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.

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.

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.

Synthesized nanoparticles, biomimetic nanoparticles and extracellular vesicles for treatment of autoimmune disease: Comparison and prospect.

An emerging strategy is needed to treat autoimmune diseases, many of which are chronic with no definitive cure. Current treatments only alleviate symptoms and have many side effects affecting patient quality of life. Recently, nanoparticle drug delivery systems, an emerging method in medicine, has been used to target cells or organs, without damaging normal tissue. This approach has led to fewer side effects, along with a strong immunosuppressive capacity. Therefore, a nanotechnology approach may help to improve the treatment of autoimmune diseases. In this review, we separated nanoparticles into three categories: synthesized nanoparticles, biomimetic nanoparticles, and extracellular vesicles. This review firstly compares the typical mechanism of action of these three nanoparticle categories respectively in terms of active targeting, camouflage effect, and similarity to parent cells. Then their immunomodulation properties are discussed. Finally, the challenges faced by all these nanoparticles are described.

Multifunctional exosome-mimetics for targeted anti-glioblastoma therapy by manipulating protein corona.

Targeted drug delivery to the glioblastoma (GBM) overcoming blood-brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers. Here, multifunctional exosomes-mimetics (EM) are developed and decorated with angiopep-2 (Ang) for enhancing GBM drug delivery by manipulating PC. Docetaxel (DTX)-loaded EM with Ang modification (DTX@Ang-EM) show less absorption of serum proteins and phagocytosis by macrophages. Ang-EM show enhanced BBB penetration ability and targeting ability to the GBM. Ang-EM-mediated delivery increase the concentration of DTX in the tumor area. The multifunctional DTX@Ang-EM exhibits significant inhibition effects on orthotopic GBM growth with reduced side effects of the chemotherapeutic. Findings from this study indicate that the developed DTX@Ang-EM provide a new strategy for targeted brain drug delivery and GBM therapy.

Artificial exosomes for translational nanomedicine.

Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include 'nanovesicles (NVs)', 'exosome-mimetic (EM)' and 'hybrid exosomes (HEs)', which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

Oral microemulsion based delivery system for reducing reproductive and kidney toxicity of Tripterygium glycosides.

Aim: To reduce the toxic effects and achieve efficiency of Tripterygium glycosides, an oral microemulsion was designed. Method: After estimating its stability and characterisation, an animal experiment was held to evaluate its toxicity in vivo, using male and female Sprague Dawley rats. Result: The maximum loading amount of microemulsion to Tripterygium glycosides was 18.87 mg/ml. And comparing to control, the Tripterygium glycoside microemulsion can maintain a normal level of the number of sperms, the weight of testicle, testosterone (∼2.5 ng/mL) and BUN (∼5 mmol/L) to male rats. For female rats, it can prevent the ovary to be atrophy and keep FSH to be stable (>2100 ng/L). The weaker injury induced by drug-loaded microemulsion to rats also could be observed in histological sections to kidney and reproductive organs. Conclusions: Although the blank microemulsion had slight toxicity, it mitigated the toxicity of Tripterygium glycosides to kidney and reproductive system.

A microemulsion of puerarin-phospholipid complex for improving bioavailability: preparation, in vitro and in vivo evaluations.

Puerarin is a phytochemical with various pharmacological effects, but poor water solubility and low oral bioavailability limited usage of puerarin. The purpose of this study was to develop a new microemulsion (ME) based on phospholipid complex technique to improve the oral bioavailability of puerarin. Puerarin phospholipid complex (PPC) was prepared by a solvent evaporation method and was characterized by X-ray diffraction and infrared spectroscopy. Pseudo-ternary phase diagrams were constructed to investigate the effects of different oil on the emulsifying performance of the blank ME. Intestinal mucosal injury test was conducted to evaluate safety of PPC-ME, and no sign of damage on duodenum, jejunum and ileum of rats was observed using hematoxylin-eosin staining. In pharmacokinetic study of PPC-ME, a significantly greater Cmax (1.33 µg/mL) was observed when compared to puerarin (Cmax 0.55 µg/mL) or PPC (Cmax 0.70 µg/mL); the relative oral bioavailability of PPC-ME was 3.16-fold higher than puerarin. In conclusion, the ME combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of puerarin.

In vitro and in vivo evaluation of puerarin-loaded PEGylated mesoporous silica nanoparticles.

Puerarin, which is extracted from Chinese medicine, is widely used in China and mainly used as a therapeutic agent for the treatment of cardiovascular diseases. Owing to its short elimination half-life in human beings, frequently intravenous administration of high doses of puerarin may be needed, which possibly leads to severe and acute side effects. The development of an effective sustained-release drug delivery system is urgently needed. In this study, PEGylated mesoporous silica nanoparticles (PEG-MSNs) had become a preferred way to prolong the half-life and improve the bioavailability of drugs. The release of puerarin from PEG-MSNs was pH dependent, and the release rate was much faster at lower pH than that at higher pH. Moreover, the PEG-MSNs exhibited improved blood compatibility over the MSNs in terms of low hemolysis, and it could also reduce the side effect of hemolysis induced by PUE. Compared with puerarin, PUE-loaded PEG-MSNs showed a 2.3-fold increase in half-life of puerarin and a 1.47-fold increase in bioavailability. Thus, the PEG-MSNs hold the substantial potential to be further developed as an effective sustained-release drug delivery system.

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.

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.

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.

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.

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.

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.

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.

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.

Recent Advance of Nanomaterial-Mediated Tumor Therapies in the Past Five Years.

Cancer has posed a major threat to human life and health with a rapidly increasing number of patients. The complexity and refractory of tumors have brought great challenges to tumor treatment. In recent years, nanomaterials and nanotechnology have attracted more attention and greatly improved the efficiency of tumor therapies and significantly prolonged the survival period, whether for traditional tumor treatment methods such as radiotherapy, or emerging methods, such as phototherapy and immunotherapy, sonodynamic therapy, chemodynamic therapy and RNA interference therapeutics. Various monotherapies have obtained positive results, while combination therapies are further proposed to prevent incomplete eradication and recurrence of tumors, strengthen tumor killing efficacy with minimal side effects. In view of the complementary promotion effects between different therapies, it is vital to utilize nanomaterials as the link between monotherapies to achieve synergistic performance. Further development of nanomaterials with efficient tumor-killing effect and better biosafety is more in line with the needs of clinical treatment. In a word, the development of nanomaterials provides a promising way for tumor treatment, and here we will review the emerging nanomaterials towards radiotherapy, phototherapy and immunotherapy, and summarized the developed nanocarriers applied for the tumor combination therapies in the past 5 years, besides, the advances of some other novel therapies such as sonodynamic therapy, chemodynamic therapy, and RNA interference therapeutics have also been mentioned.

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.