Efficacy and safety of general anesthesia deep brain stimulation for dystonia: an individual patient data meta-analysis of 341 cases.

OBJECTIVE: The efficacy and safety of deep brain stimulation (DBS) under general anesthesia for the treatment of dystonia have not yet been confirmed with high level of evidence. This meta-analysis with pooled individual patient data aims to assess the clinical outcomes and identify the potential prognostic factors of dystonia patients who underwent general anesthesia DBS. METHODS: We searched PubMed, Web of Science, and Embase for articles describing patients with dystonia who underwent asleep DBS and had individual Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores. The relative improvement in BFMDRS scores was considered the primary outcome. Pearson correlation analyses and multivariate linear regression analysis were conducted to explore the prognostic factors. RESULTS: A total of 34 studies involving 341 patients were included. The mean postoperative improvement in BFMDRS-M (BFMDRS movement subscale) and BFMDRS-D (BFMDRS disability subscale) scores were 58.6±36.2% and 48.5±38.7% at the last follow-up visit, respectively, with a mean follow-up time of 22.4±27.6 months. Age at surgery and disease duration showed a negative correlation with the percent improvement of BFMDRS-M (%) at the last visit (r=-0.134, P=0.013; r=-0.165, P=0.006). In the stepwise multivariate regression, only disease duration remained a relevant factor. Additionally, the adverse events were acceptable. CONCLUSION: General anesthesia DBS is a safe, effective, and feasible option for dystonia patients in the long term. Shorter disease duration predicts better clinical outcomes.

Effect of microRNA-128 on cisplatin resistance of glioma SHG-44 cells by targeting JAG1.

This current study intends to investigate the effect of microRNA-128 (miR-128) on cisplatin (DDP) resistance in glioma SHG-44 cells. SHG-44/DDP cells were transfected with miR-128 antisense oligonucleotide (ASO) and assigned into blank, resistance, NC, anti-miR-128, miR-128 mimic, si-JAG1, and anti-miR-128 + si-JAG1 groups. qRT-PCR and Western blotting were employed for determining expression of miR-128, JAG1, Bax and Bcl-2. MTT assay, Giemsa staining, and flow cytometry were applied to detect DDP resistance, cellular morphology, and cell cycle, respectively. JAG1 is targeted and negatively regulated by miR-128. In in vitro experiments, compared with the blank group, the rest groups exhibited declined miR-28 and Bax expression, lowered cell inhibition rate and apoptosis rate, but elevated JAG1 and Bcl-2 expression with cells arrested in the S phase. Compared with the resistance group, the anti-miR-128 group showed decreasedBax expression along with a lowered cell inhibition rate and apoptosis rate, but increased JAG1 and Bcl-2 expression with reduced cells arrested in the S phase; while the miR-128 mimic group showed an opposite trend; the si-JAG1 group showed decreased Bcl-2 expression and reduced cells in the S phase. In in vivo experiments, compared with the resistance group, the tumor growth rate, tumor volume, and weight as well as JAG1 expression accelerated in the anti-miR-128 group; whereas the miR-128 mimic and si-JAG1 groups exhibited an opposite trend. Our findings demonstrated that miR-128 ASO transfection might down-regulate the expression of miR-128 in SHG-44/DDP and up-regulate the DDP resistance in SHG-44/DDP cells, providing a potential treatment target for glioma.

A Modified Dura Puncture Procedure to Reduce Brain Shift in Deep Brain Stimulation Surgery: One Institution's Experience.

Objective: The therapeutic effect of deep brain stimulation (DBS) surgery mainly depends on the accuracy of electrode placement and the reduction in brain shift. Among the standard procedures, cerebrospinal fluid (CSF) loss or pneumocephalus caused by dura incision (DI) is thought to be the main reason for brain shift and inaccuracy of electrode placement. In the current study, we described a modified dura puncture (DP) procedure to reduce brain shift and compare it with the general procedure of DBS surgery in terms of electrode placement accuracy. Materials and Methods: We retrospectively analyzed a series of 132 patients who underwent DBS surgery in Wuhan Union Hospital from December 2015 to April 2021. According to the different surgery procedures, patients were classified into two cohorts: the DI group (DI cohort) had 49 patients who receive the general procedure, and the DP group (DP cohort) had 83 patients who receive the modified procedure. Postoperative pneumocephalus volume (PPV) and CSF loss volume, electrode fusion error (EFE), and trajectory number were calculated. Meanwhile, intraoperative electrophysiological signal length (IESL), electrode implantation duration, and other parameters were analyzed. Results: In the current study, we introduced an improved electrode implantation procedure for DBS surgery named the DP procedure. Compared with the general DI cohort (n = 49), the modified DP cohort (n = 83) had a shorter electrode implantation duration (p < 0.0001), smaller PPV, lower CSF leakage volume (p < 0.0001), and smaller EFE (p < 0.0001). There was no significant difference in IESL (p > 0.05) or adverse events (perioperative cerebral haematoma, skin erosion, epilepsy, p > 0.05) between the two cohorts. Conclusion: The DP procedure is a modified procedure that can reduce brain shift and ensure implantation accuracy during DBS surgery without adverse events.

Growth factors contribute to the mediation of angiogenic capacity of glioma-associated mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are important components of stromal cell populations and serve a crucial role in tumor growth and progression. Previously, our laboratory successfully isolated and cultured MSCs from human glioma issues and demonstrated that glioma-associated mesenchymal stem cells (gb-MSCs) participate in and maintain tumor angiogenesis. Furthermore, growth factors, such as fibroblast growth factor and vascular endothelial cell growth factor, were demonstrated to be associated with endothelial cell tube formation. However, the effect of transforming growth factor ß1 (TGF-ß1) and platelet-derived growth factor-BB (PDGF-BB) on the angiogenic activity of gb-MSCs remains unknown. The present study aimed therefore to explore their effects in gb-MSCs angiogenesis. In the present study, gb-MSCs were isolated from patients with glioma and were characterized using flow cytometry and differentiation experiments. Furthermore, the results from tube formation assay revealed that TGF-ß1 and PDGF-BB could mediate the angiogenic capacity of gb-MSCs in vitro. In addition, results from immunofluorescence demonstrated that gb-MSCs expressed TGF-ß1R and PDGFR, which are the receptors for TGF-ß1 and PDGF-BB, respectively. Taken together, these findings indicated that TGF-ß1 and PDGF-BB may serve a crucial role in mediating gb-MSC angiogenesis, which might provide a therapeutic strategy for targeting the angiogenic capacity of gb-MSCs in patients with glioma.

Cell fusion in cancer hallmarks: Current research status and future indications.

Cell fusion is involved in several physiological processes, such as reproduction, development and immunity. Although cell fusion in tumors was reported 130 years ago, it has recently attracted great interest, with recent progress in tumorigenesis research. However, the role of cell fusion in tumor progression remains unclear. The pattern of cell fusion and its role under physiological conditions are the basis for our understanding of the pathological role of cell fusion. However, the role of cell fusion in tumors and its functions are complicated. Cell fusion can directly increase tumor heterogeneity by forming polyploids or aneuploidies. Several studies have reported that cell fusion is associated with tumorigenesis, metastasis, recurrence, drug resistance and the formation of cancer stem cells. Given the diverse roles cell fusion plays in different tumor phenotypes, methods based on targeted cell fusion have been designed to treat tumors. Research on cell fusion in tumors may provide novel ideas for further treatment.

CD90low glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells.

BACKGROUND: The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. METHODS: Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. RESULTS: Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. CONCLUSIONS: CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.

Roles of long non-coding RNAs in the hallmarks of glioma.

Glioma is one of the most common types of tumor of the central nervous system. Due to the aggressiveness and invasiveness of high-level gliomas, the survival time of patients with these tumors is short, at ~15 months, even after combined treatment with surgery, radiotherapy and/or chemotherapy. Recently, a number of studies have demonstrated that long non-coding RNA (lncRNAs) serve crucial roles in the multistep development of human gliomas. Gliomas acquire numerous biological abilities during multistep development that collectively constitute the hallmarks of glioma. Thus, in this review, the roles of lncRNAs associated with glioma hallmarks and the current and future prospects for their development are summarized.

Dehydrocavidine attenuates d-galactose induced learning and memory impairment in rats.

OBJECTIVE: Dehydrocavidine (DEH) is the major component of a plant corydalis saxicola Bunting, which is used to treat the patients with hepatic disorders, there is still no report about the effect of DEH on the brain disorder. In this study, the effect and mechanism of DEH on d-galactose (d-gala) induced learning and memory impairment in rats was investigated. METHODS: A learning and memory impairment rat model was employed by chronic intraperitoneal injection of d-gala and intragastric administration of DEH, then Morris water maze test was used to investigate the effect of DEH on learning and memory impairment, Golgi stain and biochemical methods, real time PCR were used to investigate underlying mechanism. RESULTS: Intraperitoneal injection of d-gala could induced severe learning and memory impairment in rats, intragastric administration of DEH could effectively attenuates these deficits. Golgi staining showed DEH supplementary could restored the density of spines to 5.7±1.16 spines per 10µm in the DEH+d-gala group (p<0.05). DEH supplementary administration reversed the lipid peroxides and restored the enzymes activities to reduce oxidative damage (p<0.05). DEH supplementary administration could reduced the production of NO and PGE2 and the mRNA expression of iNOS and COX-2 (p<0.05). CONCLUSIONS: DEH could attenuates d-gala induced learning and memory impairment in rats by enhancing synaptic plasticity, reducing oxidative damage and limiting the neuroinflammation.

Current status and potential challenges of mesenchymal stem cell-based therapy for malignant gliomas.

Glioma, which accounts for more than 30% of primary central nervous system tumours, is characterised by symptoms such as headaches, epilepsy, and blurred vision. Glioblastoma multiforme is the most aggressive, malignant, and lethal brain tumour in adults. Even with progressive combination treatment with surgery, radiotherapy, and chemotherapy, the prognosis for glioma patients is still extremely poor. Compared with the poor outcome and slowly developing technologies for surgery and radiotherapy, the application of targeted chemotherapy with a new mechanism has become a research focus in this field.Moreover, targeted therapy is promising for most solid tumours. The tumour-tropic ability of stem cells, including neural stem cells and mesenchymal stem cells, provides an alternative therapeutic approach. Thus, mesenchymal stem cell-based therapy is based on a tumour-selective capacity and has been thought to be an effective anti-tumour option over the past decades. An increasing number of basic studies on mesenchymal stem cell-based therapy for gliomas has yielded complex outcomes.In this review, we summarise the biological characteristics of human mesenchymal stem cells, and the current status and potential challenges of mesenchymal stem cell-based therapy in patients with malignant gliomas.

CD90 determined two subpopulations of glioma-associated mesenchymal stem cells with different roles in tumour progression.

Human glioma-associated mesenchymal stem cells (gbMSCs) are the stromal cell components that contribute to the tumourigenesis of malignant gliomas. Recent studies have shown that gbMSCs consist of two distinct subpopulations (CD90+ and CD90- gbMSCs). However, the different roles in glioma progression have not been expounded. In this study, we found that the different roles of gbMSCs in glioma progression were associated with CD90 expression. CD90high gbMSCs significantly drove glioma progression mainly by increasing proliferation, migration and adhesion, where as CD90low gbMSCs contributed to glioma progression chiefly through the transition to pericytes and stimulation of vascular formation via vascular endothelial cells. Furthermore, discrepancies in long non-coding RNAs and mRNAs expression were verified in these two gbMSC subpopulations, and the potential underlying molecular mechanism was discussed. Our data confirm for the first time that CD90high and CD90low gbMSCs play different roles in human glioma progression. These results provide new insights into the possible future use of strategies targeting gbMSC subpopulations in glioma patients.