Kidney organoids are a type of three-dimensional cellular aggregates derived from primary tissues or stem cells cultured in vitro. Under specific induction conditions, these cell aggregates can differentiate into complex renal nephron structures, including glomeruli, proximal tubules, and distal tubules. These cells have been demonstrated to possess a remarkable capacity for self-renewal and self-organization, demonstrating a high degree of structural and functional similarity to the structure of kidney organs and the certain renal functions. Due to their ability to replicate the key renal structures and functions, they hold significant potential in various areas of kidney disease research, including novel drug development, disease modeling, personalized medicine, and therapeutic interventions for kidney diseases. In this review, we summarize the recent advancements in organoid culture technology and the applications of organoids in kidney diseases. The technical challenges and current limitations of organoid technology and possible solutions are also discussed. The aim of this review is to promote the development of organoid technology and to provide the theoretical knowledge for researchers in related fields.
Intervertebral disc degeneration (IDD) is a chronic degenerative disorder, with oxidative stress being one of the primary driving mechanisms of IDD. Hydroxysafflor yellow A (HSYA), a major active component of safflower, exhibits potent antioxidant, anti-inflammatory, and anti-apoptotic properties. However, its role in IDD remains unclear. To explore the mechanism underlying HSYA’s protection against tert-butyl hydroperoxide (TBHP)-induced oxidative stress in chondrocytes. Chondrocytes were treated with TBHP (100 µM) to establish an oxidative stress model, followed by administration of HSYA (5, 10, and 20 µM). Cell viability and apoptosis were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Lipid peroxidation levels were evaluated by immunofluorescence. The protein expression levels of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), SRY-box transcription factor 9 (SOX9), type II collagen (COL2), matrix metalloproteinase 3 (MMP-3), type X collagen (COL10), and runt-related transcription factor 2 (RUNX2) were analyzed by western blot analysis. mRNA expression of SLC7A11, GPX4, COL10, and RUNX2 was determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Calcium deposition in endplate chondrocytes was examined by Alizarin Red staining. Compared with the control group, treatment with TBHP markedly reduced chondrocyte viability, promoted ferroptosis, and significantly elevated intracellular lipid peroxidation levels. Furthermore, TBHP exposure triggered a prominent increase in chondrocyte apoptosis, cartilage endplate (CEP) degeneration, and chondrocyte calcification. Notably, all these findings were dose-dependently reversed by HSYA intervention. However, SLC7A11 knockdown abolished the protective effects of HSYA against TBHP-induced chondrocyte damage. In summary, our findings indicate that HSYA protects chondrocytes from TBHP-induced oxidative stress, ferroptosis, apoptosis, and calcification, and alleviates CEP degeneration, at least partly associated with SLC7A11/GPX4-related redox regulation, providing in vitro experimental evidence for exploring its value in IDD-related research.
Teleost myogenesis differs from mammalian systems, and well-characterized fish myogenic cell models remain limited. Tetrandrine, a bisbenzylisoquinoline alkaloid, impairs myogenesis and induces atrophy-associated responses in mammalian models, but its effects on teleost myogenic cells remain unclear. This study examined tetrandrine responses in black sea bream (Acanthopagrus schlegelii) myogenic cell lines. Cells were treated with tetrandrine to assess cytotoxicity, proliferative growth, myogenic differentiation, and associated cellular responses. Tetrandrine showed concentration-dependent cytotoxicity at higher concentrations, and 1, 3, and 5 µM were selected for subsequent experiments. Under growth conditions, tetrandrine exerted modest, cell line-dependent effects on proliferation. In contrast, tetrandrine markedly inhibited myogenic differentiation, as shown by reduced myotube formation, decreased fusion index, and suppressed expression of myogenic regulatory genes, including Pax7, MyoD, Myog, and MyHC. To examine whether proteolytic or oxidative stress-related processes contributed to this phenotype, cells were co-treated with MG-132, chloroquine, or N-acetylcysteine. These treatments did not restore tetrandrine-impaired myotube fusion, although MG-132 partially restored MyHC expression and tetrandrine induced a cell line-dependent increase in intracellular ROS. Fluo-4-based Ca²⁺ measurements further showed that acute tetrandrine treatment attenuated KCl-induced Ca²⁺ responses in differentiated cells, whereas undifferentiated cells showed little change. These findings suggest that altered depolarization-linked Ca²⁺ handling may contribute to tetrandrine-associated inhibition of myogenic differentiation in this teleost cell system.
Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a global health burden with limited therapies. Berberine (BBR) shows promise against MASLD, but its molecular mechanisms remain unclear. Network pharmacology predicted BBR-MASLD intersecting targets, followed by protein-protein interaction (PPI) network construction, GO/KEGG enrichment, and molecular docking. In vitro validation used FFA-induced HepG2 steatosis cells with Oil Red O staining, triglyceride assay, RT-qPCR, and Western blot for p-AKT/AKT. From 147 intersecting targets, six functional core targets were identified: AKT1, IL6, TP53, TNF, IL1B, and BCL2. Enrichment analyses implicated insulin resistance, lipid metabolism, and inflammation. Molecular docking confirmed strong BBR–core protein binding. In vitro, BBR dose-dependently reduced lipid accumulation and triglyceride levels, downregulated lipogenic (SREBP-1c) and pro-inflammatory (IL-6, IL-1β, TNF-α) genes, and restored insulin signaling (AKT1) and apoptosis-related (TP53) gene expression.BBR increased the p-AKT (Ser473)/total AKT ratio as shown by Western blot. BBR attenuates lipid accumulation and partially reverses steatosis-related transcriptional changes in an FFA-induced HepG2 model, including restoration of AKT1 signaling at both mRNA and protein phosphorylation levels. These findings suggest that BBR exerts protective effects againstearly hepatocellular steatosist hrough coordinated regulation of lipid metabolism, inflammation, and stress-related targets. This study provides a network-based rationale for further in vivo and mechanistic investigation in MASLD, and identifies potential pharmacodynamic biomarkers for future clinical trials.
Hemidesmus indicus (L) R. Br. root extract-mediated silver nanoparticles (HiAgNPs) were synthesized and evaluated for anticancer activity against ovarian cancer cells. GC–MS analysis identified forty bioactive compounds in the root extract, which facilitated the green synthesis of nanoparticles. Characterization using UV–visible spectroscopic analysis showed a surface plasmon resonance peak at 428 nm, while SEM revealed predominantly spherical nanoparticles. On the other hand, DLS revealed a size distribution peak at 222.2 d.nm, whereas zeta potential was found to be -20.9 mV. Further, EDX analysis confirmed the presence of silver (Ag) and oxygen (O), and FTIR revealed distinct patterns in the stretching vibrations of their functional groups, indicating the presence of capping agents in the nanoparticles. Antioxidant activity was assessed using DPPH and FRAP assays. MTT assay demonstrated significant dose- and time-dependent cytotoxicity of HiAgNPs against SKOV3 cells. Apoptotic induction was confirmed through nuclear morphology, acridine orange/ethidium bromide staining, migration assays, and RT-PCR analysis of Bax, Bcl2 and Caspase 3 genes. Overall, this study highlights HiAgNPs as a promising eco-friendly therapeutic candidate for treating ovarian cancer .
To explore the function and molecular mechanism of BACH2 in septic lung injury induced by lipopolysaccharide (LPS). We established LPS-induced septic lung injury models in mice and human bronchial epithelial BEAS-2B cells. By overexpressing/knocking down BACH2 and knocking down Nrf2, combined with pathological staining, molecular biology and cell experiment techniques, we detected the levels of lung tissue injury, inflammation and pulmonary fibrosis, and verified the regulatory relationship between BACH2 and Nrf2. In the lung tissues of mice with LPS-induced septic lung injury, the expression level of BACH2 was decreased in a time-dependent pattern. Overexpression of BACH2 significantly alleviated LPS-induced pathological injury of mouse lung tissues, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines and the degree of pulmonary fibrosis. BACH2 could directly bind to the -2000 -1800 bp region of the Nrf2 promoter and upregulate its expression, and knockdown of Nrf2 completely reversed the lung protective effect of BACH2. BACH2 exerts anti-inflammatory and anti-fibrotic effects by directly binding to and activating the Nrf2 signaling pathway, thereby ameliorating LPS-induced septic lung injury. The BACH2/Nrf2 axis may serve as a candidate molecular target for further preclinical research on septic lung injury treatment.
Periodontitis (PDT) is a chronic inflammatory disease driven by a dysregulated host immune response, with neutrophils playing a pivotal role. Chromosomal instability (CI) has emerged as a potent trigger of inflammation, yet its involvement in non-malignant diseases like PDT remains unexplored. Bulk RNA-seq data from gingival tissues between PDT patients and healthy control(HC) were analyzed via Limma framework to identify differentially expressed genes (DEGs) and CI-associated DEGs. WGCNA pinpointed a module correlated with neutrophil infiltration. Next, CI and neutrophil(CIN)-associated signature were acquired by integrating Limma and WGCNA results. NMF was used for molecular subtyping based on CIN-associated signature. A machine learning framework constructed a diagnostic model, with SHAP analysis identifying the hub gene based on PDT training and validation bulk profiles. Single-cell RNA-seq data validated cellular-level findings, and cutting-edge analytical framework inferred TFF3 functional impact at neutrophil of PDT patients in a temporal and spatial manners. The AI platform DrugReflector screened for therapeutic compounds for PDT patients, and in vitro assays examined the expression of hub gene. We identified 5 CI and neutrophil(CIN)-associated signature for PDT patients, which can guide the forecasting of PDT pathogenesis and PDT patient stratification. Besides, TFF3 can be considered as CIN-associated up-regulated pathogenic factor involved in PDT pathogenesis, which was mainly expressed in neutrophil. BRD-K92455082 as a candidate therapeutic agent targeting TFF3 for the treatment of PDT. This study first identifies a novel CIN-associated co-expression patterns in PDT. TFF3 can be considered as a candidate hub gene associated with a pro-inflammatory neutrophil state, providing new insights into the molecular taxonomy of PDT.
Mitochondria-targeted antioxidants have emerged as a promising frontier in drug discovery, offering advantages over conventional antioxidants owing to recent technological advances. As the primary intracellular source of reactive oxygen species (ROS) mitochondria play a critical role in cellular health. Consequently, excessive mitochondrial ROS generation is heavily implicated in the pathogenesis of cardiovascular, neurodegenerative, and metabolic disorders. The etiopathogenesis of cardiovascular disease is mainly due to the dysfunction of mitochondria. Therefore, mitochondrial dysfunction is a novel curious target for developing new drug therapies. In this study, mitochondrial antioxidant (Ru-TPP-GGN) was prepared by incorporating triphenylphosphonium (TPP) conjugated rutin into guar gum nanoparticles (GGN) and was evaluated against angiotensin II (Ang II) induced hypertrophy in the H9c2 cell lines. The size of the synthesized Ru-TPP-GGN was about ≈ 15 nm, and it was subjected to detailed characterization to confirm its nano-characteristics. The cytoxicity analysis showed that the Ru-TPP-GGN was nontoxic to the cells. The cells treated with Ang II showed abnormalities in mitochondria with surplus superoxide generation, an increase in atrial natriuretic peptide (ANP) (125.75
Post-intracerebral hemorrhage brain injury (post-ICH BI), a cerebrovascular subtype, has limited early diagnostic markers and difficulties in controlling secondary injury. This study evaluated serum LINC01094 for early diagnosis of post-ICH BI and its regulation of neuronal apoptosis and inflammation via targeting miR-128-3p. Eighty-nine patients with early post-ICH BI and 106 controls with high-risk factors underwent qPCR to measure serum LINC01094 and miR-128-3p levels. ROC curve, logistic regression, and correlation analyses were used to assess their clinical value. A post-ICH BI cell model was established using OGD/R combined with Hemin-CM, and the effects of LINC01094 silencing alone or co-inhibition of miR-128-3p were evaluated via qPCR, CCK-8, Western blot, and ELISA. Serum LINC01094 was significantly increased in post-ICH BI patients, while miR-128-3p was decreased. A strong negative correlation was observed between the two. The AUC for serum LINC01094 in diagnosing post-ICH BI was 0.877. High LINC01094 expression was an independent risk factor for disease onset and positively correlated with hemorrhage volume and NIHSS score, but negatively correlated with GCS score. In cell experiments, LINC01094 silencing enhanced SH-SY5Y proliferation, reduced pro-apoptotic proteins (Bax, p38α, caspase-3), suppressed pro-inflammatory cytokines (IL-1β, TNF-α, IL-6), increased SOD and CAT activity, and lowered NSE and S100B levels. Co-inhibition of miR-128-3p reversed the protective effects of LINC01094 silencing. LINC01094 serves as a potential biomarker for early diagnosis and severity assessment of post-ICH BI. In vitro evidence suggests the LINC01094/miR-128-3p axis may contribute to neuronal injury, offering valuable new insights for clinical management.
Gundelia komagenensis Fırat, an endemic member of the Asteraceae family, was investigated for its phytochemical composition, antioxidant, enzyme inhibitory, cytotoxic, and computationally predicted pharmacological properties. Methanol (MeOH) and dichloromethane (DCM) extracts prepared from the aerial parts of Gundelia komagenensis were evaluated using ABTS and FRAP antioxidant assays, enzyme inhibition tests against acetylcholinesterase (AChE), α-glucosidase, and α-amylase, LC-MS/MS profiling, MTT-based cytotoxicity assays, and integrated in silico analyses. Both extracts exhibited antioxidant activity; among the extracts, DCM had a lower ABTS IC₅₀ value than MeOH (13.7 vs.14.5 µg/mL). DCM also had lower IC₅₀ values for AChE, α-glucosidase, and α-amylase than MeOH (1.132–1.372 µg/mL). LC-MS/MS revealed solvent-dependent profiles, with chlorogenic acid, vanillin, trans-cinnamic acid, and gentisic acid predominating in MeOH, and vanillin, trans-cinnamic acid, and luteolin in DCM. The MeOH extract of G. komagenensis did not exhibit significant cytotoxicity against either MIA PaCa-2 or HUVEC cells. In contrast, the DCM extract reduced MIA PaCa-2 cell viability in a concentration-dependent manner while exerting relatively limited effects on HUVEC cells, suggesting a selective cytotoxicity tendency under the tested conditions. Computational analyses identified chlorogenic acid as the most promising bioactive constituent. Molecular docking showed the highest binding affinities toward AChE, α-glucosidase, and α-amylase, while molecular dynamics simulations and MM-GBSA calculations supported the stability of the corresponding protein–ligand complexes. Network pharmacology suggested that the identified phenolics may regulate disease-related pathways through AP-1/NF-κB-associated targets. Chlorogenic acid emerged as a key multi-target candidate warranting further experimental validation.
Impaired healing of osteoporotic femoral neck fractures is a serious problem facing the clinic. There is a lack of effective preoperative prognostic indicators, and the underlying molecular mechanisms require further exploration. In this retrospective cohort study, 160 patients with osteoporotic femoral neck fractures were enrolled, with 71 exhibiting poor healing and 89 normal healing. Serum samples were collected upon admission, prior to surgery. Expression of miR-99b-3p and BMP8A was detected via qRT-PCR. The preliminary discriminatory ability of miR-99b-3p was evaluated using ROC curves. The effects of miR-99b-3p on cell viability and osteogenic activity in MC3T3-E1 and hBMSCs were assessed using CCK-8, while osteogenic marker expression (RUNX2, ALP, FN1, Osteocalcin) was analyzed via qPCR, and protein-level mechanistic validation was performed via Western blotting. Targeting of the BMP8A 3’UTR by miR-99b-3p was validated via dual-luciferase assay. Serum miR-99b-3p was significantly upregulated in patients with poor healing (P < 0.001) and showed a significant negative correlation with BMP8A (Adjusted partial r = -0.755, P < 0.001). ROC analysis indicated that serum miR-99b-3p showed preliminary discriminatory ability for identifying poor healing (AUC = 0.859, 95
Pancreatic cancer is one of the most malignant solid tumors, with a five-year survival rate of less than 10
Background Oral lichen planus (OLP) is a prevalent chronic disease affecting the oral mucosa, and its pathogenesis remains not fully understood. This study aims to examine the regulatory mechanism of METTL14/FDX1 in the development of OLP. Methods Macrophage polarization and METTL14/FDX1 expression were analyzed in mucosal tissues from OLP patients and controls via immunofluorescence, RT-qPCR, and ELISA. In vitro, THP-1-derived macrophages were transfected with METTL14 or FDX1 targeting/overexpression vectors to assess their roles in polarization (flow cytometry) and cytokine secretion (ELISA). The METTL14-FDX1 interaction and m6A modification were confirmed by RIP and MeRIP-PCR. Functional outcomes were evaluated in a macrophage-keratinocyte co-culture system (flow cytometry) and in an imiquimod-induced OLP mouse model treated with sh-METTL14. Results The abnormal accumulation of M1 macrophage was identified in mucosa of OLP patients. Upregulation of m6A-related key enzyme METTL14 was identified in macrophages of OLP patients, which was associated with inflammation of OLP. Mechanically, METTL14 knockdown reduced mRNA stability of FDX1 through m6A modification, thereby limiting the transcriptional expression of FDX1 in macrophage. Functionally, METTL14 overexpression promoted macrophage M1 polarization through upregulating FDX1. Additionally, macrophages with METTL14 knockdown inhibited keratinocytes apoptosis by polarizing to M2. In vivo, METTL14 knockdown alleviated inflammation in OLP mouse model by driving macrophage M2 polarization. METTL14, via upregulating FDX1, also promoted the production of T-helper cell-associated inflammatory cytokines (IFN-γ, IL-17) integral to OLP pathology. Conclusion METTL14 knockdown alleviates inflammation in OLP by driving macrophage M2 polarization through mediating FDX1 m6A modification.
Demyelination is a hallmark of many neurological diseases such as Multiple sclerosis. The cuprizone (CPZ) model is as an optical model for the investigation of white matter lesions (WMLs). In this study, the treatment effects and mechanisms of Epimedium flavonoids (EF) on the CPZ-induced demyelination model were explored. After feeding chow containing 0.2
The optimization of culture conditions for primary vascular cells remains challenging, as cell viability alone does not necessarily reflect preserved molecular identity or functional stability. Human umbilical vein endothelial cells (HUVECs) and Human aortic vascular smooth muscle cells (T/G HA-VSMCs) are highly sensitive to their microenvironment, and non-specific or poorly standardized supplements may sustain survival while disrupting gene expression and phenotypic integrity. Human platelet lysate (HPL) has emerged as a human-derived alternative to conventional supplements. However, its role as a supplement rather than a complete serum replacement remains insufficiently explored in vascular cell culture systems. This research innovates by evaluating HPL and CM as complementary supplements to FBS rather than standard specific medium. HUVECs and T/G HA-VSMC were cultured in Dulbecco’s Modified Eagle Medium supplemented with 10
This study aimed to investigate the biological functions and underlying molecular mechanisms of circular RNA plasmacytoma variant translocation 1 (circPVT1) in the progression of thyroid cancer.The expression levels of circPVT1 in thyroid tumor tissues and cell lines were compared to normal controls, and its association with clinicopathological features was analyzed. Functional assays were performed to assess the effects of circPVT1 silencing on thyroid cancer cell migration, invasion, and glucose metabolism. The interaction between circPVT1 and miR-195-5p was validated using bioinformatics prediction, RNA pull-down, dual-luciferase reporter assays, and RNA fluorescence in situ hybridization (FISH). The target relationship between miR-195-5p and pyruvate dehydrogenase kinase 4 (PDK4) was examined via luciferase reporter and Western blot assays. Rescue and epistasis experiments were conducted by restoring miR-195-5p expression or knocking down PDK4 in circPVT1-overexpressing cells. The role of the circPVT1/miR-195-5p/PDK4 axis was further validated in vivo using subcutaneous xenograft and experimental lung metastasis models.circPVT1 was significantly upregulated in thyroid tumors and cell lines, and its high expression correlated with advanced TNM stage and lymph node metastasis. Silencing circPVT1 suppressed migration, invasion, and glycolytic metabolism of thyroid cancer cells. Mechanistically, circPVT1 acted as a sponge for miR-195-5p, downregulating its expression, and miR-195-5p directly targeted and inhibited PDK4. Restoration of miR-195-5p or knockdown of PDK4 reversed the oncogenic phenotypes induced by circPVT1 overexpression. In vivo, circPVT1 promoted tumor growth and lung metastasis, which were attenuated by co-expression of miR-195-5p. Molecular analysis of lung metastases confirmed the dysregulation of the circPVT1/miR-195-5p/PDK4 axis within metastatic lesions.CircPVT1 promotes migration, invasion, glycolytic metabolism, and metastasis in thyroid cancer by sponging miR-195-5p and upregulating PDK4. These findings highlight the circPVT1/miR-195-5p/PDK4 axis as a potential therapeutic target for thyroid cancer intervention.
SOX4 participates in cell differentiation, but its regulatory function and underlying mechanism in the osteogenic differentiation of MC3T3-E1 cells remain elusive. Immunofluorescence staining was used to detect SOX4 subcellular localization and co-localization with NLRP3. Alizarin Red staining was applied to evaluate osteogenic differentiation. RT-PCR and Western blot assays quantified mRNA and protein levels of SOX4, osteogenic markers (OPN, OCN, RUNX2), inflammatory cytokines, and pyroptosis-related proteins (NLRP3, caspase-1, GSDMD). JASPAR predicted SOX4 binding sites in the NLRP3 promoter and ChIP-qPCR was used to validate it. Dual-luciferase reporter assay was applied to assesse transcriptional regulation. Rescue experiments were performed via co-transfection of SOX4 and NLRP3 overexpression vectors. SOX4 was upregulated during MC3T3-E1 osteogenic differentiation. SOX4 overexpression reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), increased IL-10, and inhibited pyroptosis. SOX4 directly bound to the NLRP3 promoter to suppress its transcription. NLRP3 overexpression reversed SOX4-induced enhancement of osteogenic differentiation and marker expression. SOX4 promotes MC3T3-E1 osteogenic differentiation by directly inhibiting NLRP3 transcription, thereby regulating inflammation and pyroptosis.
Abelmoschus moschatus i.a. a prostrate herb that is grown for its seed in tropical portions of Africa, South America, and Asia. It is a member of the Malvaceae family and also referred to Mushkdana. This plant has been reported for diuretic, antioxidant, antiproliferative, and antimicrobial activities along with its traditionally used in relieve spasms of the digestive track, aching joints and also considered as insecticide. Thus, anti-arthritic action of hydro-alcoholic extract of Abelmoschus moschatus seeds (EEAMS) were investigated in rats with arthritis caused by Complete Freund’s adjuvant (CFA). In the present work powdered Abelmoschus moschatus seeds were extracted using 70
Sepsis-associated acute respiratory distress syndrome (SA-ARDS) is a severe disease with high morbidity and mortality. Emerging evidence indicates that ferroptosis plays a critical role in the development of SA-ARDS. However, the key regulatory targets and underlying molecular mechanisms remain to be further elucidated. Weighted gene co-expression network analysis (WGCNA) was performed based on the GSE66890 dataset to identify SA-ARDS-related gene modules. Candidate genes were screened by intersecting WGCNA module genes with ARDS-related targets from the GeneCards database and ferroptosis-related genes from FerrDb. An in vitro SA-ARDS model was established in HuLEC-5a cells using lipopolysaccharide (LPS). Cell viability, inflammatory cytokine levels, apoptosis, and ferroptosis-related parameters, including ROS, MDA, 4-HNE, and Fe2+ levels, were evaluated using MTT, ELISA, flow cytometry, and corresponding assay kits. The mRNA and protein expression levels were determined by RT-qPCR and Western blot. The transcriptional regulation of topoisomerase II alpha (TOP2A) by GATA binding protein 2 (GATA2) was verified using JASPAR prediction, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. All cellular experiments were performed using three independent biological replicates. WGCNA identified the salmon and cyan modules as significantly associated with SA-ARDS. Intersection analysis identified TOP2A as a key ferroptosis-related gene in SA-ARDS. TOP2A was significantly upregulated in LPS-induced HuLEC-5a cells. Knockdown of TOP2A markedly alleviated LPS-induced cellular injury, as evidenced by enhanced cell viability, reduced levels of inflammatory cytokines (IL-6, IL-8, TNF-α), decreased apoptosis rate, and lowered ROS and Fe2+ accumulation, reduced MDA and 4-HNE levels, restored GPX4 and SLC7A11 expression, and decreased ACSL4 expression, along with increased expression of endothelial barrier-related proteins. GATA2 directly bound to the TOP2A promoter and activated its transcription. TOP2A overexpression reversed the protective effects of GATA2 knockdown in LPS-induced HuLEC-5a cells. GATA2 transcriptionally activated TOP2A expression, which in turn promoted ferroptosis and exacerbated LPS-induced HuLEC-5a cell injury.
To elucidate the key role and underlying mechanisms of C-C motif chemokine ligand 11 (CCL11) in cancer-associated fibroblasts (CAFs)-mediated prostate cancer (PCa) progression. In this study, we analyzed the dataset GSE85606 and validated the upregulation of CCL11 in CAFs using ELISA and qRT-PCR, demonstrating its strong correlation with established CAF biomarkers. Using CAFs-conditioned medium, recombinant human CCL11, specific siRNA, and CDK5 plasmid or siRNA in PCa cell lines, we investigated the functional role of CCL11. RNA-seq and TCGA database analyses predicted a CCL11’s downstream target (CDK5). Transwell, wound healing, and flow cytometry assays, along with Western blot, were employed to assess the effects of CCL11 on migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) pathways. The results indicate that CCL11, predominantly secreted by PCa-derived CAFs, significantly enhances the migration and invasion of PCa cells, suppresses their apoptosis, and activates the EMT pathway, largely through regulating CDK5 expression. Collectively, our findings suggest that CAFs-derived CCL11 may represent a potential therapeutic target for PCa.
