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BackgroundIn the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach.MethodsBetween April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts.ResultsOur investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%–8.0% range, and were highest in 45–54-year olds. When compared with 35–44-or 45–54-year olds, HPV prevalence was highest in 55–64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35–44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7–100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3–82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45–54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55–64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7–100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0–80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771–0.920] vs. 0.812 [95% CI: 0.734–0.891], P = 0.236).ConclusionsPrimary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35–44 and 55–64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35–44 year old females.

Abstract 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.

Abstract 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.

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.

Abstract The efficacy of osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, has been evaluated in glioblastoma (GBM) through preclinical and clinical trials. However, the underlying mechanism of osimertinib-induced GBM cell death and the underlying resistance mechanism to osimertinib remains unclear. Here, we demonstrate that Osimertinib induces paraptosis in GBM cells, as evidenced by the formation of cytoplasmic vacuoles, accumulation of ubiquitinated proteins, and upregulation of endoplasmic reticulum (ER) stress markers like CHOP. Additionally, neither apoptosis nor autophagy was involved in the osimertinib-induced cell death. RNAseq analysis revealed ER stress was the most significantly downregulated pathway upon exposure to osimertinib. Consistently, pharmacologically targeting the PERK-eIF2α axis impaired osimertinib-induced paraptosis. Notably, we show that the expression of thyroid receptor-interacting protein 13 (TRIP13), an AAA+ATPase, alleviated osimertinib-triggered paraptosis, thus conferring resistance. Intriguingly, MK-2206, an AKT inhibitor, downregulated TRIP13 levels and synergized with Osimertinib to suppress TRIP13-induced high GBM cell growth in vitro and in vivo. Together, our findings reveal a novel mechanism of action associated with the anti-GBM effects of osimertinib involving ER stress-regulated paraptosis. Furthermore, we identify a TRIP13-driven resistance mechanism against Osimertinib in GBM and offer a combination strategy using MK-2206 to overcome such resistance.

Abstract 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

Bovine milk-derived exosomes (BMDEs) have emerged as a fruitful area of investigation in age-related disease therapeutics. Through the utilization of BMDEs, researchers possess the capacity to unveil novel treatments and therapeutic interventions that have the potential to enhance the quality of life for elderly individuals across the globe. Studies have provided evidence of the efficacy of BMDEs in facilitating the regenerative processes of bone and cartilage, thus establishing their potential as a viable therapeutic avenue for addressing conditions like osteoarthritis. Although BMDEs show promise as a prospective research route for tackling age-related illnesses, including Parkinson's disease, osteoporosis, and skin rejuvenation, other unanswered questions still demand more exploration. Concerns have been raised regarding the safety and efficacy of BMDEs, especially regarding their human administration, and researchers must carefully examine these concerns to identify alternatives. In conclusion, BMDEs are an area ripe for investigation into the prevention and treatment of age-related diseases.

Abstract 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.

Malignant gliomas occur more often in adults and may affect any part of the central nervous system (CNS). Although their results could be better, surgical excision, postoperative radiation and chemotherapy, and electric field therapy are today’s mainstays of glioma care. However, bacteria can also exert anti-tumor effects via mechanisms such as immune regulation and bacterial toxins to promote apoptosis, inhibit angiogenesis, and rely on their natural characteristics to target the tumor microenvironment of hypoxia, low pH, high permeability, and immunosuppression. Tumor-targeted bacteria expressing anticancer medications will go to the cancer site, colonize the tumor, and then produce the therapeutic chemicals that kill the cancer cells. Targeting bacteria in cancer treatment has promising prospects. Rapid advances have been made in the study of bacterial treatment of tumors, including using bacterial outer membrane vesicles to load chemotherapy drugs or combine with nanomaterials to fight tumors, as well as the emergence of bacteria combined with chemotherapy, radiotherapy, and photothermal/photodynamic therapy. In this study, we look back at the previous years of research on bacteria-mediated glioma treatment and move forward to where we think it is headed.

Purpose: To analyze and review the progress of glucose metabolism-based molecular imaging in detecting tumors to guide clinicians for new management strategies.Summary: When metabolic abnormalities occur, termed the Warburg effect, it simultaneously enables excessive cell proliferation and inhibits cell apoptosis. Molecular imaging technology combines molecular biology and cell probe technology to visualize, characterize, and quantify processes at cellular and subcellular levels in vivo. Modern instruments, including molecular biochemistry, data processing, nanotechnology, and image processing, use molecular probes to perform real-time, non-invasive imaging of molecular and cellular events in living organisms.Conclusion: Molecular imaging is a non-invasive method for live detection, dynamic observation, and quantitative assessment of tumor glucose metabolism. It enables in-depth examination of the connection between the tumor microenvironment and tumor growth, providing a reliable assessment technique for scientific and clinical research. This new technique will facilitate the translation of fundamental research into clinical practice.

Abstract 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.

Abstract Background Increasing studies have reported that oncogenes regulate components of the immune system, suggesting that this is a mechanism for tumorigenesis. Aurora kinase A (AURKA), a serine/threonine kinase, is involved in cell mitosis and is essential for tumor cell proliferation, metastasis, and drug resistance. However, the mechanism by which AURKA is involved in immune response regulation is unclear. Therefore, this study aimed to investigate the role of AURKA in immune regulation in triple‐negative breast cancer (TNBC). Methods Peripheral blood mononuclear cells (PBMCs) were co‐cultured with TNBC cells. The xCELLigence Real‐Time Cell Analyzer‐MP system was used to detect the killing efficiency of immune cells on TNBC cells. The expression of immune effector molecules was tested by quantitative real‐time polymerase chain reaction (qRT‐PCR) to evaluate immune function. Furthermore, to validate AURKA‐regulated immune response in vivo, 4T1 murine breast cancer cell line with AURKA overexpression or downregulation was engrafted into BALB/c mice. The distribution and proportion of immune cells in tumors were further evaluated by immunohistochemistry and flow cytometry. Results Downregulation of AURKA in TNBC cells increased immune response by activating CD8+ T cell proliferation and activity. Nuclear rather than cytoplasmic AURKA‐derived programmed death‐ligand 1 (PD‐L1) expression was independent of its kinase activity. Mechanistic investigations showed that nuclear AURKA increased PD‐L1 expression via an MYC‐dependent pathway. PD‐L1 overexpression mostly reversed AURKA silencing‐induced expression of immune effector molecules, including interleukin‐ (IL‐2), interferon‐γ (IFN‐γ), and perforin. Moreover, AURKA expression was negatively correlated with the enrichment and activity of tumor‐infiltrating CD8+ T cells in 4T1 engrafted BALB/c mouse model. Conclusions Nuclear AURKA elevated PD‐L1 expression via an MYC‐dependent pathway and contributed to immune evasion in TNBC. Therapies targeting nuclear AURKA may restore immune responses against tumors.

As a new programmed cell death process, ferroptosis has shown great potential and uniqueness in experimental and treatment-resistant cancer models. Currently, the main tools for drug research targeting ferroptosis are tumor cells cultured in vitro and tumor models established in rodents. In contrast, increasing evidence indicates that reactivity may differ from modifications in mice or humans in the process of drug screening. With the blossoming of 3D culture technology, tumor organoid culture technology has gradually been utilized. Compared with traditional 2D culture and tumor tissue xenotransplantation, tumor organoids have a significantly higher success rate. They can be cultured quickly and at a lower cost, which is convenient for gene modification and large-scale drug screening. Thus, combining 3D cell culture technology, drug monitoring, and ferroptosis analysis is necessary to develop the impact of ferroptosis-related agents in tumor treatment.

The different human papillomavirus (HPV) strains cause warts in various regions of the body. However, considering that the status and genotype distribution of HPV infection in women in Shenyang remain unknown, herein, we investigated the epidemiological characteristics of high-risk HPV (HR-HPV) infection in women in Shenyang, as well as the current state of HPV infection in Shenyang, to provide a theoretical basis for the prevention and treatment of cervical cancer. From December 2018 to December 2021, 6,432 urban and rural women from the Liaoning Cancer Hospital and the Sujiatun Women and Infants’ Hospital were assessed via the Thinprep cytology test (TCT) and HR-HPV detection. Of the 5,961 women enrolled, 739 were HPV positive (12.40%) and 562 were TCT positive (9.43%). Statistical analyses identified the following HPV risk factors: high school education or lower [OR = 1.426 (1.199–1.696), p < 0.001], age at first sexual encounter ≤ 19 years [OR = 1.496 (1.008–2.220), p = 0.046], and number of sexual partners > 1 [OR = 1.382 (1.081–1.768), p = 0.010], atypical squamous cells of undetermined significance (ASCUS) and above [OR = 10.788 (8.912–13.060), p < 0.001], non-condom-based contraception [OR = 1.437 (1.103–1.871), p = 0.007], nationalities other than Han [OR = 1.690 (1.187–2.406), p = 0.004], rural residence [OR = 1.210 (1.031–1.419), p = 0.020]. Compared to the HPV infection rate of women aged 56–65, that in women aged 35–45 [OR = 0.687 (0.549–0.860), p = 0.001] and 46–55 [OR = 0.740 (0.622–0.879), p = 0.001] decreased significantly. To conclude, risk factors of HPV infection among female patients include high school age and below, initial sexual encounter at age ≤ 19 years, number of sexual partners > 1, ASCUS and above, non-condom contraception, nationalities other than Han nationality and rural population. Collectively, this study provides insights for the improved prevention and treatment of cervical cancer.

ObjectiveCervical cancer screening is very important in the prevention and treatment of cervical cancer. In China, the cervical screening strategy needs to be improved. To explore a suitable cervical screening strategy in China, we evaluated the performance of the human papillomavirus (HPV) E6/E7 mRNA (Aptima HPV (AHPV)) assay in primary screening and different triage strategies for women undergoing routine cervical screening.MethodsA total of 10,002 women aged 35 to 65 years of age were recruited in Liaoning Province and Qingdao City, China. Specimens were tested by liquid-based cytology (LBC) and the AHPV assay, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all high-risk HPV (HR-HPV)-positive samples. Test characteristics were calculated based on histological review.ResultsWe identified 109 women with high-grade squamous intraepithelial lesion or worse (HSIL+), including six with cervical cancer. The sensitivity of AHPV was clearly higher than that of LBC (92.7 [95% CI: 87.2, 97.2] vs. 67.9 [95% CI: 59.6, 76.1], p < 0.001). The specificity of AHPV was 93.0 (95% CI: 92.5, 93.5), which was lower than that of LBC (95.2 [95% CI: 94.8, 95.6], p < 0.001). There was no statistical difference between the positive predictive value of AHPV and LBC (13.5 [95% CI: 11.2, 16.2] vs. 14.3 [95% CI: 11.4, 17.6], p = 0.695). The difference of area under the curve (AUC) values between the AHPV test (0.928 [95% CI: 0.904, 0.953]) and LBC test (0.815 [95% CI: 0.771, 0.860]) in detecting HSIL+ was statistically significant (p < 0.001). Finally, among the three triage strategies, both the sensitivity (73.4 [95% CI: 65.1, 81.7]) and AUC (0.851 [95% CI: 0.809, 0.892]) of AHPV genotyping with reflex LBC triage were the greatest.ConclusionIn summary, the AHPV assay is both specific and sensitive for detecting HSIL+ and may be suitable for use in primary cervical cancer screening in China. AHPV genotyping with reflex LBC triage may be a feasible triage strategy.

Cervical cancer is the most common gynecological malignancy and screening for risk factors with early detection has been shown to reduce the mortality. In this study, we aimed to analyze the characteristics and risk factors of human papillomavirus (HPV) infection and precancerous lesions in women and provide clinical evidence for developing strategies to prevent cervical precancerous lesions and cancer in women. Furthermore, we evaluated the influencing factors for high-risk HPV infection. From April 2018 to December 2021, 10,628 women were recruited for cervical cancer screening at Liaoning Cancer Hospital, Shenyang Sujiatun District Women’s and Infants Hospital, Benxi Manchu Autonomous County People’s Hospital, and Shandong Affiliated Hospital of Qingdao University. The study participants were tested to determine if they were HPV-positive (HPV +) or underwent thinprep cytology test (TCT) for atypical squamous cells of undetermined significance (ASCUS) and above. Furthermore, colposcopies and biopsies were performed for the histopathological examination. Finally, 9991 cases were included in the statistical analysis, and the factors influencing HPV infection and those related to cervical cancer and precancerous lesions were analyzed. HPV + infection, high-grade squamous intraepithelial lesion-positive (CINII +) in cervical high-grade intraepithelial neoplasia, and early cervical cancer diagnosis rates were 12.45, 1.09, and 95.41%, respectively. The potential risk factors for HPV were education ≤ high school [odds ratio (OR) = 1.279 (1.129–1.449), P < 0.001], age at initial sexual activity ≤ 19 years [OR = 1.517 (1.080–2.129), P = 0.016], sexual partners > 1 [OR = 1.310 (1.044–1.644), P = 0.020], ASCUS and above [OR = 11.891 (10.105–13.993), P < 0.001], non-condom contraception [OR = 1.255 (1.059–1.487), P = 0.009], and HSIL and above [OR = 1.541 (1.430–1.662), P < 0.001]. Compared with women aged 56–65 and 35–45 years [OR = 0.810 (0.690–0.950), P = 0.010] the HPV infection rate was significantly lower in those aged 46–55 years [OR = 0.79 (0.683–0.915), P = 0.002]. Furthermore, ≤ high school age [OR = 1.577 (1.042–2.387), P = 0.031], not breastfeeding [OR = 1.763 (1.109–2.804), P = 0.017], ASCUS and above [OR = 42.396 (28.042–64.098), P < 0.001] were potential risk factors for cervical cancer and precancerous lesions. In women with HPV infection, ≤ high school education level, initial sexual activity at ≤ 19 years of age, number of sexual partners > 1, ASCUS and above, non-condom contraception, HSIL and above were risk factors for HPV infection. Compared with women aged 56–65 years, those aged 35–45 and 46–55 years had significantly lower HPV infection rates, and high school age and below, non-breastfeeding, and ASCUS and above were all potential risk factors for cervical cancer and precancerous lesions.

Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan–Meier method. A protein–protein interaction network was constructed using STRING software. The “ClusterProfiler” package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan–Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.

The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.

Circular RNAs (circRNAs) are a class of single-stranded covalently closed non-coding RNAs without a 5′ cap structure or 3′ terminal poly (A) tail, which are expressed in a variety of tissues and cells with conserved, stable and specific characteristics. Glioblastoma (GBM) is the most aggressive and lethal tumor in the central nervous system, characterized by high recurrence and mortality rates. The specific expression of circRNAs in GBM has demonstrated their potential to become new biomarkers for the development of GBM. The specific expression of circRNAs in GBM has shown their potential as new biomarkers for GBM cell proliferation, apoptosis, migration and invasion, which provides new ideas for GBM treatment. In this paper, we will review the biological properties and functions of circRNAs and their biological roles and clinical applications in GBM.

Glioblastoma is the most common and aggressive primary central nervous system malignant tumors. With the development of targeted sequencing and proteomic profiling technology, some new tumor types have been established and a series of novel molecular markers have also been identified. The 2021 updated World Health Organization classification of central nervous system tumors first mentioned the classification of adult glioma and pediatric glioma based on the molecular diagnosis. Thus, we used single-cell RNA sequencing analysis to explore the diversity and similarities in the occurrence and development of adult and pediatric types. ASTN2, which primarily encodes astrotactin, has been reported to be dysregulated in various neurodevelopmental disorders. Although some studies have demonstrated that ASTN2 plays an important role in glial-guided neuronal migration, there are no studies about its impact on glioblastoma cell migration. Subsequent single-cell RNA sequencing revealed ASTN2 to be a hub gene of a cell cluster which had a poor effect on clinical prognosis. Eventually, a western blot assay and a wound-healing assay first confirmed that ASTN2 expression in glioblastoma cell lines is higher than that in normal human astrocytes and affects the migration ability of glioblastoma cells, making it a potential therapeutic target.

UM-164 is a dual inhibitor of c-Src and p38 MAPK, and has been a lead compound for targeting triple-negative breast cancer. UM-164 shows stronger binding to the active sites of Src compared with the conventional Src inhibitor Dasatinib. While Dasatinib has displayed some inhibitory effects on glioma growth in clinical trials, whether UM-164 can suppress glioma growth has not been reported. Here we show that UM-164 suppressed the proliferation, migration and spheroid formation of glioma cells, and induced cell cycle arrest in the G1 phase. Moreover, UM-164 triggered YAP translocation to the cytoplasm and reduced the activity of YAP, as evidenced by a luciferase assay. Accordingly, UM-164 markedly decreased the expression levels of YAP target genes CYR61 and AXL. Importantly, ectopic expression of wild-type YAP or YAP-5SA (YAP constitutively active mutant) could rescue the anti-proliferative effect induced by UM-164. Intriguingly, p38 MAPK appears to play a greater role than Src in UM-164-mediated inhibition of YAP activity. Furthermore, the in vitro anti-glioma effect mediated by UM-164 was confirmed in a xenograft glioma model. Together, these findings reveal a mechanism by which UM-164 suppresses the malignant phenotypes of glioma cells and might provide a rationale for UM-164-based anti-glioma clinical trials.

Whether N6‐Methyladenosine (m6A)‐ and ferroptosis‐related genes act on immune responses to regulate glioma progression remains unanswered. Data of glioma and corresponding normal brain tissues were fetched from the TCGA database and GTEx. Differentially expressed genes (DEGs) were identified for GO and KEGG enrichment analyses. The FerrDb database was based to yield ferroptosis‐related DEGs. Hub genes were then screened out using the cytoHubba database and validated in clinical samples. Immune cells infiltrating into the glioma tissues were analysed using the CIBERSORT R script. The association of gene signature underlying the m6A‐related ferroptosis with tumour‐infiltrating immune cells and immune checkpoints in low‐grade gliomas was analysed. Of 6298 DEGs enriched in mRNA modifications, 144 were ferroptosis‐related; NFE2L2 and METTL16 showed the strongest positive correlation. METTL16 knockdown inhibited the migrative and invasive abilities of glioma cells and induced ferroptosis in vitro. NFE2L2 was enriched in the anti‐m6A antibody. Moreover, METTL16 knockdown reduced the mRNA stability and level of NFE2L2 (both p < 0.05). Proportions of CD8+ T lymphocytes, activated mast cells and M2 macrophages differed between low‐grade gliomas and normal tissues. METTL16 expression was negatively correlated with CD8+ T lymphocytes, while that of NFE2L2 was positively correlated with M2 macrophages and immune checkpoints in low‐grade gliomas. Gene signatures involved in the m6A‐related ferroptosis in gliomas were identified via bioinformatic analyses. NFE2L2 interacted with METTL16 to regulate the immune response in low‐grade gliomas, and both molecules may be novel therapeutic targets for gliomas. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]