Protein Profiles and Novel Molecular Biomarkers of Schizophrenia Based on 4D-DIA Proteomics.

Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.

Methionine sulfoxide suppresses adipogenic differentiation by regulating the mitogen-activated protein kinase signaling pathway.

In this study, methionine sulfoxide (MetO) was identified as an active metabolite that suppresses adipogenesis after screening obese individuals versus the normal population. MetO suppressed the gene and protein expression of CCAAT/enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 4 (FABP4), and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) during human preadipocyte (HPA) differentiation. Adipogenesis decreased following MetO treatment; however, the preadipocyte number, proliferation, and apoptosis were unaffected. The activity of phosphorylated extracellular signal-related kinase (P-ERK) of the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited in HPA after MetO treatment. Furthermore, treatment of preadipocytes with the selective P-ERK1/2 agonist Ro 67-7476 abolished the effect of MetO against adipogenesis suggesting that MetO function is dependent on the MAPK pathway. The mechanistic insights of adipogenesis suppression by MetO presented in this study shows its potential as an antiobesity drug.

[Quality standard study on Entadae Semen].

OBJECTIVE: To establish the quality standard of Entadae Semen, and provide scientific basis for its quality control. METHOD: TLC and HPLC were used for qualitative identification and quantitative analysis of phaseoloidin and entadamide A-O-ß-D-glucopyranoside in Entadae Semen. The test of water content, ash and ethanol-soluble extractives of Entadae Semen was carried out according to the methods recorded in appendix of Chinese Pharmacopeia (2010 edition). RESULT: The TLC was well separated with clear spots. The linear range of phaseoloidin was between 0.014 to 2.747 g x L(-1) (r = 0.999 6, n = 9) with an average recovery rate of 101.06% (RSD 0.90%, n = 6); the linear range of entadamide A-O-ß-D-glucopyranoside was between 0.002 to 0.452 g x L(-1) (r = 0.999 7, n = 9) withan average recovery rate of 101.52% (RSD 1.09%, n = 6). The content of phaseoloidin in sample is between 5.12% to 9.24%, entadamide A-O-ß-D-glucopyranoside is between 0.55% to 2.17%, alcohol-soluble extracts is between 30.9% to 45.2%, water is between 6.6% to 8.6%, and total ash is between 2.4% to 2.9%. CONCLUSION: The established standard is acceptable for quality control of Entadae Semen.

Bioactive peptides PDBSN improve mitochondrial function and suppression the oxidative stress in human adiposity cells.

Introduction: Mitochondria are essential for generating cellular energy and are significant in the pathogenesis of obesity. Peptide PDBSN has been demonstrated to inhibit the adipogenic differentiation of adipocytes in vitro and improves metabolic homoeostasis in vivo. Therefore, in this study, we further investigated the effects of PDBSN on the morphology, synthesis, and function of adipocyte mitochondria. Methods: Human visceral and subcutaneous primary preadipocytes (HPA-v and HPA-s) were cultured into mature adipocytes. Intracellular triglyceride content was assessed using oil-red O staining and tissue triglyceride determination. Gene and protein levels associated with mitochondrial synthesis were detected using real-time quantitative polymerase chain reaction and western blotting. Mitochondrial membrane potentials and ROS were detected using fluorescent indicators. Morphological changes were observed by electron microscopy. Results: PDBSN significantly increased mitochondrial membrane potential (MMP), while decreasing intracellular triglyceride (TG) and intracellular reactive oxygen species (ROS) levels. On the other hand, the transcription and protein levels of genetic marker genes PGC1-α and MTFA were significantly up-regulated after PDBSN administration. Further studies showed that transcriptional and protein levels of mitochondrial fusion and fission genetic markers MFN1, MFN2, NRF1, and DRP1 increased. Conclusion: PDBSN significantly reduces intracellular TG and ROS levels and increases MMP. The maximum respiratory capacity in adults significantly increases after PDBSN administration, and ROS levels are significantly reduced. This suggests that PDBSN improves mitochondrial function to some extent, which not only provides an essential basis for the pathophysiology of obesity but also provides insights for the development of new drugs to treat obesity and metabolic diseases.

Parental smoking exposure before and during pregnancy and offspring attention-deficit/hyperactivity disorder risk: A Chinese child and adolescent cohort study.

Background: Previous studies revealed that maternal smoking exposure during pregnancy was an essential risk factor for offspring developing attention-deficit/hyperactivity disorder (ADHD). The impact of paternal smoking exposure 1 year before pregnancy on offspring ADHD risk is still unclear. Methods: The present study included 2,477 school-age children and their parents from the Shanghai Child and Adolescent Health Cohort who had complete data for offspring ADHD diagnosis and parents' smoking exposure before and during pregnancy information. A multivariate logistic regression model and Firth's logistic regression model were used to determine the associations of paternal smoking and parental smoke exposure patterns before and during pregnancy with offspring ADHD risk. Results: Children whose fathers smoked before pregnancy had a higher risk of developing ADHD [odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.35-4.98] compared to those whose fathers had never been exposed to smoking. Similarly, parents who were exposed to smoking or second-hand smoke before pregnancy had 1.96 times (OR = 1.96, 95% CI: 1.19-3.22) more likely to have offspring with ADHD. Moreover, children whose parents were exposed to smoking both before and during pregnancy were 2.01 times (OR = 2.01, 95% CI: 1.29-3.12) more likely to develop ADHD. Conclusion: Paternal smoking before pregnancy and parental smoking exposure 1 year ahead of and throughout pregnancy were all risk factors for offspring developing ADHD.

Serum lipid profiles and post-stroke depression in acute ischemic stroke patients.

Purpose: Post-stroke depression (PSD) is a psychiatric complication after stroke that leads to poorer stroke outcomes. Recent observational studies have indicated that lipid profiles were associated with a higher risk of stroke and depression. This study aims to further explore the possible relationship between serum lipid profiles and the development of PSD. Methods: A total of 373 acute ischemic stroke patients were examined. Serum lipid profiles including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) were measured within 24 hrs of admission. Depression symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17) at the one-month follow-up, and HAMD scores ≥7 indicated a diagnosis of PSD. Results: A total of 114 patients were diagnosed with PSD at the one-month follow-up, for a percentage of 30.6%. There were significant differences in HDL-C levels (P<0.001), LDL-C levels (P=0.002) and the LDL/HDL ratio (P<0.001) between the PSD and non-PSD groups, but no differences were observed in TGs, TC, Apo A1 or Apo B. Low serum HDL-C levels (r = -0.157, P<0.001) and elevated LDL-C levels (r =0.139, P=0.002) and the LDL/HDL ratio (r =0.227, P<0.001) were associated with HAMD scores. After adjusting for the NIHSS score, BI score, mRS score and alcohol consumption in the logistic analysis, low HDL-C levels and the highest quartile (≥3.07) of the LDL/HDL ratio were independently associated with the development of PSD (OR =0.250, 95% CI, 0.077-0.813, P=0.021 and OR =1.874, 95% CI, 1.050-3.347, P=0.034, respectively). Conclusion: Decreased levels of HDL-C and elevated levels of LDL/HDL ratio are associated with PSD. HDL-C and the LDL/HDL ratio are independent predictors of PSD.

High serum nerve growth factor concentrations are associated with good functional outcome at 3 months following acute ischemic stroke.

BACKGROUND: Previous studies in animal model have demonstrated that neurotrophins were associated with functional outcome following stroke. However, the relationship between serum nerve growth factor (NGF) and functional outcome in stroke patients has not been explored. Our objective was to investigate the association between serum NGF concentrations at admission and functional outcome of patients at 3 month after stroke. METHODS: One-hundred eight-five patients with acute ischaemic stroke were recruited in our study. Serum NGF concentrations were measured by ELISA at admission. The stroke severity at admission was assessed by the National Institute of Health Stroke Scale (NIHSS). The modified Rankin Scale (mRS) was used to assess the functional outcome of patients at 3 month after stroke. In addition, 100 healthy controls were recruited. RESULTS: Serum NGF concentrations were higher in good functional outcome group (mRS score of 0-2) than that in poor functional outcome group (mRS score of 3-6) (9.51 ±â€¯2.33 vs. 8.12 ±â€¯1.61, P < 0.001). Meanwhile, the serum NGF concentrations in healthy group were lower than that in acute ischemic stroke patients (7.17 ±â€¯1.49 vs. 9.15 ±â€¯2.24, P < 0.001). Moreover, our results demonstrated that high serum NGF concentrations (>9.21 ng/l) were independently associated with the better functional prognosis at 3 months following the occurrence of stroke (OR 0.048, 95% CI 0.012-0.185, P < 0.001). CONCLUSIONS: High concentrations of serum NGF at admission may predict good functional outcome of patients at 3 months after acute cerebral ischemia stroke.

Association between serum malondialdehyde levels and depression during early methamphetamine withdrawal.

Some evidence suggested that malondialdehyde (MDA) as a marker of oxidative stress played an important part in modulating the activities of depression. Methamphetamine (METH) dependence often lead to depression that may associate with MDA. In this study, our purpose was to explore the association between serum MDA levels and depression during METH withdrawal. 179 METH-dependent patients were recruited in this study and 144 (80.4%) finished the assessment. We measured serum MDA at 532 nm spectrophotometrically at admission. The short form of the Beck Depression Inventory (BDI-13) was used to evaluate depression symptoms. Patients were identified to have depression symptoms with the BDI score ≥ 8. As a result, 89 (61.8%) of the remaining 144 METH-dependent patients were identified to have depression symptoms. Patients with depression symptoms showed significantly higher serum MDA levels than non-depression patients (3.42 ± 1.60 nmol/ml vs. 2.43 ± 1.25 nmol/ml; p < 0.001). After controlling for potential confounding variables in our logistic model, serum MDA levels were independently associated with the development of depression during early METH withdrawal (OR =1.952, 95% CI, 1.414-2.694, p < 0.001). Furthermore, our study found a positive association between Beck Depression Inventor (BDI) score in early METH abstinence and serum MDA levels (r =0.185; p = 0.026). Our results indicated that higher serum MDA levels were related to higher risk of depression symptoms during early METH withdrawal.

Association between vitamin D receptor BsmI polymorphism and bone mineral density in pediatric patients: A meta-analysis and systematic review of observational studies.

BACKGROUND: Vitamin D and the vitamin D receptor (VDR) are important in the metabolic processes that affect bone mineral density (BMD). However, the effect of VDR BsmI polymorphism on BMD in pediatric patients is still unclear. METHODS: Eligible studies were identified from the following electronic databases: PubMed, Embase, the Cochrane Library, and the Chinese CNKI and Wanfang databases before October 1, 2016. Data were extracted from the eligible studies, and associations between VDR BsmI polymorphism and BMD in pediatric patients were estimated with weighted mean differences (WMDs) and 95% confidence intervals (CIs). Subgroup analysis of ethnicity and sensitivity analyses were used to identify sources of heterogeneity. RESULTS: A significant difference was observed between VDR BsmI polymorphism and pediatric BMD levels of the lumbar spine (LS) in the corecessive model (bb vs BB + Bb: WMD = -0.23, 95% CI [-0.35, -0.11], P < 0.01). No significant relationship was found in the dominant, recessive, or codominant models for LS BMD (BB vs Bb: WMD = -0.56, 95% CI [-1.58, 0.46], P = 0.29; BB vs bb: WMD = -0.54, 95% CI [-1.49, 0.41], P = 0.27; and BB vs Bb + bb: WMD = -0.45, 95% CI [-1.71, 0.26], P = 0.22). In addition, we found no remarkable association between the BsmI polymorphism and BMD levels of the femoral neck (FN) in children (BB vs Bb: WMD = -1.08, 95% CI [-3.13, 0.96], P = 0.30; BB vs bb: WMD = 0.98, 95% CI [-0.89, 2.85], P = 0.31; BB vs Bb + bb: WMD = -0.061, 95% CI [-0.30, 0.17], P = 0.61; and bb vs BB + Bb: WMD = 0.82, 95% CI [-0.59, 2.32], P = 0.25). CONCLUSION: Our meta-analysis found that the VDR BsmI genetic polymorphism was correlated with LS BMD level in pediatric patients: compared with those with the B allele, children with the bb genotype were less likely to have lower BMD levels. No significant difference was identified in the pediatric FN BMD levels.

High Serum Levels of Malondialdehyde and 8-OHdG are both Associated with Early Cognitive Impairment in Patients with Acute Ischaemic Stroke.

Post-stroke cognitive impairment (PSCI) is an increasingly prevalent sequel after stroke that may associate with poor functional outcome and increased risk of recurrent stroke. We aimed to explore the relationship between oxidative stress biomarkers and the presence of PSCI. 193 first-ever acute ischaemic stroke patients were consecutively enrolled in the current study. The oxidative stress biomarkers malondialdehyde (MDA) and 8-hydroxydeoxyquanosine (8-OHdG) were measured within 24 h after admission. Cognition function was evaluated by the Mini-Mental State Examination (MMSE) at 1 month after stroke. Serum levels of 8-OHdG and MDA were both significantly higher in the PSCI (p < 0.001) compared with the non-PSCI group. Both the serum levels of both 8-OHdG and MDA were negatively correlated with the MMSE score. Receiver operating characteristic curve analysis was used to evaluate 8-OHdG and MDA as markers of a high risk of PSCI and produced area under curve values of 0.700 and 0.793. Adjusted logistic regression showed that serum 8-OHdG and MDA levels remained as independent markers of PSCI. High serum levels of malondialdehyde and 8-OHdG are associated with the presence of PSCI at 1 month after stroke.

Low serum 25-hydroxyvitamin D concentrations in chronic insomnia patients and the association with poor treatment outcome at 2months.

BACKGROUND: The association between low 25-hydroxyvitamin D [25(OH)D] and sleep disorder has been reported. We investigated whether serum concentrations of 25(OH)D are altered in chronic insomnia patients. The relationship between serum concentrations of 25(OH)D and the treatment outcome in patients at 2months was also investigated. METHODS: In total, 181 chronic insomnia patients were consecutively recruited. All patients received pharmacotherapy for the treatment of chronic insomnia. Serum 25(OH)D concentrations were quantified by a competitive electrochemiluminescence protein binding assay. Treatment outcomes were defined as "response" versus "non-response", according to the change of the Pittsburgh Sleep Quality Index (PSQI). We also recruited 100 healthy subjects as a control group. RESULTS: Fifty-four out of 181 (29.8%) patients met the criteria for non-response. Chronic insomnia patients had significantly lower 25(OH)D concentrations compared with healthy controls (23.01±9.18 vs 27.17±6.41ng/ml, P<0.001). Non-response patients also had significantly lower 25(OH)D concentrations than those with response. Vitamin D deficiency(25(OH)D concentrations<20ng/ml) was independently associated with a higher probability of treatment non-response at 2months (odds ratio 11.636, 95% confidence interval 3.966-34.142, P<0.001). CONCLUSIONS: Measurement of serum 25(OH)D concentrations are probably useful for judging treatment outcomes of pharmacotherapy in chronic insomnia patients.

Low serum uric acid levels in chronic insomnia patients: A case-control study.

Recent studies have demonstrated the presence of oxidative stress in insomnia patients. Uric acid (UA) is regarded as one of the most important antioxidants that may attenuate oxidative stress. The aim of our study was to investigate whether there is an alteration of serum UA levels in chronic insomnia patients. The association between sleep quality and serum UA in chronic insomnia patients was also investigated. We recruited 300 chronic insomnia patients and 300 age- and gender-matched normal controls. The uricase-PAP method was used to measure the concentration of UA both in patient and normal control subjects. The Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality of chronic insomniac participants. As a result, significantly lower serum UA levels were observed in patients with chronic insomnia when compared with normal control subjects (279.56±65.80 vs. 299.10±61.17µmol/L, t=-3.991, p<0.001). Low serum UA levels were correlated with high PSQI scores in multiple linear regression models (ß=-0.322, p<0.001). Our results suggested that low serum UA levels were associated with the presence and severity of chronic insomnia.