Cell Density Regulates Antibody Accessibility and Metabolic Turnover of Gangliosides in Human Glioma Cells

The effects of cell density on the gangliosides of 4 human glioma cell lines were studied. The cell lines used were KG-1C (GM3-dominant) , A172 and H4 (GM2-dominant), and Hs683 (GM3, GM2-co-dominant) cells. All these cell lines showed higher immunofluorescence with anti-ganglioside antibodies in FACS analysis at sparse density than at confluent density. Steric hindrance from cell surface proteins had been removed by the pretreatment of the cells with trypsin. The chemical content of gangliosides was consistent throughout the time of cell growth. The mechanisms of crypticity of gangliosides at confluent culture were under investigation. We first evaluated the metabolic turnover rate of gang-liosides at different cell densities. The results clearly showed a more rapid turn-over of gangliosides at sparse density from approximately 2 to 4 fold in terms of radioactivities of incorporated tritium into gangliosides. The profiles of labeled gangliosides were also different between the sparse and confluent cultures. We speculate that better accessibilities of antibodies toward gangliosides should be facilitated by the same mechanism which should, in turn, provide easier access of carbohydrate-hydrolysis enzymes to gangliosides at sparse cell density in order to keep an enhanced turnover rate

Reduction of glycolipids with D-PDMP, a glucosylceramide synthetase inhibitor, caused cell growth inhibition, enhanced cell adhesion, and facilitated cell motility in human glioma cells

Glycolipid synthesis inhibitor, D-PDMP, not only inhibited the production of glycolipid but also inhibited cell growth in human glioma cell line KG-1C in a cell cycle non-dependent manner. The reduction of glycolipid from the cell membrane allowed us to study the biological functions of glycolipids. The ability of cells to adhere to collagen was enhanced by the reduction of glycoli-pids, and random cell migration was also activated by the effect of D-PDMP. The results supported our speculation that glycolipids might function in cell growth, adherence and locomotion

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

Abstract 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

Single-Cell Sequencing Analysis Identified ASTN2 as a Migration Biomarker in Adult Glioblastoma

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

Unlock the power of bovine milk-derived exosomes for degenerative diseases associated with aging

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

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

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

Overexpression of microRNA-129-5p in glioblastoma inhibits cell proliferation, migration, and colony-forming ability by targeting ZFP36L1

Glioblastoma multiforme (GBM) is a highly invasive cancer with a high recurrence rate. The prognosis of GBM patients remains poor, even after standard surgical resection combined with chemoradiotherapy. Thus, there is an urgent need for new therapeutic targets in GBM. In recent years, microRNAs have received considerable attention due to their important role in tumor development and progression. In this study, we investigated the role of miR-129-5p and miR-129-5p/ZFP36L1 axis in GBM tumorigenesis. Analysis of GSE103228 microarray data from the GEO database showed that miR-129-5p was significantly downregulated in GBM vs. normal brain tissues. Quantitative reverse transcription PCR analysis of miR-129-5p expression in seven GBM cell lines (LN229, A172, U87, T98G, U251, H4, and LN118) vs. normal human astrocytes (NHA) showed miR-129-5p was significantly downregulated in GBM cells. Overexpression of miR-129-5p in LN229 and A172 cells significantly suppressed cell proliferation, migration, invasion, and colony-forming ability. Target Scan analysis identified ZFP36L1 as the target of miR-129-5p. UALCAN dataset analysis found that ZFP36L1 was significantly upregulated in GBM vs. normal brain tissues, and high ZFP36L1 expression was positively associated with poor survival of GBM patients. Western blot analysis demonstrated that ZFP36L1 was significantly upregulated in seven GBM cell lines vs. NHA. Overexpression of miR-129-5p in LN229 and A172 cells significantly inhibited ZFP36L1 mRNA and protein expression, while overexpression of ZFP36L1 in LN229 and A172 cells reversed miR-129-5p-mediated inhibition on GBM tumorigenesis. Our results revealed an important role of miR-129-5p in the negative regulation of ZFP36L1 expression in GBM, suggesting new candidates for targeted therapy in GBM patients

Application of Multiparametric Intraoperative Ultrasound in Glioma Surgery

Gliomas are the most invasive and fatal primary malignancy of the central nervous system that have poor prognosis, with maximal safe resection representing the gold standard for surgical treatment. To achieve gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of currently available equipment, developing a real-time image-guided resection technique that provides reliable functional and anatomical information during intraoperative settings is imperative. Nowadays, the application of intraoperative ultrasound (IOUS) has been shown to improve resection rates and maximize brain function preservation. IOUS, which presents an attractive option due to its low cost, minimal operational flow interruptions, and lack of radiation exposure, is able to provide real-time localization and accurate tumor size and shape descriptions while helping distinguish residual tumors and addressing brain shift. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound, three-dimensional ultrasound, navigable ultrasound, ultrasound elastography, and functional ultrasound, could help to achieve GTR during glioma surgery. The current review describes current advancements in ultrasound technology and evaluates the role and limitation of IOUS in glioma surgery

Additional file 1 of Breast cancer screening and early diagnosis in China: a systematic review and meta-analysis on 10.72 million women

Additional file 1: Table S1. The summary of detailed search keywords. Table S2. PRISMA checklist. Table S3. The pooled breast cancer detection rates in different subgroups of organized screening programs (China, 2010-2023). Table S4. The pooled early-stage (0–II) breast cancer detection rates in different subgroups of organized screening programs (China, 2010-2023). Table S5. The pooled proportion of early-stage (0–II) breast cancer in different subgroups of organized screening programs (China, 2010-2023). Figure S1. Forest plot of pooled breast cancer detection rate (China, 2010-2023) (A) opportunistic screening; (B) population screening. Figure S2. Forest plot of pooled early-stage (0–II) cancer detection rate (China, 2010-2023) (A) opportunistic screening; (B) population screening. Figure S3. Forest plot of pooled the proportion of early-stage (0–II) cancer (China, 2010-2023) (A) opportunistic screening; (B) organized screening