Liquid chromatography-mass spectrometry-based metabolomic profiling reveals sex differences of lipid metabolism among the elderly from Southwest China.

BACKGROUND: The sexual dimorphism represents one of the triggers of the metabolic disparities while the identification of sex-specific metabolites in the elderly has not been achieved. METHODS: A group of aged healthy population from Southwest China were recruited and clinical characteristics were collected. Fasting plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomic analyses were performed. Differentially expressed metabolites between males and females were identified from the metabolomic analysis and metabolite sets enrichment analysis was employed. RESULTS: Sixteen males and fifteen females were finally enrolled. According to clinical characteristics, no significant differences can be found except for smoking history. There were thirty-six differentially expressed metabolites between different sexes, most of which were lipids and lipid-like molecules. Twenty-three metabolites of males were increased while thirteen were decreased compared with females. The top four classes of metabolites were fatty acids and conjugates (30.6%), glycerophosphocholines (22.2%), sphingomyelins (11.1%), and flavonoids (8.3%). Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins were significantly enriched in metabolite sets enrichment analysis. CONCLUSIONS: Significant lipid metabolic differences were found between males and females among the elderly. Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins may partly account for sex differences and can be potential treatment targets for sex-specific diseases.

Lipid metabolic dysregulation is involved in Parkinson's disease dementia.

Dementia is very common in the late stage of patient with Parkinson's disease (PD). We aim to explore its underlying pathogenesis and identify candidate biomarkers using untargeted metabolomics analysis. Consecutive PD patients and healthy controls were recruited. Clinical data were assessed and patients were categorized into Parkinson's disease without dementia (PDND) and Parkinson's disease dementia (PDD). Fast plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomics analysis was performed. Based on the identified differentially-expressed metabolites from the metabolomics analysis, multivariate linear regression analyses and receiver operating characteristic (ROC) curves were further employed. According to the clinical data, the mean ages of PDND and PDD patients were significantly higher than those of healthy controls. The incidence of hypercholesterolemia was decreased in PDD patients. PDD patients also had lower levels of triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B. There were 24 and 57 differentially expressed metabolites in PDD patients when compared with the healthy controls and PDND patients from the metabolomics analysis. Eleven lipid metabolites were simultaneously decreased between these two groups, and can be further subcategorized into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and prenol lipids. The plasma levels of the eleven metabolites were positively correlated with MMSE score and can be candidate biomarkers for PDD patients with areas under the curve ranging from 0.724 to 0.806 based on the ROC curves. Plasma lipoproteins are significantly lower in PDD patients. A panel of eleven lipid metabolites were also decreased and can be candidate biomarkers for the diagnosis of PDD patients. Lipid metabolic dysregulation is involved in the pathogenesis of Parkinson's disease dementia.

A novel hippocampus metabolite signature in diabetes mellitus rat model of diabetic encephalopathy.

Diabetic encephalopathy (DE) is one of the chronic complications of diabetes. Even then, the molecular mechanism underlying DE remains unexplored. In this study, we have made an attempt to investigate the metabolic changes associated with the streptozocin (STZ)-induced cognitive dysfunction in the hippocampus of the rat model, a classical rodent model for DE, with the help of Gas Chromatography-Mass Spectrometry-based method. The STZ injections led to the rise of mean blood glucose levels in the diabetes mellitus (DM) group of rats as compared to the control (CON) group of rats throughout the experiment. However, we did not find any significant difference between the blood glucose levels of the DM & the CON groups of rats before the STZ injection. The results indicated a behavioral and morphological cognitive dysfunction in the DM groups of rats. The metabolomic investigation of these DE rats demonstrated a lower level of N-acetylaspartate and dihydroxyacetone phosphate accompanied by a higher level of homocysteine and glutamate as against the CON group of rats. The outcome of this study may unravel the underlying pathophysiological mechanism of DE. Also, the metabolomic data from this study may provide a platform for the development of DE biomarkers.

SIRT1: The Value of Functional Outcome, Stroke-Related Dementia, Anxiety, and Depression in Patients with Acute Ischemic Stroke.

BACKGROUND: The outcome of ischemic stroke depends on multiple factors and their function of each other. Studies have shown that Sirtuin1 (SIRT1) plays a chief role in the key procedure during ischemia/hypoxia by protecting against cellular stress and controlling the metabolic pathways. AIMS: To explore the alterations in serum SIRT1 concentrations in acute ischemic stroke (AIS) patients and the relationship between SIRT1 and poststroke dementia, anxiety, and depression. METHODS: One hundred and twenty four consecutive patients with clinically diagnosed AIS were recruited to participate in the study. Serum SIRT1 levels were measured using a commercially available ELISA equipment for SIRT1 (Cusabio, Wuhan, China). In 1 year after admission, the severity of stroke was assessed with the National Institutes of Health Stroke Scale score, and the functional outcome was measured by a modified Rankin scale, the Hamilton Anxiety Scale scores were evaluated to define patients with or without anxiety, and the Hamilton Depression Scale scores for depression. RESULTS: We found the levels of serum SIRT1 was significantly higher (P = .036) in AIS patients (.62 ± .77 ng/mL) compared with healthy control subjects (.45 ± .69 ng/mL), but not significantly higher SIRT1 concentration (.58 ± .69 versus .64 ± .81 ng/mL, P = .298) than patients in the unfavorable functional outcome group. CONCLUSIONS: There is no potential diagnostic and prognostic role of SIRT1 in AIS-related dementia, anxiety, and depression. The role of SIRT1 in AIS among human race needs to be further investigated.

Increased Serum Alkaline Phosphatase in Patients with Acute Ischemic Stroke.

BACKGROUND: Stroke is one of the most common causes of disability and death. Higher alkaline phosphatase (ALP) levels have been associated with poor functional outcomes and mortality in previous studies. We investigated alterations in serum ALP concentrations and functional outcomes in patients with acute ischemic stroke (AIS). METHODS: Patients with first-ever AIS were recruited to participate in the study. Serum ALP levels were measured using a Cobas Integra 400 Plus automatic biochemical analyzer, and severity of stroke was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score on admission. Functional outcome was measured using the modified Rankin scale 1 year after admission. RESULTS: Serum ALP concentration was increased in patients with AIS (81.75 ± 20.49 versus 69.93 ± 16.12 U/L, P = .000) and the optimal ALP cutoff point for diagnosing patients with AIS was 81.50 U/L, with a sensitivity of 49.5% and specificity of 78.9%. However, there was no significant correlation between ALP and NIHSS scores (r = .170, P = .085) and ALP was not significantly different between favorable and unfavorable functional outcomes (81.76 ± .60 versus 81.70 ± 20.54 U/L, P = .802). CONCLUSIONS: Serum ALP concentration, which was increased in patients with AIS, might represent a low-potency biomarker for the diagnosis of AIS. However, this was not significantly correlated with NIHSS scores or the functional outcome after 1 year.

Decreased serum proNGF concentration in patients with Parkinson's disease.

Parkinson's disease (PD), a progressive and age-related neurodegenerative condition, is a common neurodegenerative disorder. However, no validated biomarkers for PD have been identified to date. Accumulating evidence supports the role of proNGF-p75NTR-sortilin signaling in the neurodegeneration and pathogenesis of PD. The aim of our study was to investigate alterations in serum proNGF concentrations in PD patients and related anxiety. Seventy-seven consecutive PD patients and 39 healthy controls were enrolled, and clinical data were collected. Modified Hoehn-Yahr Staging Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hamilton Anxiety (HAMA) Scale scores were assessed upon admission. Serum proNGF concentration was compared between that of PD patients and healthy controls. Pearson correlation coefficients were determined to explore the relationship between proNGF concentration and UPDRS, Hoehn-Yahr, and HAMA scores. Received operating characteristic (ROC) curves and proNGF optimal cutoff point were used to distinguish PD and related anxiety. The median concentration of proNGF was significantly lower (p = 0.000) in PD patients (94.91 ng/L, range 85.92-118.06 ng/L) compared with that of healthy controls (106.67 ng/L, range 102.39-122.06 ng/L). The optimal proNGF cutoff point for distinguishing PD patients was 102.29 ng/L, and the sensitivity and specificity values were 87.0 and 100%, respectively. proNGF concentration positively correlated with UPDRS (r = 0.281, p = 0.013), Hoehn-Yahr (r = 0.260, p = 0.023), and HAMA (r = 0.276, p = 0.015) scores. Our results indicate that serum proNGF concentration may represent a biomarker for PD and its role in the pathogenesis of PD thus warrants further investigation.

Blend Sign on Computed Tomography: Novel and Reliable Predictor for Early Hematoma Growth in Patients With Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Early hematoma growth is not uncommon in patients with intracerebral hemorrhage and is an independent predictor of poor functional outcome. The purpose of our study was to report and validate the use of our newly identified computed tomographic (CT) blend sign in predicting early hematoma growth. METHODS: Patients with intracerebral hemorrhage who underwent baseline CT scan within 6 hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Significant hematoma growth was defined as an increase in hematoma volume of >33% or an absolute increase of hematoma volume of >12.5 mL. The blend sign on admission nonenhanced CT was defined as blending of hypoattenuating area and hyperattenuating region with a well-defined margin. Univariate and multivariable logistic regression analyses were performed to assess the relationship between the presence of the blend sign on nonenhanced admission CT and early hematoma growth. RESULTS: A total of 172 patients were included in our study. Blend sign was observed in 29 of 172 (16.9%) patients with intracerebral hemorrhage on baseline nonenhanced CT scan. Of the 61 patients with hematoma growth, 24 (39.3%) had blend sign on admission CT scan. Interobserver agreement for identifying blend sign was excellent between the 2 readers (κ=0.957). The multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and presence of blend sign on baseline CT scan to be independent predictors of early hematoma growth. The sensitivity, specificity, positive and negative predictive values of blend sign for predicting hematoma growth were 39.3%, 95.5%, 82.7%, and 74.1%, respectively. CONCLUSIONS: The CT blend sign could be easily identified on regular nonenhanced CT and is highly specific for predicting hematoma growth.

Geniposide exerts the antidepressant effect by affecting inflammation and glucose metabolism in a mouse model of depression.

Depression is a severe mental illness affecting patient's physical and mental health. However, long-term effects of existing therapeutic modalities for depression are not satisfactory. Geniposide is an iridoid compound highly expressed in gardenia jasminoides for removing annoyance. The activity of geniposide against depression has been widely studied while most studies concentrated on the expression levels of gene and protein. Herein, the aim of the present study was to employ non-target metabolomic platform of serum to investigate metabolic changes of depression mice and further verify in hippocampus for analyzing the antidepressant mechanism of geniposide. Then we discovered that 9 metabolites of serum were significantly increased in depressive group (prostaglandin E2, leukotriene C4, arachidonic acid, phosphatidylcholine (PC, 16:0/16:0), LysoPC (18:1 (9Z)/0:0), phosphatidylethanolamine (14:0/16:0), creatine, oleamide and aminomalonic acid) and 6 metabolites were decreased (indoxylsulfuric acid, testosterone, lactic acid, glucose 6-phosphate, leucine and valine). The levels of arachidonic acid, LysoPC, lactic acid and glucose 6-phosphate in hippocampus were consistent change with serum in depression mice. Most of them showed significant tendencies to be normal by geniposide treatment. Metabolic pathway analysis indicated that arachidonic acid metabolism and glucose metabolism were the main pathogenesis for the antidepressant effect of geniposide. In addition, the levels of serum tumor necrosis factor-α and interleukin-1 were increased in depressive mice and reversed after geniposide treatment. This study revealed that abnormal metabolism of inflammatory response and glucose metabolism of the serum and hippocampus involved in the occurrence of depressive disorder and antidepressant effect of geniposide.

Testosterone synthesis was inhibited in the testis metabolomics of a depression mouse model.

INTRODUCTION: Depression is a common emotional disorder. Previous studies have suggested that depression is associated with the central nervous system. Recent studies have suggested that reduced testosterone level is the core inducement of depression. Testis is the vital organ for the synthesis of testosterone. How does testis mediate depression is still unknown. OBJECTIVES: We adopted a classical depression model of mouse caused through chronic mild stress (CMS). The metabolomics liquid chromatography-mass spectrometry was adopted to analyse the influence of CMS on testis metabolism. Then we confirmed the possible abnormal metabolism of the testis in depression mice by pathway analysis and molecular biological technique. RESULTS: Compared with control mice, 16 differential metabolites were found in CMS mice by multivariate statistical analysis. In comparison with control mice, CMS mice showed higher levels for campesterol, ribitol, citric acid, platelet activating factor, guanosine, cytosine and xanthine and lower levels for docosahexaenoic acid, hippuric acid, creatine, testosterone, dehydroepiandrosterone, progesterone, l-carnitine, acetyl carnitine and propionyl carnitine. The pathway analysis indicated that these differential metabolites are associated with steroid hormone synthesis, purine metabolism and phenylalanine metabolism. In addition, we also first discovered that testicular morphology in depression mice was damaged and steroid hormone synthetases (including steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage) were inhibited. CONCLUSION: These findings may be helpful to parse molecular mechanisms of pathophysiology of depression. It also pointed out the direction to search for potential therapy schedules for male depression and provide novel insights into exploring the pathogenesis of male depression.

A novel urinary metabolite signature for diagnosing major depressive disorder.

Major depressive disorder (MDD) is a prevalent and debilitating mental disorder. Yet, there are no objective biomarkers available to support diagnostic laboratory testing for this disease. Here, gas chromatography-mass spectrometry was applied to urine metabolic profiling of 126 MDD and 134 control subjects. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to identify the differential metabolites in MDD subjects relative to healthy controls. The OPLS-DA analysis of data from training samples (82 first-episode, drug-naïve MDD subjects and 82 well-matched healthy controls) showed that the depressed group was significantly distinguishable from the control group. Totally, 23 differential urinary metabolites responsible for the discrimination between the two groups were identified. Postanalysis, 6 of the 23 metabolites (sorbitol, uric acid, azelaic acid, quinolinic acid, hippuric acid, and tyrosine) were defined as candidate diagnostic biomarkers for MDD. Receiver operating characteristic analysis of combined levels of these six biomarkers yielded an area under the receiver operating characteristic curve (AUC) of 0.905 in distinguishing training samples; this simplified metabolite signature classified blinded test samples (44 MDD subjects and 52 healthy controls) with an AUC of 0.837. Furthermore, a composite panel by the addition of previously identified urine biomarker (N-methylnicotinamide) to this biomarker panel achieved a more satisfactory accuracy, yielding an AUC of 0.909 in the training samples and 0.917 in the test samples. Taken together, these results suggest this composite urinary metabolite signature should facilitate development of a urine-based diagnostic test for MDD.

Relationship Between Hypertension and Basilar Atherosclerosis in Chinese Han Population: A High-Resolution Magnetic Resonance Imaging Study.

Objective: To investigate the relationship between hypertension and basilar atherosclerosis evaluated by high-resolution magnetic resonance imaging (HR-MRI) in the Chinese Han population. Methods: High resolution-MRI vessel wall imaging was performed in selected 193 patients for various indications. Multivariable logistic regression models based on odds ratio (OR) with their associated 95% confidence interval (CI) were used to assess the relationship between hypertension and basilar artery (BA) plaque, moderate or severe stenosis of BA plaque, and vulnerable plaque. A linear regression model was used to assess the relationship between hypertension and BA plaque numbers. Results: Patients with hypertension had a higher proportion of BA plaque and vulnerable plaque as well as more number of enhancements of BA plaque and serious plaque compared with normotensive patients (all values of p < 0.05). Multivariable logistic regression analysis indicated that patients with hypertension had an increased risk for and more number of enhancements of BA plaque (adjusted-OR: 4.32, 95% CI 1.89-9.88, p < 0.001; adjusted-ß: 0.55, 95% CI 0.14-0.96, p = 0.009, respectively) and had a higher proportion of moderate or severe stenosis of BA plaque and vulnerable plaque (adjusted-OR: 3.08, 95% CI 0.77-12.32, p = 0.111; adjusted-OR: 4.52, 95% CI 1.50-13.64, p = 0.007, respectively) compared with the normotensive group. Moreover, there was a saturation effect of age on the prevalence of BA plaque and vulnerable plaque. Conclusion: Hypertension was the independent risk factor of BA plaque and vulnerable plaque assessed by HR-MRI in the Chinese Han population.

Case report: Recreational nitrous oxide abuse triggered peripheral neuropathy possibly through the immune-mediated pathogenesis.

Nitrous oxide (N2O), commonly known as laughing gas, is widely used in clinical practice and food industry. However, an increasing number of young people have been abusing N2O for recreational purpose, resulting in many functional disorders and sometimes irreversible nerve damage. We present the case of a 20-year-old N2O abuser who gradually developed peripheral neuropathy after continuously inhaling N2O for 2 months. The neurological symptoms of the patient had kept exacerbation for the next 2 months until she came for medical care sitting in a wheelchair. We suggested the patient halting N2O intake and supplementing methylcobalamine according to the standardized protocol. Her symptoms had partly recovered during the following 2 weeks but remained unchanged in another 2 weeks. Antibodies against ganglioside complexes were detected and anti-GM1 IgM antibodies were positive in both cerebrospinal fluid and serum. Intravenous immunoglobulin was given as an additional treatment and the patient's symptoms had significantly recovered further. The patient discharged walking by herself. Then she has been continuously followed up in outpatient department for the next 4 months and taking steroid hormone as well as methylcobalamine. Her symptoms gradually disappeared and all the electrophysiological parameters significantly improved. With this case we were able to show that N2O-related peripheral neuropathy is not only a metabolic disorder but also an immune-mediated disease. N2O intake can trigger a mimic Guillain-Barré syndrome.

Tryptophan-5-HT pathway disorder was uncovered in the olfactory bulb of a depression mice model by metabolomic analysis.

Major depression (MD) is a severe mental illness that creates a heavy social burden, and the potential molecular mechanisms remain largely unknown. Lots of research demonstrate that the olfactory bulb is associated with MD. Recently, gas chromatography-mass spectrometry-based metabolomic studies on depressive rats indicated that metabolisms of purine and lipids were disordered in the olfactory bulb. With various physicochemical properties and extensive concentration ranges, a single analytical technique could not completely cover all metabolites, hence it is necessary to adopt another metabolomic technique to seek new biomarkers or molecular mechanisms for depression. Therefore, we adopted a liquid chromatography-mass spectrometry metabonomic technique in the chronic mild stress (CMS) model to investigate significant metabolic changes in the olfactory bulb of the mice. We discovered and identified 16 differential metabolites in the olfactory bulb of the CMS treatments. Metabolic pathway analysis by MetaboAnalyst 5.0 was generated according to the differential metabolites, which indicated that the tryptophan metabolism pathway was the core pathogenesis in the olfactory bulb of the CMS depression model. Further, the expressions of tryptophan hydroxylase (TpH) and aromatic amino acid decarboxylase (AAAD) were detected by western blotting and immunofluorescence staining. The expression of TpH was increased after CMS treatment, and the level of AAAD was unaltered. These results revealed that abnormal metabolism of the tryptophan pathway in the olfactory bulb mediated the occurrence of MD.

The disturbance of lipid metabolism is correlated with neuropsychiatric symptoms in patients with Parkinson's disease.

OBJECTIVE: We aimed to identify the detailed relationships between serum lipid levels and neuropsychiatric symptoms in patients with Parkinson's disease (PD). METHODS: Consecutive PD patients and healthy controls were recruited and demographic data were collected. The disease stages of PD patients were assessed using Hoehn-Yahr scale while neuropsychiatric symptoms were determined using Hamilton depression rating scale (HAMD), Hamilton anxiety rating scale (HAMA), and mini-mental state examination scale. Fast serum samples were obtained and the serum levels of lipids were identified. Linear regression analyses and correlation analyses were performed to explore the relationships between serum lipid levels and neuropsychiatric symptoms. RESULTS: The serum levels of triglyceride had significantly decreased while the levels of HDL-c and lipoprotein a had increased in PD patients. Linear regression analyses confirmed that the levels of triglyceride were mainly correlated with age and HAMA score, the levels of HDL-c were correlated with disease duration and gender, and the levels of lipoprotein a were correlated with HAMD score. Correlation analyses further confirmed that the levels of triglyceride were negatively correlated with HAMA score when the levels of lipoprotein a were negatively correlated with HAMD score. CONCLUSIONS: Lipid metabolism is significantly correlated with neuropsychiatric disorders in PD patients.

Metabolomics profiling reveals altered lipid metabolism and identifies a panel of lipid metabolites as biomarkers for Parkinson's disease related anxiety disorder.

OBJECTIVES: Anxiety disorder is a common non-motor symptom in patient with Parkinson's disease (PD). We aimed to explore its pathogenesis and identify plasma biomarkers using untargeted metabolomics analysis. METHODS: Consecutive PD patients and healthy controls were recruited. Clinical data were assessed and patients with Parkinson's disease related anxiety disorder (PDA) were recognized. Fast plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomics analysis was performed. Based on the differentially expressed metabolites from the above metabolomics analysis, correlation analyses and receiver operating characteristic curves (ROC) were further employed. RESULTS: According to the clinical data, PDA patients had lower plasma levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B. There were thirty-nine differentially expressed metabolites in PDA patients when compared with the other two groups from the metabolomics analysis, respectively. Fourteen lipid metabolites were simultaneously altered between these two groups, and all of them were significantly decreased. They can be further subcategorized into fatty acyls, glycerolipids, sterol lipids, sphingolipids, and prenol lipids. The plasma levels of thirteen metabolites were negatively correlated with HAMA scores except 10-oxo-nonadecanoic acid. Based on the ROC curves, the fourteen lipid metabolites can be diagnostic biomarkers for PDA patients separately and the areas under the curve of the fourteen lipid metabolites ranged from 0.681 to 0.798. CONCLUSIONS: Significantly lower plasma lipoproteins can be found in PDA patients. A panel of fourteen lipid metabolites were also significantly decreased and can be clinical biomarkers for the diagnosis of PDA patients.

Dopaminergic System Alteration in Anxiety and Compulsive Disorders: A Systematic Review of Neuroimaging Studies.

Objective: The dopaminergic system is involved in many psychiatric disorders as a GABAergic, serotonergic, and glutamatergic system. A systematic review and meta-analysis was performed to elucidate the alteration of the dopaminergic system in anxiety and compulsive disorders. Methods: The databases of Pubmed, Embase, and ScienceDirect were searched and articles reporting the involvement of the dopaminergic system in patients with anxiety disorder and obsessive compulsive disorder (OCD) were recognized. The key research data were extracted from the included articles and standardized mean differences were calculated using meta-analyses if there were more than two studies with obtainable data. Sensitivity analyses were further performed to detect the stability of results, and the qualities of all the included studies were assessed using the Newcastle Ottawa scale. Results: Finally, we identified 8 and 11 studies associated with anxiety disorder and OCD for further analysis, respectively. Most consistently, the striatal dopamine D2 receptor (D2R) of OCD patients had decreased while no significant correlation was found between striatal D2R and disease severity. The striatal dopamine transporter (DAT) had not been significantly altered in both the anxiety disorder and OCD patients. The heterogeneity values from the meta-analyses were extremely high while those results remained stable after sensitivity analyses. Inconsistent data were found in the striatal D2R of patients with anxiety disorder. Limited data had suggested that dopamine synthesis increased in most regions of the cerebral cortex and cerebellum in OCD patients. Conclusions: The most convincing finding was that the D2 receptor decreased in patients with obsessive compulsive disorder. The dopamine transporter may have no relationship with anxiety and compulsive disorder.

Integrated Metabolomics and Proteomics Analysis Reveals Plasma Lipid Metabolic Disturbance in Patients With Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly with a pathogenesis that remains unclear. We aimed to explore its pathogenesis through plasma integrated metabolomics and proteomics analysis. The clinical data of consecutively recruited PD patients and healthy controls were assessed. Fasting plasma samples were obtained and analyzed using metabolomics and proteomics methods. After that, differentially expressed metabolites and proteins were identified for further bioinformatics analysis. No significant difference was found in the clinical data between these two groups. Eighty-three metabolites were differentially expressed in PD patients identified by metabolomics analysis. These metabolites were predominately lipid and lipid-like molecules (63%), among which 25% were sphingolipids. The sphingolipid metabolism pathway was enriched and tended to be activated in the following KEGG pathway analysis. According to the proteomics analysis, forty proteins were identified to be differentially expressed, seven of which were apolipoproteins. Furthermore, five of the six top ranking Gene Ontology terms from cellular components and eleven of the other fourteen Gene Ontology terms from biological processes were directly associated with lipid metabolism. In KEGG pathway analysis, the five enriched pathways were also significantly related with lipid metabolism (p < 0.05). Overall, Parkinson's disease is associated with plasma lipid metabolic disturbance, including an activated sphingolipid metabolism and decreased apolipoproteins.

Absence of gut microbiota during early life affects anxiolytic Behaviors and monoamine neurotransmitters system in the hippocampal of mice.

The gut microbiome is composed of an enormous number of microorganisms, generally regarded as commensal bacteria. Resident gut bacteria are an important contributor to health and significant evidence suggests that the presence of healthy and diverse gut microbiota is important for normal cognitive and emotional processing. Here we measured the expression of monoamine neurotransmitter-related genes in the hippocampus of germ-free (GF) mice and specific-pathogen-free (SPF) mice to explore the effect of gut microbiota on hippocampal monoamine functioning. In total, 19 differential expressed genes (Htr7, Htr1f, Htr3b, Drd3, Ddc, Maob, Tdo2, Fos, Creb1, Akt1, Gsk3a, Pik3ca, Pla2g5, Cyp2d22, Grk6, Ephb1, Slc18a1, Nr4a1, Gdnf) that could discriminate between the two groups were identified. Interestingly, GF mice displayed anxiolytic-like behavior compared to SPF mice, which were not reversed by colonization with gut microbiota from SPF mice. Besides, colonization of adolescent GF mice by gut microbiota was not sufficient to reverse the altered gene expression associated with their GF status. Taking these findings together, the absence of commensal microbiota during early life markedly affects hippocampal monoamine gene-regulation, which was associated with anxiolytic behaviors and monoamine neurological signs.

Prognostic value of Sirtuin1 in acute ischemic stroke and its correlation with functional outcomes.

BACKGROUND: The blood-brain barrier is impaired in patients with stroke. The release of protein markers such as Sirtuin1 (SIRTl) into circulation may be useful to assess the prognosis of patients with cerebrovascular disease. In this study, we investigated the predictive value of SIRT1 levels in acute ischemic stroke (AIS) patients. METHODS: In all, 101 AIS patients and 38 healthy controls were enrolled, and blood samples were collected within 72 hours of stroke onset. SIRT1 was analyzed using a commercially available enzyme-linked immunosorbent assay kit. On admission, neurological status was assessed by the standardized National Institutes of Health Stroke Scale (NIHSS). Functional outcomes were measured 1 year after admission using the modified Rankin scale. RESULTS: Compared with the control group, SIRT1 was significantly increased in the AIS group (0.63 ±â€Š0.75 vs 0.48 ±â€Š0.80 ng/mL; P ≤ 0.05). However, there was no significant correlation between SIRT1 and NIHSS score at admission (r = -0.01, P = .920). In addition, with an unadjusted odds ratio of 0.862 (95% confidence interval 0.495-1.502), SIRT1 was not significantly correlated with functional outcomes. CONCLUSIONS: Serum concentrations of SIRT1 have no significant predictive value for favorable functional outcome after acute stroke in our study.

Complementary and alternative therapies for restless legs syndrome: An evidence-based systematic review.

Restless legs syndrome (RLS) is defined as an irresistible urge to move the legs, which is usually accompanied by paresthesias or dysesthesias at least twice weekly, and affects 2%-4% of adults in Europe and North America. This systematic review assesses the current complementary and alternative options for RLS and the potential benefits of those treatments on sleep quality, mood disorder, and quality of life. A systematic search of the PubMed, Embase, Cochrane, and Web of Science databases was conducted. Eighteen studies met the inclusion criterion, which included the use of the international RLS study group criteria. Complementary and alternative therapies have been found to be effective in both primary and secondary RLS. The severity of primary RLS symptoms can be significantly ameliorated by exercise training, transcutaneous spinal direct current stimulation, pneumatic compression devices, light therapy, repetitive transcranial magnetic stimulation, and acupuncture. Pneumatic compression devices and yoga also improve RLS-related disorders. Exercise training is highly efficacious in the reduction of symptom severity in uremic RLS and related effects such as poor quality of life. Endovenous laser ablation may be a good choice for patients with concurrent RLS and superficial venous insufficiency.