Changes in fecal microbiota composition and the cytokine expression profile in school-aged children with depression: A case-control study.

Depression in childhood negatively affects the growth and development, school performance, and peer or family relationships of affected children, and may even lead to suicide. Despite this, its etiology and pathophysiology remain largely unknown. Increasing evidence supports that gut microbiota plays a vital role in the development of childhood depression. However, little is known about the underlying mechanisms, as most clinical studies investigating the link between gut microbiota and depression have been undertaken in adult cohorts. In present study, a total of 140 school-aged children (6-12 years) were enrolled, including 92 with depression (male/female: 42/50) and 48 healthy controls (male/female: 22/26) from Lishui, Zhejiang, China. Illumina sequencing of the V3-V4 region of the 16S rRNA gene was used to investigate gut microbiota profiles while Bio-Plex Pro Human Cytokine 27-plex Panel was employed to explore host immune response. We found that, compared with healthy controls, children with depression had greater bacterial richness and altered ß-diversity. Pro-inflammatory genera such as Streptococcus were enriched in the depression group, whereas anti-inflammatory genera such as Faecalibacterium were reduced, as determined by linear discriminant analysis effect size. These changes corresponded to altered bacterial functions, especially the production of immunomodulatory metabolites. We also identified the presence of a complex inflammatory condition in children with depression, characterized by increased levels of pro-inflammatory cytokines such as IL-17 and decreased levels of anti-inflammatory cytokines such as IFN-γ. Correlation analysis demonstrated that the differential cytokine abundance was closely linked to changes in gut microbiota of children with depression. In summary, key functional genera, such as Streptococcus and Faecalibacterium, alone or in combination, could serve as novel and powerful non-invasive biomarkers to distinguish between children with depression from healthy ones. This study was the first to demonstrate that, in Chinese children with depression, gut microbiota homeostasis is disrupted, concomitant with the activation of a complex pro-inflammatory response. These findings suggest that gut microbiota might play an important role in the pathogenesis of depression in school-aged children, while key functional bacteria in gut may serve as novel targets for non-invasive diagnosis and patient-tailored early precise intervention in children with depression.

Circ_0003489 facilitates multiple myeloma progression by targeting miR-433-3p/PBX3 axis.

BACKGROUND: Multiple myeloma (MM) is a relatively common hematologic tumor, and the study of non-coding RNAs in MM is gradually increasing. Our study aimed to reveal the regulatory mechanism of circular RNA_0003489 (circ_0003489)/microRNA-433-3p (miR-433-3p)/Pre-B-cell leukemia homeobox 3 (PBX3) axis in MM. METHODS: Circ_0003489, miR-433-3p and PBX3 contents were measured by real-time quantitative PCR or western blot. Functionally, MM cell proliferation and apoptosis were evaluated using cell counting kit-8, flow cytometry and EdU assays. Interaction between miR-433-3p and circ_0003489 or PBX3 was confirmed with the application of dual-luciferase reporter assay and RNA pull down assay. RESULTS: Circ_0003489 and PBX3 were upregulated, while miR-433-3p was downregulated in MM tissues. Circ_0003489 knockdown or miR-433-3p overexpression remarkably suppressed MM proliferation and increased apoptosis in vitro. In terms of mechanism, circ_0003489 could sponge miR-433-3p to regulate PBX3. Besides, miR-433-3p downregulation or PBX3 overexpression reversed the inhibition effect of circ_0003489 knockdown on MM progression. CONCLUSION: Circ_0003489 facilitated MM progression by targeting miR-433-3p/PBX3 axis, suggesting that it might be a potential target for MM.

Association between C-reactive protein levels and development of post-stroke depression: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Different prospective cohort studies have focused on the C-reactive protein (ie, a pentameric protein) biomarker as a predictor of post-stroke depression. In this review and meta-analysis, we will attempt to synthesize the evidence for the association between C-reactive protein and the development of post-stroke depression. METHODS: We systematically searched five academic databases for relevant studies according to the PRISMA guidelines. We evaluate the comparative levels of C-reactive protein in patients with stroke and/without depression, and analyzed the hazard ratio to evaluate the overall risk of C-reactive protein levels in patients with stroke. RESULTS: We selected eligible studies with 2534 patients (mean age: 65.2 ± 5.9 years) from the initial 10 926 studies in the databases. Increased C-reactive protein levels (Hedge's g, 0.84) in patients with stroke and depression as compared to patients with stroke without depression. Increased levels of C-reactive protein were associated with the onset of depression (Hazard's ratio, 1.6) in patients with stroke. CONCLUSION: Our findings provide an association of C-reactive protein with the development of post-stroke depression, and present higher levels than patients with stroke without depression. Additionally, our findings support the role of C-reactive protein levels as markers for predicting depression in patients with stroke.

Association between CpG island DNA methylation in the promoter region of RELN and positive and negative types of schizophrenia.

OBJECTIVE: To explore the association between CpG island methylation in the promoter region of RELN and positive (type I) and negative (type II) types of schizophrenia, and investigate serum interleukin (IL)-1ß, IL-6, and myelin basic protein (MBP) in schizophrenia. METHODS: Levels of CpG island methylation in the promoter region of RELN were detected in peripheral blood of patients with schizophrenia (experimental group) and healthy individuals (control group), and serum IL-1ß, IL-6, and MBP were measured. RESULTS: The positive rate of CpG island methylation in the promoter region of RELN was higher in the experimental group than in the control group; however, there were no significant differences between type I and II patients. There were differences in Positive and Negative Syndrome Scale (PANSS) scores and serum IL-1ß, IL-6, and MBP between type I and II patients. Furthermore, there were positive correlations between serum IL-1ß, IL-6, and MBP and PANSS scores (negative symptoms) in type II patients. CONCLUSION: CpG island methylation in the promoter region of RELN was associated with schizophrenia, but not with its clinical type. There may be different pathological mechanisms in type I and II schizophrenia, and type II schizophrenia may be associated with serum IL-1ß, IL-6, and MBP.

Application value of UPLC-MS/MS in detecting serum concentration of anti-schizophrenic drugs in patients with mental illnes.

OBJECTIVE: This study was designed to demonstrate the accuracy of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in detecting serum concentration of anti-schizophrenic drugs in patients with mental illness. METHODS: The study participants were 186 schizophrenia patients treated in our hospital. Serum concentrations of anti-schizophrenic drugs in Chinese patients with mental illness were evaluated according to the reference intervals of drug therapy recommended in the guidelines. RESULTS: Five drugs, namely Aripiprazole (ARI), Amisulpride (AMI), Olanzapine (OLA), Paliperidone (PAL) and Ziprasidone (ZIP) all showed good linearity within the linear range. The within-day precision of the above five drugs was all between 1.3%-8.9% and the inter-day precision was between 1.8%-7.6%, with within-day and inter-day relative standard deviations (RSDs) less than 15.00% and accuracy ranging from 87.00% to 106.73%. However, AMI had a mean blood concentration of 436.31±241.05 ng/mL (median concentration: 379.34 ng/mL), which was significantly higher than the reference range (100-320 ng/mL) recommended in the guidelines. Good recovery rates (86.21%-99.77%) were obtained after the samples were stored at room temperature for 24 h, at 4°C for 48h and at -20°C for half a year. CONCLUSIONS: Given that UPLC-MS/MS renders more accurate results in detecting the concentration of psychotropic drugs, it can be applied clinically to detect the concentration of therapeutic drugs in patients with mental illness.

Expression characteristics of peripheral blood genes reveal potential biomarkers and candidate therapeutic targets for Parkinson's disease.

In neurodegenerative disease, Parkinson's disease is the second most common one. Current demographic trends tell that by 2030, the risk of prevalence is close to 4% and the incidence is expected to double. Understanding the detailed process of Parkinson's disease can help us to figure out new biomarkers and candidate therapeutic targets for the diagnosis and progression of PD. This study is based on modularity for in-depth analysis and exploration of critical genes in the pathogenesis of Parkinson's disease, intended to identify the molecular processes of Parkinson's disease. According to the hypergeometric test, by performing differential analysis, enrichment analysis, co-expression module analysis, network connectivity analysis and finally, the ncRNA (non-coding RNA) and transcription factor that regulate the module were predicted. Based on the above methods, we obtained ten co-expression modules, including 2180 differential genes. Among them, RB1, IL7, and other genes were significantly differentially expressed in PD patients, and they had existing regulation in dysfunction modules, which was identified as Key genes in PD. The biological processes involved in the modular genes, for example, regulate lymphocyte activation, signal release, cellular calcium homeostasis, regulation of inflammatory responses, and regulation of exocytosis. This behavior significantly regulates signaling pathways such as cytokine-cytokine receptor interactions. Further, we identified ncRNA pivot including miR-25-3p. Also, transcription Factors pivot such as RELA, STAT1 significantly regulate dysfunction modules. This study can help to reveal all Parkinson's core dysfunction modules and potential regulatory factors as well as essential genes and the study assists to improve our understanding of its pathogenesis. The study can also be used to determine treatment goals and measure the effectiveness of interventions to provide predictive biomarkers and candidate therapeutic targets.

Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis.

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS.

Open-label, randomized, multiple-center, parallel study comparing glycemic responses and safety profiles of Glucerna versus Fresubin in subjects of type 2 diabetes mellitus.

Since the increase of prevalence of type 2 diabetes mellitus (T-2DM), the replacing quickly absorbed carbohydrates with a fat source rich in monounsaturated fatty acid to provide improved glycemic control in these patients has become an important assistant therapy. In the present study, we compared glycemic response and safety of two nutritional products, Glucerna and Fresubin, in Chinese subjects with T-2DM. Overall, 203 T-2DM subjects were randomly assigned (1:1) to either Glucerna or Fresubin. The primary endpoint was the adjusted area under the curve (adj-AUC) for plasma glucose at 0-240 min. Blood samples were collected at 0, 30, 60, 90, 120, 180, and 240 min to compare the adjusted area under the curve (AUC) for the change in plasma glucose or insulin from 0 to 240 min. Adjusted peak values and times of glucose and insulin responses and adjusted glucose and insulin values were collected at the same time points. Safety parameters were also evaluated. The adjusted AUC for the change in plasma glucose in the Glucerna group was significantly lower than in Fresubin group (5.60 +/- 5.88 mmol/l*h vs. 7.97 +/- 6.32 mmol/l*h, P = 0.0061), as was the adjusted peak value of glucose (3.51 +/- 2.04 mmol/l vs. 4.69 +/- 1.99 mmol/l, P < 0.0001). Glucerna subjects had a longer adjusted peak time to insulin response compared to Fresubin subjects (105.00 +/- 43.4 min vs. 88.81 +/- 37.69 min, P = 0.0050). Glucerna subjects also experienced more gradual changes in glucose and insulin values. In conclusion, Glucerna provided better control of postprandial plasma glucose and insulin levels in Chinese subjects with T-2DM. Variation of postprandial glucose tended to be relatively stable after patients took Glucerna. Study results suggest that Glucerna may be beneficial in the reduction of postprandial glycemia.

Preserved postischemic heart function in sucrose-fed type 2 diabetic OLETF rats.

Cardiovascular disease is one of the most important causes of morbidity and mortality in diabetes mellitus, but there has been controversy over functional impairment of diabetic hearts and their tolerance to ischemia. We studied ischemic heart function in type 2 diabetic rats with different degrees of hyperglycemia and its relationship with cardiac norepinephrine release. Otsuka Long-Evans Tokushima Fatty rats (OLETF) and age-matched Long-Evans Tokushima Otsuka normal rats (LETO) were used. One group of OLETF rats was given 30% sucrose in drinking water (OLETF-S). Hearts were isolated and perfused in a working heart preparation and subjected to 30 min ischemia followed by 40 min reperfusion at age of 12 months. Hemodynamics and coronary norepinephrine overflow were examined. Fasting plasma glucose in OLETF increased markedly at 12 months and sucrose administration exacerbated hyperglycemia in diabetic rats (LETO 6.6 +/- 0.5, OLETF 8.3 +/- 0.7, OLETF-S 15.0 +/- 1.7 mmol/L, P < 0.01). Basic cardiac output in OLETF was decreased as compared with LETO and OLETF-S (LETO 29.4 +/- 2.5, OLETF 24.0 +/- 2.4, OLETF-S 27.0 +/- 0.9 ml/min/g, P < 0.05) and remained very low after ischemia, while in OLETF-S it was well preserved (OLETF 4.2 +/- 2.1, OLETF-S 13.7 +/- 2.6 ml/min/g, P < 0.01). Correspondently, cardiac norepinephrine released during ischemia and reperfusion was lower in OLETF-S (OLETF 2.3 +/- 1.0, OLETF-S 0.7 +/- 0.1 pmol/ml, P < 0.01). Thus, OLETF hearts were more vulnerable to ischemia but sucrose feeding rendered their hearts resistant to ischemia. Less norepinephrine release may play a role in preventing postischemic functional deterioration in sucrose-fed diabetic hearts.