The high levels of glutamate might involve in neurogenesis after brain injuries. However, the mechanisms are not fully understood. In this study, we investigated the effect of glutamate on the proliferation of rat embryonic neural stem/progenitor cells (NSCs) through regulating the vascular endothelial growth factor (VEGF) expression of astrocytes (ASTs) in vitro, and the cyclin D1 expression of NSCs. The results showed that glutamate promoted the expression and secretion of VEGF of rat astrocytes by activating group I mGluRs. Astrocyte conditioned medium-containing Glu [ACM (30%)] promoted the proliferation of embryonic NSCs compared with normal astrocyte conditioned medium+Glu [N-ACM (30%)+Glu (30 μM)] by increasing cell activity, diameter of neurospheres, bromodeoxyuridine (BrdU) incorporation and cell division; while ACM+VEGF neutralizing antibody [ACM (30%)+VEGF NAb (15 μg/ml)] significantly inhibited the proliferation of embryonic NSCs compared with ACM (30%). ACM (30%) increased the expressions of cyclin D1 and decreased cell death compared with N-ACM (30%)+Glu (30 μM). ACM (30%)+VEGF NAb (15 μg/ml) decreased the expressions of cyclin D1 and increased cell death compared with ACM (30%). These results demonstrated that glutamate could also indirectly promote the proliferation of rat embryonic NSCs through inducing the VEGF expression of ASTs in vitro, and VEGF may increase the expression of cyclin D1. These finding suggest that glutamate may be a major molecule for regulating embryonic NSC proliferation and facilitate neural repair in the process of NSC transplants after brain injuries.
OBJECTIVE: To investigate the chemopreventive effect and mechanisms of epigallocatechin‐3‐gallate (EGCG) and folic acid on N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced gastrointestinal cancer in rats, and to investigate and compare the combinatorial effects of EGCG and folic acid on the chemoprevention of gastrointestinal carcinogenesis. METHODS: A total of 159 healthy male Wistar rats were randomly divided into seven groups to have the MNNG in drink (group M), MNNG in drink and EGCG in the feed (group ME), MNNG in drink and folic acid in the feed (group MF), MNNG in drink and EGCG + folic acid in the feed (group MEF), EGCG in the feed (group E), folic acid in the feed (group F) or normal feed (group C), respectively. At 44 weeks, all the rats were killed and assessed for the presence of gastrointestinal tumor. The occurrence of cancer was evaluated by histology. Ki‐67 in cancerous tissues and in situ apoptosis were determined by immunohistochemical staining or terminal deoxyribonucleotide transferase‐mediated nick‐end labeling (TUNEL) assay, respectively. RESULTS: The experiment was completed in 157 rats (98.74%). As compared with group M, the tumor incidence of group MEF decreased significantly ( P = 0.011). Ki‐67 expression in cancerous tissues of group ME and MEF also decreased significantly ( P = 0.038, P = 0.009), while apoptosis of group ME, MF and MEF increased significantly ( P = 0.000, P = 0.003, P = 0.000). CONCLUSION: EGCG combined with folic acid has an obvious chemopreventive effect on gastrointestinal carcinogenesis induced by MNNG in rats.
OBJECTIVE To investigate the relationship between creeping fat and inflammatory activity as well as the prognosis of ileo‐colonic Crohn's disease (CD), based on a quantitative analysis of energy spectral computed tomography (CT). METHODS A total of 40 patients with CD and 40 with other gastrointestinal diseases who underwent an energy spectral CT scanning between March 2014 and March 2015 were retrospectively enrolled. The endoscopic severity of CD was evaluated by the simple endoscopic score for Crohn's disease (SES‐CD). The slope of the Hounsfield unit (HU) curve (λ HU ) was measured and calculated on energy spectral CT images. Visceral and subcutaneous fat areas were also measured. The relationship between the quantitative data of creeping fat as well as the fat area and CD inflammation were analyzed. RESULTS The λ HU of creeping fat in patients with CD increased with the severity of intestinal inflammation (moderate/severe vs mild: −0.17 ± −0.68 vs −0.49 ± −0.61, P < 0.01). Moreover, the λ HU of creeping fat around the intestinal segments without lesions in CD was significantly larger than that in the controls (−1.19 ± −0.56 vs − 1.42 ± −0.45, P < 0.01). The λ HU was more accurate for detecting inflammatory lesions in CD than for calculating visceral fat. It was significantly correlated with SES‐CD ( r = 0.66, P < 0.01) and moderately correlated with the Harvey–Bradshaw index ( r = 0.414, P < 0.01). CONCLUSION The quantitative analysis of creeping fat using energy spectral CT is an effective method in inflammatory evaluation in patients with CD.
Peripheral nerves are able to regenerate spontaneously after injury. An increasing number of studies have investigated the mechanism of peripheral nerve regeneration and attempted to find potential therapeutic targets. The various bioinformatics analysis tools available, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) networks can effectively screen the crucial targets of neuroregeneration.GSEA and PPI networks were constructed through ingenuity pathway analysis and sequential gene expression validation ex vitro to investigate the molecular processes at 1, 4, 7, and 14 days following sciatic nerve transection in rats.Immune response and the activation of related canonical pathways were classified as crucial biological events. Additionally, neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), neuregulin 1 (NRG1), nuclear factor of activated T cells 2 (NFATC2), midline 1 (MID1), GLI family zinc finger 2 (GLI2), and ventral anterior homeobox 1 (VAX1), which were jointly involved in both immune response and axonal regeneration, were screened and their mRNA and protein expressions following nerve injury were validated. Among them, the expression of VAX1 continuously increased following nerve injury, and it was considered to be a potential therapeutic target.The combined use of GSEA and PPI networks serves as a valuable way to identify potential therapeutic targets for neuroregeneration.
Increasing studies have suggested that microRNAs (miRNAs) are involved in the development of gliomas. MicroRNA-216a has been reported to be a tumor-associated miRNA in many types of cancer, either as an oncogene or as a tumor suppressor. However, little is known about the function of miR-216a in gliomas. The present study was designed to explore the potential role of miR-216a in gliomas. We found that miR-216a was significantly decreased in glioma tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, migration, and invasion of glioma cells. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) was identified as a target gene of miR-216a in glioma cells by bioinformatics analysis, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Moreover, miR-216a overexpression inhibited the Wnt/β-catenin signaling pathway. The restoration of LGR5 expression markedly reversed the antitumor effect of miR-216a in glioma cells. Taken together, these findings suggest a tumor suppressor role for miR-216a in gliomas, which inhibits glioma cell proliferation, migration, and invasion by targeting LGR5. Our study suggests that miR-216a may serve as a potential therapeutic target for future glioma treatment.
Hundreds of millions of people worldwide suffer from peripheral nerve damage resulting from car accidents, falls, industrial accidents, residential accidents, and wars. The purpose of our study was to further investigate the effects of Wallerian degeneration (WD) after rat sciatic nerve injury and to screen for critical long noncoding RNAs (lncRNAs) in WD. We found H19 to be essential for nerve degeneration and regeneration and to be highly expressed in the sciatic nerves of rats with WD. lncRNA H19 potentially impaired the recovery of sciatic nerve function in rats. H19 was mainly localized in the cytoplasm of Schwann cells (SCs) and promoted their migration. H19 promoted the apoptosis of dorsal root ganglion (DRG) neurons and slowed the growth of DRG axons. The lncRNA H19 may play a role in WD through the Wnt/β-catenin signaling pathway and is coexpressed with a variety of crucial mRNAs during WD. These data provide further insight into the molecular mechanisms of WD.
Objectives To assess the prevalence and potential risk factors of latent tuberculosis infection ( LTBI ) in Chinese patients with inflammatory bowel disease ( IBD ) and to evaluate the role of chest computed tomography ( CT ) in the screening of LTBI . Methods A single‐center retrospective study was conducted and all IBD patients who had been screened for LTBI by T‐SPOT . TB between December 2011 and January 2016 were enrolled in the study. Both inpatient and outpatient records were collected and comprehensively reviewed. Results Altogether 534 IBD patients were included. The positivity rate of T‐SPOT . TB was 18.0% overall, 31.9% in IBD unclassified, 22.5% in ulcerative colitis and 13.0% in Crohn's disease patients, respectively. Age, history of TB and the administration of immunosuppressants were significantly associated with T‐SPOT . TB positivity. Among 123 patients who underwent serial testing, the conversion and reversion rate of T‐SPOT.TB was 10.2% and 42.9%, respectively. Furthermore, 102 of 447 (22.8%) patients who underwent chest computed tomography ( CT) were found with abnormal CT findings suggestive of LTBI . The concordance rate was 75% between the T‐SPOT.TB and chest CT with a kappa value of 0.25 (95% CI 0.15–0.35). Conclusions The prevalence of LTBI in IBD patients is high in China. Chest CT is recommended as an alternative to IGRA for screening LTBI of IBD patients before commencing immunosuppressive therapy in high‐prevalence regions.
To investigate whether intracerebral hemorrhage (ICH) can promote neurogenesis in the dentate gyrus (DG) of rat hippocampus.Western blot analysis, immunohistochemical staining, and immunofluorescent double labeling combined with confocal microscope were used to detect neurogenesis in the DG of the hippocampus in rats after ICH.The expression of DCX protein in the ipsilateral DG of the hippocampus was enhanced in the rats 1 day after ICH (0.202∓0.062) as compared with that in normal rats (0.127∓0.088), reaching the peak level at 14 days (0.771∓0.108, P<0.01) and beginning to decrease at 28 days (0.582∓0.121, P<0.01). Meanwhile, DCX-positive cells and BrdU-positive cells, and DCX/BrdU double-labeled cells were detected in the DG of the hippocampus. Compared with those in the control group, BrdU/NeuN double-labeled cells were markedly increased in the granular cell layer of the DG at 28 days after ICH (1.808∓1.020 vs 5.654∓1.671, P<0.01).ICH can promote neurogenesis in the DG of rat hippocampus.
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