BACKGROUND: It has been found that many substances can promote the differentiation of bone marrow mesenchymal stem cells into neural lineage in vitro, but the effect of peroxiredoxin 6 on bone marrow mesenchymal stem cells has not been studied. OBJECTIVE: To explore the effects of peroxiredoxin 6 on the proliferation of rat bone marrow mesenchymal stem cells and the ability to differentiate into neural lineages in vitro. METHODS: Bone marrow mesenchymal stem cells of Sprague-Dawley rats were cultured and passaged by whole bone marrow adherent culture in vitro into passage 3. The cells were assigned to five groups: PBS group, 1, 10, 100 μg/L and 1 mg/L peroxiredoxin 6 groups. CCK-8 assay was used to measure the absorbance at 450 nm of each group of cells for 9 consecutive days. Cell growth curves were drawn. Enzyme linked immunosorbent assay was utilized to measure absorbance at 450 nm in platform period. A relatively optimal concentration of peroxiredoxin 6 was selected to induce bone marrow mesenchymal stem cells to differentiate into neural lineages. PBS served as the control group. After 7 days of differentiation, immunofluorescence staining and western blot assay were used to detect the expression of neuronal marker protein NSE and glial cell marker protein GFAP. RESULTS AND CONCLUSION: (1) 1, 10 and 100 μg/L peroxiredoxin 6 groups complied with the general growth rule of bone marrow mesenchymal stem cells, and 10 μg/L was the optimal mass concentration. (2) NSE and GFAP immunofluorescence staining showed positive reaction after peroxiredoxin 6 induction; NSE and GFAP expression levels were higher than those in the control group. (3) The results of in vitro experiments show that the proper concentration of peroxiredoxin 6 can promote the proliferation of bone marrow mesenchymal stem cells and induce differentiation into neural lineage.

Aneurysmal subarachnoid hemorrhage (aSAH) has high disability and mortality.Cerebral vasospasm is the main cause of ischemic neurological deficit and even cerebral infarction after aSAH.At present,there are many studies on molecular signaling pathways of cerebral vasospasm.This article reviews the signaling pathways of cerebral vasospasm after aSAH.

Studies have shown that bone marrow mesenchymal stem cells (BMSCs) transplantation can restore the sensory and motor function of patients with ischemic stroke. BMSCs transplantation is a promising therapeutic strategy because of its ability to differentiate into neuron-like cells. This article reviews the inducers that promote BMSCs to differentiate into neuron-like cells in vitro.

Glioma,especially glioblastoma,is one of the most common malignancies in the central nervous system.Traditional surgery combined with radiotherapy and chemotherapy did not significantly change the survival time of gliomas.Invasive growth,high heterogeneity and existence of glioma stem cell are the main causes of tumor recurrence.In addition,various immune cells and cytokines secreted by them in tumor microenvironment,as well as their activation status,are the key factors affecting tumor progress and effecacy of various immunotherapy.Interleukin (IL)-33 is a member of IL-1 gene family,and in recent years,it has been confirmed that IL-33 is highly expressed in some brain tumors,and IL-33 is the main coordinator of microenvironment regulation in brain tumors.In this paper,we will introduce the immunosuppressive state of brain tumors and their microenvironment and the limitation of tumor growth and immunotherapy,and recent advance that cytokine regulate and intervene the microenvironment of glioma to adapt tumor-lytic virus-immunotherapy.

Objective To study the in vitro killing effect of novel small molecule inhibitors, ribosomal S6 kinase1 (RSK1) inhibitor (BI-D1870) and polo-like kinase 1 (PLK1) inhibitor (BI2536), combined with recombinant attenuated vesicular stomatitis virus VSVΔM51 on various glioma cells. Methods (1) In vitro cultured GL261, CT2A and HS68 cells were divided into control group, rapamycin group, BI-D1870 group, BI-2536 group, VSVΔM51 group, rapamycin +VSVΔM51 group, BI-D1870+VSVΔM51 group, and BI2536+VSVΔM51 group; pretreatments with 100 nmol/L rapamycin, 10 μmol/L BI-D1870, and 100 nmol/L BI-2536 for 2 h were given to the cells from the above groups, respectively, and then, they were infected with VSVΔM51 virus at 0.1 mutiplicity of infection (MOI); at 72 h after treatments, the cell survival rate was determined by Alarma Blue method; VSV△M51 virus was infected at 10 MOI one h after pretreatment with the above drugs, apoptosis of GL261 cells was detected by cleaved caspase-3 staining 24 h after that; the expression of apoptotic protein polyadp-ribosomal polymerase (PARP) was detected by Western blotting; Annexin V-FITC/propidium iodide double staining was used to detect the cell apoptosis. (2) GL261 and CT2A cells were divided into VSVΔM51 group, rapamycin+VSVΔM51 group, BI-D1870+VSVΔM51 group, and BI2536+ VSVΔM51 group; VSV△M51 virus was infected at 0.1 MOI one h after pretreatment with the above drugs,; 48 h after treatments, fluorescence microscope was used to detect the expression of green fluorescent protein (GFP); IVIS200 in vivo imaging system was used to detect the changes of cell virus luciferase in the 4 groups. (3) Fifteen CT2A intracranial implanted glioma model mice were divided into VSVΔM51 group, BID-1870+VSVΔM51 group and BI2536+VSVΔM51 group according to random number table method (n=5); mice in the latter two groups were intraperitoneally injected with BI-1870 (100 mg/kg) or intravenously injected with BI-2536 (20 mg/kg); 24 h after that, mice in the three groups were intravenously injected with virus VSVΔM51; virus luciferase was detected by IVIS200 in vivo imaging system 24 and 72 h after treatments; the grouping and treatments of GL261 intracranial glioma model mice were the same as above, the expression of virus GFP was observed under fluorescence microscope 48 h after treatments, and virus titers of these mice were detected by virus plaque assay. Results (1) As compared with the control group, rapamycin group, BI-D1870 group, BI-2536 group, and VSVΔM51 group, the rapamycin+VSVΔM51 group, BI-D1870+VSVΔM51 group, and BI2536+VSVΔM51 group had significantly lower cell survival rate (P<0. 05); cleaved Caspase-3 staining showed no cell apoptosis in the control group, a small amount of apoptotic corpuscles in the rapamycin group, BI-D1870 group, BI-2536 group, and VSVΔM51 group, but obvious increased amount of apoptotic corpuscles in the rapamycin+VSVΔM51 group, BI-D1870+VSVΔM51 group, and BI2536+ VSVΔM51 group; Western blotting indicated that GL261 and CT2A cells from the control group, rapamycin group, BI-D1870 group, BI-2536 group, and VSVΔM51 group had lower cleaved PARP expression level than those from the rapamycin+VSVΔM51 group, BI-D1870+VSVΔM51 group, and BI2536+VSVΔM51 group. The results of Annexin V-FITC/propidium iodide double staining were consistent with those of cleaved Caspase-3 staining. (2) As compared with VSVΔM51 group and rapamycin+VSVΔM51 group, BI-D1870+VSVΔM51 group and BI2536+VSVΔM51 group had significantly increased GFP expression and statistically higher intensity of virus luciferase (P<0.05). (3) CT2A cells in the VSVΔM51 group, BID-1870+VSVΔM51 group and BI2536+VSVΔM51 group had increased intensity of virus luciferase successively, with significant differences (P<0.05); GL261 cells in the VSVΔM51 group, BID-1870+VSVΔM51 group and BI2536+VSVΔM51 group had increased virus titers successively, with significant differences (P<0.05). Conclusion Both small molecule inhibitors promote the replication of VSVΔM51 virus and enhance the killing effect on glioma cells, and its synergistic effect is obviously better than rapamycin.

Ischemic stroke patients are often accompanied by complications such as gastrointestinal bleeding, microbiological disorders, and constipation, while intestinal microbiological disorders can affect the progress and prognoses of ischemic stroke. Researchers have found two-way communication between the brain and the intestines, and they communicate with each other through various mechanisms, called gut-brain axis or brain-gut axis. However, researches on ischemic stroke and brain-gut axis are still in its infancy, and further understanding of the potential relation between ischemic stroke and brain-gut axis may be helpful in developing new methods for the treatments of ischemic stroke. This paper reviews the relation between ischemic stroke and brain-gut axis to open up new ideas for preventions and treatments of ischemic stroke.