MiRNAs are involved in aberrant DNA methylation through regulation of DNA methyltransferases (DNMTs) in the pathogenesis and progression of glioblastomas (GBM). MiR-152-3p was down-expressed in human malignancies, and served as a tumor suppressor. Neurofibromatosis type 2 (NF2) was significantly decreased in GBM tissues with a high level of methylation. However, the link between miR-152-3p, DNMT1 and methylation of NF2 in GBM is not clearly established. This study was conducted to detect the mechanism between miR-152-3p, DNMT1 and NF2 in GBM. The levels of DNMT1 and NF2 expression were studied by qRT-PCR, Western blot, immunofluorescence, and immumohistochemical staining. Methylation in the promoter region of NF2 was detected by methylation-specific PCR and bisulfate genomic sequencing PCR. Cell proliferation was examined by Cell-Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assay, and cell invasion was evaluated by transwell assay. Flow cytomery and Hoechst staining were used to analyze cell apoptosis. A dual luciferase system was used to confirm the relationship between miR-152-3p and DNMT1. Methylation of NF2 and DNMT1 was markedly increased, and miR-152-3p was downregulated in GBM tissues and glioma cells. Both knockdown of DNMT1 and overexpression miR-152-3p showed that demethylation activated the expression of NF2. Furthermore, miR-152-3p directly targeted DNMT1. Both miR-152-3p overexpression and DNMT1 knockdown significantly induced cell apoptosis and inhibited invasive activity. This was also observed after NF2 overexpression. These results indicated that miR-152-3p can inhibit glioma cell proliferation and invasion activities by decreasing DNMT1. The restoration of miR-152-3p may have therapeutic application in the treatment of GBM.

Introduction: Sonodynamic therapy (SDT) has good targeting and non-invasive advantages in the treatment of solid cancers, and checkpoint blockade immunotherapy is also a promising treatment to cure cancer. However, their antitumor effects are not sufficient due to some inherent factors. Some studies that combined SDT with immunotherapy or nanoparticles have managed to enhance its efficiency to treat cancers. Methods: In this work, an effective therapeutic strategy that can potentiate the antitumor efficacy of anti-PD-L1 antibody (aPD-L1) is developed by the use of cascade immuno-sonodynamic therapy (immuno-SDT). Titanium dioxide (TiO₂), a nanostructured agent for SDT, sonosensitizer Chlorin e6 (Ce6), and immunological adjuvant CpG oligonucleotide (CpG ODN), are used to construct a multifunctional nanosonosensitizer (TiO₂-Ce6-CpG). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of TiO₂-Ce6-CpG under ultrasound (US) treatment. Results: The characterization tests showed that the nanosonosensitizers are polycrystalline structure with homogeneous sizes, resulting in a good drug loading efficiency. The innovative nanosonosensitizers (TiO₂-Ce6-CpG) can not only effectively inhibit tumor growth but also stimulate the immune system to activate the adaptive immune responses, using the TiO₂-Ce6 to augment SDT and the immune adjuvant CpG to enhance the immune response. After combined with the aPD-L1, the synergistic effect could not only efficiently inhibit the primary tumor growth but also lead to an inhibition of the non-irradiated pre-existing distant tumors by inducing a strong tumor-specific immune response. Conclusion: In this study, we present an effective strategy for tumor treatment by combining nanosonosensitizer-augmented SDT and aPD-L1 checkpoint blockade. This work provides a promising strategy and offers a new vision for treating malignant tumors.

A near-infrared (NIR)-responsive Aurod@pNIPAAm-PEGMA nanogel was synthesized in two steps, growing a PEGMA monolayer on the surface of gold nanorods (AuNRs), followed by in situ polymerization and cross-linking of N-iso-propylacrylamide (NIPAAm) and poly-(ethylene glycol)-methacrylate (PEGMA). The AuNRs and Aurod@pNIPAAm-PEGMA nanogel were characterized by UV–vis spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy, respectively. The lower critical solution temperature of the Aurod@pNIPAAm-PEGMA nanogel could be tuned by changing the molar ratio of NIPAAm/PEGMA. The NIR-mediated drug release behavior of the Aurod@pNIPAAm-PEGMA nanogel was studied with zinc phthalocyanines (ZnPc4) as a drug model. It was also demonstrated that the loaded ZnPc4 could keep the capability of generating singlet oxygen, and the in vitro study showed a great photodynamic therapy (PDT) effect on Hela cells. It thus indicated the potential of this Aurod@pNIPAAm-PEGMA nanogel for application as a drug carrier in PDT, which might make contributions to oncotherapy.

Background: Low‐grade gangliogliomas (GGs) are rare tumors of the central nervous system in adults. This study aims to define their characteristics, prognostic factors, and the impact of different treatment patterns on survival.Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the potential clinicopathological factors of low‐grade GGs in adult patients (age ≥18 years). Kaplan–Meier method and Cox regression model were utilized to evaluate the associations between variables and overall survival (OS).Results: A total of 703 adult patients diagnosed with low‐grade GGs were identified between 2004 and 2016, with a median follow‐up period of 60.0 months. The median age at diagnosis was 32.0 years, with 50.1% of patients being male, 84.2% white people, and 40.2% of married status. The predominant tumor site was located in temporal lobe (38.8%). The median OS time for the whole cohort was not reached. The 5‐ and 10‐year OS rates for patients underwent gross total resection (GTR) were 92.5% and 87.2%, respectively. Univariate and multivariate analysis showed age, gender, tumor site, and treatment pattern were significant factors for OS. The employment of adjuvant radiotherapy (RT) and/or chemotherapy would significantly shorten OS time.Conclusions: This is the largest retrospective study of adult low‐grade GGs up to date. Younger age, female gender, temporal lobe location, and GTR indicated better survival. Adjuvant RT and/or chemotherapy should not be considered after whatever surgery in adult patients with low‐grade GGs, unless the malignant transformation has been confirmed.

Although endovascular treatment is a promising approach, blood blister-like aneurysms (BBAs) still present treatment challenges. This study aimed to assess the effectiveness and safety of flow diverter device-assisted coiling (FDDAC) for the treatment of BBAs, which are broad based and friable with a high rebleeding risk. Eight patients (five females and three males) who presented with subarachnoid hemorrhages (SAH) due to BBA ruptures between May 2020 and May 2022 were retrospectively enrolled. All patients were treated by flow diverter device (Tubridge) adjunctive coil embolization using a semi-deploying technique. The demographic information, angiographic data, interval between admission and treatment, materials, therapy, clinical outcomes (including periprocedural and intraprocedural mortality and morbidity), and follow-up results of all patients were reviewed. The mean age of the patients with BBAs was 48.5 years (range 31–62 years); aneurysm sizes ranged from 2.2 × 1.7 mm to 4.6 × 3.2 mm, and the median Hunt–Hess score was 3. All aneurysms were completely closed at follow-up, and all 8 patients had excellent clinical outcomes (modified Rankin scores = 0–2) at discharge. Angiograms showed complete aneurysm occlusion after 6 months to 1 year. In addition, there were no cases of re-rupture, re-treatment, or recurrence of the aneurysms. FDDAC is safe to use in patients with BBAs and provides an alternative treatment option for this disease.

Impact of homogeneous and heterogeneous risk factors on the incidence and prognosis of brain metastases in patients with hepatocellular carcinoma Xiaoning Lin, Pengfei Zhang, Rong Huang, Yanlin Huang, Jin Sun, Huili Zheng, Xinhua Tian, Xiaomin Wang