Open Life Sciences最新文献

Radiotherapy is an important cancer treatment for breast cancer patients, improving overall survival; however, it can lead to a common complication, radiation-induced heart disease (RIHD). N6-methyladenosine (m6A) RNA modification plays a critical role in the regulation of myocardial function. The aim of this study is to investigate the effect of m6A modification on cardiac injury following radiotherapy for breast cancer. Cardiac dysfunction was assessed by echocardiography and hematoxylin and eosin staining. The expression of ALKBH5 was analyzed by quantitative real-time PCR, western blot, and immunohistochemistry. The underlying mechanism was investigated using methylated RNA immunoprecipitation (MeRIP), RIP, and dual-luciferase reporter assays. The results showed that in RIHD, ALKBH5 expression was upregulated in breast cancer patients after radiotherapy and in RIHD mouse models. ALKBH5 downregulated the m6A modification level of Toll-like receptor 4 (TLR4). Overexpression of TLR4 abolished the inhibitory effect of ALKBH5 silencing on RIHD in mice. In summary, this study revealed a novel regulatory mechanism of ALKBH5-mediated m6A demethylation in RIHD, which could provide a promising therapeutic strategy for cardiac dysfunction following radiotherapy in breast cancer patients.

Gastric cancer is among the most common gastrointestinal malignancies with high morbidity and mortality rates, highlighting the need to further elucidate its pathogenesis and identify effective therapeutic targets. The regulatory factor X (RFX) gene family encodes transcription factors implicated in the development and progression of several cancers. Although RFX5 has been reported to influence tumor progression in various malignancies, its specific role in gastric adenocarcinoma remains unclear. In this study, we investigated the functional effects of RFX5 in gastric adenocarcinoma. Our findings revealed that RFX5 is highly expressed in gastric adenocarcinoma tissues. Silencing of RFX5 significantly inhibited cell proliferation and migration, while promoting apoptosis in gastric adenocarcinoma cells. Mechanistically, RFX5 knockdown activated the silent information regulator transcript 1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) signaling axis. These results suggest that RFX5 facilitates the growth and motility of gastric adenocarcinoma cells and suppresses apoptosis, at least in part, through modulation of the SIRT1/AMPK pathway.

Breast cancer (BC) is a major global health concern, ranking among the most common neoplasms and representing one of the leading causes of cancer-related deaths worldwide. Early recognition and classification of BC subtypes are crucial for improving patient outcomes. Therefore, identifying novel biomarkers with diagnostic and prognostic significance is of great importance. The Wnt signaling pathway plays a significant role in BC by influencing various cell cycle regulation processes and stem cell renewal. This study aims to identify novel Wnt-associated biomarker panels for BC patients, composed of multiple molecular factors. A series of bioinformatical analyses have been employed, including weighted gene co-expression network analysis, differential expression analysis, Kaplan-Meier survival analysis, logistic regression model evaluation, and receiver operating characteristic construction. Thus, this study revealed potential diagnostic and prognostic signatures based on comprehensive analyses of BC patient data sourced from The Cancer Genome Atlas database. Consequently, four gene signatures were constructed: two differentiate ER+ from ER-BC: TTC8, SLC5A7, and PLCH1 for overall survival (OS); ZNF695, SLC7A5, and PLCH1 for disease free survival (DFS), while the other two effectively distinguish tumor from normal samples: SPC25, ANLN, KPNA2, SLC7A5 for OS; SPC25, KIF20A, SKA3, DTL, CDCA3, ANLN, TTK, RAD54L, MYBL2, ZNF695, and SLC7A5 for DFS.

Pure red cell aplasia (PRCA) is a rare blood disorder that is characterized by severe hypo-erythroid bone marrow hypoplasia leading to severe anemia that usually does not respond to standard treatment. In patients with chronic kidney disease (CKD), especially in those patients who are erythropoiesis-stimulating agent (ESA) resistant, management can be quite difficult. In this case report, we will present a 67-year-old woman with CKD (not on dialysis) who presented with refractory anemia (hemoglobin 45-65 g/L) and was ultimately diagnosed with PRCA after bone marrow aspirate. This patient had previously received treatment (ESAs, iron supplementation, and multiple blood transfusions) without improvement in her blood counts. After initiation of oral Roxadustat 100 mg t.i.w., her hemoglobin increased gradually and stabilized between 100 and 106 g/L, and she no longer required blood transfusions. This case report highlights the potential role of Roxadustat as a new therapeutic option for PRCA and ESA-resistant CKD. While these data are encouraging, larger controlled studies are going to be required to evaluate measures of efficacy, dosing, and long-term safety in this population.

Exosomes are important mediators of intercellular communication, primarily through the transfer of miRNAs. However, the mechanisms regulating exosome secretion and miRNA cargo loading in T cells remain incompletely understood. In this study, we investigated the effects of bee venom (BV), a natural compound with known immunomodulatory activity, on the exosomal miRNA profile in human Jurkat T cells. The non-cytotoxic concentration of BV (2 μg/mL) was identified using the CCK-8 assay. Exosomes were isolated from BV-treated and control cells and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis (NTA), with NTA also used to quantify particle concentration for assessing changes in secretion levels. High-throughput sequencing identified 74 differentially expressed miRNAs (44 upregulated, 30 downregulated), which were validated by quantitative real-time PCR. Functional enrichment analyses (gene ontology, kyoto encyclopedia of genes and genomes, disease ontology, Reactome) revealed associations with pathways related to neural development, cell cycle regulation, and tumorigenesis. BV treatment significantly promoted exosome release and selectively altered miRNA cargo. These findings suggest that BV modulates T cell-derived exosome output and composition, providing mechanistic insights into how it may influence immune-related signaling pathways.

[This corrects the article DOI: 10.1515/biol-2022-1062.].

Excessive intracellular copper accumulation triggers cuproptosis, a novel regulated cell death process with therapeutic potential. Analyzing 566 The Cancer Genome Atlas samples alongside lung adenocarcinoma (LUAD)-specific microarray and single-cell sequencing data, we identified 109 cuproptosis-associated genes, of which C1QBP and PFKP emerged as key prognostic markers. Four-gene risk model stratified patients into high- and low-risk groups with distinct survival outcomes, where high-risk scores correlated with advanced TNM stages. Clinical validation confirmed that elevated C1QBP/PFKP expression in LUAD tissues predicted shorter progression-free survival. Functional assays demonstrated that silencing C1QBP or PFKP increased intracellular copper concentration, suppressed proliferation, and inhibited invasion, mechanistically linking these genes to cuproptosis dysregulation. Our findings nominate C1QBP/PFKP as actionable targets for LUAD therapy, offering both prognostic biomarkers and copper-metabolism-directed treatment strategies.

Cell proliferation and epithelial-mesenchymal transition (EMT) are two common tumor phenotypes closely linked to malignant tumor progression. Genes regulating tumor progression often exhibit consistent regulatory trends in these phenotypes; however, certain genes may display inconsistent regulatory patterns in tumor proliferation and EMT. In this investigation, initial transcriptomic and tumor database analyses revealed that alcohol dehydrogenase 5 (ADH5) is downregulated in non-small cell lung cancer (NSCLC) tissues and correlates negatively with NSCLC prognosis. Subsequent experimental manipulation of ADH5 levels in tumor cells demonstrated that ADH5 overexpression decreased proliferation while enhancing migration and invasion capacities in NSCLC cells. Moreover, ADH5 overexpression hindered xenograft tumor growth in nude mice. However, ADH5 knockdown yielded contrasting outcomes by stimulating NSCLC cell proliferation while impeding migration and invasion abilities. Notably, ADH5 overexpression triggered EMT through Smad2/Smad3 activation, leading to the upregulation of SRY-Box Transcription Factor 9. TGFbetaR1/ALK5 inhibitor SB431542 was able to alleviate the effects of ADH5 overexpression on NSCLC cells. This study indicates a critical role of ADH5 in tumors associated with cancer cell growth inhibition but EMT activation. These findings underscore ADH5 as a potential regulator of NSCLC cell plasticity, emphasizing its promise as a therapeutic target for NSCLC management.

Clove, Syzygium aromaticum, is a medicinal plant from the Myrtaceae family with various applications in traditional medicine. The plant has been studied for its analgesic, anti-inflammatory, antiviral, and anticancer properties. This study focuses on the green synthesis of silver nanoparticles using clove leaf extract. The synthesized NPs were characterized using chemical methods and their anticancer activity was tested against a leukemia cell line, along with the signaling pathway that followed. The AgNPs were synthesized in a spherical shape and were less than 50 nm in size. The cytotoxic effects of the AgNPs on PCS-800-011 primary peripheral blood mononuclear cells and 32D-FLT3-ITD leukemia cells were evaluated over 48 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cancer cells showed reduced viability with an IC₅₀ value of 162 µg/mL after exposure to the AgNPs. Through a detailed examination of the mTOR pathway, it was observed that AgNPs can alter the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting 32D-FLT3-ITD cell growth and death. This pathway may contribute to the inhibition of the cell cycle and induction of apoptosis by AgNPs. For this reason, AgNPs may be used as a natural anti-cancer treatment for leukemia.

Pathogenic co-infections in plants significantly impact microbial diversity and disease outcomes, yet their effects on microbial community structure and ecological processes remain unclear. Tobacco plants were co-infected with Ralstonia solanacearum and Neocosmospora falciformis. 16S ribosomal RNA and internal transcribed spacer amplicon sequencing were used to assess bacterial and fungal communities, respectively, in infected tobacco stems. The results were compared between co-infected and healthy control tobacco plants to assess the effects of infection. Co-infection reduced microbial diversity and shifted community structure, promoting ecological specialization. Network analysis revealed synergistic interactions between the pathogens, enhancing virulence through positive correlations with certain microbial taxa. Conversely, some taxa exhibited antagonistic effects, potentially limiting pathogen proliferation. Deterministic processes were found to dominate microbial community assembly under infection conditions, significantly reshaping the microbial landscape compared to healthy control plants. This study highlights the profound effects of co-infection on microbial diversity, community composition, microbial interactions, and community assembly processes in tobacco plants. These findings provide valuable insights for developing more targeted plant disease management strategies by manipulating microbial communities.