The network characteristics in schizophrenia with prominent negative symptoms: a multimodal fusion study.

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

Exosomal microRNA-15a from mesenchymal stem cells impedes hepatocellular carcinoma progression via downregulation of SALL4.

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM.

Colorectal cancer (CRC) is the third most common cancer worldwide, and liver metastasis presents a major cause of CRC-associated death. Extensive genomic analysis has provided valuable insight into the pathogenesis and progression of CRC; however, a comprehensive proteogenomic characterization of CRC liver metastasis (CLM) has yet to be reported. Here, we analyzed the proteomes of 44 paired normal colorectal tissues and CRC tissues with or without liver metastasis, as well as analyzed genomics of CRC characterized previously by The Cancer Genome Atlas (TCGA) to conduct integrated proteogenomic analyses. We identified a total of 2,170 significantly deregulated proteins associated with CLM, 14.88% of which were involved in metabolic pathways. The mutated peptide number was found to have potential prognosis value, and somatic variants revealed two metabolism-related genes UQCR5 and FDFT1 that frequently mutated only in the liver metastatic cohort and displayed dysregulated protein abundance with biological function and clinical significance in CLM. Proteogenomic characterization and integrative and comparative genomic analysis provides functional context and prognostic value to annotate genomic abnormalities and affords a new paradigm for understanding human colon and rectal cancer liver metastasis.

[Effects of pure total flavonoids from Citrus changshan-huyou on blood lipid metabolism in hyperlipidemic rats].

To observe and investigate the effects and mechanisms of the pure total flavonoids from Citrus changshan-huyou(PTFC) on blood lipid metabolism in hyperlipidemic rats. SD rats were fed with high fat diet for 4 weeks to induce hyperlipidemic rats model, meanwhile three dosages (50, 100, 200 mg•kg ⁻¹â€¢d ⁻¹) of PTFC were administrated intragastrically for 4 weeks respectively.After 2 weeks of modeling, their tail blood was taken and serum TC, TG, and HDL-C levels were detected by biochemical method and their body weight was measured. After 4 weeks of modeling, their body weight was measured and liver weight was measured, then the levels of TC, TG, HDL-C, LDL-C, ALT, AST, MDA and SOD in serum were detected to calculate lipid comprehensive index(LDL-C/HDL-C and LDL-C/TC ratios) and atherogenic index(AI); in addition, MDA and SOD levels were detected by biochemical method. The hitopathological changes of the liver tissues were observed by HE staining; the protein expression levels of PPAR-α, Lpl, and Lipc were detected by ELISA; and the mRNA expression levels of PPAR-α in the liver tissue were detected by Real-time PCR. The results showed that gavage administration of the PTFC significantly decreased the body weight, liver weight, liver index, serum ALT and AST activities, the levels of serum TC, TG, LDL-C, LDL-C/HDL-C, AI and increased serum HDL and LDL/TC level. Moreover, the PTFC significantly enhanced SOD activity and decreased the concentration of MDA in serum and liver tissue. Further mechanism investigation indicated that PTFC inhibited serum lipid accumulation by increasing the expressions PPAR-α, Lpl, Lipc protein and PPAR-α mRNA of the liver tissues. PTFC could actively regulate blood lipid metabolism by ameliorating hepatic function, improving the body's antioxidant capacity, lowering levels of oxidative stress, as well as positively regulating the expression levels of PPAR-α, Lpl, Lipc protein and PPAR-α mRNA of the liver tissues in rats.

CpG island methylator phenotype and Helicobacter pylori infection associated with gastric cancer.

AIM: To investigate the association between the CpG island methylator phenotype (CIMP) and serum Helicobacter pylori (H. pylori) levels for clinical prediction of gastric cancer (GC) progression. METHODS: We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction. Serum samples from 40 healthy persons were examined at the same time. The genes examined were APC, WIF-1, RUNX-3, DLC-1, SFRP-1, DKK and E-cad. H. pylori infection in serum was assayed with an anti-H. pylori immunoglobulin G antibody test and a rapid urease test. RESULTS: The frequencies of high-level methylation in GC tissues for the seven genes were: 48% for APC, 57.33% for WIF-1, 56% for RUNX-3, 50.67% for DLC-1, 52% for SFRP-1, 54.67% for DKK, and 48% for E-cad. The frequencies in GC serum were 30.67% for APC, 34.67% for WIF-1, 37.33% for RUNX-3, 29.33% for DLC-1, 33.33% for SFRP-1, 32% for DKK, and 26.67% for E-cad. CIMP+ (defined as ≥ 3 methylated genes) was associated with 47 (62.67%) GC tissue samples and 44 (58.67%) GC serum samples. CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons. Of the 75 GC cases, 51 (68%) were H. pylori+, and 24 (32%) were H. pylori-. Of the 51 H. pylori+ cases, 36 were CIMP+ and 15 were CIMP-. In contrast, for the 24 H. pylori- cases, 11 were CIMP+, and 13 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ(2) = 4.27, P < 0.05). Of the 51 H. pylori+ GC patients, 34 were CIMP+ and 17 were CIMP-, while among the 24 H. pylori- GC cases, 10 were CIMP+ and 14 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ(2) = 4.21, P < 0.05). A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H. pylori+/CIMP+ cases and the H. pylori+/CIMP- cases or CIMP- cases associated with H. pylori assayed in serum (P < 0.05). However, there were no significant differences in survival rates between the two groups. CONCLUSION: H. pylori+/CIMP+ cases are associated with higher rates of metastasis and recurrence than H. pylori+/CIMP- cases. Serum may be useful for examining CIMP status.

Cognitive and neurochemical alterations in hyperhomocysteinemic rat.

Accumulating data have shown that the level of serum homocysteine in patients with mild cognitive impairment, vascular dementia and Alzheimer's disease is higher than normal while the underlying mechanism is not fully understood. Here, a hyperhomocysteinemic rat model was made by maintaining rats on a diet high in methionine. The cognitive behavior, level of monoamine neurotransmitters in brain homogenates and brain-derived neurotrophic factor (BDNF) in cerebral spinal fluid (CSF) were compared between high-methionine diet and control group. The high-methionine diet group presented longer mean latency of escape and lesser time in target quadrant in morris maze test, lower level of serotonin and dopamine in cortex homogenates and lower level of BDNF in CSF. Together, our findings provide evidence that hyperhomocysteinemia could cause alterations of monoamine and neurotrophic factor, which might be further pathogenetic mechanisms underlying the cognitive deterioration.