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.

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.

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.

The association between genetic variation in interleukin-10 gene and susceptibility to Henoch-Schönlein purpura in Chinese children.

Interleukin-10 (IL-10), one of the anti-inflammatory cytokines, plays a major role in the pathogenesis of Henoch-Schönlein purpura (HSP). In present study, we investigated the association between genetic variation in IL-10 gene and susceptibility to HSP in a Chinese childhood population. Considering the overlapping clinical manifestations during the course of disease, the relation between IL-10 gene polymorphisms and HSP clinical heterogeneity was also assessed. We analyzed three IL-10 tag single nucleotide polymorphisms (SNPs; rs3021094, rs3790622, and rs1800872) using the Sequenom MassARRAY system by means of matrix-assisted laser desorption ionization-time of flight mass spectrometry method in 182 patients with HSP and 202 healthy controls. For the frequency of alleles, genotypes, and haplotypes of IL-10 SNPs, no significant differences were observed between HSP patients and controls. In addition, we did not find any association of IL-10 gene polymorphisms with the clinical manifestations of HSP. Our results suggest that genetic variation in IL-10 gene is unlikely to confer susceptibility to HSP in Chinese children.

Association of TLR4 gene polymorphisms with childhood Henoch-Schönlein purpura in a Chinese population.

Recent studies demonstrated that aberrant activation of Toll-like receptor (TLR) 4 was involved in the pathogenesis of Henoch-Schönlein purpura (HSP). In this study, we evaluated the association between TLR4 gene polymorphisms and the risk of childhood HSP in a Chinese population. A total of 175 HSP patients and 186 controls were recruited in this case-control study. Three single-nucleotide polymorphisms of the TLR4 gene (rs1927914, rs10759932 and rs1927907) were genotyped using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and Sequenom MassARRAY system. Our results revealed that a significantly reduced risk for HSP was associated with the G allele (OR = 0.71; p = 0.023) and G/G genotype (OR = 0.49; p = 0.021) of rs1927914. We also showed that rs1927914 variant decreased the risk of HSP in recessive inheritance model (OR = 0.55; p = 0.035, G/G vs A/A + A/G). In addition, we observed that a significantly decreased frequency of the haplotype GTC (rs1927914-rs10759932-rs1927907) in HSP patients compared with controls (OR = 0.56; p = 0.028). Our data suggested that TLR 4 rs1927914 polymorphism was associated with the decreased susceptibility to HSP in the Chinese children.

Correlation among geometric, densitometric, and mechanical properties in mandible and femur of osteoporotic rats.

We have previously demonstrated bone loss of the mandible and femur in experimental osteoporotic rats and its prevention by medication, using peripheral quantitative computed tomography (pQCT). In the present study, the mechanical properties of the mandible and femur and the correlation to their geometric and densitometric properties were studied in ovariectomized rats with or without etidronate treatment. Fifty-four Wistar strain SPF female rats, 26 weeks old, were randomly assigned to four groups: (1) Basal group (12 rats, 1.0% Ca diet); (2) Sham group (Sham-operated, 12 rats, 0.1% Ca diet); (3) OVX group (ovariectomized, 15 rats, 0.1% Ca diet); (4) Treated group (OVX + etidronate, 15 rats, 0.1% Ca diet). Total bone mineral density (BMD), cortical BMD, cross-sectional cortical bone area, cross-sectional cortical bone thickness, crosssectional moment of inertia (CSMI), and polar strength index (SSI) of the mandible and femur were measured by pQCT. The failure load of mandible and femur was evaluated by three-point bending. The failure load of both bones was significantly lower in the Sham group compared with the Basal group. The OVX group further had a 8% and 7% decrease in the failure load for mandible and femur, respectively, compared to the Sham group. Treatment with etidronate led to an increase in the failure load compared with the OVX group. The failure load was related to the pQCT-assessed variables, especially with cortical bone area and total BMD. Moreover, the geometric and densitometric properties and failure load in the mandible showed a correlation to those in the femur.

Prevention of trabecular bone loss in the mandible of ovariectomized rats.

The effect of therapeutic agents on trabecular bone loss in the mandible was investigated in ovariectomized rats. Eighty-seven Wistar SPF female rats were ovariectomized (OVX) or given a sham operation (Sham), and maintained on a diet containing 0.1% calcium. Four weeks later, groups of OVX rats were treated with estriol (E3), calcitonin (CT), etidronate, or 2-carboxyethylgermanium sesquioxide (Ge-132). The Basal group was maintained on a diet containing 1.0% calcium, and the OVX and sham groups on a diet containing 0.1% calcium. The trabecular bone mineral density (BMD) and trabecular bone mineral content (BMC) in 11 mandibular slices from 0.5 mm at the mesial margin of the first molar to 0.5 mm at the distal margin of the third molar, were measured using peripheral Quantitative Computed Tomography (pQCT). The BMD in the OVX group was lower than that in the Sham group, and decreased BMC was observed only in the molar region. BMD and BMC were increased in the etidronate-treated group, but only BMC was increased in the CT group. E3 treatment increased BMD and BMC; significant increases were also observed beneath the molar. Ge-132 treatment increased both BMD and BMC, especially the latter.

Mandible bone loss in osteoporosis rats.

Change in the mandible during the development of osteoporosis has not been studied extensively. Thus, the present study was undertaken to clarify the target loci in the mandible during the development of experimental osteoporosis in aged female rats. Experimental osteoporosis was studied in 76 Wistar strain female rats, 35 weeks old, by means of ovariectomy and dietary calcium deficiency. The rats were divided into the following three groups: (1) group 1, unoperated basal control (Basal), maintained on a diet containing 1.0% calcium; (2) group 2, sham-operated (Sham), maintained on a diet containing 0.01% calcium; and (3) group 3, ovariecomized (OVX), maintained on a diet containing 0.01% calcium. Fifteen rats of each group, except the basal rats (10 and 6 rats), were killed at 3 and 6 months following ovariectomy, respectively. The mandible was extracted, cleaned, and then subjected to bone mineral content (BMC) and bone mineral density (BMD) analyses using a peripheral quantitative computed tomography (pQCT) bone scanner. Each mandible was scanned from the mesial margin of the first molar to distal margin of the second molar. The results showed that dietary calcium deficiency and ovariectomy caused significant decreases of trabecular and cortical BMCs and BMDs in Sham and OVX rats compared with Basal rats. Decreases due to dietary calcium deficiency were greater than those caused by ovariectomy. However, significant age-related changes were not observed in BMC and BMD in Sham and OVX rats for 3-6 months. In addition, the cortical and trabecular BMCs and BMDs obtained were found to relate to location in the mandible for each group.

Effect of various temperatures on phosphatidylglycerol biosynthesis in thylakoid membranes.

Lipid unsaturation, the major factor to maintain thylakoid membrane fluidity, is affected by temperature. In this work, we analysed the molecular species composition of phosphatidylglycerol (PG) in thylakoid membranes during spinach (Spinacia oleracea) and squash (Cucurbita pepo) cotyledon growth to investigate how the growth temperature affects the PG biosynthesis. Of the 10 molecular species detected, temperature affected mainly the relative content of molecular species containing linolenic acid (18:3) and those containing palmitic acid (16:0) at the sn-1 position of glycerol backbone. Lowering the temperature induced an increase in the former and a decrease in the latter. The relative content of molecular species containing 18:3 or 16:0 at the sn-1 position of the glycerol backbone were correlated with temperature. Our results indicate that the substrate selectivity of the glycerol-3-phosphate acyltransferase (GPAT) in chloroplasts towards 16:0 or oleic acid (18:1) and the activity of fatty acid desaturases are greatly affected by temperature. In addition, changes in the relative content of PG molecular species induced by variations in growth temperature depended mainly on the substrate selectivity of GPAT.