Upregulation of microRNA-762 suppresses the expression of GIPC3 in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE), especially neuropsychiatric SLE (NPSLE), is a complex systemic autoimmune disease, characterized by variable course and multiple organ dysfunction. Our study aimed to identify crucial microRNA (miRNAs) in SLE and NPSLE. METHODS: Totally 12 cases of serum specimens were collected from General Hospital of Ningxia Medical University (SLE = 4, NPSLE = 4, control = 4). After miRNA sequencing, differential expression analysis, miRNA target prediction, and miRNA-messenger RNA (mRNA) regulatory network construction were performed to identify the hub miRNAs. The expression of target gene was determined by quantitative reverse transcription-polymerase chain reaction and Western blot. RESULTS: There were 79 and 59 differentially expressed miRNAs (DEmiRNAs) in NPSLE versus Control, and SLE versus Control, respectively. Among 35 overlapped DEmiRNAs, 5 upregulated miRNAs' (hsa-miR-762, hsa-miR-4270, hsa-miR-3663-3p, hsa-miR-4778-5p, and hsa-miR-4516) target genes were supported by at least six databases. The miRNA-mRNA network indicated that core miRNA hsa-miR-762 regulated 1270 target genes. MiR-762 was significantly upregulated in SLE and NPSLE, and over expression of miR-762 significantly suppressed GIPC PDZ domain containing family member 3 (GIPC3) expression in SLE and NPSLE. CONCLUSIONS: Upregulation of hub miRNA miR-762 can suppress the expression of GIPC3 in both SLE and NPSLE samples, which is probably involved in the development of SLE and NPSLE. Meanwhile, along with the development from SLE to NPSLE, miR-762 exhibits higher expression.

Effect of the interference with DRP1 expression on the biological characteristics of glioma stem cells.

In the present study, a model of glioma stem cells (GSCs) was established and combined with molecular targeting drugs in order to observe its inhibitory effect on the proliferation and biological characteristics of GSCs, with the aim of providing a potential target for the treatment of glioma. On the basis of a relatively classical induction strategy with neuron induction medium, a large number of GSC-like cells in good condition and globular growth were amplified in vitro, which had the potential to differentiate into neurons, oligodendrocytes and astrocytes/glioma cells. It was observed that the interference with dynamin-related protein 1 expression using Mdivi-1, a mitochondrial mitotic inhibitor, at the optimal concentration, decreased the expression level of stem cell-associated genes, inhibited proliferation and promoted apoptosis in GSCs. The present study provided an experimental basis for a novel strategy of cancer treatment with tumor stem cells as the target.

Small molecular compounds efficiently convert human fibroblasts directly into neurons.

No effective treatment is currently available for neurodegenerative diseases, and existing pharmacotherapy is inconsistent with severe side effects. Cell replacement therapy is promising for neurodegenerative disease treatment, and the induction of neurons is an unmet need for such therapy. The present study investigated the potential of a combined medium composed of conditioned medium and eight small molecular compounds in reprogramming human foreskin fibroblasts (HFFs) into neurons. HFFs were cultured from foreskin and then induced by small molecules to generate neurons. The results demonstrated that the conditioned medium containing forskolin, RepSox, SP600125, CHIR99021, Go6983, Y­27632, IXS9 and I­BET151 effectively induced human fibroblasts to change into neurons in vitro. Following a 30­day induction, the cells exhibited neuronal properties as determined by morphological and phenotypical alterations. The induced cells exhibited expression of neuronal markers, including class III ß­tubulin, microtubule­associated protein 2, vesicular glutamate transporter 1 and γ­aminobutyric acid, accompanied by increased expression of neuronal transcription factors, including neuronal differentiation 1 and achaete­scute family bHLH transcription factor 1, and decreased expression levels of fibroblast­specific genes. Furthermore, these cells also exhibited electrophysiological properties of neurons. Notably, the course of cell morphological alterations demonstrated the differentiation of fibroblasts into neurons. The present study provided a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons.

High-glucose Induced Mitochondrial Dynamics Disorder of Spinal Cord Neurons in Diabetic Rats and its Effect on Mitochondrial Spatial Distribution.

STUDY DESIGN: A randomized, double-blind, controlled trial. OBJECTIVE: Few studies have investigated the changes in mitochondrial dynamics in spinal cord neurons. Meanwhile, the distribution of mitochondria in axons remains unclear. In the present study, the investigators attempted to clarify these questions and focused in observing the changes in mitochondrial spatial distribution under a high-glucose environment. SUMMARY OF BACKGROUND DATA: Mitochondrial dynamics disorder is one of the main mechanisms that lead to nervous system diseases due to its adverse effects on mitochondrial morphology, function, and axon distribution. High-glucose stress can promote the increase in mitochondrial fission of various types of cells. METHODS: The lumbar spinal cord of type 1 diabetic Sprague-Dawley rats at 4 weeks was observed. VSC4.1 cells were cultured and divided into three groups: normal control group, high-glucose intervention group, and high-glucose intervention combined with mitochondrial fission inhibitor Mdivi-1 intervention group. Immunohistochemistry and immunofluorescence methods were used to detect the expression of mitochondrial marker VDAC-1 in the spinal cord. An electron microscope was used to observe the number, structure, and distribution of mitochondria. Western blot was used to detect VDAC-1, fusion protein MFN1, MFN2, and OPA1, and fission protein FIS1 and DRP1. Living cell mitochondrial staining was performed using MitoTracker. Laser confocal microscopy and an Olympus live cell workstation were used to observe the mitochondrial changes. RESULTS: The mitochondrial dynamics of spinal cord related neurons under an acute high-glucose environment were significantly unbalanced, including a reduction of fusion and increase of fission. Hence, mitochondrial fission has the absolute advantage. The total number of mitochondria in neuronal axons significantly decreased. CONCLUSION: Increased mitochondrial fission and abnormal distribution occurred in spinal cord related neurons in a high-glucose environment. Mdivi-1 could significantly improve these disorders of mitochondria in VSC4.1 cells. Mitochondrial division inhibitors had a positive significance on diabetic neuropathy. LEVEL OF EVIDENCE: N/A.

Overexpression of PRDM13 inhibits glioma cells via Rho and GTP enzyme activation protein.

PR (PRDI­BFI and RIZ) domain containing (PRDM) proteins have been shown to be important in several types of human cancer. PRDM13, a member of the PRDM family, contains transcriptional regulators involved in modulating several cellular processes. However, the function of PRDM13 in glioma remains to be elucidated. The purpose of the present study was to evaluate the expression and effect of PRDM13 on glioma cells. It was found that the expression of PRDM13 was reduced in glioma cells, and the overexpression of PRDM13 significantly decreased the proliferation, migration and invasion of U87 glioma cells. Through validation of RNA­sequencing analysis, genes regulating cell proliferation and migration were classified from Gene Ontology sources. In addition, PRDM13 was shown to be associated with Rho protein and GTP enzyme activation protein. The over-expression of PRDM13 upregulated deleted in liver cancer 1 (DLC1) to inhibit the proliferation and invasion of U87 cells. In conclusion, PRDM13 decreased the proliferation and invasion of U87 cells, and may be of potential value for glioma therapy.

Correlation of Serum Soluble Interleukin-7 Receptor and Anti-C1q Antibody in Patients with Systemic Lupus Erythematosus.

Background. Serum concentrations of soluble interleukin-7 receptor (sIL-7R) and anti-C1q antibody have recently been identified as unique serological markers for lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE). In this study, we evaluated the correlation of serum sIL-7R and anti-C1q in SLE patients. Methods. Sera from 134 patients with SLE and 84 healthy cohorts were tested for levels of sIL-7R and anti-C1q antibodies in terms of ELISA. Correlations of the sIL-7R and anti-C1q autoantibodies were evaluated. Results. The serum concentrations of sIL-7R and anti-C1q antibodies were significantly higher in SLE patients and LN patients in comparison with healthy individuals/controls and SLE patients with non-LN, respectively. In addition, both sIL-7R and anti-C1q concentrations were found to significantly correlate with the SLE disease activity as evaluated by SLEDAI scores. Interestingly, the serum sIL-7R concentration was strongly correlated with the level of anti-C1q antibodies (r = 0.2871, p = 0.0008) but not statistically correlated with other serological markers, including the anti-dsDNA and complements C3 and C4 concentrations in SLE patients. Conclusion. Both serum sIL-7R and anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that they may be reliable serological markers for identification of SLE patients with active diseases and LN.

Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis.

OBJECTIVE: An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. METHODS: The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. RESULTS: The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. CONCLUSION: Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease.