Changes of serum MMP-9, NSE, MPO levels and prognostic influencing factors in patients with intracranial aneurysm undergoing interventional embolization at different treatment timing.

Background: To analyzes the changes in serum levels of matrix metalloproteinase-9 (MMP-9), neuroenolase (NSE), myeloperoxidase (MPO) and prognostic factors in patients with intracranial aneurysm (IA) undergoing interventional embolization at different treatment times. Methods: A retrospective analysis was made of 200 IA patients admitted to our department from January 2018 to June 2021 was performed. All patients underwent interventional embolization. According to the timing of surgery, the patients were divided into an early group (n=120, onset to surgery ≤72 h) and a delayed group (n=80, onset to surgery >72 h). The effect of embolization, complications and neurological deficit scale (NDS) scores were compared between the two groups. Serum MMP-9, NSE and MPO levels were compared before and after surgery, and the prognosis of all patients within 2 years after surgery was assessed by the Glasgow outcome scale (GOS) and divided accordingly into the good prognosis group (n=147) and the poor prognosis group (n=53) accordingly, and the prognostic factors influencing the patients were analyzed univariately and multifactorially.

Development of a tumor microenvironment-related prognostic signature in glioma to predict immune landscape and potential therapeutic drugs.

The involvement of the tumor microenvironment (TME) in the biology of gliomas has expanded, while it is yet uncertain its potential of supporting diagnosis and therapy choices. According to immunological characteristics and overall survival, cohorts of glioma patients from public databases were separated into two TME-relevant clusters in this analysis. Based on differentially expressed genes between TME clusters and correlative regression analysis, a 21-gene molecular classifier of TME-related prognostic signature (TPS) was constructed. Afterward, the prognostic efficacy and effectiveness of TPS were assessed in the training and validation groups. The outcome demonstrated that TPS might be utilized alone or in conjunction with other clinical criteria to act as a superior prognostic predictor for glioma. Also, high-risk glioma patients classified by TPS were considered to associate with enhanced immune infiltration, greater tumor mutation, and worse general prognosis. Finally, possible treatment medicines specialized for different risk subgroups of TPS were evaluated in drug databases.

Gold-Nanoparticle-Enhanced Radio-Fluorogenic Hydrogel Sensor for Low Radiation Doses in Clinical Radiotherapy.

Radio-fluorogenic hydrogel dosimeters are urgently needed in radiotherapy for 3D dose verification. However, few hydrogel sensors have been reported at low absorbed doses under 2 Gy which meets the requirements of clinical practice. Here, we report a new type of gold-nanoparticle-enhanced radio-fluorogenic agarose hydrogel with coumarin as the dose-responsive material. An optimal composition of 3 wt% of agarose, 0.1 mM of gold nanoparticles, and 0.5 mM coumarin was selected. The addition of gold nanoparticles enhanced the hydroxyl radicals generated from the radiolysis of water, which can react with coumarin and generate fluorescent 7-hydroxy-coumarin and, eventually, achieve low-dose verification of 0-2.4 Gy with a high linear correlation coefficient. These findings provide an effective method for 3D dose verification, and will inspire the development of other radio-fluorogenic sensing hydrogels as well.

Deanxit and tandospirone relieved unexplained limb edema in a depressed pituitary adenoma survivor: A case report.

Our case report describes a 45-year-old woman who suffered from limb edema for 2 months. We focused on tumor recurrence and other common potential diseases based on the pituitary adenoma history. However, none of the examinations showed any abnormality. Later, her continuous complaints about the family relationship and depressed mood came into sight, and a psychiatry consultation was arranged. Following that, she was diagnosed with major depressive disorder. After several days of Deanxit and tandospirone treatment, the patient's limb edema dramatically subsided. This is the first case of limb edema associated with depression. This highlights the importance of awareness of mental illness for non-psychiatrists, especially in patients with severe somatic symptoms, but with negative results.

Crosstalk between H1975 tumor cells and platelets to induce the proliferation, migration and tube formation of vascular endothelial cells.

Activated platelets (PLTs) participate in the regulation of tumor angiogenesis, and tumors can activate PLTs. Whether co-culture of lung carcinoma with PLTs improves the function of human umbilical vein endothelial cells (HUVECs) requires further investigation. The present study aimed to investigate the impact of H1975 cell crosstalk with PLTs on the proliferation, migration and tube formation of HUVECs. Following generation of cell-derived supernatants and construction of the co-culture system, Cell Counting Kit-8, flow cytometry, transmission electron microscopy and a meter for epithelial measurement were performed to detect the proliferative ability of HUVECs. Furthermore, the wound healing and Transwell migration assays were performed to detect the migratory ability of HUVECs. A tube formation assay was performed to assess angiogenesis, ELISA was applied to detect the content of vascular endothelial growth factor (VEGF) and western blotting was carried out to measure the expression levels of VEGF receptor 2 (VEGFR2) in HUVECs. Compared with single-cultured HUVECs (control), co-culture with H1975 cells and PLTs (Exp_HP) improved cell proliferation, increased the proportion of cells in the S-phase, destroyed the cell ultrastructure and decreased transepithelial electrical resistance in HUVECs. In addition, a higher relative migration rate, greater number of migrated cells, stronger tube-forming ability and increased expression of VEGF and VEGFR2 were detected in the Exp_HP group compared with the control group. The properties of HUVECs in Exp_H (co-cultured with H1975 cells) were similar to those in Exp_HP, but significantly weaker. Taken together, the results of the present study suggest that tumor cells interacting with PLTs may play an important role in tumor angiogenesis by affecting or mediating changes in the properties of vascular endothelial cells (VECs).

Amniotic Mesenchymal Stem Cells Decrease Aß Deposition and Improve Memory in APP/PS1 Transgenic Mice.

Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-ß peptide (Aß) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aß-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.

Disrupted-in-Schizophrenia-1 Attenuates Amyloid-ß Generation and Cognitive Deficits in APP/PS1 Transgenic Mice by Reduction of ß-Site APP-Cleaving Enzyme 1 Levels.

Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for a wide range of major mental disorders, including schizophrenia, major depression, and bipolar disorders. Recent reports suggest a potential role of DISC1 in the pathogenesis of Alzheimer's disease (AD), by referring to an interaction between DISC1 and amyloid precursor protein (APP), and to an association of a single-nucleotide polymorphism in a DISC1 intron and late onset of AD. However, the function of DISC1 in AD remains unknown. In this study, decreased levels of DISC1 were observed in the cortex and hippocampus of 8-month-old APP/PS1 transgenic mice, an animal model of AD. Overexpression of DISC1 reduced, whereas knockdown of DISC1 increased protein levels, but not mRNA levels of ß-site APP-Cleaving Enzyme 1 (BACE1), a key enzyme in amyloid-ß (Aß) generation. Reduction of BACE1 protein levels by overexpression of DISC1 was accompanied by an accelerating decline rate of BACE1, and was blocked by the lysosomal inhibitor chloroquine, rather than proteasome inhibitor MG-132. Moreover, overexpression of DISC1 in the hippocampus with an adeno-associated virus reduced the levels of BACE1, soluble Aß40/42, amyloid plaque density, and rescued cognitive deficits of APP/PS1 transgenic mice. These results indicate that DISC1 attenuates Aß generation and cognitive deficits of APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1. Our findings provide new insights into the role of DISC1 in AD pathogenesis and link a potential function of DISC1 to the psychiatric symptoms of AD.

Paeoniflorin inhibits human glioma cells via STAT3 degradation by the ubiquitin-proteasome pathway.

We investigated the underlying mechanism for the potent proapoptotic effect of paeoniflorin (PF) on human glioma cells in vitro, focusing on signal transducer and activator of transcription 3 (STAT3) signaling. Significant time- and dose-dependent apoptosis and inhibition of proliferation were observed in PF-treated U87 and U251 glioma cells. Expression of STAT3, its active form phosphorylated STAT3 (p-STAT3), and several downstream molecules, including HIAP, Bcl-2, cyclin D1, and Survivin, were significantly downregulated upon PF treatment. Overexpression of STAT3 induced resistance to PF, suggesting that STAT3 was a critical target of PF. Interestingly, rapid downregulation of STAT3 was consistent with its accelerated degradation, but not with its dephosphorylation or transcriptional modulation. Using specific inhibitors, we demonstrated that the prodegradation effect of PF on STAT3 was mainly through the ubiquitin-proteasome pathway rather than via lysosomal degradation. These findings indicated that PF-induced growth suppression and apoptosis in human glioma cells through the proteasome-dependent degradation of STAT3.

Downregulation of HTATIP2 expression is associated with promoter methylation and poor prognosis in glioma.

Glioma is an aggressive tumor with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of glioma. HTATIP2 is a novel tumor suppressor gene, which is frequently silenced by epigenetic mechanisms in many caners. However, the expression of HTATIP2 and how it is regulated in glioma are unknown. Hence, we assessed whether loss of HTATIP2 expression occurs in glioma, and, if so, what is the mechanism of such loss. We found that HTATIP2 expression was absent or diminished in primary gliomas compared with normal brain tissue. In vitro experiments showed that HTATIP2 expression could be restored via 5-aza-2'deoxycytidine treatment in U87 and U251 cell lines. Methyl-specific PCR indicated that the two cell lines and 60% primary gliomas carried aberrant methylated HTATIP2 alleles while normal brain tissue did not. Pyrosequencing confirmed these results and showed a higher density of methylation in the minimal promoter element, which contains four Sp1 binding sites in primary gliomas, than in normal brain tissue. Finally, we found that the overall survival was significantly higher in patients with positive HTATIP2 expression than those with loss of HTATIP2 expression. Overexpression of HTATIP2 inhibited glioma proliferation and growth in vitro. Taken together, the present study showed that loss of HTATIP2 expression was a frequent event in glioma and is associated with poor prognosis. Promoter methylation may be an underlying mechanism.