Experimental Cell Research[JOURNAL]
Sun
200 papers
ANXA1 inhibits ferroptosis in HUVECs via negative regulation of ferritinophagy.
Wang J, Jia J, Cao Z … +5 more , Cai Z, Zhang K, He J, Wu C, Wang Z
Exp Cell Res · 2026 Jan · PMID 41241173 · Publisher ↗
Ferroptosis is a phospholipid peroxidation-mediated and iron-dependent cell death form. Inhibiting ferroptosis is a promising strategy for the prevention and treatment of cardiovascular diseases. Annexin A1 (ANXA1) is an...
Ferroptosis is a phospholipid peroxidation-mediated and iron-dependent cell death form. Inhibiting ferroptosis is a promising strategy for the prevention and treatment of cardiovascular diseases. Annexin A1 (ANXA1) is an endogenous anti-inflammatory mediator that plays an important regulatory role in cardiovascular diseases such as atherosclerosis, especially in inflammation suppression, protecting the heart from injury, and regulating vascular function. Ac2-26 is a synthetic peptide derived from the N-terminal 26 amino acids of ANXA1, which retains its anti-inflammatory properties. However, the regulatory mechanism of ANXA1 in atherosclerosis (AS) is not yet fully understood. This study aims to explore the specific role of ferroptosis in HUVECs and demonstrate that ANXA1 can disrupt ferritinophagy and protect endothelial function. Treatment with Ac2-26 or ANXA1-overexpressing HUVECs alleviated RSL3-induced endothelial cell dysfunction and inhibited lipid peroxidation, as evidenced by a reduction in ferrous ion levels and upregulation of GPX4, FTH1, and SLC7A11 protein expression, along with a downregulation of LC3-II and NCOA4 expression. In contrast, knockdown of ANXA1 in HUVECs failed to suppress the outcome of ferroptosis. Furthermore, co-immunoprecipitation analysis revealed that ANXA1 overexpression prevented ferritin degradation by disrupting the NCOA4-FTH1 protein-protein interaction, reducing the bioavailability of intracellular ferrous ions, thereby blocking ferroptosis. In conclusion, our findings identify a novel mechanism, showing that ANXA1 can inhibit ferroptosis via ferritinophagy, thereby alleviating endothelial dysfunction, which may provide a new therapeutic avenue for AS.
lincRNA-p21 drives apoptosis and calcification of vascular smooth muscle cell via small extracellular vesicles under hyperphosphatemic conditions in chronic kidney disease.
Hao J, Wang S, Hao L
Exp Cell Res · 2026 Jan · PMID 41241172 · Publisher ↗
Vascular calcification, a major contributor to cardiovascular morbidity, involves pathological osteogenic transdifferentiation of vascular smooth muscle cell (VSMC) under hyperphosphatemic conditions in chronic kidney di...
Vascular calcification, a major contributor to cardiovascular morbidity, involves pathological osteogenic transdifferentiation of vascular smooth muscle cell (VSMC) under hyperphosphatemic conditions in chronic kidney disease. This study investigates the role of lincRNA-p21 and small extracellular vesicles in phosphate-induced mouse aortic smooth muscle cell (MASMC) calcification. Exposure to phosphate (2.6 mmol/L) triggered time-dependent calcification, characterized by enhanced calcium deposition, endoplasmic reticulum remodeling, and intracellular calcium accumulation (p < 0.05 vs. 24/48-h controls). Concurrently, the expression of osteogenic markers (BGP, OCN, and OPN) and lincRNA-p21 was significantly upregulated, whereas the expression of contractile phenotype-specific markers (SM22α, SM-MHC, and SM α-actin) was markedly down-regulated. This pattern of gene expression was correlated with MASMC osteogenic transdifferentiation. Small extracellular vesicles isolated from phosphate-treated MASMC exhibited elevated lincRNA-p21 levels (p < 0.05) and induced calcification and apoptosis in recipient cells, suggesting small extracellular vesicles-mediated propagation of calcific signals. Functional studies demonstrated that lincRNA-p21 overexpression exacerbated calcification, apoptosis, and osteogenic marker expression, while its knockdown attenuated these effects (p < 0.05). Time-course analyses revealed lincRNA-p21 dynamically regulates small extracellular vesicles secretion, calcium accumulation, and apoptotic pathways, acting as a molecular switch driving phosphate-induced calcification. These findings establish lincRNA-p21 as a critical mediator of MASMC calcification via small extracellular vesicles-dependent mechanisms, offering insights into therapeutic strategies for vascular calcification.
Effects of everolimus on circadian gene expression and cell fate in synchronized Caco-2 cells.
Ozturk Civelek D, Goncu B, Goncu S … +1 more , Okyar A
Exp Cell Res · 2025 Dec · PMID 41235964 · Publisher ↗
OBJECTIVES: Circadian rhythms regulate key biological processes, including cell proliferation and metabolism, and their disruption is implicated in colorectal cancer (CRC). mTOR signaling interacts bidirectionally with t...
OBJECTIVES: Circadian rhythms regulate key biological processes, including cell proliferation and metabolism, and their disruption is implicated in colorectal cancer (CRC). mTOR signaling interacts bidirectionally with the circadian clock, yet how mTOR inhibition modulates clock gene dynamics and cellular behavior in intestinal models remains unclear. This study aimed to investigate the effects of everolimus, an mTOR inhibitor, on circadian gene expression, cell viability, apoptosis, and cell cycle progression in synchronized Caco-2 cells, with consideration of cell confluency and Circadian Time (CT). METHODS: Caco-2 cells were synchronized using serum shock at 20 % and 70 % confluency. Time-series samples were collected across multiple CTs (CT6-CT60). Gene expression (BMAL1, PER2, mTOR) was assessed by qRT-PCR using ACTB and RPLP0 as reference genes. Rhythmicity was evaluated via Cosinor analysis. Cell viability, apoptosis, and cell cycle dynamics were analyzed using the Muse™ Cell Analyzer following everolimus treatment (1-50 μM). RESULTS: RPLP0 proved to be a more stable reference gene than ACTB. BMAL1 exhibited stronger rhythmic expression than PER2, particularly at 20 % confluency. Everolimus (50 μM) significantly reduced cell viability in a time-dependent manner, with the greatest effect at CT6 and CT18 (p < 0.0001). Apoptosis was markedly increased at CT6 (+38.5 %) and moderate at CT18, indicating circadian modulation of drug sensitivity. Serum shock alone shifted cell cycle distribution, decreasing G0/G1 and increasing G2/M phase populations (p < 0.01). Everolimus altered BMAL1 and PER2 expression rhythms and significantly reduced mTOR expression at CT30, where baseline mTOR levels were highest. Cosinor analysis confirmed rhythmicity in BMAL1/RPLP0 and mTOR/RPLP0 profiles under low confluency. CONCLUSION: Our findings demonstrate that everolimus influences circadian gene expression and exerts time-dependent antiproliferative and pro-apoptotic effects in Caco-2 cells. These results support the potential of circadian timing as a strategy to enhance mTOR-targeted therapies in CRC.
Targeting LncRNA MEG3 to modulate ER stress and autophagy: A CRISPR/Cas9-based strategy in AKI-to-CKD transition.
Puri B, Majumder S, Gaikwad AB
Exp Cell Res · 2026 Jan · PMID 41232706 · Publisher ↗
Acute kidney injury (AKI) to chronic kidney disease (CKD) transition is a progressive, long-term kidney dysfunction driven by complex pathophysiological processes, including persistent endoplasmic reticulum (ER) stress a...
Acute kidney injury (AKI) to chronic kidney disease (CKD) transition is a progressive, long-term kidney dysfunction driven by complex pathophysiological processes, including persistent endoplasmic reticulum (ER) stress and impaired autophagy, contributing to fibrosis. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been implicated in endoplasmic reticulum (ER) stress and autophagy in several diseases, but its role in kidney injury and fibrosis during AKI-to-CKD transition remains unclear. Our previous transcriptomic analysis revealed that MEG3 is dysregulated during this transition, prompting us to explore its functional role. In this study, we investigated the function of MEG3 in ER stress-autophagy crosstalk during the AKI-to-CKD transition. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9)-mediated MEG3 knockout in NRK-52E cells was confirmed by T7 endonuclease assay, quantitative real-time polymerase chain reaction (qRT-PCR), and fluorescence in-situ hybridization (FISH) assay. Functionally, MEG3 knockout markedly attenuated ER stress and apoptosis, as shown by reduced expression of BiP, CHOP, ATF6, ATF4, p-PERK, p-eIF2α, along with restoration of the Bax/Bcl-2 balance. Autophagy activity was restored, with increased Beclin-1 and LC3B expression and decreased p62 accumulation. Furthermore, fibrotic progression was reduced, as indicated by lower levels of fibronectin and collagen I. Notably, tauroursodeoxycholic acid (TUDCA, 400 μM) acted synergistically with MEG3 knockout, further suppressing ER stress and fibrosis markers compared to either treatment alone. These findings demonstrate that MEG3 promotes maladaptive ER stress and impaired autophagy in tubular epithelial cells, driving AKI-to-CKD transition. Targeting MEG3 through CRISPR-based strategies or in combination with TUDCA may represent a promising therapeutic strategy to mitigate fibrosis and slow disease progression.
Gastrodin produces therapeutic effects against preeclampsia by activating Wnt 3a signaling and inhibiting ferroptosis.
Xu Q, Xuan G, Zhu C … +4 more , Zhu B, An Z, Jin M, Tang C
Exp Cell Res · 2026 Jan · PMID 41223957 · Publisher ↗
Preeclampsia (PE) is a multisystem disorder with increased maternal and perinatal mortality and morbidity while the treatment of PE remains largely unknown in clinic. Therefore, it is necessary to find more effective the...
Preeclampsia (PE) is a multisystem disorder with increased maternal and perinatal mortality and morbidity while the treatment of PE remains largely unknown in clinic. Therefore, it is necessary to find more effective therapeutic methods of PE. We report herein that, Tianma Gouteng Decoction (TGD) generates protective effects against PE by activating Wnt 3a/β-catenin signaling and simultaneously suppressing ferroptosis in placental trophoblast cells. Particularly, Gastrodin (Gtd), the active component in TGD, plays a major role in protection against PE. Mechanistically, Gtd up-regulates the Wnt 3a/β-catenin signaling activity by inducing Wnt 3a mRNA expression, resulting in the increased expression of β-catenin-controlled target genes. On the other hand, Gtd-triggered Wnt activation obviously exerts negative effects on ferroptosis by promoting expression levels of the anti-ferroptosis proteins accompanied by the down-regulated reactive oxygen species (ROS) production and total iron content but the up-regulated L-Glutathione (GSH) levels. Consistently, Gtd-administration reveals apparent anti-hypertensive effects in a PE-like mouse model with diminished ferroptosis, whereas deactivation of β-catenin by administration with the specific antagonist ICG001 disrupts the protective effects derived from Gtd. Therefore, our results provide an innovative basis for the role of Gtd as a new therapy for PE.
MSX2 serves as a chondroprotective factor in osteoarthritis: insights from expression analysis and functional validation studies.
Wu S, Li B, Tao F … +4 more , Song W, Zhang G, Wang R, Tian Z
Exp Cell Res · 2026 Jan · PMID 41205853 · Publisher ↗
OBJECTIVE: Despite the high prevalence of osteoarthritis (OA), molecular mechanisms underlying cartilage destruction remain incompletely understood. This study investigated the expression pattern and functional role of m...
OBJECTIVE: Despite the high prevalence of osteoarthritis (OA), molecular mechanisms underlying cartilage destruction remain incompletely understood. This study investigated the expression pattern and functional role of muscle segment homeobox 2 (MSX2) in osteoarthritis pathogenesis. METHODS: Differential gene expression analysis was performed using three independent Gene Expression Omnibus (GEO) datasets (GSE55457, GSE12021, and GSE114007) to examine MSX2 expression in osteoarthritic versus normal cartilage. Expression patterns were validated in primary chondrocytes from human osteoarthritis patients and mouse osteoarthritis models using Western blot and quantitative reverse transcription polymerase chain reaction (RT-PCR). Functional studies employed both loss-of-function and gain-of-function approaches through intra-articular injection of adeno-associated virus expressing MSX2-specific short hairpin ribonucleic acid (shRNA) or MSX2 overexpression constructs. Cartilage morphology, proteoglycan content, chondrocyte apoptosis, matrix markers, and inflammatory responses were assessed through histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining. RESULTS: MSX2 was consistently downregulated in osteoarthritic samples across all datasets, with validation confirming reduced MSX2 protein and messenger ribonucleic acid (mRNA) levels in both human patients and mouse models (p < 0.05). MSX2 knockdown significantly exacerbated cartilage degeneration, increased chondrocyte apoptosis, and disrupted matrix homeostasis by reducing anabolic markers type II collagen (COL2) and aggrecan (ACAN) while upregulating matrix metalloproteinase 13 (MMP13). Additionally, MSX2 knockdown enhanced inflammatory responses, evidenced by increased macrophage infiltration and tumor necrosis factor-alpha (TNFα) expression. Conversely, MSX2 overexpression demonstrated chondroprotective effects with improved cartilage morphology and reduced apoptosis. CONCLUSION: MSX2 serves as a critical chondroprotective factor maintaining cartilage homeostasis. Its downregulation contributes to osteoarthritis pathogenesis through disruption of matrix homeostasis, promotion of chondrocyte apoptosis, and enhancement of inflammatory responses. These findings identify MSX2 as a potential therapeutic target for osteoarthritis treatment.
Berberine overcomes paclitaxel resistance in triple-negative breast cancer by inhibiting HSP90-mediated BRCA1 phosphorylation.
Li J, Zhu X, Feng L … +5 more , Liu X, Xiao Y, Zhang Y, Lu C, Zhao W
Exp Cell Res · 2026 Jan · PMID 41197758 · Publisher ↗
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, and chemotherapy remains a major component of the standard therapy. Although there is an initial response, the tumor will inevitably d...
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, and chemotherapy remains a major component of the standard therapy. Although there is an initial response, the tumor will inevitably develop resistance to paclitaxel (PTX) treatment. Berberine (BBR) exhibits excellent anti-cancer activity in a variety of tumor cells and drug-resistant tumor cells. In the in vitro experiments of the study, the effect of BBR on PTX resistance was explored through proliferation assay, flow cytometry. The effects of combined treatment of BBR and PTX on DNA damage in TNBC cells were evaluated by colony formation assay, comet assay and γ-H2AX staining. Western blot and immunofluorescence revealed that HSP90 was highly expressed in the tolerant strain. BBR promotes the ubiquitination and degradation of HSP90 through the ubiquitin-protease system, further inhibits the expression of its client protein p-BRCA1 and improves the sensitivity of PTX treatment. Cell lines overexpressing hsp90 were constructed and it was found that Hsp90 could reverse the sensitivity of BBR to PTX. In addition, a model of transplanted tumors in nude mice was constructed to further verify the regulatory effect of BBR on PTX resistance in TNBC. Collectively, our findings demonstrate that BBR targets HSP90 to activate p-BRCA1-mediated DNA damage, thereby sensitizing non-BRCA-mutated TNBC to PTX. These results suggest HSP90 inhibition as a therapeutic strategy to circumvent chemotherapy resistance and a potential biomarker for predicting TNBC treatment response.
Modelling CubAm function and regulation in proximal tubular cells using iPSC-derived kidney organoids.
Llorens-Cebrià C, Bouwens D, Van Der Velde M … +12 more , Duran M, Salvadó-Pau M, Martínez-Díaz I, Vilardell-Vilà J, Meseguer A, Kramann R, Ferrer-Costa R, Soler MJ, López-Hellín J, Cantero-Recasens G, Jansen J, Jacobs-Cachá C
Exp Cell Res · 2025 Dec · PMID 41192745 · Publisher ↗
Idiopathic nephrotic syndrome (INS) associated to focal segmental glomeruloesclerosis or minimal change disease is characterized by the presence of heavy levels of proteinuria. Filtrated proteins are normally actively re...
Idiopathic nephrotic syndrome (INS) associated to focal segmental glomeruloesclerosis or minimal change disease is characterized by the presence of heavy levels of proteinuria. Filtrated proteins are normally actively reabsorbed in the proximal tubule by the megalin-cubilin-amnionless complex, located at the apical membrane of the proximal tubule epithelial cells. Megalin has a transmembrane domain but cubilin needs to interact with amnionless to reach the cell membrane in a complex known as CubAm. While megalin has a wide variety of ligands only a few proteins are exclusively transported by binding CubAm; one of those is Apolipoprotein A-I (ApoA-I). The reabsorption of Apolipoprotein A-I (ApoA-I) seems to be impaired in INS but this aspect of INS is difficult to study due to the low expression of CubAm in cultured proximal tubular cells as well as in other in vitro tubular modelling approaches. Here we show that RPTEC/TERT-1 cells cultured in monolayer barely express cubilin and amnionless proteins. In contrast, proximal tubular cells of induced Pluripotent Stem Cells (iPSCs)-derived kidney organoids showed robust expression of CubAm. In addition, protein overload induced an increase of the number of proximal tubular cells expressing cubilin that is reversed when the stimuli is removed. Finally, exogenously added ApoA-I targets cubilin suggesting that the CubAm complex is functional in our iPSCs-derived kidney organoids. Thus, kidney organoids provide a valuable system for modelling specific aspects of INS, including the impact of protein overload on tubular cells and the CubAm-mediated endocytosis of ApoA-I, which is thought to be impaired in these conditions.
The RPE-derived NF-κB/HO-1/MCP-1 pathway mediated microglia recruitment involved in the outer blood-retinal barrier breakdown in experimental diabetic retinopathy.
Shu Y, Liu D, Xie H … +3 more , Zhang C, Bi Y, Zhang J
Exp Cell Res · 2026 Jan · PMID 41176205 · Publisher ↗
PURPOSE: To investigate the mechanisms underlying the microglia recruitment and its causal role in the breakdown of the outer blood-retinal barrier (oBRB) in diabetic retinopathy (DR). METHODS: The Sprague-Dawley rats we...
PURPOSE: To investigate the mechanisms underlying the microglia recruitment and its causal role in the breakdown of the outer blood-retinal barrier (oBRB) in diabetic retinopathy (DR). METHODS: The Sprague-Dawley rats were adopted to establish diabetic model by intraperitoneal injection of streptozotocin. Twelve weeks later, the retinal pigment epithelium (RPE)-choroid complexes and retinal paraffin sections were examined with immunofluorescence. RNA-sequencing was performed on glyoxal-treated ARPE-19 cells, followed by bioinformatic analysis to identify significant genes and pathways. Transwell assays were employed to establish the co-culture system and investigate the interactions between ARPE-19 and BV2 microglial cells. The results were further validated by the inhibitor or siRNAs targeting NF-κB, HO-1, and MCP-1. RESULTS: In 12-week diabetic rat retinas, microglia were observed to accumulate in the vicinity of the RPE cells, accompanied by the disruption of ZO-1. The expressions of ZO-1 and occludin remained largely unchanged in ARPE-19 cells when treated with glyoxal alone. However, when co-cultured with BV2 microglial cells, the expression levels of ZO-1 and occludin in glyoxal-treated ARPE-19 cells were significantly decreased, which were effectively prevented by siMCP-1. Mechanistically, RNA-sequencing analysis revealed that the activation of the NF-κB/HO-1/MCP-1 pathway in glyoxal-treated ARPE-19 cells significantly contributed to the recruitment of microglia. The above effects were reversed by BAY 11-7082, siHO-1 or siMCP-1. CONCLUSION: Under diabetic conditions, microglia are recruited by RPE cells via the NF-κB/HO-1/MCP-1 pathway, which subsequently results in the oBRB breakdown. This study provides a novel mechanistic insight for the interaction between microglia and RPE cells, and implies a potential therapeutic strategy for the treatment of DR.
KHSRP protects colorectal cancer cells against ferroptosis by regulating GPX4 expression through interaction with hnRNPM.
Ding X, Zhang N, Zhan S … +1 more , Ding W
Exp Cell Res · 2025 Dec · PMID 41176204 · Publisher ↗
Ferroptosis is an iron-dependent form of programmed cell death driven by the accumulation of lipid peroxides. KHSRP, an RNA-binding protein, is known to orchestrate diverse cellular processes, including cell differentiat...
Ferroptosis is an iron-dependent form of programmed cell death driven by the accumulation of lipid peroxides. KHSRP, an RNA-binding protein, is known to orchestrate diverse cellular processes, including cell differentiation, proliferation, and lipid metabolism. However, its potential role in modulating ferroptosis in cancer remains unclear. In this study, we found that elevated KHSRP expression was associated with poor prognosis in colorectal cancer (CRC) patients. Knockdown of KHSRP significantly elevated lipid peroxidation, increased malondialdehyde (MDA) accumulation, and reduced glutathione (GSH) levels, ultimately triggering ferroptosis in CRC cells. Mechanistically, we discovered that KHSRP interacts with the splicing factor hnRNPM, which directly binds to GPX4 mRNA. Critically, hnRNPM overexpression effectively rescued the decrease in GPX4 expression and the ferroptotic phenotype induced by KHSRP knockdown. These results suggest that the KHSRP-hnRNPM complex binds to GPX4 mRNA and acts as a key regulator of its post-transcriptional fate to sustain GPX4 expression. Overall, our results uncover a novel regulatory mechanism whereby high KHSRP expression protects CRC cells from ferroptosis. Targeting the KHSRP-hnRNPM-GPX4 axis to overcome ferroptosis resistance represents a promising therapeutic strategy for CRC.
Activation of STING sensitizes melanoma cells to radiation through ROS-induced NLRP3.
Wang J, Tang S, Yang T … +8 more , Geng F, Tang X, Xia R, Zhang X, Bai H, Xiong H, Yu D, Zhang S
Exp Cell Res · 2025 Dec · PMID 41176203 · Publisher ↗
BACKGROUND: Melanoma is an aggressive malignancy with one of the highest mortality rates among skin cancers. Radiotherapy is a common treatment modality, but radioresistance remains a significant challenge. The stimulato...
BACKGROUND: Melanoma is an aggressive malignancy with one of the highest mortality rates among skin cancers. Radiotherapy is a common treatment modality, but radioresistance remains a significant challenge. The stimulator of interferon genes (STING) pathway has been implicated in antitumor immunity and cancer treatment, yet its role in melanoma radiosensitivity is poorly understood. OBJECTIVE: This study aimed to investigate the role of STING in enhancing the radiosensitivity of cutaneous melanoma cells and to explore the underlying mechanisms involving reactive oxygen species (ROS) and the NLRP3 inflammasome. METHODS: Using TCGA database analysis, we examined the correlation between cGAS-STING pathway expression and melanoma patient survival. In vitro experiments were conducted on A375 and B16F10 melanoma cell lines, where STING was overexpressed or activated using the STING agonist cGAMP. Cell viability, apoptosis, ROS levels, and NLRP3/ASC complex activity were assessed following radiation treatment. In vivo studies involved tumor-bearing mice treated with cGAMP and radiation to evaluate tumor growth and survival. RESULTS: High expression of cGAS and STING was associated with improved survival in melanoma patients. STING overexpression or cGAMP treatment significantly reduced cell viability, increased ROS levels, and enhanced apoptosis in irradiated melanoma cells. Mechanistically, the activation of STING elevated NLRP3/ASC complex activity, and the NLRP3 inhibitor CY-09 reversed the radiosensitization effects. In vivo, cGAMP combined with radiation suppressed tumor growth and improved survival in melanoma-bearing mice. CONCLUSION: STING enhances radiosensitivity of melanoma through ROS-NLRP3 axis, and combining STING agonists with radiotherapy may be a new strategy to overcome radioresistance.
The role and mechanism of fatty acid-binding protein 7 in spinal reactive astrocytes in prolonged postoperative pain induced by high-fat diet.
Zheng H, Zhang X, Li M … +6 more , Wang Y, Guo S, Jiang M, Xu R, Huang Y, Ma Z
Exp Cell Res · 2025 Dec · PMID 41151675 · Publisher ↗
Obesity markedly exacerbates nociceptive sensitivity and substantially compromises the quality of life of affected people. Astrocytes orchestrate metabolic regulation and homeostatic maintenance in the central nervous sy...
Obesity markedly exacerbates nociceptive sensitivity and substantially compromises the quality of life of affected people. Astrocytes orchestrate metabolic regulation and homeostatic maintenance in the central nervous system. Notably, fatty acid binding protein 7 (FABP7) is highly expressed in astrocytes that governs intracellular fatty acid uptake and transport. While systemic hyperlipidemia is pathognomonic of obesity, the mechanistic contribution of FABP7 in astrocytes to obesity-associated pain pathophysiology remains poorly characterized. The present study established a model of high-fat diet (HFD)-induced obesity combined with a standardized hind paw surgical incision paradigm, aiming to unveil the role of astrocytic FABP7 in HFD-induced chronic pain. Furthermore, an in vitro high-fat environment was induced by palmitic acid (PA),aiming to investigate the molecular mechanisms by which primary astrocytes were activated into the A1 phenotype to mediate neuroinflammation. FABP7 was overexpressed in the spinal dorsal of HFD mice. The activation of A1-type astrocytes and neuroinflammation cascades involving elevated iNOS eventually resulted in mechanical allodynia in HFD mice. Pharmacological inhibition of FABP7 via an intraperitoneal administration of SBFI-26 (20 mg/kg) significantly attenuated the paw withdrawal mechanical threshold and inhibited the A1-type astrocytes activation. PA-induced high-fat conditions promoted lipid droplet accumulation and upregulated FABP7 in astrocytes. Pharmacological inhibition of FABP7 using SBFI-26 (100 μmol/L) significantly suppressed the neurotoxic C3-positive A1 astrocyte phenotype, reduced intracellular lipid droplet accumulation, thereby inhibiting the activation of A1-type astrocytes and alleviating neuroinflammation. Overall, FABP7-mediated astrocytic reprogramming was a critical nexus bridging obesity with chronic pain. A1-astrocyte polarization initiated neuroinflammatory amplification, forming a feedforward loop perpetuating central sensitization. Our findings are expected to offer a viable target for metabolic pain management.
EIF4A3-mediated localization of circDNAJC16 sequesters miR-93-5p to suppress lung adenocarcinoma progression via CDKN1A-regulated cell cycle and EMT.
Yang L, Fan Y, Wang Y … +5 more , Yan C, Guan Z, Li Y, Su X, Huang X
Exp Cell Res · 2025 Dec · PMID 41138842 · Publisher ↗
Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer subtype, exhibits high mortality due to metastasis and therapeutic resistance. While circular RNAs (circRNAs) are implicated in oncogenesis, their fu...
Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer subtype, exhibits high mortality due to metastasis and therapeutic resistance. While circular RNAs (circRNAs) are implicated in oncogenesis, their functional mechanisms and upstream regulation in LUAD remain incompletely characterized. This study identifies circDNAJC16 (hsa_circ_0000018) as significantly downregulated in advanced-stage LUAD (Stage III-IV vs. I-II, p = 0.001), where its low expression independently predicts poor survival (HR = 1.93, p = 0.043). Functional characterization demonstrates that circDNAJC16 overexpression suppresses in vivo tumor growth (volume reduction: 26.56 %, p < 0.001) through cytoplasmic sequestration of oncogenic miR-93-5p, thereby activating CDKN1A/p21 to induce G0/G1 cell cycle arrest and inhibit proliferation, while concurrently suppressing metastasis via epithelial-mesenchymal transition (EMT) regulation. Crucially, the RNA-binding protein eIF4A3 binds upstream flanking introns of the host DNAJC16 pre-mRNA, driving selective nuclear retention of circDNAJC16 and redirecting linear DNAJC16 mRNA to the cytoplasm - a bifurcation mechanism essential for tumor suppression. These findings identify circDNAJC16 downregulation as a negative prognostic indicator in LUAD and reveal its dual tumor-suppressive roles: cytoplasmic sequestration of miR-93-5p activating CDKN1A-mediated cell cycle arrest, coupled with eIF4A3-governed nuclear retention controlling functional subcellular localization. Significantly, this work is the first to demonstrate eIF4A3-mediated circRNA compartmentalization, establishing circDNAJC16 as a novel prognostic biomarker and therapeutic target for LUAD.
Developmental delay in DCP2 of Drosophila melanogaster is due to disruption in the regulation of ecdysone signaling.
Chaudhary GR, Yadav V, Roy JK
Exp Cell Res · 2025 Dec · PMID 41135857 · Publisher ↗
The balance between mRNA synthesis and degradation plays an important role in gene regulation, their perturbation can lead to deleterious consequences to the cell. In eukaryotes, mRNA is degraded by a decapping protein-2...
The balance between mRNA synthesis and degradation plays an important role in gene regulation, their perturbation can lead to deleterious consequences to the cell. In eukaryotes, mRNA is degraded by a decapping protein-2 (DCP2). A hypomorph mutant allele of DCP2, DCP2, identified in our lab, shows delayed moulting, pupariation and absolute lethality in pupal stages. In Drosophila, moulting and pupariation are primarily regulated by ecdysone which is modulated by a few regulators synthesized by the larval brain, some are stimulatory such as Prothoracicotropic hormone (PTTH) and Drosophila insulin-like peptides (Dilps); whereas some are inhibitory, such as Lgr3-expressing neurons. We aimed to investigate the cause of the delay in moulting and pupariation in DCP2 homozygous mutants. Through our RNA Seq data, we found downregulated expression of brain-derived neuropeptides such as PTTH and Dilps which were further confirmed and validated through qRT-PCR and semiquantitative PCR. Furthermore, we assessed the mRNA level of Lgr3 which was found to be upregulated in the larval CNS of DCP2 homozygotes suggesting insufficient production of stimulatory modulators. Further, providing 20H-ecdysone exogenously through diet, curtailed the extended larval life. We propose that the larval CNS of DCP2 homozygotes produces insufficient brain-derived neuropeptides to stimulate the prothoracic gland to synthesize the ecdysone required for moulting and metamorphosis.
A tRNA-derived fragment tiRNA-Met-CAT-002 induced by myocardial ischemia/reperfusion injury inhibits cardiomyocyte autophagy by regulating Bnip3.
Deng L, Weng Y, Lin J … +7 more , Zhong L, Tang Z, Lin S, Huang W, Cheng Z, Lu K, Ye B
Exp Cell Res · 2025 Dec · PMID 41135856 · Publisher ↗
Myocardial ischemia/reperfusion (I/R) injury is a significant contributor to the development of heart failure. This study investigates the differential expression of tRNA-derived small RNAs (tsRNAs) during I/R and explor...
Myocardial ischemia/reperfusion (I/R) injury is a significant contributor to the development of heart failure. This study investigates the differential expression of tRNA-derived small RNAs (tsRNAs) during I/R and explores their potential functional implications. Through tRF & tiRNA sequencing, we identified 115 tsRNAs exhibiting significant changes in expression following I/R. Notably, tiRNA-Met-CAT-002 was found to be upregulated via the hypoxia/hypoxia-inducible factor 1 subunit α (HIF1α)/angiogenin (ANG) signaling axis. Our findings suggest that Bnip3 represents a crucial target for tiRNA-Met-CAT-002. Mechanistically, mimics of tiRNA-Met-CAT-002 reduced Bnip3 protein expression by directly targeting the 3' untranslated region (UTR) of its mRNA in a manner resembling microRNA activity. Furthermore, tiRNA-Met-CAT-002 was observed to decrease autophagy levels while enhancing cell viability under hypoxia/reoxygenation (H/R) conditions. In conclusion, this study underscores the substantial role of tsRNAs in the pathophysiology of I/R injury, with tiRNA-Met-CAT-002 potentially serving as a protective factor by attenuating autophagy levels.
Molecular mechanisms of cuproptosis in osteoarthritis: Pathways, crosstalk, and therapeutic opportunities.
Shen Y, Liu M, Botchway BOA … +2 more , Zhang Y, Liu X
Exp Cell Res · 2025 Dec · PMID 41125160 · Publisher ↗
Osteoarthritis (OA), the most prevalent degenerative joint disorder worldwide, continues to impose significant personal and societal burdens due to the absence of effective disease-modifying therapies. Recent advances in...
Osteoarthritis (OA), the most prevalent degenerative joint disorder worldwide, continues to impose significant personal and societal burdens due to the absence of effective disease-modifying therapies. Recent advances in metallobiology have identified cuproptosis, a copper (Cu)-dependent regulated cell death pathway, as a potential driver of OA pathogenesis. In OA, dysregulated Cu homeostasis has been linked to oxidative stress, inflammatory signalling activation, mitochondrial dysfunction, and direct chondrocyte injury. Mechanistically, Cu overload promotes aggregation of lipoylated tricarboxylic acid (TCA) cycle enzymes and destabilisation of iron-sulfur clusters, thereby impairing mitochondrial integrity and cellular metabolism. Emerging evidence also highlights extensive crosstalk between cuproptosis and ferroptosis, mediated largely by glutathione depletion and glutathione peroxidase 4 (GPX4) dysfunction, which amplifies oxidative damage in joint tissues. This review synthesises current evidence on Cu metabolism, the regulation and function of cuproptosis-related genes (CRGs), and their roles in immune infiltration, inflammatory signalling, and cartilage degeneration in OA. We further examine the interplay between cuproptosis and ferroptosis, and critically evaluate therapeutic strategies, including Cu chelation, antioxidant reinforcement, and pathway modulation, that may offer disease-modifying potential. By integrating these mechanistic insights, we aim to define new translational opportunities for OA management and outline priority areas for future research.
Corrigendum to 'Simvastatin inhibits the development of radioresistant esophageal cancer cells by increasing the radiosensitivity and reversing EMT process via the PTEN-PI3K/AKT pathway' [Exp Cell Res. 2018 Jan 15;362(2):362-369].
Jin Y, Xu K, Chen Q … +5 more , Wang B, Pan J, Huang S, Wei Y, Ma H
Exp Cell Res · 2025 Oct · PMID 41107173 · Publisher ↗
Abstract loading — click title to view on PubMed.
Bone marrow mesenchymal stem cell-derived exosomes HADH alleviate vitiligo by activating the Nrf2/HO-1 pathway.
Tang S, Li X, Xi J
Exp Cell Res · 2025 Dec · PMID 41106767 · Publisher ↗
BACKGROUND: Vitiligo is a chronic skin disorder that significantly impairs patients' quality of life. Exosomes (Exos) have been reported to hold therapeutic promise for vitiligo. This study aimed to investigate the molec...
BACKGROUND: Vitiligo is a chronic skin disorder that significantly impairs patients' quality of life. Exosomes (Exos) have been reported to hold therapeutic promise for vitiligo. This study aimed to investigate the molecular mechanism by which bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) ameliorate vitiligo. METHODS: In vitro vitiligo cell model was established by hydrogen peroxide (HO)-induced melanocytes. A mouse model of vitiligo was also established. Immunofluorescence, cell counting kit-8, 2',7'-dichlorofluorescein diacetate, enzyme linked immunosorbent assay, flow cytometry, real-time quantitative PCR, western blotting, hematoxylin-eosin, Masson-Fontana, and immunohistochemistry staining experiments were elucidated to explore the molecular mechanism of BMSC-Exos in relieving vitiligo. RESULTS: HO treatment reduce the cell viability, superoxide dismutase and catalase activities, and promote reactive oxygen species production, pyroptosis, the expression of NLRP3, ASC, IL-1β and IL-18 proteins in melanocytes. BMSC-Exos treatment effectively counteracted these detrimental effects. Knockdown of exosomal HADH derived from BMSC enhanced HO-induced oxidative stress and pyroptosis in melanocytes. Mechanistically, BMSC-Exos attenuated HO-induced oxidative stress and pyroptosis by mediating HADH delivery to activate the Nrf2/HO-1 pathway. Moreover, these results were further confirmed by experiments in a mouse model of vitiligo. CONCLUSION: BMSC-Exos can alleviate vitiligo by delivering HADH to activate the Nrf2/HO-1 pathway. This study provides insights for exploring new treatments for vitiligo.
Integrative multi-omics analysis identifies mitochondria- and ferroptosis-related prognostic genes in cervical cancer.
Jia L, Cui X, Li X … +1 more , Li R
Exp Cell Res · 2025 Dec · PMID 41106766 · Publisher ↗
BACKGROUND: Mitochondria and ferroptosis are crucial in tumorigenesis. However, their specific role in cervical cancer (CC) remains unclear. This study aimed to identify and validate prognostic genes linked to mitochondr...
BACKGROUND: Mitochondria and ferroptosis are crucial in tumorigenesis. However, their specific role in cervical cancer (CC) remains unclear. This study aimed to identify and validate prognostic genes linked to mitochondrial function and ferroptosis in CC. METHODS: Publicly available datasets were analyzed, including 306 CC tumor samples from The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC), with survival data for 293 samples, a training set of 24 normal and 33 tumor tissues (GSE9750), and a validation set of 300 tumor tissues (GSE44001). Prognostic genes associated with mitochondria-related genes (MRGs) and ferroptosis-related genes (FRGs) were identified through machine learning, univariate Cox regression, Weighted Gene Co-expression Network Analysis (WGCNA), Mendelian randomization (MR), differential expression analysis, and multivariate Cox analysis. A risk model was constructed and validated, with the High-Risk Group (HRG) and Low-Risk Group (LRG) defined by optimal risk score thresholds. Independent prognostic analysis, functional enrichment, immune infiltration profiling, and single-cell resolution studies were conducted to explore the underlying molecular mechanisms. Additionally, gene expression was validated in five paired clinical samples (5 tumor/5 normal tissues) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: HSDL2, AMACR, and CBR3 were identified as prognostic genes. The risk model indicated significantly poorer survival rates in HRG patients (P < 0.05). It demonstrated strong predictive performance, with area under the curve (AUC) values exceeding 0.7 in both the training and validation sets. The risk score, tumor (T) stage, and lymph node (N) stage were identified as independent prognostic factors for a nomogram model (hazard ratio (HR ≠ 1, P < 0.5). Pathways co-enriched by these markers, such as allograft rejection, were investigated. Immune infiltration analysis revealed significant differences between HRG and LRG in M0 macrophages and resting myeloid dendritic cells (mDCs) (P < 0.5). Macrophages and epithelial/cancer cells were identified as key contributors to CC progression, exhibiting 13 and 7 distinct differentiation states, respectively, in pseudo-time analysis. Notably, HSDL2 and CBR3 expression levels were significantly different between normal and CC samples (P < 0.05). CONCLUSION: HSDL2, AMACR, and CBR3 were established as prognostic biomarkers for CC. The risk model demonstrated robust predictive accuracy, offering a scientific foundation for clinical prognosis prediction in CC.
Maternal Protein Restriction promotes Cardiac Disorders by Disrupting Heart Developmental Morphophysiology in Young Male Offspring Rats.
Sobrinho Lemos L, Naia Fioretto M, Tenori Ribeiro I … +13 more , Annibal Barata L, Alessandra Maciel F, Leonardo Fagundes F, Mattos R, Frediani Portela LM, Barboza JM, Souza de Oliveira B, Emílio de Almeida K, Alcantara Dos Santos SA, Hiruma Lima CA, de Arruda Miranda JR, Zambrano E, Justulin LA
Exp Cell Res · 2025 Oct · PMID 41106765 · Publisher ↗
In recent years, cardiovascular diseases have been one of the leading causes of death worldwide. Epidemiological and experimental studies have linked adverse intrauterine conditions with an susceptibility to cardiovascul...
In recent years, cardiovascular diseases have been one of the leading causes of death worldwide. Epidemiological and experimental studies have linked adverse intrauterine conditions with an susceptibility to cardiovascular and metabolic diseases in subsequent generations, a concept related to the Developmental Origins of Health and Disease (DOHaD). Here, we evaluated the maternal protein restriction (MPR), and its harmful effects on the cardiac morphophysiology of offspring in early life. During gestation and lactation, the pregnant rats were divided into two groups: Control (CTR), which received a normoprotein diet (17% protein), and Gestational and Lactational Low-Protein (GLLP), which received a hypoprotein diet (6% protein). At postnatal day 21, the offspring were euthanized. There was a decrease in serum levels of IGF1, an increase in testosterone, and a decrease in several phenotypic parameters in the heart, such as the size of cardiomyocytes and their nuclei, collagen, reticular and elastic fibers, and mast cells in the GLLP group. We observed that MPR led to electrical disorders in the heart (bradycardia), in addition to impacting angiogenic proteins (high Aquaporin1 and PECAM-1), and proteins associated with the antioxidant system (low Peroxiredoxin 4 and high GSTpi expressions) in the GLLP group. These adverse effects early in life increase the risk of pathophysiological remodeling of the heart, with the potential for hypertension, hypertrophy, and cardiovascular disease later in life.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe