symptoms were assessed and the level of Trp metabolites and MCFAs and LCFAs for plasma samples from patients with MDD (n = 24) or SCH (n = 22) and healthy controls (HC, n = 23) were obtained and analyzed. Results: We observed changes in Trp metabolites and MCFAs and LCFAs with MDD and SCH and found that Trp and its metabolites, such as N-formyl-kynurenine (NKY), 5-hydroxyindole-3-acetic acid (5-HIAA), and indole, as well as omega-3 polyunsaturated fatty acids (N3) and the ratio of N3 to omega-6 polyunsaturated fatty acids (N3: N6), decreased in both MDD and SCH patients. Meanwhile, levels of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) decreased in SCH patients, and there was a significant difference in the composition of MCFAs and LCFAs between MDD and SCH patients. Moreover, the top 10 differential molecules could distinguish the two groups of diseases from HC and each other with high reliability. Conclusions: This study provides a further understanding of dysfunctional Trp and FA metabolism in adult patients with SCH or MDD and might develop combinatorial classifiers to distinguish between these disorders.

Celastrus orbiculatus Extract Inhibits Immune Inflammatory Thrombotic State of B-Lymphoma.

OBJECTIVE: To investigate the inhibitory effect of Celastrus orbiculatus extracts (COE) on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in vivo. METHODS: The 38B9 lymphoma cells were treated with COE (160 µ g/mL) and CTX (25 µ mol/L). The apoptosis rate and cell cycle of each group were detected by flow cytometry. The secretion of inflammatory factors, including interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α), in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). In vivo, BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma model. COE (3 mg·kg-1·d-1) and CTX (40 mg·kg-1·d-1) were administered to the model mice, respectively. The expression of plasma inflammatory factors (IL-6, IL-10 and TNF-α) and thrombus indexes, including D-dimer (D-D), von Willebrand factor (vWF) and tissue factor (TF), were detected by ELISA before tumor bearing (1 d), after tumor formation (14 d) and after intervention (21 d). PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps (NETs). Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2 (CLEC-2). The tumor growth and survival of mice were recorded. RESULTS: The 38B9 lymphoma cells were apoptotic after the intervention of COE and CTX. The ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells (P<0.05), and S phase cells decreased in CTX intervented cells (P<0.05). Also, the secretion level of IL-6 was significantly reduced after COE or CTX intervention (P<0.05), and IL-10 was significantly increased (P<0.05). Furthermore, the tumor mass was reduced, and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in non-intervented mice. The significantly lower levels of TNF-α, IL-6, NETs, TF, DD and CLEC-2, as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice (P<0.05). CONCLUSION: COE has a mild and stable anti-tumor effect, which can reduce the secretion of inflammatory factors by lymphoma cells and regulate thrombophilic state caused by tumor inflammatory microenvironment.

[The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice].

OBJECTIVE: To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice. METHODS: Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice. RESULTS: After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05). CONCLUSION: Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

rTMS ameliorates depressive-like behaviors and regulates the gut microbiome and medium- and long-chain fatty acids in mice exposed to chronic unpredictable mild stress.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. METHODS: Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. RESULTS: CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. CONCLUSION: These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.

High-frequency repetitive transcranial magnetic stimulation regulates neural oscillations of the hippocampus and prefrontal cortex in mice by modulating endocannabinoid signalling.

BACKGROUND: Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified. METHODS: The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice. RESULTS: Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS. LIMITATIONS: The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated. CONCLUSION: Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS.

[Inhibitory Effect of Interference with PD-L1 Expression on B-cell lymphoma in Mice].

OBJECTIVE: To investigate the potential inhibitory effect of interference with PD-L1 on B cell lymphoma in mice. METHODS: Three shRNA vectors for mouse CD274 (PD-L1) were constructed and transiently transfected into 293T cells. RT-qPCR was used to validate the interference efficiency of CD274. The shRNA vector that interfere efficiently with CD274 expression was packaged by using lentivirus packaging system to generate shRNA lentivirus, and then transfected into A20 lymphoma cell line. The methyl thiazol terazolium (MTT) assay was used to detect proliferation after 48 h culture of CD274-sh A20 cells. Meanwhile, BALB/c mice were hypodermically infected with CD274-sh A20 cells. Infected mice were observed daily and assessed to visualize tumor by in vivo fluorescence imaging. RESULTS: The proliferation rate of CD274-sh A20 cells in vitro was significantly lower than that of A20 cells (P<0.05). The tumor size detected by in vivo fluorescence imaging showed a significant reduce in tumor bearing mice with CD274-sh compared with other tumor bearing mice. And the weight and size of tumor in CD274-sh group were also significantly reduced compared with other group (P<0.05). Moreover, the survival time of tumor bearing mice in CD274-sh group was longer than that of the PD-L1 high expression group. CONCLUSION: PD-L1 plays an important role in the incidence and the progression of lymphoma, and the shRNA-based PD-L1 knockdown can inhibit cell proliferation of A20 cells and partly suppress tumor growth.

Rectal nonsteroidal anti-inflammatory drugs, glyceryl trinitrate, or combinations for prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: A network meta-analysis.

BACKGROUND: Acute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammatory drugs (NSAIDs) are more beneficial in preventing post-ERCP pancreatitis (PEP). Randomized controlled trials (RCTs) have also demonstrated the efficacy of glyceryl trinitrate (GTN). We conducted a network meta-analysis to compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination. AIM: To compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination. METHODS: A systematic search was done for full-text RCTs of PEP in PubMed, Embase, Science Citation Index, and the Cochrane Controlled Trials database. Inclusion and exclusion criteria were used to screen for eligible RCTs. The major data were extracted by two independent reviewers. The frequentist model was used to conduct this network meta-analysis and obtain the pairwise OR and 95%CI. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS: Twenty-four eligible RCTs were selected, evaluating seven preventive strategies in 9416 patients. Rectal indomethacin 100 mg plus sublingual GTN (OR: 0.21, 95%CI: 0.09-0.50), rectal diclofenac 100 mg (0.34, 0.18-0.65), sublingual GTN (0.34, 0.12-0.97), and rectal indomethacin 100 mg (0.49, 0.33-0.73) were all more efficacious than placebo in preventing PEP. The combination of rectal indomethacin and sublingual GTN had the highest surface under the cumulative ranking curves (SUCRA) probability of (92.2%) and was the best preventive strategy for moderate-to-severe PEP with a SUCRA probability of (89.2%). CONCLUSION: Combination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.

The Impact of Electroacupuncture Early Intervention on the Brain Lipidome in a Mouse Model of Post-traumatic Stress Disorder.

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

Hydrogen-rich water ameliorates neuropathological impairments in a mouse model of Alzheimer's disease through reducing neuroinflammation and modulating intestinal microbiota.

Hydrogen exhibits the potential to treat Alzheimer's disease. Stereotactic injection has been previously used as an invasive method of administering active hydrogen, but this method has limitations in clinical practice. In this study, triple transgenic (3×Tg) Alzheimer's disease mice were treated with hydrogen-rich water for 7 months. The results showed that hydrogen-rich water prevented synaptic loss and neuronal death, inhibited senile plaques, and reduced hyperphosphorylated tau and neurofibrillary tangles in 3×Tg Alzheimer's disease mice. In addition, hydrogen-rich water improved brain energy metabolism disorders and intestinal flora imbalances and reduced inflammatory reactions. These findings suggest that hydrogen-rich water is an effective hydrogen donor that can treat Alzheimer's disease. This study was approved by the Animal Ethics and Welfare Committee of Shenzhen University, China (approval No. AEWC-20140615-002) on June 15, 2014.

[Synergistic Reaction Mechanism of Cu0@Fe3O4 Activated PMS for Degradation of p-nitrophenol].

A Cu0/PMS system mainly relies on the leaching of copper ions to degrade the pollutants and adapt to the narrow pH range (<7). To solve this defect, we studied the properties and reaction mechanism of Cu0@Fe3O4 magnetic core-shell material, which was successfully prepared using co-precipitation method, taking PNP as the target pollutant. The results showed that: ① a degradation rate of 96% can be achieved within 60 min for 5 mg ·L-1 PNP, 200 mg ·L-1 Cu0@Fe3O4, and 0.5 mmol ·L-1 PMS at a natural pH value (5.65); ② the Cu0@Fe3O4/PMS system can be regarded as a heterogeneous reaction system because TCu, TCu+, and iron leaching were almost negligible; ③ on comparing the performance of the Cu0@Fe3O4/PMS system and Cu0/PMS system in the pH range of 3 to 11, it was discovered that the method by which Cu0 activates the PMS to degrade the PNP was successfully changed by coating a layer of Fe3O4. The Cu0@Fe3O4/PMS system has a good degradation performance towards PNP in the pH range of 5-9; ④ SO-4 · and HO · existed in the reaction system, and their contribution rates to the reaction system were 34% and 60% ; HO · was the dominant free radical; ⑤ A bimetallic synergy exists between Fe and Cu. The presence of Cu(Ⅰ) can promote the reduction of Fe(Ⅲ) to Fe(Ⅱ), thereby forming a good redox cycle and improving the durability of the reaction system.

[Expression Difference of RhoH Gene in Leukemia and Its Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significance of RhoH gene in bone marrow cells of leukemia patients. METHODS: 31 cases of leukemia and 15 cases of non-tumor as controls were collected. The expression of RhoH in bone marrow cells was detected by real-time quantitative PCR (RQ-PCR). The median expression level of RhoH was used as the cut-off value. The newly diagnosed patients were divided into RhoH high expression group and low expression group. The relationship of different RhoH expression levels with clinical features and prognosis of newly diagnosed patients was analyzed. RESULTS: The mRNA expression of RhoH in the bone marrow cells of 31 cases of leukemia was significantly lower than that in the control group, mRNA expression of RhoH in the ALL group was significantly lower than that in AML group (P＜0.05). Compared with the RhoH high expression group, the proportion of bone marraw blasts and LDH level in the RhoH low expression group was significantly increased (P＜0.05), but there were no significant differences in clinical features such as age, white blood cell count, hemoglobin level, platelets count, PCT and CRP level (P＞0.05). In AML, the recurrence rate after standard chemotherapy in RhoH low expression group was higher than that in high expression group, while the expression of RhoH not correlated with other prognostic genes of AML. In ALL, the recurrence rate in RhoH low expression group was not statistically significant different from that in high expression group. CONCLUSION: RhoH may be involved in the genesis of acute leukemia. In AML, RhoH expression negatively correlates with recurrence rate, which can be used as a prognostic indicator independently. In ALL, RhoH may participate in the disease process through other mechanism.

[Effect of Coagulation and Platelet Activation on Tumor-Associated Hypercoagulable State in Lymphoma-Bearing Mice].

OBJECTIVE: To investigate the coagulation abnormality and tumor-associated hypercoagulable state in lymphoma-bearing mice by measuring the changes in coagulation indices (D-D, vWF, TF) and platelet activation indices (P-selectin, GPIIbIIIa). METHODS: The mouse model with lymphoma was established by the subcutaneous injection of 38B9 lymphoma cells into BALB/c mice, and the tumor formation was evaluated by using MRI and B ultrasonography. The D-D, vWF and TP levels of blood samples from inner canthal vein of tumor-bearing mice on 1 d, 14 d and 21 d were detected by using ELISA, the platelet activation indices (P-selectin, GPIIbIIIa) were detected by using flow cytometry. RESULTS: The lymphoma-bearing mouse model was successfully established. The levels of D-D, vWF and TF as well as platelet activation indices P-selectin and GPIIbIIIa in the peripheraI blood were significantly higher than those of control group (P<0.05). CONCLUSION: Lymphoma-bearing mice showed abnormalities of coagulation and platelet activation, which relates with the tumor hypercoagulable state in lymphoma-bearing mice.

Effect of telehealth interventions on major cardiovascular outcomes: a meta-analysis of randomized controlled trials.

BACKGROUND: Telehealth interventions (THI) were associated with lower levels of cardiovascular risk factors in adults, whereas the effect of THI on cardiovascular disease (CVD) still remains controversial. A meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCT) which investigated potential impact of THI on the incidence of CVD in patients with or without prior CVD. METHODS: PubMed, EmBase, and the Cochrane Library were searched to identify RCTs to fit our analysis through December 2016. Relative risk (RR) with its 95% confidence interval (CI) was used to measure the effect of THI using a random-effect model. Sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. RESULTS: Eight RCTs were included and with a total of 1635 individuals. The summarized results indicated that participants who received THI showed a significant reduction of the CVD incidence as compared with usual care (RR: 0.59; 95% CI: 0.47-0.74; P < 0.001). Furthermore, the effect of THI was greater in patients with history of CVD (RR: 0.55; 95% CI: 0.44-0.70; P < 0.001) than in patients without history of CVD (RR: 0.99; 95% CI: 0.51-1.94; P = 0.977). Sensitivity analysis suggested that the intervention effect persisted and the conclusion was not changed. Subgroup analysis indicated mean age, study quality might play an important role on the risk of CVD. CONCLUSIONS: The findings of this study indicated THI could reduce the recurrence of CVD. Further large-scale trials are needed to verify the effect of THI on CVD in healthy individuals.

Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a meta-analysis.

AIM: To assess the effectiveness of pancreatic stents for preventing pancreatitis in high-risk patients after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: PubMed, Embase, Science Citation Index, and Cochrane Controlled Trials Register were searched to identify relevant trials published in English. Inclusion and exclusion criteria were used to screen for suitable studies. Two reviewers independently judged the study eligibility while screening the citations. The methodological quality of the included trials was assessed using the Jadad scoring system. All results were expressed as OR and 95%CI. Data were analyzed using Stata12.0 software. RESULTS: Ten eligible randomized controlled trials were selected, including 1176 patients. A fixed-effects model in meta-analysis supported that pancreatic duct stents significantly decreased the incidence of post-ERCP pancreatitis (PEP) in high-risk patients (OR = 0.25; 95%CI: 0.17-0.38; P < 0.001). Pancreatic stents also alleviated the severity of PEP (mild pancreatitis after ERCP: OR = 0.33; 95%CI: 0.21-0.54; P < 0.001; moderate pancreatitis after ERCP: OR = 0.30; 95%CI: 0.13-0.67; P = 0.004). The result of severe pancreatitis after ERCP was handled more rigorously (OR = 0.24; 95%CI: 0.05-1.16; P = 0.077). Serum amylase levels were not different between patients with pancreatic stents and control patients (OR = 1.08; 95%CI: 0.82-1.41; P = 0.586). CONCLUSION: Placement of prophylactic pancreatic stents may lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate the severity of this condition.

A screen of suitable inducers for germline differentiation of chicken embryonic stem cells.

Differentiation of germ cells from embryonic stem cells in vitro could have great application for treating infertility and provide an excellent model for uncovering molecular mechanisms of germline generation. In this study, we aim to screen the suitable inducers that may prove the efficiency of driving chicken embryonic stem cells (ES cells) toward germ cells. The male ES cells were separeted into different groups: single retinoic acid (RA) treatment, co-cultured with sertoli cell feeder with RA induction, cultured on matrix proteins (fibronectin, laminin and collagen) with RA treatment, cultured on fibronectin with sertoli cell feeder and RA induction, and single bone morphogenetic protein 4 (BMP4) treatment. Quantitative RT-PCR and immunoourescence were performed to characterize the ES cells differentiation process. The results showed that spermatogonial stem cells (SSCs)-like were not detected in single RA and RA with collagen groups, but were observed in the other groups. The expression of ES specific genes (Nanog and Sox2) was decreased while SSCs marker genes (Dazl, Stra8, integrin α6, integrinß1 and C-kit) was remarkably increased. The multiple comparsion results showed that the expression of SSCs marker genes in RA with sertoli cells group was significantly higher than the other groups(P<0.05). Collectively, our results suggested that chicken ES cells possess the potency to differentiate into SSCs-like cells in vitro through RA, matrix proteins, sertoli cells and BMP4 induction, of which co-cultured with sertoli cell feeder with RA induction was proved to be the best.

Three-component domino reactions for regioselective formation of bis-indole derivatives.

A microwave-assisted regioselective reaction dealing with arylglyoxal monohydrate, diverse N-aryl enaminones, and indoles to achieve 3,2'- and 3,3'-bis-indoles by varying a substituted indole substrate is reported. The 2-unsubstituted indoles resulted in the 3,2'-bis-indole skeleton, whereas indoles bearing a methyl or phenyl group at C2 led to the 3,3'-bis-indoles with simultaneous formation of three sigma-bonds. The procedures feature excellent regioselectivity, short reaction times, convenient one-pot manner, and operational simplicity.