Injectable and Radiopaque Liquid Metal/Calcium Alginate Hydrogels for Endovascular Embolization and Tumor Embolotherapy.

Improved endovascular embolization can contribute to assistant treatment for patients. However, many traditional embolic materials, such as metal microcoils or liquid embolic agents, are associated with limitations of coil migration or recanalization. Herein, as the first trial, an injectable and radiopaque liquid metal/calcium alginate (LM/CA) hydrogel is introduced and fabricated as a candidate for endovascular embolization and tumor embolotherapy through developing LM droplets as radiopaque units into biocompatible calcium alginate cross-linked network. The adoption of LM droplets makes hydrogels radiopaque under X-ray and CT scan, which significantly facilitates the tracking of material location during surgical vascular operation. In addition, in vitro and in vivo experiments prove that such smart hydrogel could convert from liquid to solid rapidly via cross-linking, showing pretty flexible and controllable functions. Benefiting from these properties, the hydrogel can be performed in blood vessels through injection via syringes and then served as an embolic material for endovascular embolization procedures. In vivo experiments demonstrate that such hydrogels can occlude arteries and block blood flow until they ultimately lead to ischemic necrosis of tumors and partial healthy tissues. Overall, the present LM/CA hydrogels are promising to be developed as new generation embolic materials for future tumor embolotherapy.

PTPRR regulates ERK dephosphorylation in depression mice model.

BACKGROUND: The Protein tyrosine phosphatase receptor type R (PTPRR), which regulates the dephosphorylation of the downstream mitogen-activated protein kinase (MAPK) steering cell proliferation, apoptosis and synaptic plasticity, may be involved in the pathogenesis of depression. METHODS: Lentiviral vectors were utilized to express the PTPRR constitutively in the hippocampal dentate gyrus (DG) of mice before or after chronic mild stress. Behavior tests, MAPK levels, neuronal apoptosis and cell proliferation in the hippocampal DG were examined. RESULTS: Without chronic mild stress (CMS), the lenti-shPTPRR mice showed shorter immobility time in the tail suspension test than controls, while the lenti-PTPRR mice exhibited significantly less sucrose intake and increased immobility time in the forced swim tests than control mice, indicating increased prodepressant-like effects of PTPRR in lenti-PTPRR mice. Similarly, under CMS, the lenti-shPTPRR mice had more sucrose intake, shorter immobility time in the forced swim test and tail suspension test compared to controls, and lenti-PTPRR mice had less sucrose intake and longer immobility time in forced swim test and tail suspension test, exhibiting increased susceptibility to depressive-like behaviors and greater sensitivity to CMS. Besides, the Phospho-ERK1/2(p-ERK) had significant lower phosphorylation in lenti-PTPRR group and higher expression in lenti-shPTPRR group, both without CMS. The Lenti-PTPRR mice exposed to CMS had significant lower p-ERK, and the lenti-shPTPRR mice exposed to CMS had significant higher p-ERK and lower p-P38. Moreover, there were more cells underwent apoptosis in lenti-PTPRR group ,with and without CMS. In cell proliferation, less BrdU positive cells were observed in lenti-PTPRR mice than controls. CONCLUSION: The site-specific lentiviral injections resulted in the PTPRR over-expression in the hippocampal DG and subsequent increased ERK dephosphorylation, which leads to more neuron apoptosis, less cell proliferation, depression onset and increased sensitivity to CMS. PTPRR/ERK pathway could be potential target for depression therapy.

Cerebralcare Granule® attenuates cognitive impairment in rats continuously overexpressing microRNA-30e.

Previous studies have demonstrated that dysregulation of micro (mi)RNAs is associated with the etiology of various neuropsychiatric disorders, including depression and schizophrenia. Cerebralcare Granule® (CG) is a Chinese herbal medicine, which has been reported to have an ameliorative effect on brain injury by attenuating blood­brain barrier disruption and improving hippocampal neural function. The present study aimed to evaluate the cognitive behavior of rats continuously overexpressing miRNA­30e (lenti­miRNA­30e), prior to and following the administration of CG. In addition, the mechanisms underlying the ameliorative effects of CG were investigated. The cognitive ability of the rats was assessed using an open­field test and a Morris water maze spatial reference/working memory test. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect neuronal apoptosis in the dentate gyrus of the hippocampus. Immunohistochemical analysis and western blotting were conducted to detect the expression levels of B­cell lymphoma 2 (BCL­2) and ubiquitin­conjugating enzyme 9 (UBC9), in order to examine neuronal apoptosis. The lenti­miRNA­30e rats exhibited increased signs of anxiety, depression, hyperactivity and schizophrenia, which resulted in a severe impairment in cognitive ability. Furthermore, in the dentate gyrus of these rats, the expression levels of BCL­2 and UBC9 were reduced and apoptosis was increased. The administration of CG alleviated cognitive impairment, enhanced the expression levels of BCL­2 and UBC9, and reduced apoptosis in the dentate gyrus in the lenti­miRNA­30e rats. No significant differences were detected in behavioral indicators between the lenti­miRNA­30e rats treated with CG and the normal controls. These findings suggested that CG exerts a potent therapeutic effect, conferred by its ability to enhance the expression levels of BCL­2 and UBC9, which inhibits the apoptotic process in neuronal cells. Therefore, CG may be considered a potential therapeutic strategy for the treatment of cognitive impairment in mental disorders.

Continuous GSK-3ß overexpression in the hippocampal dentate gyrus induces prodepressant-like effects and increases sensitivity to chronic mild stress in mice.

BACKGROUND: Glycogen synthase kinase-3 (GSK-3) has been linked to prodepressant-like effects in rodents. However, the roles of GSK-3ß and the hippocampal dentate gyrus in regulating these behavioral effects remain unclear. METHODS: A lentiviral vector was utilized to site-specifically express GSK-3ß constitutively in the hippocampal DG in a mouse model of CMS. We examine the forced swim, tail suspension and the sucrose intake test. Acute and chronic administrations were conducted by dissolving fluoxetine hydrochloride (10ml/kg). We examine behavior tests as before, cellular apoptosis, proliferation and differentiation in the hippocampus. RESULTS: GSK-3ß expression levels persistently and significantly increased in the hippocampus following lenti-GSK-3ß injections. In mice previously exposed to CMS, pre-injection of lentivirus-expressing GSK-3ß into the hippocampal dentate gyrus significantly decreased sucrose preferences in the sucrose intake test and increased immobility times in both forced swim and tail suspension tests. In addition, fluoxetine resulted in similar antidepressant-like effects following chronic, but not acute, administrations under the same experimental conditions. Cellular apoptosis was observed in the hippocampal DG using TUNEL, revealing many TUNEL-positive cells in the lenti-GSK-3ß mice. There were no significant changes in proliferation and differentiation. LIMITATIONS: We did not measure more biomarkers which were regulated by GSK-3ß. CONCLUSIONS: Results from this study demonstrated that site-specific injection of a lentivirus induced continuous GSK-3ß expression in the hippocampal dentate gyrus of mice, resulting in prodepressant-like effects and increased sensitivity to chronic mild stress. Furthermore, chronic fluoxetine administration reversed these prodepressant-like effects and decreased neuronal apoptosis in the hippocampal DG in GSK-3ß-overexpressing mice.

[The post-injury regenerating ability of temporomandibular joint of rats exposed to the repeated + Gz forces].

OBJECTIVE: To observe the post-injury regenerating ability of temporomandibular joint of rats exposed to the repeated + Gz forces. METHODS: One hundred and eight male rats were randomly assigned to 9 groups, with 12 rats in each group. Group A was normally fed serving as the blank control group. Group B was only fixed with rat-kept devices for 5 minutes as the fixed control group. Group C was borne +1 Gz for 5 minutes. In the same position as group C, group D, E, F, G, H and I were repeatedly exposed to +10 Gz for 30 seconds each time with 5 times a day and +1 Gz for 1 minutes as a interval. The 6 groups were treated in the condition above for 4 days a week and 4 weeks in total. The rats in group A, B, C and D were killed on the next day after the centrifuge. The rats in group E, F, G, H and I were killed at 1, 2, 4, 8 and 12 weeks after the centrifuge, respectively. After the rats were killed, temporomandibular joint were taken for observation under optical microscope, scanning electron-microscope (SEM) and transmission electron-microscope (TEM). RESULTS: There was no significant difference observed in group A, B and C. But in group D, E, F, G, H and I pathologic injuries and self-regeneration were seen in TMJ in different degrees. CONCLUSIONS: The injury of TMJ could regenerate gradually with time.