[Research progress of transcriptomics and proteomics in schizophrenia].

Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.

Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice.

BACKGROUND: Accumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism. RESULTS: A high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet. CONCLUSIONS: These results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.

Silver ion-induced mitochondrial dysfunction via a nonspecific pathway.

Silver, once regarded as a safe noble metal for humans, has been widely used in industrial and commercial products, especially in nanometer biomaterials. It is now well known that Ag+ is biologically active and is able to interact with the cell membrane, proteins and DNA. However, very little is understood about the potential impacts of Ag+ at the sub-cellular level. Our work investigated the potential toxicity of Ag+ on mitochondria isolated from rat livers by examining the mitochondrial morphology, respiration, swelling, membrane fluidity and reactive oxygen species (ROS) generation. We observed that Ag+ significantly affects the mitochondrial structure and function, including mitochondrial swelling, collapse of the transmembrane potential, change of permeability and fluidity, decline of the respiratory rate, and acceleration of ROS, indicating that Ag+ should be seriously regarded as a potentially hazardous substance. Moreover, we conclude that Ag+ injures the mitochondrial structure and function by a nonspecific approach, in which the interaction is unregulated by inherent parts such as the mitochondria permeability transition pore (MPTP). These results help us learn more about the toxicity of Ag+ at the subcellular (mitochondrial) level and influence future biological and medical applications of Ag-based materials.

Active site-targeted carbon dots for the inhibition of human insulin fibrillation.

Carbon nano-dots (C-Dots) possess great benign properties, making them ideal for use in biomedical fields, especially due to their high aqueous solubility, outstanding photoluminescence (PL), favorable biocompatibility, low toxicity, chemical inertness, and easy functionalization properties. Herein, the C-Dots with sizes of about 2.4 ± 0.9 nm and containing the groups -OH, C[double bond, length as m-dash]C and C[double bond, length as m-dash]O, were shown to prolong the lag phase of human insulin (HI) fibrillation following a dose-dependent manner in an in vitro study. The spontaneous growth of fibrils after a lag phase was accompanied by exothermic heat, determined by isothermal titration calorimetry (ITC), demonstrating the inhibitory effect of C-Dots. Moreover, as the dose of C-Dots was increased to 4 mg mL-1, the fibrillation process could be totally deterred for more than half a month. However, the deterrent effect of the C-Dots on HI fibrillation disappeared when just a few fibril seeds were added. This is because the association constant of HI monomers interacting with fibril seeds (K2: 1.56 × 105 M-1) is much larger than that with C-Dots (K2: 8.28 × 103 M-1), as determined by analyzing the ITC results. An ''active-site targeted'' inhibitory mechanism has also been proposed. The "active site" is mainly on the B-chain of HI, and the ITC results show that the binding between the C-Dots and HI monomers is mainly driven by the electrostatic force. This is the first time that the anti-fibrillation mechanism in the presence of C-Dots has been analyzed by ITC. These results indicate that ITC is a promising approach for comprehensively clarifying the mechanisms of protein fibrillation inhibition.

Comparison of gSSR and EST-SSR markers for analyzing genetic variability among tomato cultivars (Solanum lycopersicum L.).

In order to study genetic variability and develop better strategies for the utilization of 48 tomato cultivars from America, China, the Netherlands, and Portugal, genomic simple sequence repeat (gSSR) and EST-derived SSR (EST-SSR) markers were applied. In all, 15 of 82 gSSR and 18 of 115 EST-SSR markers showed polymorphic loci. There were 995 and 2072 clear fragments amplified by polymorphic gSSR and EST-SSR markers, respectively. The total and average number of alleles detected by EST-SSRs (75, 4.2) was more than gSSRs (54, 3.6) as a result of some multi-locus EST-SSRs. A lower polymorphism information content value was found in gSSRs (0.529) compared to EST-SSRs (0.620). Similarity coefficient matrixes of the 48 tomato cultivars were established based on the gSSRs and EST-SSRs, and UPGMA dendrograms were constructed from the gSSRs and EST-SSRs similarity coefficient matrixes. A high similarity was observed between the gSSRs and EST-SSRs dendrograms. Genetic variability of four tomato populations from different countries showed that the observed number of alleles and Nei's genetic diversity were highest in the American population, and the effective number of alleles was highest in the Dutch population. The estimated genetic structure showed some tomato cultivars from different countries shared a common genetic background, which might be related to gene flow. It was inferred that both gSSR and EST-SSR markers were effective to assess genetic variability of tomato cultivars, and the combination of both markers could be more effective for genetic diversity analysis in tomato.

Genetic diversity of cultivated and wild tomatoes revealed by morphological traits and SSR markers.

In the current study, morphological traits and molecular markers were used to assess the genetic diversity of 29 cultivated tomatoes, 14 wild tomatoes and seven introgression lines. The three components of the principal component analysis (PCA) explained 78.54% of the total morphological variation in the 50 tomato genotypes assessed. Based on these morphological traits, a three-dimensional PCA plot separated the 50 genotypes into distinct groups, and a dendrogram divided them into six clusters. Fifteen polymorphic genomic simple- sequence repeat (genomic-SSR) and 13 polymorphic expressed sequence tag-derived SSR (EST-SSR) markers amplified 1115 and 780 clear fragments, respectively. Genomic-SSRs detected a total of 64 alleles, with a mean of 4 alleles per primer, while EST-SSRs detected 52 alleles, with a mean of 4 alleles per primer. The polymorphism information content was slightly higher in genomic-SSRs (0.49) than in EST-SSRs (0.45). The mean similarity coefficient among the wild tomatoes was lower than the mean similarity coefficient among the cultivated tomatoes. The dendrogram based on genetic distance divided the 50 tomato genotypes into eight clusters. The Mantel test between genomic-SSR and EST-SSR matrices revealed a good correlation, whereas the morphological matrices and the molecular matrices were weakly correlated. We confirm the applicability of EST-SSRs in analyzing genetic diversity among cultivated and wild tomatoes. High variability of the 50 tomato genotypes was observed at the morphological and molecular level, indicating valuable tomato germplasm, especially in the wild tomatoes, which could be used for further genetic studies.

-173G/C polymorphism in the promoter of MIF is associated with hepatitis B virus infection in a Chinese Han population.

In addition to the host immune response, genetic and environmental factors play crucial roles in the manifestation of hepatitis B virus (HBV) infection. The macrophage migration inhibitory factor (MIF) -173G/C polymorphism (rs755622), located in the promoter region of MIF, may play integral roles in diverse processes, including the immune response. Thus, the MIF -173G/C polymorphism may influence the immune response to HBV during natural infection. We investigated whether the MIF -173G/C polymorphism was associated with susceptibility to HBV infection in a Chinese Han population. A total of 596 HBV infection cases and 612 age-matched controls were recruited for the study. Genotyping of the MIF -173G/C polymorphism was performed using the allele-specific polymerase chain reaction method. The frequencies of the alleles and genotypes in patients and controls were compared using the χ(2) test. Carriers of the variant C allele in MIF -173 G/C were at significantly higher risk of HBV infection than carriers of the wild-type allele (P = 0.032, odds ratio = 0.799, 95% confidence interval = 0.651-0.981). However, there was no significant difference in the distribution of MIF -173G/C genotypes between case and control groups in either population (P = 0.096, degrees of freedom = 2). Our findings indicate that the G to C base change in MIF -173 G/C confers an increased risk of development of HBV infection by altering the expression of MIF in our Chinese Han population.

A novel random amplified polymorphic DNA-based strategy for genetic diversity analysis and identification of tomatoes.

Cultivar identification diagrams (CIDs) provide a rapid and efficient approach for identifying cultivars based on random amplified polymorphic DNA (RAPD) markers. In this paper, 64 tomato cultivars were identified using a CID. Using RAPD profiles, clustering analysis was performed to analyze genetic diversity. The results showed that 8 RAPD primers could completely separate the 64 cultivars according to the obtained polymorphic bands; a CID of the 64 tomato cultivars was then constructed. As verification of the CID validity, 8 randomly selected cultivars were investigated and proven to be well distinguished. In addition, 33 DNA bands were obtained, 20 (60.6%) of which were polymorphic. Genetic distances were calculated with a range of 0.032 to 1.402. Clustering analysis showed that the 64 tomato cultivars were divided into 4 groups with a similarity coefficient of 0.40. Using this novel strategy, with the same RAPD data, both CID and clustering analysis can simultaneously determine tomato cultivars and their genetic diversity.

Effect of tanshinone IIA on cardiomyocyte hypertrophy and apoptosis in spontaneously hypertensive rats.

In the present study, the effects of tanshinone IIA (TSN) on the prevention of left ventricular hypertrophy (LVH) and apoptotic processes were observed in spontaneously hypertensive rats (SHRs). A total of 18 SHRs (age, 8 weeks) were randomly divided into three groups. The SHRs in the control group (group S8) were sacrificed at week 8 of the experiment. The SHRs in the treatment group (group D18) and the placebo group (group S18) were injected with TSN and distilled water (1 ml/kg body weight/day), respectively, for 10 weeks, commencing at week 8, and were subsequently sacrificed at week 18. The systolic blood pressure (SBP) and left ventricular mass index (LVMI) were determined. Using hematoxylin and eosin and van Gieson staining, together with immunohistological methods, cardiomyocyte size and diameter, collagen volume fraction (CVF) and perivascular circumferential area (PVCA) were measured. Evaluation of Bcl-2, Bax and p53 expression levels for apoptosis analysis was performed using western blotting. It was observed that the SBP, LVMI, cardiomyocyte size and diameter, CVF, PCVA and cardiomyocyte apoptosis index (Bax and p53 expression) were increased significantly in group S18 compared with group S8. However, Bcl-2 expression levels were decreased in group S18 compared with group S8. The administration of TSN in group D18 resulted in higher Bcl-2 expression levels and significantly decreased LVMI, cardiomyocyte size and diameter, CVF, PCVA, Bax and p53 expression levels compared with group S18. LVH and apoptosis of the cardiac tissues increased with the increasing age of the SHRs. TSN may inhibit the development of LVH and decrease the level of apoptosis in SHRs, possibly via the upregulation of Bcl-2 and the downregulation of Bax and p53 expression.

Calcium binding protein containing neurons in the gliotic mouse hippocampus with special reference to their afferents from the medial septum and the entorhinal cortex.

In CA1 area and the hilus of the dentate gyrus of the mouse hippocampus, drastic reduction of NeuN, calbindin, calretinin, or parvalbumin immunopositive neurons was shown at 3, 7 and 60 days after pilocarpine-induced status epilepticus. In gliotic CA1 area at 60 days, few dendritic branches of calcium binding protein immunopositive neurons could be found suggesting reorganization of the afferents of surviving calcium binding protein immunopositive neurons. Calbindin, calretinin, or parvalbumin and 5-bromo-2'-deoxyuridine (BrdU) double labeling showed that calcium binding protein immunopositive neurons in gliotic CA1 area at 60 days were surviving instead of newly generated neurons. Iontophoretic injection of Phaseolus vulgaris leucoagglutinin into the medial septum and the nucleus of the diagonal band of Broca or the lateral entorhinal cortex showed contacts between Phaseolus vulgaris leucoagglutinin immunopositive en passant and terminal boutons and surviving calcium binding protein immunopositive neurons in the hippocampus. The presence in the gliotic hippocampus of enlarged and/or aggregated bouton-like structures 60 days after pilocarpine-induced status epilepticus is indicative for the reorganization of connections between the hippocampal afferents and surviving hippocampal neurons. This reconstruction could be a factor in the ongoing epileptic activity in this model of mesial temporal lobe epilepsy.