Plant-derived nanovesicles offer a promising avenue for anti-aging interventions.

Over the past few years, the study of plant-derived nanovesicles (PDNVs) has emerged as a hot topic of discussion and research in the scientific community. This remarkable interest stems from their potential role in facilitating intercellular communication and their unique ability to deliver biologically active components, including proteins, lipids, and miRNAs, to recipient cells. This fascinating ability to act as a molecular courier has opened up an entirely new dimension in our understanding of plant biology. The field of research focusing on the potential applications of PDNVs is still in its nascent stages. However, it has already started gaining traction due to the growing interest in its possible use in various branches of biotechnology and medicine. Their unique properties and versatile applications offer promising future research and development prospects in these fields. Despite the significant progress in our understanding, many unanswered questions and mysteries surround the mechanisms by which PDNVs function and their potential applications. There is a dire need for further extensive research to elucidate these mechanisms and explore the full potential of these fascinating vesicles. As the technology at our disposal advances and our understanding of PDNVs deepens, it is beyond doubt that PDNVs will continue to be a subject of intense research in anti-aging therapeutics. This comprehensive review is designed to delve into the fascinating and multifaceted world of PDNV-based research, particularly focusing on how these nanovesicles can be applied to anti-aging therapeutics.

Breast cancer screening and early diagnosis in China: a systematic review and meta-analysis on 10.72 million women.

BACKGROUND: The incidence of breast cancer among Chinese women has gradually increased in recent years. This study aims to analyze the situation of breast cancer screening programs in China and compare the cancer detection rates (CDRs), early-stage cancer detection rates (ECDRs), and the proportions of early-stage cancer among different programs. METHODS: We conducted a systematic review and meta-analysis of studies in multiple literature databases. Studies that were published between January 1, 2010 and June 30, 2023 were retrieved. A random effects model was employed to pool the single group rate, and subgroup analyses were carried out based on screening model, time, process, age, population, and follow-up method. RESULTS: A total of 35 studies, including 47 databases, satisfied the inclusion criteria. Compared with opportunistic screening, the CDR (1.32‰, 95% CI: 1.10‰-1.56‰) and the ECDR (0.82‰, 95% CI: 0.66‰-0.99‰) were lower for population screening, but the proportion of early-stage breast cancer (80.17%, 95% CI: 71.40%-87.83%) was higher. In subgroup analysis, the CDR of population screening was higher in the urban group (2.28‰, 95% CI: 1.70‰-2.94‰), in the breast ultrasonography (BUS) in parallel with mammography (MAM) group (3.29‰, 95% CI: 2.48‰-4.21‰), and in the second screening follow-up group (2.47‰, 95% CI: 1.64‰-3.47‰), and the proportion of early-stage breast cancer was 85.70% (95% CI: 68.73%-97.29%), 88.18% (95% CI: 84.53%-91.46%), and 90.05% (95% CI: 84.07%-94.95%), respectively. CONCLUSION: There were significant differences between opportunistic and population screening programs. The results of these population screening studies were influenced by the screening process, age, population, and follow-up method. In the future, China should carry out more high-quality and systematic population-based screening programs to improve screening coverage and service.

Carbonic anhydrase IX inhibitor S4 triggers release of DAMPs related to immunogenic cell death in glioma cells via endoplasmic reticulum stress pathway.

BACKGROUND: Immunogenic cell death (ICD), which releases danger-associated molecular patterns (DAMP) that induce potent anticancer immune response, has emerged as a key component of therapy-induced anti-tumor immunity. The aim of this work was to analyze whether the carbonic anhydrase IX inhibitor S4 can elicit ICD in glioma cells. METHODS: The effects of S4 on glioma cell growth were evaluated using the CCK-8, clonogenic and sphere assays. Glioma cell apoptosis was determined by flow cytometry. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of S4-treated cells were concentrated for the determination of HMGB1and HSP70/90 expression by immunoblotting. RNA-seq was performed to compare gene expression profiles between S4-treated and control cells. Pharmacological inhibition of apoptosis, autophagy, necroptosis and endoplasmic reticulum (ER) stress was achieved by inhibitors. In vivo effects of S4 were evaluated in glioma xenografts. Immunohistochemistry (IHC) was performed to stain Ki67 and CRT. RESULTS: S4 significantly decreased the viability of glioma cells and induced apoptosis and autophagy. Moreover, S4 triggered CRT exposure and the release of HMGB1 and HSP70/90. Inhibition of either apoptosis or autophagy significantly reversed S4-induced release of DAMP molecules. RNA-seq analysis indicated that the ER stress pathway was deregulated upon exposure to S4. Both PERK-eIF2α and IRE1α- XBP1 axes were activated in S4-treated cells. Furthermore, pharmacological inhibition of PERK significantly suppressed S4-triggered ICD markers and autophagy. In glioma xenografts, S4 significantly reduced tumor growth. CONCLUSIONS: Altogether, these findings suggest S4 as a novel ICD inducer in glioma and might have implications for S4-based immunotherapy. Video Abstract.

A Meta-Analysis of Calcium Intake and Risk of Glioma.

BACKGROUND: A meta-analysis was conducted to investigate the correlation between calcium intake and the risk of brain tumors (especially glioma). METHODS: The PubMed, Web of Science, and Embase databases were searched for relevant papers on the association between calcium intake and glioma as of August 22, 2021. The odds ratio (OR) with a 95% confidence interval (CI) was calculated using a random-effects model. Egger's test was conducted to assess publication bias. RESULTS: The meta-analysis includes four studies. The meta-analysis showed that calcium intake and the risk of brain tumors have a significant negative relationship (OR = 0.28; 95% CI: 0.11 to 0.72; P = 0.008). Dose-response analysis showed that for every 100 mg/day increase in calcium intake, the risk of glioma decreased by 7% (OR = 0.93; 95% CI: 0.88 to 0.98). In addition, compared with humans without calcium intake, when calcium intake is 455 mg/day, 800 mg/day and 1000 mg/day, the risk of glioma is 0.65 (95% CI 0.43, 0.97), 0.55 (95% CI 0.37, 0.82) and 0.37 (95% CI 0.15, 0.86). CONCLUSION: There is a significant negative association between calcium intake and brain tumors (especially gliomas), but more high-quality studies are needed to verify these results.

Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma.

Small extracellular vesicles (SEVs) are extracellular vesicles containing DNA, RNA, and proteins and are involved in intercellular communication and function, playing an essential role in the growth and metastasis of tumors. SEVs are present in various body fluids and can be isolated and extracted from blood, urine, and cerebrospinal fluid. Under both physiological and pathological conditions, SEVs can be released by some cells, such as immune, stem, and tumor cells, in a cytosolic manner. SEVs secreted by tumor cells are called tumor-derived exosomes (TEXs) because of their origin in the corresponding parent cells. Glioma is the most common intracranial tumor, accounting for approximately half of the primary intracranial tumors, and is characterized by insidious onset, high morbidity, and high mortality rate. Complete removal of tumor tissues by surgery is difficult. Chemotherapy can improve the survival quality of patients to a certain extent; however, gliomas are prone to chemoresistance, which seriously affects the prognosis of patients. In recent years, TEXs have played a vital role in the occurrence, development, associated immune response, chemotherapy resistance, radiation therapy resistance, and metastasis of glioma. This article reviews the role of TEXs in glioma progression, drug resistance, and clinical diagnosis.

An immune-related nomogram model that predicts the overall survival of patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma accounts for approximately 40% of all primary lung cancers; however, the mortality rates remain high. Successfully predicting progression and overall (OS) time will provide clinicians with more options to manage this disease. METHODS: We analyzed RNA sequencing data from 510 cases of lung adenocarcinoma from The Cancer Genome Atlas database using CIBERSORT, ImmuCellAI, and ESTIMATE algorithms. Through these data we constructed 6 immune subtypes and then compared the difference of OS, immune infiltration level and gene expression between these immune subtypes. Also, all the subtypes and immune cells infiltration level were used to evaluate the relationship with prognosis and we introduced lasso-cox method to constructe an immune-related prognosis model. Finally we validated this model in another independent cohort. RESULTS: The C3 immune subtype of lung adenocarcinoma exhibited longer survival, whereas the C1 subtype was associated with a higher mutation rate of MUC17 and FLG genes compared with other subtypes. A multifactorial correlation analysis revealed that immune cell infiltration was closely associated with overall survival. Using data from 510 cases, we constructed a nomogram prediction model composed of clinicopathologic factors and immune signatures. This model produced a C-index of 0.73 and achieved a C-index of 0.844 using a validation set. CONCLUSIONS: Through this study we constructed an immune related prognosis model to instruct lung adenocarcinoma's OS and validated its value in another independent cohost. These results will be useful in guiding treatment for lung adenocarcinoma based on tumor immune profiles.

A Comparison of Epidemiological Characteristics of Central Nervous System Tumours in China and Globally from 1990 to 2019.

BACKGROUND: Despite their great disease burden, there have been few studies on the epidemiology of central nervous system tumours (CNSTs) in China. We used the latest data updated by GBD to analyse the trends of incidence, mortality, and disability-adjusted life years (DALYs) for CNSTs in China versus globally. METHODS: Epidemiological data on CNSTs were extracted from GBD 2019. We used Joinpoint regression analysis to calculate the magnitude and direction of the trends and the age-period-cohort method to analyse the age, period, and cohort effects of the trend. RESULTS: From 1990 to 2019, the 106.52% increase in Chinese incident cases was higher than the global increase (94.35%). The 67.32% increase in cancer deaths and 16.03% increase in DALYs were lower than the global increases (cancer death: 76.36%; DALYs: 40.06%). The age-standardized incidence rates (ASIRs) in China were higher than the global ASIRs, and the increase in China was higher than that globally. Although the age-standardized mortality rates and age-standardized DALY rates in China were higher, their increases in China were less than those globally. Both in China and globally, the number and incidence, mortality, and DALYs by age group showed a bimodal distribution (younger than 5 years and older), and the peak in the older age group showed a backwards trend. The proportion of incident cases, cancer deaths, and DALYs also increased in the older age group. In the age-period-cohort model, the local drifts in the older age group were above zero. CONCLUSIONS: The burden of CNSTs is very serious in China, and we should pay attention to the key populations, early diagnosis technology, improvements in medical technology, and ways to reduce medical costs. We believe our results could help policymakers allocate resources efficiently to reduce the burden of CNSTs.

Application of molecular imaging technology in tumor immunotherapy.

Cancer immunotherapy, due to its high anti-tumor efficacy, has attracted considerable attention globally from experts in various fields. However, immunotherapy could be severely toxic; not all patients may respond, thus requiring combination therapy. Therefore, a reasonable selection strategy for early treatment is urgently needed. It is vital to capture the dynamic, heterogeneous, and complex tumor behavior considering the absence of ideal companion biomarkers. Since tumor immune response involves tumor cells, several other cell types, and molecules in the tumor microenvironment, detection is very complex and variable. However, molecular imaging technology, namely the non-invasive whole-body molecular imaging by positron emission tomography and single-photon emission computed tomography, has shown considerable promise in tumor detection and cancer immunotherapy response. Identification of potential novel imaging biomarkers will allow a personalized treatment plan for every patient. Future imaging strategies for these molecules used alone or in combination or continuously, might help stratify patients before or during the early stages of immunotherapy, and might address the immunotherapy challenges encountered by the oncologists.

Administration with hyperoside sensitizes breast cancer cells to paclitaxel by blocking the TLR4 signaling.

Breast cancer is a malignancy and one of the most frequent causes of cancer death among women worldwide. Paclitaxel is a common chemotherapeutic drug and has recently been shown to facilitate tumor cell escape during cytotoxic chemotherapy by inducing inflammatory mediators and pro-survival protein expression. Hyperoside is a flavonoid glycoside compound and exerts anti-inflammation, and anti-tumor growth properties. However, its function in breast cancer chemosensitivity remains poorly elucidated. In this study, hyperoside exhibited little cytotoxicity to normal human breast mammary epithelial cell lines, and also protected against paclitaxel-induced cytotoxicity in MCF-10A. Importantly, treatment with hyperoside engendered not only inhibition of cell viability, but also potentiated cancer cell sensitivity to paclitaxel in TLR4-positive breast cancer MDA-MB-231 cells by suppressing cell viability, and increasing cell apoptosis and caspase-3 activity. Nevertheless, although hyperoside exposure restrained cell viability, its treatment presented little effects to paclitaxel sensitivity in TLR4-null HCC1806 cells. Intriguingly, paclitaxel stimulation activated the TLR4-NF-κB signaling, which was reversed after hyperoside administration. Concomitantly, hyperoside also attenuated paclitaxel-mediated anti-apoptotic Bcl-2 expression, but enhanced the effects of paclitaxel on pro-apoptotic Bax expression, and pro-inflammatory cytokine IL-6 and IL-6 levels in MDA-MB-231 cells. Importantly, restoring the TLR4 pathway overturned hyperoside-evoked chemosensitivity to paclitaxel in MDA-MB-231 cells. Thus, hyperoside may elevate breast cancer cell sensitivity to paclitaxel by blocking TLR4 activation-mediated pro-inflammatory and pro-survival approaches, thereby endorsing its usefulness as a promising therapeutic combination to overcome chemosensitivity in breast cancer.

Role of Exosomes in the Progression, Diagnosis, and Treatment of Gliomas.

Gliomas are the most common primary malignant brain tumors associated with a low survival rate. Even after surgery, radiotherapy, and chemotherapy, gliomas still have a poor prognosis. Extracellular vesicles are a heterogeneous group of cell-derived membranous structures. Exosomes are a type of extracellular vesicles, their size ranges from 30 nm to 100 nm. Recent studies have proved that glioma cells could release numerous exosomes; therefore, exosomes have gained increasing attention in glioma-related research. Recent studies have confirmed the importance of extracellular vesicles, particularly exosomes, in the development of brain tumors, including gliomas. Exosomes mediate intercellular communication in the tumor microenvironment by transporting biomolecules (proteins, lipids, deoxyribonucleic acid, and ribonucleic acid); thereby playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can traverse the blood-brain barrier and promote tumor progression by modifying the tumor microenvironment. Based on their structural and functional characteristics, exosomes are demonstrating their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting glioma cells. Therefore, exosomes are a promising therapeutic target for the diagnosis, prognosis, and treatment of malignant gliomas. More research will be needed before exosomes can be used in clinical applications. Here, we describe the exosomes, their morphology, and their roles in the diagnosis and progression of gliomas. In addition, we discuss the potential of exosomes as a therapeutic target/drug delivery system for patients with gliomas.

Long noncoding RNA MT1JP inhibits proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway.

This study is carried out to elucidate the role of long noncoding RNAs (lncRNAs) MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells through the regulation of PTEN/Akt signaling pathway. The expression of MT1JP in 80 normal brain tissues and 138 glioma tissues, as well as glioma cell lines, was detected by quantitative reverse-transcription polymerase chain reaction. Besides, glioma cells with overexpression and low expression of MT1JP were constructed to confirm the role of MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells and the growth of glioma cells in vivo through the regulation of PTEN/Akt signaling pathway. MT1JP expression was downregulated in glioma tissues and cells. The low expression of MT1JP was considered as an independent risk factor for predicting overall survival in gliomas. After transfection of MT1JP overexpression plasmid, glioma cells showed decreased proliferation, migration and invasion ability, increased apoptosis rate, and decreased the tumorigenic ability of nude mice. The trends were opposite in glioma cells transfected with MT1JP poor expression plasmid. Collectively, our study suggests that lncRNA MT1JP is responsible for inhibiting proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway.

The biological macromolecule Nocardia rubra cell-wall skeleton as an avenue for cell-based immunotherapy.

Promoting the antitumor effects of cell-based immunotherapy for clinical application remains a difficult challenge. Nocardia rubra cell-wall skeleton (N-CWS) is an immunotherapeutic agent for cancers that have been proven to possess the ability to activate immune response without showing toxicity. However, its effects on immune cells that are derived from tumor patients and cultured in vitro remain unclear. As expected, N-CWS can enhance the proliferation and viability of cytokine-induced killer (CIK) cells, dendritic cells (DCs), and natural killer (NK) cells. The maturation of DCs and specific cytotoxicity against NK cells and CIK cells were consistently promoted. The TUNEL-staining and the Annexin V/propidium iodide assay revealed that after treatment with N-CWS, the stimulated CIK/NK cells could induce DNA breaks in tumor cells. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed upregulation of proapoptotic biomarkers (caspase-3 and caspase-9) and a downregulation of the antiapoptotic biomarker Bcl-2 in the tumor cells of the N-CWS-treated group, indicating that N-CWS could induce hepatocellular carcinoma cell apoptosis via CIK/NK cells. Finally, CIK/NK cells could notably suppress the invasion and migration of tumor cells in the presence of N-CWS. Our study provides evidence that N-CWS could significantly increase the growth of CIK cells, DCs, and NK cells, particularly due to its robust antitumor activities by inducing apoptosis, and attenuate the invasion and migration of tumor cells.

Sirtuin1 activator SRT2183 suppresses glioma cell growth involving activation of endoplasmic reticulum stress pathway.

BACKGROUND: Glioblastoma (GBM) is an extremely deadly form of brain cancer with limited treatment options and thus novel therapeutic modalities are necessary. Histone deacetylase inhibitors (HDACi) have demonstrated clinical and preclinical activities against GBM. (Silent mating type information regulation 2 homolog, Sirt1) abbreviated as Sirtuin 1, has been implicated in GBM. We explored the activity of the Sirt1 activator SRT2183 in glioma cell lines in terms of biological response. METHODS: The effects of SRT2183 on glioma cell growth and neurosphere survival were evaluated in vitro using the CCK-8, clonogenic and neurosphere assays, respectively. Glioma cell cycle arrest and apoptosis were determined by flow cytometry. SRT2183-induced autophagy was investigated by detection of GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta, conversion of the nonlipidated form of LC3 (LC3-I) to the phosphatidylethanolamine-conjugated form (LC3-II). Acetylation of STAT3 and NF-κB in SRT2183-treated glioma cells was examined using immunoprecipitation. The expression levels of anti-apoptotic proteins were assayed by immunoblotting. RESULTS: SRT2183 suppressed glioma cell growth and destroyed neurospheres in vitro. Furthermore, SRT2183 induced glioma cell cycle arrest and apoptosis, accompanying by upregulation of the pro-apoptotic Bim and downregulation of Bcl-2 and Bcl-xL. Notably, ER stress was triggered in glioma cells upon exposure to SRT2183 while the pre-exposure to 4-PBA, an ER stress inhibitor, significantly antagonized SRT2183-mediated growth inhibition in glioma cells. In addition, SRT2183 induced autophagy in glioma cells and pharmacological modulation of autophagy appeared not to affect SRT2183-inhibited cell growth. Of interest, the acetylation and phosphorylation of p65 NF-κB and STAT3 in glioma cells were differentially affected by SRT2183. CONCLUSIONS: Our data suggest the ER stress pathway is involved in SRT2183-mediated growth inhibition in glioma. Further investigation in vivo is needed to consolidate the data.

MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma.

BACKGROUND: Glioma is the most prevalent malignant tumor in human central nervous systems. Recently, the development of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has been reported to be closely correlated with tumor progression, but its effect and molecular mechanism underlying radioresistance remains unclear in glioma. METHODS: The expression of miR-153-3p was determined in radioresistant glioma clinical specimens as well as glioma cell lines exposed to irradiation (IR) using quantitative real-time PCR. Cell viability, proliferation and apoptosis were then evaluated by MTT assay, colony formation assay, Flow cytometry analysis and caspase-3 activity assay in glioma cells (U87 and U251). Tumor forming was evaluated by nude mice model in vivo. TUNEL staining was used to detect cell apoptosis in nude mice model. The target genes of miR-153-3p were predicted and validated using integrated bioinformatics analysis and a luciferase reporter assay. RESULTS: Here, we found that miR-153-3p was down-regulated in radioresistant glioma clinical specimens as well as glioma cell lines (U87 and U251) exposed to IR. Enhanced expression of miR-153-3p promoted the radiosensitivity, promoted apoptosis and elevated caspase-3 activity in glioma cells in vitro, as well as the radiosensitivity in U251 cell mouse xenografs in vivo. Mechanically, B cell lymphoma-2 gene (BCL2) was identified as the direct and functional target of miR-153-3p. Moreover, restoration of BCL2 expression reversed miR-153-3p-induced increase of radiosensitivity, apoptosis and caspase-3 activity in U251 cells in vitro. In addition, clinical data indicated that the expression of miR-153-3p was significantly negatively associated with BCL2 in radioresistance of glioma samples. CONCLUSIONS: Our findings suggest that miR-153-3p is a potential target to enhance the effect of radiosensitivity on glioma cells, thus representing a new potential therapeutic target for glioma.

Effectiveness and Safety of Ultra-low-dose Fluorescein Sodium-Guided Resection of Malignant Glioma.

BACKGROUND: This study analyzed the effectiveness and safety of ultra-low dose fluorescein sodium (FL)-guided malignant glioma resection and its potential to predict the pathological characteristics of glioma. METHODS: Sixty patients who underwent FL-guided glioma resection were randomly divided into test (1 mg/kg) and control (5 mg/kg) groups. A retrospective analysis included 30 patients with gliomas who did not undergo FL-guided surgery; these patients were included as a blank control group. Surgical outcomes, Karnofsky performance scores (KPS), and progression-free survival (PFS) at 6 months postoperatively were compared between the 3 groups. The sensitivity and specificity of FL and the relationship between the intensity of FL and Glial fibrillary acidic protein (GFAP) or Ki-67 expression were compared. RESULTS: The total tumor resection rates in the test, control, and blank control groups were 90% (27/30), 86.7% (26/30), and 60% (18/30), respectively. There were significant differences (P < 0.05) in the extent of resection, KPS, and PFS at 6 months after surgery between the test and control groups and the blank control group; however, no significant differences (P > 0.05) were observed between the test and control groups. The intensity of FL and the Ki67 positivity rate (P < 0.05) were directly proportional, but this relationship was not observed with GFAP. CONCLUSIONS: Ultra-low-dose FL-guided resection of malignant gliomas is safe and effective. The Ki67 positivity rate was directly proportional to the intensity of FL, indicating its potential to predict gliomas during pathological examination.

Identification and validation of prognostic genes and immune landscape signatures based on a fatty acid oxidation­related risk score model in glioma.

Fatty acid oxidation (FAO) plays a crucial role in glioma metabolism and its interaction with the immune microenvironment. The aim of the present study was to investigate the relationship between FAO-related genes and glioma by constructing gene clusters using a glioma cohort. A total of 287 differentially expressed genes related to FAO were identified and the top 50 genes were selected based on their P-values. Subsequently, patients were classified into two distinct gene subtypes (A and B) based on these genes. Scores for each patient were calculated using the 50 genes and the patients were divided into the high and low-score groups accordingly. Patients in subtype B exhibited higher tumor grades and poor prognostic factors such as older age and worse survival rates. The high-score subgroup had unfavorable indicators, including isocitrate dehydrogenase 1 wild-type, high tumor grade and 1p19q non-codeleted, while immune checkpoint expression was generally higher in the high-score subgroup. The constructed scoring model was validated using an external dataset, and the tissue inhibitor of metalloproteinase 1 gene was identified through protein interaction analysis, suggesting its potential involvement in glioma malignancy and promotion of glioblastoma proliferation. In conclusion, FAO-related genes may contribute to tumor development through immune mechanisms and the present study may provide novel insights for potential therapeutic strategies in glioma treatment.

The role of ferroptosis in central nervous system damage diseases.

Ferroptosis is a form of cell death, i.e., programmed cell death characterized by lipid peroxidation and iron dependence, which has unique morphological and biochemical properties. This unique mode of cell death is driven by iron-dependent phospholipid peroxidation and regulated by multiple cell metabolic pathways, including redox homeostasis, iron metabolism, mitochondrial activity, and the metabolism of amino acids, lipids, and sugars. Many organ injuries and degenerative pathologies are caused by ferroptosis. Ferroptosis is closely related to central nervous system injury diseases and is currently an important topic of research globally. This research examined the relationships between ferroptosis and the occurrence and treatment of central nervous system injury diseases. Additionally, ferroptosis was assessed from the aspect of theory proposal, mechanism of action, and related signaling pathways per recent research. This review provides a relevant theoretical basis for further research on this theory, the prospect of its development, and the prevention and treatment of such diseases.

Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK.

BACKGROUND: Ferroptosis, a non-apoptotic form of cell death induced by accumulation of free iron ions and lipid peroxidation, its importance for cancer treatment is gradually being recognized. Research on the anti-cancer mechanism of juglone is accumulating. However, the specific mechanism by which it directs glioblastoma (GBM) to death is unknown. METHODS: We used in vitro and in vivo experiments to explore the anti-GBM effect generated by juglone through the ferroptosis pathway. RESULTS: Juglone mainly causes cell death by inducing ferroptosis. Mechanistically, juglone can significantly activate the phosphorylation of p38MAPK. According to transcriptome sequencing and protein interaction analysis, the Nrf2-GPX4 signaling pathway is identified as the primary pathway through which juglone mediates ferroptosis. In vitro and in vivo experiments further verified that juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway. CONCLUSION: Juglone induces ferroptosis and inhibits the growth of GBM by targeting the Nrf2/Gpx4 signaling pathway and thus holds promise as a novel ferroptosis inducer or anti-GBM drug.

Exosomes-mediated crosstalk between glioma and immune cells in the tumor microenvironment.

Gliomas are the most common primary malignant tumors in the central nervous system. However, conventional treatments, such as surgical resection and postoperative combined chemo- and radio-therapy, are ineffective in improving patients' long-term survival. The tumor microenvironment (TME) consists of stromal cells, tumor components, and innate and acquired immune cells, and these cells, along with the extracellular matrix, regulate and communicate intercellularly to promote TME formation. The immune microenvironment plays a vital role in the development of glioma. Exosomes, which are extracellular vesicles (EVs), facilitate intercellular communication and regulation within the TME. Tumor cells can release exosomes to transmit messages, induce macrophage polarization, and inhibit immune cell activity, ultimately promoting metastasis and immune evasion. Moreover, immune cells can regulate tumorigenesis and progression through exosomes. This review summarized the biological properties of exosomes and their effects on the tumor microenvironment and provides an overview of the interactions between glioma cells and immune cells.

Unexpected worsening of doxorubicin cardiotoxicity upon intermittent fasting.

Recently in Cell Metabolism, Ozcan et al. used preclinical and clinical data to suggest that alternate-day fasting may exacerbate the cardiotoxic effects of doxorubicin through the TFEB/GDF15 pathway, leading to myocardial atrophy and impaired cardiac function. The link between caloric intake, chemotherapy-induced cachexia, and cardiotoxicity warrants more clinical attention.