Enhancing X-Ray Sensitization with Multifunctional Nanoparticles.

In the progression of X-ray-based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.

Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1.

Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and proteomic analyses were subsequently performed to determine the mRNA and protein expression profiles of pancreatic samples from SAP and AP model and normal mice. To explore the role of Hspb1 in SAP, we used Hspb1 knockout (KO) mice, a genetically engineered chronic pancreatitis strain (T7D23A), Anxa2 KO mice, and acinar cell-specific Prdx1 knockout mice. Additionally, various in vivo and in vitro assays were performed to elucidate the molecular events and direct targets of Hspb1 in acinar cells. We found that Hspb1 expression was upregulated in AP samples but significantly reduced in acinar cells from SAP samples. KO or inhibition of Hspb1 worsened AP, while AAV8-Hspb1 administration mitigated the severity of SAP and reduced remote organ damage in mice. Furthermore, AAV8-Hspb1 treatment prevented the development of chronic pancreatitis. We found that KO or inhibition of Hspb1 promoted acinar cell death through apoptosis and ferroptosis but not necroptosis or autophagy by increasing reactive oxygen species (ROS) and lipid ROS levels. Mechanistically, Hspb1 directly interacted with Anxa2 to decrease its aggregation and phosphorylation, interact with the crucial antioxidant enzyme Prdx1, and maintain its antioxidative activity by decreasing Thr-90 phosphorylation. Notably, the overexpression of Hspb1 did not have a protective effect on acinar-specific Prdx1 knockout mice. In summary, our findings shed light on the role of Hspb1 in acinar cells. We showed that targeting Hspb1/Anxa2/Prdx1 could serve as a potential therapeutic strategy for SAP.

Safe Induction of Acute Inflammation with Enhanced Antitumor Immunity by Hydrogel-Mediated Outer Membrane Vesicle Delivery.

Acute inflammation has the potential for the recruitment of immune cells, inhibiting tumor angiogenesis, metastasis, and drug resistance thereby overcoming the tumor immunosuppressive microenvironment caused by chronic inflammation. Here, an acute inflammation inducer using bacteria outer membrane vesicles (OMVs) loaded in thermal-sensitive hydrogel (named OMVs-gel) for localized and controlled release of OMVs in tumor sites is proposed. OMVs trigger neutrophil recruitment and amplify acute inflammation inside tumor tissues. The hydrogel ensures drastic inflammation is confined within the tumor, addressing biosafety concerns that the direct administration of free OMVs may cause fatal effects. This strategy eradicated solid tumors safely and rapidly. The study further elucidates one of the possible immune mechanisms of OMVs-gel therapy, which involves the assembly of antitumor neutrophils and elastase release for selective tumor killing. Additionally, tumor vascular destruction induced by OMVs-gel results in tumor darkening, allowing for combinational photothermal therapy. The findings suggest that the use of OMVs-gel can safely induce acute inflammation and enhance antitumor immunity, representing a promising strategy to promote acute inflammation application in tumor immunotherapy.

Construction of self-repairing polyethersulfone membrane with high density hydrophilic microregions by two dimensional restricted channels for enhanced dyes/salts selective separation.

Based on the dye/salts separation efficiency and membrane injury caused by serious pollution of dye/salts wastewater, this study constructed a 2D tight ultrafiltration membrane that could both solve the membrane injury problem and improve the dye/salts separation efficiency, the compatibility of good self-healing performance and penetration performance by 2D material magnesium-aluminum Layered double hydroxide (MgAl-LDH). The self-repairing of physical injury was achieved through the swelling effect of AMPS-PAN, this property was proved by permeate flux, the retention performance of salts in dye/salts solution, the comparison of scanning electron microscope (SEM), and the mechanical strength after physical injury. The healing of chemical injury occured through the reaction of CC and polyethersulfone chain breakage, which was confirmed by X-ray photoelectron spectroscopy (XPS), permeate flux, the retention performance of salts in dye/salts solution, and mechanical property. The high separation efficiency of dye/salts was achieved through 2D material MgAl-LDH, which was proved by separation selectivity ɑ. The compatibility of good self-healing performance and penetration performance was obtained by 2D material MgAl-LDH, which was proved by the penetration and self-healing performance. Morever, the membrane illustrated excellent both permeability and dye/sals separation efficiency, just like the permeate flux, the retention performance of sodium sulfate in methyl blue/sodium sulfate solution, the retention performance of Na2SO4 in methyl blue/Na2SO4 solution, the retention rate of methyl blue were 99.1 L/m2h, 12.5%, 7.9%, 97.7%, respectively. The results of pollution index and contact angle also proved that the membrane had anti-pollution performance.

Biomimetic nanodecoys deliver cholesterol-modified heteroduplex oligonucleotide to target dopaminergic neurons for the treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) aggregates called Lewy bodies leading to the gradual loss of dopaminergic (DA) neurons in the substantia nigra. Although α-syn expression can be attenuated by antisense oligonucleotides (ASOs) and heteroduplex oligonucleotide (HDO) by intracerebroventricular (ICV) injection, the challenge to peripheral targeted delivery of oligonucleotide safely and effectively into DA neurons remains unresolved. Here, we designed a new DNA/DNA double-stranded (complementary DNA, coDNA) molecule with cholesterol conjugation (Chol-HDO (coDNA)) based on an α-syn-ASO sequence and evaluated its silence efficiency. Further, Chol-HDO@LMNPs, Chol-HDO-loaded, cerebrovascular endothelial cell membrane with DSPE-PEG2000-levodopa modification (L-DOPA-CECm)-coated nanoparticles (NPs), were developed for the targeted treatment of PD by tail intravenous injection. CECm facilitated the blood-brain barrier (BBB) penetration of NPs, together with cholesterol escaped from reticuloendothelial system uptake, as well as L-DOPA was decarboxylated into dopamine which promoted the NPs toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that the nanodecoys improved the efficacy of HDO on PD mice. These findings provide insights into the development of biomimetic nanodecoys loading HDO for precise therapy of PD. STATEMENT OF SIGNIFICANCE: The accumulation of α-synuclein (α-syn) aggregates is a hallmark of PD. Our previous study designed a specific antisense oligonucleotide (ASO) targeting human SNCA, but the traumatic intracerebroventricular (ICV) is not conducive to clinical application. Here, we further optimize the ASO by creating a DNA/DNA double-stranded molecule with cholesterol-conjugated, named Chol-HDO (coDNA), and develop a DA-targeted biomimetic nanodecoy Chol-HDO@LMNPs by engineering cerebrovascular endothelial cells membranes (CECm) with DSPE-PEG2000 and L-DOPA. The in vivo results demonstrated that tail vein injection of Chol-HDO@LMNPs could target DA neurons in the brain and ameliorate motor deficits in a PD mouse model. This investigation provides a promising peripheral delivery platform of L-DOPA-CECm nanodecoy loaded with a new Chol-HDO (coDNA) targeting DA neurons in PD therapy.

Multiple delivery strategies of nanocarriers for myocardial ischemia-reperfusion injury: current strategies and future prospective.

Acute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions to restore blood flow can rapidly relieve acute myocardial ischemia, but the ensuing myocardial ischemia-reperfusion injury (MI/RI) and subsequent heart failure have become medical challenges that researchers have been trying to overcome. The pathogenesis of MI/RI involves several mechanisms, including overproduction of reactive oxygen species, abnormal mitochondrial function, calcium overload, and other factors that induce cell death and inflammatory responses. These mechanisms have led to the exploration of antioxidant and inflammation-modulating therapies, as well as the development of myocardial protective factors and stem cell therapies. However, the short half-life, low bioavailability, and lack of targeting of these drugs that modulate these pathological mechanisms, combined with liver and spleen sequestration and continuous washout of blood flow from myocardial sites, severely compromise the expected efficacy of clinical drugs. To address these issues, employing conventional nanocarriers and integrating them with contemporary biomimetic nanocarriers, which rely on passive targeting and active targeting through precise modifications, can effectively prolong the duration of therapeutic agents within the body, enhance their bioavailability, and augment their retention at the injured myocardium. Consequently, these approaches significantly enhance therapeutic effectiveness while minimizing toxic side effects. This article reviews current drug delivery systems used for MI/RI, aiming to offer a fresh perspective on treating this disease.

Bacteria-based immunotherapy for cancer: a systematic review of preclinical studies.

Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response via various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.

Coaxial electrostatic spray-based preparation of localization missile liposomes on a microfluidic chip for targeted treatment of triple-negative breast cancer.

Due to triple-negative breast cancer (TNBC) lacking specific targets for efficient therapies, nanoparticles have been widely developed to enhance efficacy and reduce the toxicity of chemotherapeutics. We prepared unique liposomes containing PTX and DOX by microfluidics-based coaxial electrostatic spray method, which have a uniform particle size, high drug loading capacity, and good stability. Meanwhile, the cRGD peptide was fused with the lipid membrane to form PTX/DOX@cRGD-Lipo, which played a GPS role in locating tumor neovascularization and further targeting TNBC cells where both overexpress αvß3. The PTX/DOX@cRGD-Lipo showed synergistic anti-tumor activity of double drugs and enhanced tumor cell apoptosis. Fluorescence microscopy and flow cytometry showed that the co-loaded targeted liposomes could be effectively absorbed by MDA-MB-231 and 4T1 cells and then released the content. In addition, the PTX/DOX@cRGD-Lipo presented excellent targeting biodistribution in vivo and a higher tumor growth inhibition rate in the orthotopic tumor mouse model. All results suggested that the double drug-loaded targeted liposome could be a promising treatment modality for TNBC.

Enhanced protection against hypoxia/reoxygenation-induced apoptosis in H9c2 cells by puerarin-loaded liposomes modified with matrix metalloproteinases-targeting peptide and triphenylphosphonium.

Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustained-release behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP double-modified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-α and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE.

Knowledge mapping of syringomyelia from 2003 to 2022: A bibliometric analysis.

BACKGROUND: Syringomyelia is a chronic, progressive disease of the spinal cord. Syringomyelia is an etiologically diverse affliction caused by disturbance of normal cerebrospinal fluid flow dynamics. Lesions are characterized by the formation of tubular cavities in the gray matter of the spinal cord and gliosis; however, the etiology is unknown and treatment methods differ. Many existing studies have focused on the relationship between other diseases and syringomyelia. There is a lack of comprehensive and objective reports on the research status of syringomyelia. Therefore, this study aimed to conduct a bibliometric analysis to quantify studies on Syringomyelia and trending issues in the last 20 years. METHODS: Articles were acquired from the Web of Science Core Collection database. We used the Library Metrology online analysis platform, BICOMB, gCLUTO, CiteSpace bibliometrics tools for analysis, VOSviewer 1.6.16 (Nees Jan van Eck and Ludo Waltman, 2010), and Microsoft Excel 2019 to perform bibliometric analysis and visualization. Individual impact and collaborative information were quantified by analyzing annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. We then identified the trending research areas of syringomyelia by analyzing the co-occurrence of keywords and co-cited references. RESULTS: From January 2003 to August 2022, 9,556 authors from 66 countries published a total of 1,902 research articles on syringomyelia in 518 academic journals. Most publications come from the United States, China, the United Kingdom, and Japan, with the United States dominating. Nanjing University and the University of Washington are the most active institutions, Dr. Claire Rusbridge has published the most papers, and Miholat has the most co-citations. The Journal of Neurosurgery has the highest number of co-cited articles, which are mainly in the fields of neurology, surgery, and biology. High-frequency keywords included syringomyelia, Chiari-I malformation, children, surgical treatment, and spinal cord. CONCLUSIONS: The number of articles on syringomyelia has increased steadily over the past two decades. At present, research on syringomyelia is mainly focused on the age of onset, potential therapeutic interventions, surgical treatment, avoidance of recurrence, and delay of pain. The use of surgical treatment of the disease and the mechanism of further treatment are the current hot research topics. The correlation between trauma and congenital factors, translational application, the effect of surgical treatment, postoperative recurrence, and complications are further hot research areas. These may provide ideas for further research into a radical cure for syringomyelia.

Bacterial outer membrane vesicles-based therapeutic platform eradicates triple-negative breast tumor by combinational photodynamic/chemo-/immunotherapy.

Bacterial outer membrane vesicles (OMVs) are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine. In this study, OMVs are demonstrated as promising antitumor therapeutics. OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity, but the therapeutic window of OMVs is narrow for its toxicity. We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) into OMVs as a therapeutic platform. We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform, providing combinational photodynamic/chemo-/immunotherapy, eradicates triple-negative breast tumors in mice without side effects. Importantly, this strategy also effectively prevents tumor metastasis to the lung. This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.

Functional insights from targeted imaging BACE1: the first near-infrared fluorescent probe for Alzheimer's disease diagnosis.

BACKGROUND: ß-Secretase (BACE1) is the vital enzyme in the pathogenic processes of Alzheimer's disease (AD). However, the development of a powerful tool with sensitivity for BACE1 determination in vivo is a challenge. METHODS: A novel NIR fluorescent probe HBAE was synthetized from 2-hydroxy-3-methylbenzaldehyde and 2-amino-benzenethiol by 5 steps. The fluorescence mechanism in the ESIPT systems of HBAE probe was insighted with time-dependent density functional theory (TD-DFT) at the TDPBE0 level with the def2-TZVP approach. The corresponding docking between HBAE and BACE1 (PDB: 5I3Y) was performed through the ducking method by DOCK6.8. Then the BBB permeability of HBAE is verified by transwell orifice plate. 22-month-old male AD-model (5XFAD) mice and age-matched wild-type mice were employed to observe the brain kinetics by intravenous injection. Finally, Immunohistochemistry was performed on the AD brain section to reveal the levels of BACE1 in hippocampus and cortex areas and other regions in AD mice through the brain tissue slices by HBAE. RESULTS: The NIR fluorescent probe HBAE was successfully applied in imaging BACE1 in AD model mice. The capability of HBAE in reflecting different level of BACE1 was performed by the specific imaging of the hippocampus region. CONCLUSIONS: We reported the first ESIPT near-infrared fluorescence probe HBAE for monitoring endogenous BACE1 in the AD live model mice, thus offering a versatile chemical tool for visualizing in the pathological processes of AD live brains. Remarkably, high resolution images showed the localization of red fluorescence stains in hippocampus of the AD brain. This study provides a promising way for functional insights from protein BACE1 in vivo.

Insight into the nature of the noncovalent interactions of furan, pyridine, and pyrazine with AtX.

CONTEXT: The σ-hole, counterintuitive σ-hole, and lone pair-π interaction complexes formed between three heterocyclic compounds (C4H4O, C5H5N, and C4H4N2) and AtX (X = F, Cl, and Br) have been investigated with the MP2/aug-cc-pVTZ. The intensity of three noncovalent interactions formed by different heterocyclic compounds was compared, and the properties of these three noncovalent interactions were discussed. SAPT analysis shows that the electrostatic energy is dominant to the stronger interactions in the σ-hole and counterintuitive σ-hole complexes, while the dispersion energy is the main force responsible for the weaker interactions in the lone pair-π complexes. NBO analysis has also been employed. METHODS: All the structures were optimized at the MP2/aug-cc-pVTZ (aug-cc-pVTZ-pp for Br to account for relativistic effects) level using the Gaussian 03W package (Gaussian, Inc., Wallingford, CT, USA). The basis bet superposition error (BSSE) is corrected using counterpoise method proposed by Boys and Bernardi. The NBO population analysis was carried out. The molecular electrostatic surface potentials of monomers were calculated by WFA-SAS program package. The interaction energies of the three types complexes were decomposed by using the symmetric adaptive perturbation theory SAPT of the open source ab initio electronic structure software package psi 4.0.0-beta5.

Nonviral delivery systems for antisense oligonucleotide therapeutics.

Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery.

Apoptotic bodies for advanced drug delivery and therapy.

Extracellular vesicles (EVs) have emerged as promising candidates for multiple biomedical applications. Major types of EVs include exosomes, microvesicles, and apoptotic bodies (ABs). ABs are conferred most properties from parent cells in the final stages of apoptosis. A wide variety of sources and stable morphological features are endowed to ABs by the rigorous apoptotic program. ABs accommodate more functional biomolecules by relying on the larger volume and maintaining their naturalness in circulation. The predominant body surface ratio of ABs facilitates their recognition by recipient cells and is advantageous for interactions with microenvironments. ABs can modulate and alleviate symptoms of numerous diseases for their origins, circulation, and high biocompatibility. In addition, ABs have been emerging in disease diagnosis, immunotherapy, regenerative therapy, and drug delivery. Here, we aim to present a thorough discussion on current knowledge about ABs. Of particular interest, we will summarize the application of AB-based strategies for diagnosis and disease therapy. Perspectives for the development of ABs in biomedical applications are highlighted.

Analysis of neuroendoscopy for the treatment of macroadenomas and giant pituitary adenomas.

Objective: This study investigated the use and effectiveness of endoscopic transnasal, transsphenoidal surgery, a minimally invasive method for the treatment of macroadenomas and giant pituitary a denomas, in a medical setting. The surgical results of 429 patients who received neuroendoscopic treatment of macroadenomas or giant pituitary adenomas were evaluated, and the experiences and lessons learned from treatment complications were assessed. Patients and methods: From January 2012 to December 2021, 429 patients with macroadenomas or giant pituitary adenomas, including 60 patients with giant adenomas (diameter ≥4 cm) and 369 patients with macroadenomas (diameter 1-4 cm), received a 3D head CT, a MRI with contrast enhancement, and an endocrinology examination prior to surgery. Preoperative clinical and radiological features, visual measurements, hormone levels, length of stay, length of surgery, postoperative stay, visual and hormone outcomes, resection range, complication and recurrence rates, and routine patient information were recorded. The patients were followed up for 6-72 months (median = 40 months). Results: Of 429 patients with macroadenomas or giant pituitary adenomas who received neuroendoscopic treatment, 348 (81.12%) had gross-total resections (GTR), 53 (12.35%) had near-total resections (NTR), and 28 (6.53%) had subtotal resections. There were 138 cases of post-operative diabetes insipidus (32.17%), including 7 cases of permanent diabetes insipidus (1.63%), 16 cases of nasal hemorrhage (3.73%), 39 cases of intraoperative cerebrospinal fluid leakage (9.09%), 4 cases of intracranial infection (0.9%), 16 cases of hypophysis (3.7%), and 15 cases of anosmia (3.50%). The clinical symptoms and endocrinology indices of the patients improved after surgery, and all patients were discharged 5-18 days (8.36 ± 2.65) postop. Conclusion: Neuroendoscopy is a safe operation with a short recovery period and hospital stay and is thus an effective method to treat macroadenomas and giant pituitary adenomas. Preoperative evaluation and prediction can help to accurately address possible intraoperative situations and improve GTR.

Endoscope-assisted microneurosurgery for intracranial aneurysms: A systematic review and meta-analysis.

BACKGROUND: In the surgical approach to treat deep-seated intracranial lesions, endoscopes can be used to assist microsurgical operations and improve outcomes. This technique is often called endoscope-assisted microneurosurgery (EAM). This systematic review and meta-analysis aimed to evaluate the feasibility, safety, and effectiveness of EAM. METHODS: We performed a meta-analysis of relevant articles identified using PubMed, Embase, and the Cochrane Central Register to assess the efficacy of EAM according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Primary outcomes were repositioning of the definitive clip, better surgical field, the overall and endoscope-related complication rates, mortality, and the rate of follow up. RESULTS: A total of 10 studies of 1,432 patients with 1,717 aneurysms treated with EAM were included. EAM led to repositioning of the definitive clip in 13% (95% CI, 9%-17%; I2 = 72.61%; p < 0.001); 77% of aneurysms treated with endoscopically assisted vision and information had a better outcome than that with standard surgery (95% CI, 52%-95%; I2 = 97.63%; p < 0.001). There was an overall complication rate of 6% (95% CI, 1%-13%; I2 = 91.39%; p < 0.001). The incidence of endoscope-related complications was 0% (95% CI, 0%-1%; I2 = 64%; p < 0.001). The mortality was 0% (95% CI, 0-1%; I2 = 0.0%); and 94% of patients had an excellent to good recovery and good outcome (95% CI, 88%-98%; I2 = 88.42%; p < 0.001). CONCLUSIONS: Our comprehensive study showed that EAM for intracranial aneurysms is feasible, the safety of the surgery is good, and the patients have a good prognosis, Therefore, we think EAM can be more widely adopted in the future.

An m6A/m5C/m1A/m7G-Related Long Non-coding RNA Signature to Predict Prognosis and Immune Features of Glioma.

Background: Gliomas are the most common and fatal malignant type of tumor of the central nervous system. RNA post-transcriptional modifications, as a frontier and hotspot in the field of epigenetics, have attracted increased attention in recent years. Among such modifications, methylation is most abundant, and encompasses N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1 methyladenosine (m1A), and 7-methylguanosine (m7G) methylation. Methods: RNA-sequencing data from healthy tissue and low-grade glioma samples were downloaded from of The Cancer Genome Atlas database along with clinical information and mutation data from glioblastoma tumor samples. Forty-nine m6A/m5C/m1A/m7G-related genes were identified and an m6A/m5C/m1A/m7G-lncRNA signature of co-expressed long non-coding RNAs selected. Least absolute shrinkage and selection operator Cox regression analysis was used to identify 12 m6A/m5C/m1A/m7G-related lncRNAs associated with the prognostic characteristics of glioma and their correlation with immune function and drug sensitivity analyzed. Furthermore, the Chinese Glioma Genome Atlas dataset was used for model validation. Results: A total of 12 m6A/m5C/m1A/m7G-related genes (AL080276.2, AC092111.1, SOX21-AS1, DNAJC9-AS1, AC025171.1, AL356019.2, AC017104.1, AC099850.3, UNC5B-AS1, AC006064.2, AC010319.4, and AC016822.1) were used to construct a survival and prognosis model, which had good independent prediction ability for patients with glioma. Patients were divided into low and high m6A/m5C/m1A/m7G-LS groups, the latter of which had poor prognosis. In addition, the m6A/m5C/m1A/m7G-LS enabled improved interpretation of the results of enrichment analysis, as well as informing immunotherapy response and drug sensitivity of patients with glioma in different subgroups. Conclusion: In this study we constructed an m6A/m5C/m1A/m7G-LS and established a nomogram model, which can accurately predict the prognosis of patients with glioma and provides direction toward promising immunotherapy strategies for the future.

Tizoxanide Promotes Apoptosis in Glioblastoma by Inhibiting CDK1 Activity.

The antiparasitic drug nitazoxanide (NTZ) has received considerable attention for its potential in cancer therapy. In this study, we demonstrate that tizoxanide (TIZ), an active metabolite of NTZ, exhibits antiglioma activity in vitro and in vivo by inducing G2/M cell cycle arrest and apoptosis. In vitro, TIZ dose-dependently inhibited the proliferation of U87, U118, and A172 human glioblastoma (GBM) cells at 48 h with IC50 values of 1.10, 2.31, and 0.73 µM, respectively. Treatment with TIZ (1 and 10 µM) also dose-dependently inhibited the colony formation of these GBM cells and accumulated ROS damage in the nucleus. In silico target fishing combined with network pharmacological disease spectrum analyses of GBM revealed that cycle-dependent kinase 1 (CDK1) is the most compatible target for TIZ and molecular docking by Molecule Operating Environment (MOE) software confirmed it. Mechanistically, TIZ inhibited the phosphorylation of CDK1 at Thr161 and decreased the activity of the CDK1/cyclin B1 complex, arresting the cell cycle at the G2/M phase. TIZ may induce apoptosis via the ROS-mediated apoptotic pathway. In vivo, TIZ suppressed the growth of established subcutaneous and intracranial orthotopic xenograft models of GBM without causing obvious side effects and prolonged the survival of nude mice bearing glioma. Taken together, our results demonstrated that TIZ might be a promising chemotherapy drug in the treatment of GBM.