Search for serum biomarkers in patients with bipolar disorder and major depressive disorder using metabolome analysis.

Objective: Bipolar disorder (BD) and major depressive disorder (MDD) are two common psychiatric disorders. Due to the overlapping clinical symptoms and the lack of objective diagnostic biomarkers, bipolar disorder (BD) is easily misdiagnosed as major depressive disorder (MDD), which in turn affects treatment decisions and prognosis. This study aimed to investigate biomarkers that could be used to differentiate BD from MDD. Methods: Nuclear magnetic resonance (NMR) spectroscopy was performed to assess serum metabolic profiles in depressed patients with BD (n = 59), patients with MDD (n = 14), and healthy controls (n = 10). Data was analyzed using partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis and t-tests. Different metabolites (VIP > 1 and p < 0.05) were identified and further analyzed using Metabo Analyst 5.0 to identify relevant metabolic pathways. Results: The metabolic phenotypes of the BD and MDD groups were significantly different from those of the healthy controls, and there were different metabolite differences between them. In the BD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, ß-glucose, pantothenic acid, mannose, glycerol, and lipids were significantly higher than those in the healthy control group, and the levels of lactate and acetoacetate were significantly lower than those in the healthy control group. In the MDD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, pyruvate, choline, acetoacetic acid, and lipids were significantly higher than those of healthy controls, and the levels of acetic acid and glycerol were significantly lower than those of healthy controls. Conclusion: Glycerolipid metabolism is significantly involved in BD and MDD. Pyruvate metabolism is significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD.

Identifying potential insecticide resistance markers through genomic-level comparison of Bemisia tabaci (Gennadius) lines.

The invasive whitefly (Bemisia tabaci) MED is one of the most economically damaging plant pests. The extensive use of insecticide over decades has led to that the invasive B. tabaci MED has developed resistance to a wide range of insecticide classes, but little is known about the genetic background associated with resistance. To this end, we conducted a comparative genome-wide analysis of single-base nucleotide polymorphisms between MED whitefly lines collected from fields that were recently infested and an insecticide-susceptible MED whitefly line collected in 1976. First, low-coverage genome sequencings were conducted on DNA isolated from individual whiteflies. The sequencing results were evaluated using an available B. tabaci MED genome as a reference. Significant genetic differences were discovered between MED whitefly lines collected from fields that were recently infested and an insecticide-susceptible MED whitefly line based on the principal component analyses. Top GO categories and KEGG pathways that might be involved in insecticide resistance development were identified, and several of them have not been previously associated with resistance. Additionally, we identified several genetic loci with novel variations including Cytochrome P450 monooxygenases (P450s), UDP-glucuronosyltransferases (UGTs), Glutathione S-transferases (GSTs), esterase, carboxyl-esterases (COE), ABC transporters, fatty acyl-CoA reductase, voltage-gated sodium channels, GABA receptor, and cuticle proteins (CPs) that were previously reported to have close associations with pesticide resistance in well-studied insect groups that provide an essential resource for the design of insecticide resistance-linked loci arrays insecticide. Our results was obtained solely on resequencing genome data sets, more pesticide bio-assays combined with omics datasets should be further used to verify the markers identified here.

Common and unique alterations of functional connectivity in major depressive disorder and bipolar disorder.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level. METHODS: In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied. RESULTS: Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD. CONCLUSIONS: Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders.

Metabolomic analysis to detect urinary molecular changes associated with bipolar depression.

Bipolar disorder (BD) is a debilitating mental disorder with complex clinical manifestations and low diagnostic accuracy. Depressive episodes are most common in the course of BD with high comorbidity and suicide rates, which present greater clinical challenges than mania and hypomania episodes. However, there are no objective biomarkers for bipolar depression. The aim of this study was to detect urinary metabolite biomarkers that could be useful for the diagnosis of bipolar depression. Nuclear magnetic resonance spectroscopy was used to profile urine samples of patients with bipolar depression (n = 37) and healthy volunteers (n = 48). Data were analyzed using Orthogonal Partial Least Square Discriminant Analysis and t-test. Differential metabolites were identified (VIP > 1 and p < 0.05), and further analyzed using Metabo Analyst 3.0 to identify associated metabolic pathways. In total, we identified seven metabolites differentially expressed in patients with BD and healthy controls. Compared with healthy group, the levels of betaine, glycerol, hippuric acid, indole sulfate, trimethylamine oxide, and urea in urine samples of BD patients were significantly higher, while the level of inositol was significantly lower. Most of these small molecules are related to lipid metabolism and gut microbiota metabolism. These differential metabolites could provide critical insight into the pathological mechanisms of bipolar depression. The results of this study provide a meaningful reference for similar and further studies in the future.

[Effects of Atorvastatin on Proliferation and Apoptosis of Leukemia Cell Line HL-60 and Its Mechanism of Signal Pathway].

OBJECTIVE: To investigate the effect of atorvastatin on proliferation and apoptosis of leukemia cell line HL-60 and its mechanism of signal pathway. METHODS: The leukemia HL-60 cells in logarithmic growth phase were seeded in 96 well plates and were treated with 1, 5 and 10 mol/L atorvastatin, then were cultured in the incubator (at 37 °C, 5% CO2) for 12 h, 24 h, 48 h. MTT colorimetric method was used to detect the proliferation leukemia cells, the apoptosis of leukemia cells was detected by flow cytometry; the expresion levels of phosphatidylinositol 3-kinase(PI3K), serine threonine protein kinase(ATK) and mTOR at mRNA and protein levels were detected by RT-PCR and Western blot respectively. The experiments included blank control group, the negative control group and drug-treated group. RESULTS: Atorvastatin could inhibit the proliferation of HL-60 cells. The treatment of HL-60 cells with 10 mol/L atorvastatin for 48 hours showed the strongest inhibition rate (39.78±3.00)% which was statistically significant different from negative control group (t=4.015, P<0.05) and the strongest induction-apoptosis effect on HL-60 cells (43.30±3.92)%, that was statistically significantly different from negative control group (t=3.624, P<0.05). After treatment with atorvastatin for 48 hours, the expression levels of PI3K,ATK and mTOR were decreased, in which the effect of 10 mol/L atorvastatin was the most obvious; The expression levels of PI3K,ATK and mTOR were decreased by (37.04±4.15)%, (53.81±3.25)% and (40.62±2.41) respectively, significantly different from the negative control (t=4.806,3.800,4.313, P<0.05). CONCLUSION: Atorvastatin may inhibit the proliferation of HL-60 cells and induce apoptosis by inhibiting the PI3K/ATK/mTOR signaling pathway.

[Expression of TRAF-6,TAK1 and TGF-ß mRNA in peripheral blood mononuclear cells of patients with diffuse large B cell lymphoma before and after chemotherapy].

This study was purposed to detect the expression levels of TRAF6, TAK1 and TGF-ß mRNA in peripheral blood mononuclear cell (PBMNC) of patients with diffuse large B cell lymphoma (DLBCL) before and after chemotherapy, and to explore the effect of chemotherapy on the activity of TRAF6/TAK1 signal pathway. The expression levels of TRAF-6, TAK1 and TGF-ß mRNA in PBMNC of 38 patients with DLBCL were detected by using the quantitative real time PCR before treatment or after two cycles of chemotherapy, 12 healthy people were served as the control. The results showed that the expression levels of TRAF-6, TAK1 and TGF-ß mRNA in PBMNC of DLBCL patients' were higher than those in healthy people. Before treatment, the expression levels of TRAF-6 and TAK1 mRNA had no significant difference as compared with healthy people (P > 0.05); after chemotherapy, the expression levels of these two genes significantly increased, and the differences both had statistically significant as compared with healthy people (P < 0.05); meanwhile the increased expression levels of these two genes after chemotherapy had statistically significant difference as compared with levels before treatment (P < 0.05) , and those expression levels were positively correlated. While the expression level of TGF-ß mRNA decreased after chemotherapy as compared with level before treatment, and the differences had statistically significantse(P < 0.05). It is concluded that the activity of TRF6/TAK1 signal pathways in PBMNC of DLBCL patients' significantly increases after chemotherapy, while the expression level of TGF-ß mRNA after chemotherapy is abviously lower than level before treatment.