Expression and potential role of FOSB in glioma.

Background: FOSB is reported to be an oncogene in a variety of tumors. However, the expression and role of FOSB in glioma remain obscure. In this study, we aimed to explore the expression of FOSB in glioma and its biological role in glioblastoma multiforme (GBM). Methods: Western blot, immunohistochemical staining, and quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect the expression of FOSB in clinical samples. FOSB was knocked down in cells to determine the effects of FOSB on the phenotypic changes of tumors by plate cloning, CCK-8 assay, and Transwell assay. Finally, subcutaneous tumorigenesis in nude mice was used to observe the tumorigenesis of glioma cell lines after the knockdown of the FOSB gene. Results: FOSB expression was higher in glioma compared with normal brain tissue. After the downregulation of FOSB, the expression of cleaved caspase-3 increased. Plate cloning and CCK-8 experiments showed that the proliferation of glioma cell lines decreased. The Transwell assay demonstrated that the glioblastoma cell lines had lower migration ability after the knockdown of FOSB. Finally, the tumor volume of U87 glioma cells in group sh-FOSB was smaller than that in the control group. The TUNEL staining in vitro showed that the apoptosis of sh-FOSB glioma cells increased. Conclusion: FOSB was highly expressed in glioma tissues. The viability of glioma cells decreased, and the ability of glioma cells to proliferate and migrate was reduced when FOSB was downregulated. Hence, FOSB may promote the development and migration of gliomas.

Expression of FOXO transcription factors in the brain following traumatic brain injury.

Traumatic brain injury (TBI) is a substantial clinical and social problem worldwide, causing high morbidity and mortality along with significant economic and medical costs. Forkhead box O transcription factors (FOXOs) have been found to play a critical role in the regulation of cell functions, such as nutrient metabolism, programmed cell death, and tumor suppression. In the central nervous system, FOXOs are reported to be pivotal regulators of learning and memory, neurite outgrowth, and axonal degeneration. However, the role of FOXOs in TBI is still unknown. Here, we investigate changes in the expression of FOXOs in the acute stage following TBI. First, we evaluated the expression of FOXO proteins in the brains of humans after TBI. A TBI model was then established in mice, and the ipsilateral cerebral cortex was collected at 3 h, 6 h, 9 h, 12 h, 24 h, and 72 h post-TBI. The dynamic expression of Foxo proteins was observed. Neuron-specific localization of Foxos was detected by double immunofluorescence staining. Following TBI, FOXO proteins in the brains of humans were significantly increased. In mice, Foxo protein levels generally peaked at 24 h. By examining co-localization with neurons, the proportion of Foxo(+) neurons was found to increase following TBI and peak at 24 h. This study reveals the time-dependent and neuron-specific expression of Foxos following TBI in mice, providing insight to enhance understanding of the role of Foxos in TBI.

FOXO4 expression associates with glioblastoma development and FOXO4 expression inhibits cell malignant phenotypes in vitro and in vivo.

BACKGROUND AND AIM: Forkhead box protein O4 (FOXO4) is a transcription factor, and aberrant FOXO4 expression is associated with development of various human cancers. This study explored the role of FOXO4 in glioma in vitro and in vivo. METHODS: FOXO4 expression was first assessed in normal brain tissues, low-grade glioma, glioblastoma multiforme (GBM), normal human astrocytes (HA), and GBM cell lines, while manipulation of FOXO4 expression in glioma cell lines was assessed using qRT-PCR, Western blot, and cell viability CCK-8, Transwell, and a nude mouse subcutaneous xenograft assays. KEY FINDINGS: The data showed downregulated FOXO4 expression in GBM tissues and cell lines. FOXO4 overexpression induced by transfection with FOXO4 cDNA significantly inhibited GBM cell proliferation, migration, and invasion, but increased tumor cells to undergo apoptosis in vitro, while suppressed growth of GBM cell subcutaneous xenografts in nude mice. In conclusion, FOXO4 possesses an anti-cancer glioma activity, which could be a novel target for future control of GBM.

[Morphological study on early development of brain derived neurophic factor-positive neurons in the frontal lobe of human fetus].

OBJECTIVE: To investigate the growth and development of brain derived neurophic factor(BDNF)-positive neurons in the frontal lobe of human fetus. METHODS: The expression of the BDNF-positive neurons in the frontal lobe of human fetus in the 2(nd),3(rd),and 4(th) month of gestation were observed with the streptavidin-biotin-complex/immunoperoxidase(SABC)method. RESULTS: By the second month of gestation,BDNF-positive neurons were seen in the subventricular layer of the frontal lobe of cerebellum.By the third month of gestation,BDNF-positive neurons in the central layer were in various shapes,with big nucleus,less cytoplasm,and small processes.By the fourth month of gestation,BDNF-positive neurons in the central layer grew larger in size,cytoplasm increased,the BDNF-positive expression was enhanced with deeper dyeing,and the nerve fibers and particles were distributed between neurons;also,the BDNF-positive neurons were seen in the marginal layer of the frontal lobe of cerebrum. CONCLUSION: BDNF-positive neurons may participate in the early development of the frontal lobe of cerebrum of human fetus.

[Morphological study on development of nerve growth factor-positive neurons in the cerebellum of human fetus].

OBJECTIVE: To investigate the growth and development of nerve growth factor (NGF)-positive neurons in the cerebellum of midanaphase human fetus. METHODS: The expression of the NGF-positive neurons in the cerebrum of human fetus was observed by immunohistochemical methods, and the integral absorbance (IA) was detected. RESULTS: By the 3rd to 4th month of gestation, neurons was seen in the ependymal, central, and marginal plate of cerebellum; the nucleus was oval and the neurons had short and small processes. By the 5th to 7th month of gestation, the number of NGF-positive neurons increased, the expressions enhanced, the nucleus was round-, oval-, or fusiform-shaped, the neurons grew larger in size, and the Purkinje cells showed NGF-positive expression. By the 8th to 10th month of gestation, the NGF-positive expression was enhanced with deeper dying, the body of Purkinje cells grew larger gradually, and the number of NGF-positive neurons in the granular cell layer and molecular layer increased. IA of the cerebellar cortical neurons of the 3rd, 4th, 5th, 6th, 7th, and 8th month of gestation showed an increasing trend, and significant difference was observed (P < 0. 05). CONCLUSION: NGF-positive neurons in the cerebellum play an important role for differentiation, proliferation, migration, and growth of neurons in the cerebellum.

[Morphology of nitric oxide synthase positive neurons in the cerebellar cortex of midanaphase human fetus].

OBJECTIVE: To investigate the growth and development of nitric oxide synthase (NOS)-positive neurons in the cerebellum of human fetus in the midanaphase. METHOD: The positive expression of the NOS-positive neurons in the cerebellum of midanaphase human fetus was observed by immunohistochemistry. RESULTS: By the sixth to seventh month of gestation, NOS-positive neurons were seen in the ependymal layer of the cerebellum. The nucleus was oval-shaped and the neurons had short and small processes. By the eighth to ninth month, NOS-positive neurons were found in the central layer of the cerebellum and the nucleus was round-, oval-, or fusiform-shaped; meanwhile, the neurons grew larger in size with richer cytoplast and heavier staining. The beaded nerve fibers reached the marginal layer and the layer became thickened on the tenth month, which generally was composed of 5 to 6 layers of NOS-positive neurons that were tightly aligned. Some NOS-positive neurons were in smaller size with the cell body and the nerve fibers grew well. CONCLUSION: Nitric oxide generated by NOS of the NOS-positive neurons in the cerebellum plays an important role in the differentiation, proliferation, and migration of neurons and gliacytes.

[Immunohistochemical study on development of nitric oxide synthase-positive neurons in the frontal lobe of cerebrum of midanaphase human fetus].

OBJECTIVE: To investigate the development of nitric oxide synthase (NOS)-positive neurons in the frontal lobe of the cerebrum of human fetus in midanaphase. METHODS: The positive expression of the NOS-positive neurons in the frontal lobe of cerebrum of human fetus was observed by immunohistochemistry. RESULTS: By the 7th to 8th month of gestation, NOS-positive neurons in the cortical plate of frontal lobe demonstrated themselves inequality of sizes and morphological difference in the deeper layers with interspersed distribution and increased NOS response, and the distribution of beaded nerve fiber was observed between neurons of cerebral tissues. By the 9th to 10th month of gestation, NOS-positive neurons in the deeper layers of cortical plate of frontal lobe developed slightly in size of the cell body with richer cytoplast, full shape and deeper dyeing and extrusive beaded nerve fibers, and the NOS-positive neurons scattered in the shallow layer of cortical plate presented with round or oval shape. The nucleus developed bigger but with sparse cytoplasm and clear nerve process. CONCLUSION: NOS-positive neurons in the deeper layer of cortical plate of lobus frontal consist of largely network of neural system and produce micro-environment with higher concentration of NO, which favors the differentiation, proliferation, migration, and development of various neurons.