METHODS: We obtained sequencing data sets (SUB12404730, SUB12422862, and SUB12421357) and transcriptome sequencing data sets (GSE111708, GSE108925, and GSE18981) from mouse models of schizophrenia using the Sequence Read Archive and the Gene Expression Omnibus databases, respectively. We performed differential expression analysis on mRNA to identify differentially expressed genes. We conducted Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine differentially expressed genes. Subsequently, we determined the intersection of differentially expressed microRNAs in plasma exosomes and in prefrontal cortex tissue. We retrieved downstream target genes of mmu-miR-146a-5p from TargetScan and used Cytoscape to visualize and map the microRNA-target gene regulatory network. We conducted in vivo experiments using MK-801-induced mouse schizophrenia models and in vitro experiments using cultured mouse neurons. The role of plasma exosomal miR-146a-5p in schizophrenia was validated using a cell counting kit, detection of lactate dehydrogenase, dual-luciferase assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis.
RESULTS: Differential genes were mainly enriched in synaptic regulation-related functions and pathways and were associated with neuronal degeneration. We found that mmu-miR-146a-5p was highly expressed in both prefrontal cortical tissue and plasma exosomes, which may be transferred to lobe cortical vertebral neurons, leading to the synergistic dysregulation of gene network functions and, therefore, promoting schizophrenia development. We found that mmu-miR-146a-5p may inhibit the Notch signalling pathway-mediated synaptic activity of mouse pyramidal neurons in the lobe cortex by targeting NOTCH1, which in turn could promote the onset and development of schizophrenia in mice.
LIMITATIONS: The study's findings are based on animal models and in vitro experiments, which may not fully replicate the complexity of human schizophrenia.
CONCLUSION: Our findings suggest that mmu-miR-146a-5p in plasma-derived exosomes may play an important role in the pathogenesis of schizophrenia. Our results provide new insights into the underlying molecular mechanisms of the disease.
OBJECTIVE: The aim of this study is an assessment of siRNA-COG3 on proliferation, invasion, and apoptosis of OC cells. In addition, siRNA-COG3 may prevent the growth of OC cancer in mice with tumors.
METHODS: Primary OC cell lines will be treated with siRNA-COG3 to assay YKL40 and identified angiogenesis by Tube-like structure formation in HOMECs. The Golgi morphology was analyzed using Immunofluorescence microscopy. Furthermore, the effects of siRNA-COG3 on the proliferation and apoptosis of cells were evaluated using MTT and TUNEL assays. Clones of the HOSEpiC OC cell line were subcutaneously implanted in FVB/N mice. Mice were treated after two weeks of injection of cells using siRNA-COG3. Tumor development suppression was detected by D-luciferin. RT-PCR and western blotting analyses were applied to determine COG3, MT1- MMP, SNAP23, and YKL40 expression to investigate the effects of COG3 gene knockdown.
RESULTS: siRNA-COG3 exhibited a substantial effect in suppressing tumor growth in mice. It dramatically reduced OC cell proliferation and triggered apoptosis (all p < 0.01). Inhibition of COG3, YKL-40, and MT1-MPP led to suppression of angiogenesis and reduction of microvessel density through SNAP23 in OC cells.
CONCLUSION: Overall, by knockdown of the COG3 gene, MT1-MMP and YKL40 were dropped, leading to suppressed angiogenesis along with decreasing migration and proliferation. SiRNACOG3 may be an ideal agent to consider for clinical trial assessment therapy for OC, especially when an antiangiogenic SNAR-pathway targeting drug.
MATERIAL AND METHODS: Thirty Sprague Dawley rats (3-monthold, 200 to 300 gm) were randomly divided into six groups, namely control (C), 4 weeks diabetes mellitus (DM1), 8 weeks DM (DM2) and three DM1 groups (VD1, VD2, and VD3) who received Vitamin D doses of 0.125, 0.25 and 0.50 μg/kg BW, respectively. After 4 weeks, daily VD was administered intraperitoneally for 30 days. Lung tissues were taken for IL- 6, MCP-1, NFKB and CD68 mRNA expression analysis and paraffin embedding. Immunohistochemical staining against CD68 and MCP-1 was conducted. Data were analysed using one-way ANOVA. p < 0.05 was considered statistically significant.
RESULTS: DM2 group represented significantly higher IL6, MCP1, NFKB and CD68 mRNA expression than Control group (p < 0.05). Meanwhile, VD2 and VD3 groups revealed significantly lower mRNA expression of IL-6, MCP1, NFKB and CD68 than DM2 (p < 0.05). Immunostaining revealed the spreading of MCP1 protein expression in lung tissue along with macrophage infiltration in the DM2 group, which was reduced in the VD2 and the VD3 groups.
CONCLUSION: VD shows a protective effect on diabetesinduced lung damage by regulating inflammation factors.
METHODS: Treatment-naive patients with invasive breast carcinoma were included in this retrospective study. Breast MRI features were recorded based on the American College of Radiology-Breast Imaging Reporting and Data System (ACR-BIRADS) criteria, with tumour size, and apparent diffusion coefficient value (ADC). The statistical association was tested with Pearson Chi-Square Test of Independence for categorical data or the Kruskal-Wallis/ Mann Whitney U test for numerical data between the MRI features and molecular subtype, receptor status, tumour grade, lymphovascular infiltration (LVI) and axillary lymph node (ALN). Multinomial logistic regression was used to test the predictive likelihood of the significant features. The breast cancer subtypes were determined via immunohistochemistry (IHC) and dual-color dual-hapten in-situ hybridization (D-DISH). The expression statuses of ER, PR, and HER-2, LVI, and ALN were obtained from the histopathology report. The ER / PR / HER-2 was evaluated according to the American Society of Clinical Oncology / College of American Pathologists.
RESULTS: The study included 194 patients; 41.8% (n = 81) Chinese, 40.7% (n = 79) Malay, and 17.5% (n = 34) Indian, involving 71.6%(n = 139) luminal-like, 12.9%(n = 25) HER-2 enriched, and 15.5%(n = 30) Triple-negative breast cancer (TNBC). TNBC was associated with rim enhancement (p = 0.002) and peritumoral oedema (p = 0.004). HER-2 enriched tumour was associated with larger tumour size (p = 0.041). Luminal-like cancer was associated with irregular shape (p = 0.005) with circumscribed margin (p = 0.003). Other associations were ER-negative tumour with circumscribed margin (p = 0.002) and PR-negative with round shape (p = 0.001). Tumour sizes were larger in ER-negative (p = 0.044) and PR-negative (p = 0.022). Rim enhancement was significantly associated with higher grade (p = 0.001), and moderate peritumoral oedema with positive axillary lymph node (p = 0.002).
CONCLUSION: Certain MRI features can be applied to differentiate breast cancer molecular subtypes, receptor status and aggressiveness, even in a multi-ethnic population.