Multimodal evaluation of the bloodstream alteration before and after combined revascularization for Moyamoya disease.

Objective: This study aimed to explore the hemodynamic changes before and after anastomosis in patients with Moyamoya disease (MMD) using multiple models. Methods: We prospectively enrolled 42 MMD patients who underwent combined revascularization. Intraoperative FLOW800 was performed before and after anastomosis, and parameters was collected, including maximum intensity, delay time, rise time, slope, blood flow index, and microvascular transit time (MVTT). Additionally, preoperative and postoperative hemodynamic parameters were measured using color Doppler ultrasonography (CDUS), including peak systolic velocity, end-diastolic velocity, resistance index (RI), pulsatility index (PI), and flow volume. Subsequently, the correlation between FLOW800 and CDUS parameters was explored. Results: A total of 42 participants took part with an average age of 46.5 years, consisting of 19 men and 23 women. The analysis of FLOW800 indicated that both the delay time and rise time experienced a substantial decrease in both the recipient artery and vein. Additionally, the MVTT was found to be significantly reduced after the surgery (5.7 ± 2.2 s vs. 4.9 ± 1.6, p = 0.021). However, no statistically significant differences were observed among the other parameters. Similarly, all postoperative parameters in CDUS hemodynamics exhibited significant alterations in comparison to the preoperative values. The correlation analysis between FLOW800 and CDUS parameters indicated a significant association between MVTT and RI and PI, no significant relationships were found among the other parameters in the two groups. Conclusion: The hemodynamic outcomes of the donor and recipient arteries demonstrated significant changes following bypass surgery. The parameter of time appears to be more precise and sensitive in assessing hemodynamics using FLOW800. Multiple evaluations of hemodynamics could offer substantial evidence for perioperative management.

Adipose-derived stem cell-derived extracellular vesicles inhibit neuroblastoma growth by regulating GABBR1 activity through LINC00622-mediated transcription factor AR.

Neuroblastoma (NB) is a huge threat to children's health. Adipose-derived stem cells-derived extracellular vesicles (ADSC-Evs) can regulate tumor progression. This study aimed to identify the role of ADSC-Evs in NB. Following ADSC-Ev isolation and identification, PKH26-labeled ADSC-Evs were cocultured with NB cells to observe the internalization of ADSC-Evs. ADSC-Ev effects on NB cell proliferation, invasion, and migration were assessed. The regulatory molecules related to NB development were predicted. The expressions of and relations among LINC00622, transcriptional factor androgen receptor (AR), and gamma-aminobutyric acid B-type receptor 1 (GABRR1) were detected and verified. LINC00622 was inhibited in ADSCs to evaluate ADSC-Ev effects on NB cells. Xenograft tumor experiment in nude mice was further performed to evaluate the effects of ADSC-Evs-carried LINC00622 on NB in vivo. ADSC-Evs inhibited NB cell proliferation, invasion, and migration. ADSC-Evs increased GABBR1 expression in NB cells. ADSC-Evs-carried LINC00622 mediated AR to promote GABBR1 expression. Silencing LINC00622 in ADSCs weakened the inhibition of ADSC-Evs on NB cell malignant behaviors. ADSC-Evs reduced tumor growth in nude mice, which was restored after inhibiting LINC00622 expression in ADSCs. We highlighted that ADSC-Evs carried LINC00622 into NB cells to inhibit transcription factor AR and promote GABBR1 expression, thus inhibiting NB cell growth.

Enhancement of Neural Stem Cell Proliferation in Rats with Spinal Cord Injury by a Combination of Repetitive Transcranial Magnetic Stimulation (rTMS) and Human Umbilical Cord Blood Mesenchymal Stem Cells (hUCB-MSCs).

BACKGROUND This study was designed to explore the combined effects of repetitive transcranial magnetic stimulation (rTMS) and human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) transplantation on neural stem cell proliferation in rats with spinal cord injury (SCI). MATERIAL AND METHODS SCI was induced in 90 rats by laminectomy at T10. Fifteen rats each were treated with 0.5 Hz rTMS or 10 Hz rTMS or underwent hUCB-MSC transplantation; 15 each were treated with 0.5 Hz rTMS+hUCB-MSCs or 10 Hz rTMS+hUCB-MSCs; and 15 were untreated (control group). The Basso, Beattie, and Bresnahan (BBB) scores and motor evoked potentials (MEPs) were measured, and all rats underwent biotin dextran-amine (BDA) tracing of the corticospinal tract (CST). The levels of expression of neural stem cell proliferation related proteins, including BrdU, nestin, Tuj1, Ng2+ and GFAP, were measured, and the levels of bFGF and EGF determined by Western blotting. RESULTS BBB scores and MEPs were increased after rTMS and hUCB-MSC transplantation, while histologically determined SCI-induced neuron apoptosis was attenuated. The numbers of BDA-positive fibers and Brdu-, nestin- and Tuj1-positive cells were markedly increased and the numbers of Ng2+- and GFAP-positive cells were markedly decreased following treatment with rTMS alone or rTMS plus hUCB-MSC transplantation. The levels of expression of bFGF and EGF were significantly upregulated following rTMS treatment and hUCB-MSC transplantation. Higher performance was observed after combined treatment with rTMS and hUCB-MSC transplantation than after either alone. CONCLUSIONS The combination of rTMS treatment and hUCB-MSC transplantation could attenuate SCI-induced neural stem cell apoptosis and motor dysfunction in rats.

FGD5-AS1 facilitates glioblastoma progression by activation of Wnt/ß-catenin signaling via regulating miR-129-5p/HNRNPK axis.

AIMS: Accumulating evidence elucidates the biological significance of long non-coding RNA (lncRNAs) in tumorigenesis and development. FGD5 antisense RNA 1 (FGD5-AS1) was previously revealed as an oncogene in several types of malignancies. However, the roles of FGD5-AS1 in glioblastoma (GBM) and its potential molecular mechanisms remain unclear. MATERIALS AND METHODS: The expression of FGD5-AS1, miR-129-5p, and heterogeneous nuclear ribonucleoprotein K (HNRNPK) mRNA were measured by qRT-PCR. Cell proliferation, invasion and apoptosis were determined by MTT, colony formation, transwell and flow cytometry assays. The protein levels of Ki-67, HNRNPK and Wnt signaling-associated genes were examined by western blot assay. The possible action mechanism of FGD5-AS1 was detected by bioinformatic tools, luciferase reporter, RIP and TOP/FOP Flash reporter assays. A nude mouse xenograft model was built to analyze the function of FGD5-AS1 in vivo. KEY FINDINGS: FGD5-AS1 expression was increased in GBM tumor tissues and cells. Knockdown of FGD5-AS1 inhibited cell proliferation and invasion in vitro, and slowed tumor growth in vivo. Mechanistically, FGD5-AS1 served as a sponge of miR-129-5p to relieve its suppression on HNRNPK. Moreover, down-regulation of HNRNPK repressed cell proliferation and invasion, while enhanced apoptosis. Additionally, si-FGD5-AS1-mediated suppression of cell proliferation and invasion was obviously reversed by the decrease of miR-129-5p or restoration of HNRNPK. Furthermore, FGD5-AS1 promoted cell growth and invasion by stimulating Wnt/ß-catenin signaling via regulation of miR-129-5p/HNRNPK. SIGNIFICANCE: FGD5-AS1 promoted GBM progression at least partly by regulating miR-129-5p/HNRNPK to activate Wnt/ß-catenin signaling, suggesting the potential of FGD5-AS1 as a candidate target to improve GBM therapy.

Long Non-Coding RNA HOXA-AS2 Enhances The Malignant Biological Behaviors In Glioma By Epigenetically Regulating RND3 Expression.

INTRODUCTION: Long non-coding RNAs (LncRNAs) have been demonstrated to play a vital role in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2), a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes, is identified as an oncogene in several malignancies, including glioma. However, the biological functions of HOXA-AS2 and its underlying molecular mechanisms in glioma progression remain to be investigated. METHOD: The expression of HOXA-AS2 and RND3 mRNA was determined using qRT-PCR analysis. The protein level of RND3 and EZH2 was measured by Western blot analysis. The biological function of HOXA-AS2 or RND3 in glioma was detected by CCK-8 assay, colony formation assays, transwell assay, and flow cytometry. Dual-luciferase reporter, RIP, RNA-protein pull down and ChIP assays were performed to explore the molecular mechanism of HOXA-AS2 in glioma. The effect of HOXA-AS2 in vivo was examined using xenograft tumor assay. RESULTS: HOXA-AS2 expression was increased in glioma tissues and cells. High HOXA-AS2 expression was associated with larger tumor size and advanced pathological stage. Functionally, knockdown of HOXA-AS2 suppressed cell proliferation and invasion, and promoted apoptosis. Mechanically, HOXA-AS2 epigenetically inhibited RND3 transcription by binding to EZH2. Moreover, overexpression of RND3 exerted similar tumor-suppressive effects to the depletion of HOXA-AS2. Furthermore, the anti-cancer effects induced by si-HOXA-AS2 were greatly reversed by silencing of RND3. Finally, knockdown of HOXA-AS2 impaired tumor growth in vivo possibly via increasing RND3 expression. CONCLUSION: Taken together, HOXA-AS2 recruits EZH2 to the promoter region of RND3 and inhibits its expression, thereby facilitating glioma progression. Our findings provide a prospective therapeutic strategy for glioma intervention.

PAS Domain Containing Repressor 1 (PASD1) Promotes Glioma Cell Proliferation Through Inhibiting Apoptosis In Vitro.

BACKGROUND PAS domain containing repressor 1 (PASD1), the cancer-testis antigen (CTA), has been reported to be aberrantly expressed in various cancer tissues and cancer cell lines; however, normal PASD1 expression can be detected in normal tissue, excluding testicular tissue. Moreover, PASD1 is reported to be abnormally expressed in various malignant tumors. However, it remains unclear whether PASD1 participates in tumorigenesis of glioma. MATERIAL AND METHODS PASD1 expression was detected by immunohistochemistry in 155 glioma tissue specimens in this study. Furthermore, the relationship of PASD1 expression with clinicopathological features in glioma cases was statistically analyzed. In addition, PASD1 was knocked down by small interference RNA (shRNA) in glioma cell line (LN229), so as to assess the potential to use it as the target for treating glioma. RESULTS Our findings suggested that PASD1 expression in glioma patients was extremely upregulated compared with that in normal tissue samples and cell lines. Moreover, PASD1 expression was found to be markedly correlated with gender, The World Health Organization grade and p53 expression; in addition, high PASD1 expression indicated poor prognosis for glioma patients. Additionally, downregulation of PASD1 inhibited the proliferation ability of cells and resulted in cell arrest at the G2/M phase, which was achieved through accelerating apoptosis. Furthermore, our results indicated that PASD1 downregulation could upregulate some apoptosis-modulating proteins at the same time it downregulated some cycle-regulating proteins. CONCLUSIONS Taken together, our findings demonstrated that PASD1, an oncogene, can potentially serve as an independent prognostic factor for glioma patients.

Design, synthesis and antiproliferative evaluation of novel sulfanilamide-1,2,3-triazole derivatives as tubulin polymerization inhibitors.

Microtubule as an important target in the cancer therapy was used to design novel tubulin polymerization inhibitors. Sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and their antiproliferative activity against three selected cancer cell lines (BGC-823, MGC-803 and SGC-7901) were evaluated. All sulfanilamide-1,2,3-triazole hybrids displayed potent inhibitory activity against all cell lines. In particular, compound 10b showed the most excellent inhibitory effect against MGC-803 cells, with an IC50 value of 0.4 µM. Cellular mechanism studies elucidated that 10b induced apoptosis by decreasing the expression level of Bcl-2 and Parp and increasing the expression level of BAX. 10b inhibited the epithelial-mesenchymal transition process by up-regulating E-cadherin and down-regulating N-cadherin. Furthermore, the tubulin polymerization inhibitory activity in vitro of 10b was 2.4 µM. In vivo anticancer assay, 10b effectively inhibited MGC-803 xenograft tumor growth without causing significant loss of body weight. These sulfanilamide-1,2,3-triazole hybrids as potent tubulin polymerization inhibitors might be used as promising candidates for cancer therapy.