Maternal separation regulates sensitivity of stress-induced depression in mice by affecting hippocampal metabolism.

Depression is a serious mental illness. Previous studies found that early life stress (ELS) plays a vital role in the onset and progression of depression. However, relevant studies have not yet been able to explain the specific effects of early stress on stress-induced depression sensitivity and individual behavior during growth. Therefore, we constructed a maternal separation (MS) model and administered chronic social frustration stress at different stages of their growth while conducting metabolomics analysis on the hippocampus of mice. Our results showed that the immobility time of mice in the forced swimming test was significantly reduced at the end of MS. Meanwhile, mice with MS experience significantly decreased total movement distance in the open field test and sucrose preference ratio in the sucrose preference test when subjected to chronic social defeat stress (CSDS) during adolescence. In adulthood, the results were the opposite. In addition, we found that level changes in metabolites such as Beta-alanine, l-aspartic acid, 2-aminoadipic acid, and Glycine are closely related to behavioral changes. These metabolites are mainly enriched in Pantothenate, CoA biosynthesis, and Beta Alanine metabolism pathways. Our experiment revealed that the effects of ELS vary across different age groups. It will increase an individual's sensitivity to depression when facing CSDS in adolescence, but it will reduce their sensitivity to depression when facing CSDS in adulthood. This may be achieved by regulating the hippocampus's Pantothenate and CoA biosynthesis and Beta Alanine metabolism pathways represented by Beta-alanine, l-Aspartic acid, 2-aminoadipic acid, and Glycine metabolites.

A sol-gel derived pH-responsive bovine serum albumin molecularly imprinted poly(ionic liquids) on the surface of multiwall carbon nanotubes.

A pH-responsive surface molecularly imprinted poly(ionic liquids) (MIPILs) was prepared on the surface of multiwall carbon nanotubes (MWCNTs) by a sol-gel technique. The material was synthesized using a 3-aminopropyl triethoxysilane modified multiwall carbon nanotube (MWCNT-APTES) as the substrate, bovine serum albumin (BSA) as the template molecule, an alkoxy-functionalized IL 1-(3-trimethoxysilyl propyl)-3-methyl imidazolium chloride ([TMSPMIM]Cl) as both the functional monomer and the sol-gel catalyst, and tetraethoxysilane (TEOS) as the crosslinking agent. The molecular interaction between BSA and [TMSPMIM]Cl was quantitatively evaluated by UV-vis spectroscopy prior to polymerization so as to identify an optimal template/monomer ratio and the most suitable pH value for the preparation of the MWCNTs@BSA-MIPILs. This strategy was found to be effective to overcome the problems of trial-and-error protocol in molecular imprinting. The optimum synthesis conditions were as follows: template/monomer ratio 7:20, crosslinking agent content 2.0-2.5 mL, temperature 4 °C and pH 8.9 Tris-HCl buffer. The influence of incubation pH on adsorption was also studied. The result showed that the imprinting effect and selectivity improved significantly with increasing incubation pH from 7.7 to 9.9. This is mainly because the non-specific binding from electrostatic and hydrogen bonding interactions decreased greatly with the increase of pH value, which made the specific binding affinity from shape selectivity strengthened instead. The polymers synthesized under the optimal conditions were then characterized by BET surface area measurement, FTIR, thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The adsorption capacity, imprinting effect, selective recognition and reusability were also evaluated. The as-prepared MWCNTs@BSA-MIPILs were also found to have a number of advantages including high surface area (134.2 m(2) g(-1)), high adsorption capacity (55.52 mg g(-1)), excellent imprinting effect (imprinting factor of up to 5.84), strong selectivity (selectivity factor of 2.61 and 5.63 for human serum albumin and bovine hemoglobin, respectively), and good reusability.

High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma.

Ubiquitin-conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression and is involved in the tumorigenesis of a variety of cancers. Previous studies have demonstrated that UBE2C is an important factor in the malignant progression of astrocytic tumors. However, the association between UBE2C expression and clinical prognosis of glioma patients has not been defined. In the present study, the expression of UBE2C in gliomas and non-cancerous brain tissues were detected by microarray and immunohistochemical analysis. The association between UBE2C expression and clinicopathological characteristics of the glioma patients was evaluated. The Kaplan-Meier method and multivariate Cox's proportional hazards model were used to analyze the survival time of the patients. The results demonstrated that the expression levels of UBE2C in anaplastic gliomas and glioblastoma (GBM) patients were significantly higher compared to low-grade gliomas, in microarray and immunohistochemistry analysis. A higher UBE2C expression was associated with a significantly decreased overall survival time in patients possessing anaplastic gliomas (P<0.01) and GBMs (P<0.05). Multivariate analysis of 80 GBM patients revealed that UBE2C expression was an independent prognostic factor. To the best of our knowledge, the present data suggest for the first time that UBE2C overexpression is strongly associated with an aggressive progression and poor outcome of malignant glioma. Therefore, UBE2C overexpression may be used as a predictor of poor prognosis in patients with malignant glioma.

Toll-like receptor 2 and -4 are involved in the pathogenesis of the Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system characterized by weakness in the limbs. To date, numerous hypotheses have been suggested to explain the pathogenesis of GBS; however, the pathogenesis of GBS remains to be elucidated. The aim of the present study was to investigate the association between Toll-like receptor (TLR) 2, TLR4 and GBS. Therefore, the mRNA of TLR2, TLR4, myeloid differentiation factor (MyD)88 and nuclear factor (NF)-κB of peripheral blood mononuclear cells (PBMCs) in patients with GBS and healthy controls was assessed. To confirm the function of TLR2 and TLR4 in the pathogenesis of GBS, PBMCs derived from patients with GBS and healthy controls were cultured with various TLR agonists. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were measured in the culture supernatant and fasting serum was obtained for the detection of anti-ganglioside antibodies. The results revealed that the mRNA levels of TLR2, TLR4, MyD88 and NF-κB were significantly increased in patients with GBS compared with those in healthy controls (P=0.003, 0.017, 0.032 and 0.015, respectively). PBMCs from patients with GBS secreted higher levels of TNF-α and IL-1ß than those from control subjects. The positive rate of immunoglobulin (Ig)G and IgM anti-ganglioside antibodies in patients with severe GBS was 42.86%, which was markedly higher than rates found in patients with mild GBS (9.09 and 18.18%, respectively). The results of the present study demonstrated that TLR2 and TLR4 are involved in the pathogenesis of GBS and that they and their associated signaling pathways may be targets for the treatment of GBS.

The diagnostic value of cerebrospinal fluids procalcitonin and lactate for the differential diagnosis of post-neurosurgical bacterial meningitis and aseptic meningitis.

OBJECTIVES: Distinguishing between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. This study aims to evaluate the combined diagnostic value of CSF procalcitonin and lactate as novel PNBM markers in hospitalized post-neurosurgery patients. DESIGN AND METHODS: This study was performed using CSF samples, collected by lumbar puncture, from 178 PNBM-suspected patients enrolled in a retrospective clinical study. The levels of CSF procalcitonin and lactate were appropriately assayed and the combined diagnostic value of these markers was assessed using receiver operating characteristic (ROC) curves, a two by two table, and non-parametric tests. RESULTS: Fifty of the 178 patients were diagnosed with PNBM, based on the clinical symptoms and laboratory results. These PNBM patients showed significantly elevated levels of CSF procalcitonin and CSF lactate compared with the non-PNBM group (p<0.001 for both). It was revealed that the cut-off values for the diagnosis of PNBM were: 0.075ng/mL (sensitivity, 68%; specificity, 73%) for procalcitonin and 3.45mmol/L (sensitivity, 90%; specificity, 85%) for lactate. A serial test combining the levels of these two markers showed decreased sensitivity (64%) and increased specificity (91%), compared with either marker alone. In contrast, a parallel test combining the levels of these both markers showed increased sensitivity (96%) and decreased specificity (65%), compared with either marker alone. CONCLUSION: Our study shows that the combined use of CSF procalcitonin and lactate can reliably distinguish between PNBM and non-PNBM and can be included in the design of diagnostic approaches to circumvent the shortcomings of conventional methods.

[Effect of acupoint massage dominant early comprehensive intervention on the prognosis of premature infants with brain injury].

OBJECTIVE: To explore the effect of acupoint massage dominant early comprehensive intervention on the prognosis of premature infants with brain injury. METHODS: Totally 210 premature infants with brain injury were assigned to the intervention group (112 cases) and the control group (98 cases). All patients received routine therapy (medicinal + routine care instructions). Patients in the intervention group additionally received acupoint massage. Those with abnormal early motion received physical sports treatment. Those with upper limbs dysfunction or with fine movement disorders received occupational therapy. Premature infants' development quotient (DQ) was performed at corrected age of 6 and 12 months by using neuropsychological development examination table for 0 - 6 years old children. The incidence of cerebral palsy was statistically calculated. RESULTS: At corrected age of 6 months, DQ of gross motor, fine motor, language three functional areas was higher in the intervention group than in the control group with significant difference (P < 0.05). At corrected age of 12 months, DQ of gross motor, fine motor, language, social and adaptive capacities was higher in the intervention group than in the control groupwith significant difference (P < 0.05). The incidence of cerebral palsy was 4.46% (5/112) in the intervention group and 12.24% (12/98) in the control group (P < 0.05). CONCLUSION: Acupoint massage dominant early comprehensive intervention could obviously improve the intelligence development level and lower the incidence of cerebral palsy in premature infants with brain injury.