Relocating NSAID into endoplasmic reticulum induces ER stress -mediated apoptosis in cancer cells

RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

From a synthetic endoplasmic reticulum (ER)-targeted NSAID library, an ibuprofen derivative was identified to induce ER stress followed by autophagy trigger apoptosis in HCT-116 colon cancer cells.

Язык: Английский

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BRCA1 is involved in sustaining rapid antler growth possibly via balancing of the p53/endoplasmic reticulum stress signaling pathway

Biology Direct, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 24, 2025

Regeneration is the preferred approach to restore structure and function after tissue damage. Rapid proliferation of cells over site damage integral process regeneration. However, even subtle mutations in proliferating may cause detrimental effects by eliciting abnormal differentiation. Interestingly deer antlers, arguably fastest regenerating mammalian tissue, have not been reported, thus far, grow malignant tumors. They provide a model understand possible mechanism which rapid regeneration achieved while avoiding development malignancies. Antler based on differentiation antler stem (AnSCs). We identified 39 hub genes regulating balance between genomic stability AnSCs during Among these genes, tumor suppressor gene, BRCA1, was found be more sensitive DNA compared that somatic cells, BRCA1 deletion via CRISPR/Cas9 resulted significantly higher levels Lack promoted cell apoptosis senescence inhibited self-renewal. RNA-seq results showed absence p53 signaling pathway up-regulated. Associated with this change, senescence-relevant-genes, CDKN1A, CDKN2A Fas were expressed, but expression cell-cycle-progression-related inhibited. In addition, endoplasmic reticulum stress (ERS) cells. Deletion gene aggravated ERS ERS-induced apoptosis. Our revealed involved sustaining growth possibly promotion repair acts maintain genome protecting from p53/ERS-induced death. Understanding mechanisms underlying role played great significance only for regenerative medicine, also understanding cancer development.

Язык: Английский

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B4GALT3 as a Key Glycosyltransferase Gene in Multiple Myeloma Progression: Insights from Bioinformatics, Machine Learning, and Experimental Validation

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Background: Glycosylation abnormalities are critical in the progression of various cancers. However, their role onset and prognosis multiple myeloma (MM) remains underexplored. This study aims to identify glycosyltransferase (GT)-related biomarkers investigate underlying mechanisms MM. Methods: GT-related genes were extracted from MMRF-CoMMpass GSE57317 datasets. Potential identified using Cox regression Lasso analyses. A Glycosyltransferase-Related Prognostic Model (GTPM) was developed by evaluating 113 machine learning algorithm combinations. The expression B4GALT3, a key gene through this model, analyzed MM bone marrow samples immunohistochemistry, quantitative PCR, western blotting. Functional roles B4GALT3 cell behavior assessed knockdown experiments, its mechanism action investigated. Results: GTPM stratified patients into high- low-risk groups, with significantly better survival group (HR = 55.94, 95% CI 40.48–77.31, p \(&#x003C;\) 0.001). model achieved AUC values 0.98 0.99 for 1-year 3-year overall survival, outperforming existing signatures (including EMC92, UAMS70, UAMS17). elevated advanced stages (p $<$ 0.001) correlated poorer survival. Knockdown reduced proliferation, invasion , increased apoptosis. Mechanistic analyses revealed that modulates via Wnt/ \(\beta\) -catenin/GRP78 pathway, primarily regulating endoplasmic reticulum (ER) stress. Conclusions: novel predicting as influencing disease progression. Experimental evidence highlights B4GALT3's modulating ER stress Wnt/\(\beta\)-catenin pathways, positioning it potential prognostic biomarker therapeutic target

Язык: Английский

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The Significance of the Activating Transcription Factor 6 Gene in the Pathogenesis of Drug Resistant Cancer

Tissue and Cell, Год журнала: 2025, Номер 93, С. 102786 - 102786

Опубликована: Фев. 10, 2025

Язык: Английский

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Coexposure to fluoride and sulfur dioxide aggravates enamel mineralization disorders in mice by disrupting calcium homeostasis-mediated endoplasmic reticulum stress

Food and Chemical Toxicology, Год журнала: 2025, Номер unknown, С. 115317 - 115317

Опубликована: Фев. 1, 2025

Язык: Английский

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PERK-Olating Through Cancer: A Brew of Cellular Decisions

Biomolecules, Год журнала: 2025, Номер 15(2), С. 248 - 248

Опубликована: Фев. 8, 2025

The type I protein kinase PERK is an endoplasmic reticulum (ER) transmembrane that plays a multifaceted role in cancer development and progression, influencing tumor growth, metastasis, cellular stress responses. activation of represents one the three signaling pathways induced during unfolded response (UPR), which triggered, particular, cells constitutively experience various intracellular extracellular stresses impair folding within ER. can lead to both pro-survival proapoptotic outcomes, depending on context extent ER stress. It helps reprogramming gene expression cells, thereby ensuring survival face oncogenic stress, such as replicative DNA damage, also microenvironmental challenges, including hypoxia, angiogenesis, metastasis. Consequently, contributes initiation, transformation, adaptation microenvironment, chemoresistance. However, sustained cell proliferation promote apoptotic death by interconnected processes, mitochondrial dysfunction, translational inhibition, accumulation stresses, specific induction multifunctional factors, CHOP. dual promoting progression suppression makes it complex target for therapeutic interventions. A comprehensive understanding intricacies pathway their impact essential effective strategies, particularly diseases like cancer, where deregulated most, if not all, solid liquid tumors. This article provides overview knowledge acquired from study animal models lines cultured vitro PERK’s functions thus highlighting potential new avenues could this protein.

Язык: Английский

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Specific cell states underlie complex tissue regeneration in spiny mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Cell proliferation is an elemental feature of epimorphic regeneration in vertebrate taxa. We previously reported that contrast to fibrotic repair observed laboratory mouse ( Mus ) strains, highly regenerative spiny mice Acomys spp.) exhibit cell cycle progression and faithfully replace missing tissue. However, little known about dynamics, specific types states may contribute complex tissue mammals. Using temporal pulse-chase experiments, we show stromal cells dimidiatus rapidly re-enter the response injury maintain tight spatiotemporal control restrict proliferative population a distal area relative injury. Conversely, incorporate thymidine analogs without division supporting S-phase arrest after D10. Deploying immunostaining scRNA-seq, identify several key (CRABP1+, αSMA+) differentially associated with regenerating versus scar Importantly, our single data revealed distinct gene expression profiles for cross-species types, identifying or healing. While CRABP1+ fibroblasts are enriched ears before injury, similar young, postnatal remain unable promote regeneration. Our underscore finely regulated dynamics proliferating during emphasize depends on multiple factors including presence ability acquire states. Differentiated , Danio while homeostatic cycling blastema formation Ambystoma Pulse-chase analog labeling shows . Following CRABP1 αSMA expressed populations but co-expressed populations. Species-specific underlie lost embryonic development ear pinna retained adulthood. Young neonatal abundant still fail execute Comparing vs. healing, injury-induced persistent

Язык: Английский

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Routine Blood Tests as Predictive Tools for Differentiating Follicular Thyroid Carcinoma From Follicular Adenoma

International Journal of General Medicine, Год журнала: 2025, Номер Volume 18, С. 733 - 744

Опубликована: Фев. 1, 2025

Background: Thyroid cancer is the most common endocrine malignancy, with an increasing incidence rate, particularly among adolescents. Follicular thyroid carcinoma (FTC), though less than papillary (PTC), presents greater diagnostic challenges, especially when differentiating from follicular adenoma (FA). Current methods lack specificity, underscoring need for a simple, cost-effective predictive model FTC.This study aimed to develop scoring system based on routine blood biomarkers distinguish between FTC and FA, facilitating early diagnosis treatment. Methods: A retrospective, single-center case-control was conducted patients diagnosed FA at Renmin Hospital of Wuhan University 2016 2022. Patients' demographic, clinicopathological characteristics, preoperative biomarker data were analyzed. Statistical tests, including chi-square, t-tests, Mann–Whitney U -tests, used compare biomarkers. Significant variables included in univariate multivariate logistic regression analyses, leading development system. The model's performance assessed using receiver operating characteristic (ROC) curves. Results: 23 26 FTC. Seven showed significant differences groups: ALB, DBIL, TBIL, LYM#, MCHC, RDW-SD, WBC. Multivariate identified ALB WBC as key predictors, forming (Score = 0.54 × - 1.10 WBC). exhibited strong (AUC 0.839), sensitivity specificity 0.808 0.826, respectively. Conclusion: developed novel biomarkers, offering non-invasive, tool FA. has clinical potential, providing feasible alternative conventional techniques. Further multicenter studies mechanistic investigations are warranted validate refine model, enhancing its utility practice. Keywords: carcinoma, albumin,

Язык: Английский

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Methylglyoxal Formation—Metabolic Routes and Consequences

Antioxidants, Год журнала: 2025, Номер 14(2), С. 212 - 212

Опубликована: Фев. 13, 2025

Methylglyoxal (MGO), a by-product of glycolysis, plays significant role in cellular metabolism, particularly under stress conditions. However, MGO is potent glycotoxin, and its accumulation has been linked to the development several pathological conditions due oxidative stress, including diabetes mellitus neurodegenerative diseases. This paper focuses on biochemical mechanisms by which contributes through formation advanced glycation end products (AGEs), interactions with antioxidant systems, involvement chronic diseases like diabetes, neurodegeneration, cardiovascular disorders. exerts effects multiple signaling pathways, NF-κB, MAPK, Nrf2, induce stress. Additionally, triggers apoptosis primarily via intrinsic extrinsic while endoplasmic reticulum (ER) mediated PERK-eIF2α IRE1-JNK signaling. Moreover, activation inflammatory RAGE crucial pathogenesis these study points out connection between carbonyl increased formation, it should be an incentive search for marker that could have prognostic significance or targeted therapeutic intervention various

Язык: Английский

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Artesunate alleviated murine ulcerative colitis by regulating immune response through inhibiting endoplasmic reticulum stress

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 26, 2025

Innate and adaptive immunity are intricately linked to the pathogenesis of ulcerative colitis (UC), with dysregulation Treg/Th17 balance M2/M1 macrophage polarization identified as critical factors. Artesunate (ARS) has previously been shown alleviate UC by inhibiting endoplasmic reticulum stress (ERS). To further investigate regulatory effects ARS on immune associated role ERS in this process, an experimental model was established using dextran sulfate sodium (DSS). Flow cytometry employed assess changes Th17/Treg cell ratio spleen intestine, while RT-qPCR used quantify transcription levels relevant genes colonic tissues. treatment significantly mitigated DSS-induced pathological damage, reduced proportion CD4+Th17 cells, downregulated mRNA expression IL-17A, IL-17F, RORγt, concurrently increasing CD4+Treg cells upregulating TGF-β expression. Additionally, restored decline enhanced Arg-1 IL-10, suppressing pro-inflammatory markers, including iNOS, IL-1β, IL-6, TNF-α. Notably, co-treatment 4-phenylbutyric acid (4-PBA, inhibitor) augmented immunoregulatory ARS, whereas 2-deoxy-D-glucose (2-DG, agonist) counteracted its protective activity against UC. These findings suggest that plays a crucial mediating therapeutic UC, particularly modulating polarization. This study provides insights into mechanistic basis offering potential avenue for intervention.

Язык: Английский

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