2D Catalytic Nanozyme Enables Cascade Enzyodynamic Effect‐Boosted and Ca²⁺ Overload‐Induced Synergistic Ferroptosis/Apoptosis in Tumor

Advanced Materials, Год журнала: 2024, Номер 36(24)

Опубликована: Март 19, 2024

Abstract The introduction of glucose oxidase, exhibiting characteristics consumption and H 2 O production, represents an emerging antineoplastic therapeutic approach that disrupts nutrient supply promotes efficient generation reactive oxygen species (ROS). However, the instability natural enzymes their low efficacy significantly impede broader application. In this context, 2D Ca Mn 8 16 nanosheets (CMO NSs) designed engineered to serve as a high‐performance nanozyme, enhancing enzyodynamic effect for ferroptosis–apoptosis synergistic tumor therapy, are presented. addition mimicking activities glutathione peroxidase, catalase, CMO NSs exhibit oxidase‐mimicking activities. This feature contributes antitumor performance through cascade catalytic reactions, involving disruption supply, self‐supply , subsequent ROS generation. exogenous 2+ released from NSs, along with endogenous enrichment induced by peroxidase‐ collectively mediate overload, leading apoptosis. Importantly, ferroptosis process is triggered synchronously output consumption. application ultrasound stimulation further enhances efficiency treatment. work underscores crucial role in therapy against tumors.

Язык: Английский

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Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions

Antioxidants, Год журнала: 2025, Номер 14(1), С. 108 - 108

Опубликована: Янв. 18, 2025

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation reactive oxygen species (ROS), calcium homeostasis, and execution apoptotic processes. Disruptions function, driven by factors such as oxidative stress, excitotoxicity, altered ion balance, lead to neuronal death contribute cognitive impairments several brain diseases. Mitochondrial can arise from genetic mutations, ischemic events, hypoxia, other environmental factors. This article highlights critical role progression diseases discusses need targeted therapeutic strategies attenuate damage, restore enhance neuroprotection.

Язык: Английский

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Targeting LINC00152 activates cAMP/Ca2+/ferroptosis axis and overcomes tamoxifen resistance in ER+ breast cancer

Cell Death and Disease, Год журнала: 2024, Номер 15(6)

Опубликована: Июнь 15, 2024

Abstract Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER + ) breast cancer, constituting around 75% of all cases. However, emergence resistance is common, necessitating identification novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen by blocking tamoxifen-induced ferroptosis, an iron-mediated cell death. Mechanistically, inhibiting reduces mRNA stability phosphodiesterase 4D ( PDE4D ), leading activation cAMP/PKA/CREB axis increased expression TRPC1 Ca 2+ channel. This causes cytosolic overload generation reactive oxygen species (ROS) is, on one hand, accompanied downregulation FTH1, a member iron sequestration unit, thus increasing intracellular Fe levels; other inhibition peroxidase activity upon reduced GPX4 xCT levels, in part cAMP/CREB. These ultimately restore tamoxifen-dependent lipid peroxidation ferroptotic death which are reversed chelating or overexpressing xCT. Overexpressing reverses inhibition-mediated sensitization de-activating cAMP/Ca /ferroptosis axis. Importantly, high significantly correlated with PDE4D/low ferroptosis worse survival multiple cohorts tamoxifen- tamoxifen-containing endocrine therapy-treated ER+ cancer patients. Overall, identified as mechanism via restoring destabilizing PDE4D, cAMP ROS peroxidation. Our findings reveal its effectors actionable targets improve clinical outcome refractory cancer.

Язык: Английский

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C-reactive protein-induced injury in Mycoplasma pneumoniae -infected lung epithelial cells is mediated by the P38 MAPK/mitochondrial apoptosis pathway

Microbiology Spectrum, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Patients with Mycoplasma pneumoniae (MP) infections have markedly higher C-reactive protein (CRP). We investigated how CRP contributes to lung epithelial cell death following MP infection. levels were assessed in children diagnosed pneumonia (MPP) and A549 cells infected MP. genetically modified overexpress CRP. Effects on viability, apoptosis, reactive oxygen species (ROS) mitochondrial membrane potential (ΔΨm) evaluated. The expression of proteins implicated the p38 MAPK/mitochondrial apoptotic pathway was analyzed. protective effects MAPK inhibitor SB203580 protector cyclosporin A (CsA) assessed. elevated both MPP patients MP-infected compared controls. Increased apoptosis reduced viability observed cells. overexpression led upregulation pathway, increased cytoplasmic Cyt C, decreased Tom 20 ΔΨm, ROS. Pretreatment or posttreatment CsA damage enhanced survival. during infection promote by activating pathway. Targeting this could offer therapeutic reduce patients.IMPORTANCEThis study provides critical information understanding pathophysiological mechanisms for concerning mediating injury. This outlines significant increase shows its direct involvement through By explaining possibility targeting connected signaling devise interventions amelioration is brought light. implications such data are not merely added knowledge disease pathobiology but also it brings new promise novel intervention strategies result improved clinical outcomes. elucidation specific molecular targets inside heralds a area regarding direction future research application humanity general broader relevance impact respiratory diseases.

Язык: Английский

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Role of Mitochondrial Dysfunction in Neuropathy

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3195 - 3195

Опубликована: Март 29, 2025

Diabetes mellitus is characterized by a state of hyperglycemia, which can lead to severe complications if left untreated or poorly managed. Diabetic peripheral neuropathy (DPN) one common complication. This condition damage the nerves that supply legs and feet as well problems with blood vessels, heart, urinary tract. To alleviate pain for patients, clinicians resort long-term treatment regimens nerve medications, are usually either anticonvulsants antidepressants. However, little understood about underlying mechanisms DPN. Many pathogenic pathways have been proposed, mitochondrial dysfunction. Mitochondrial dysfunction includes range possible deficiencies given number functions controlled located in mitochondria, including their core function bioenergetics. review focuses on bioenergetics, respiration/ATP synthesis reactive oxygen species (ROS) production, calcium homeostasis apoptosis, potential targets effective diabetic neuropathy.

Язык: Английский

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Chondroitin Sulfate‐Modified Hydroxyapatite for Caspase‐1 Activated Induced Pyroptosis through Ca Overload/ER Stress/STING/IRF3 Pathway in Colorectal Cancer

Small, Год журнала: 2024, Номер 20(43)

Опубликована: Июль 17, 2024

Immune checkpoint inhibitors, are the fourth most common therapeutic tool after surgery, chemotherapy, and radiotherapy for colorectal cancer (CRC). However, only a small proportion (≈5%) of CRC patients, those with "hot" (immuno-activated) tumors, benefit from therapy. Pyroptosis, an innovative form programmed cell death, is potentially effective means to mediate "cold" transformation tumor microenvironment (TME). Calcium-releasing hydroxyapatite (HAP) nanoparticles (NPs) trigger calcium overload pyroptosis in cells. current limitations these nanomedicines, such as poor tumor-targeting capabilities insufficient (Ca) ion release, limit their application. In this study, chondroitin sulfate (CS) used target tumors via binding CD44 receptors kaempferol (KAE) Ca homeostasis disruptor construct CS-HAP@KAE NPs that function inducers bind membrane, HAP released response acidic environment TME, enhances influx extracellular Ca, resulting intracellular pyroptosis. This associated excessive endoplasmic reticulum stress triggered activation stimulator interferon genes/interferon regulatory factor 3 pathway, ultimately transforming TME "hot".

Язык: Английский

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Micronutrient Status and Breast Cancer: A Narrative Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4968 - 4968

Опубликована: Май 2, 2024

Breast cancer is one of the most common cancers worldwide, at same time being prevalent causes women’s death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast development and progression. Another important factor in onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients their possible influence on Further, aim study was investigate impact status prevention its various therapeutic pathways. We researched meta-analyses, systemic reviews, retrospective studies, well original studies human animal models. The results these indicate a correlation between different levels decreased risk better survival rate. However, further are necessary establish adequate doses supplementation chosen exact mechanisms therapy.

Язык: Английский

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Mechanical stress facilitates calcium influx and growth of alveolar epithelial cells via activation of the BDKRB1/Ca2+/CaMKII/MEK1/ERK axis

Respiratory Research, Год журнала: 2025, Номер 26(1)

Опубликована: Апрель 28, 2025

Mechanical stress and calcium metabolism are associated with lung development various pulmonary diseases. Our previous research demonstrated that BDKRB1/Ca2+ signal transduction may be involved in dysplasia resulting from scoliosis thoracic insufficiency. Therefore, the present study aims to investigate effects of mechanical on growth influx alveolar epithelial cells, as well role signaling these processes. Flow cytometry, CCK-8, EDU staining assay were employed assess cycle, influx, activity, proliferation RLE-6TN cells subjected stresses varying amplitudes (5%, 10% 15%). RT-qPCR western blotting performed evaluate BDKRB1/Ca2+/CaMKII/MEK1/ERK cells. at effectively enhanced viability, positive ratio, S-phase percentage, Ca2+ concentration while reducing G1-phase percentage. Conversely, 15% exerted an inhibitory effect cell proliferation. Additionally, significantly upregulated expression BDKRB1, CaMKIIα/δ, p-MEK1 p-ERK1/2 Notably, BDKRB1 knockdown attenuated stress-induced increase both Moreover, blocked activation Ca2⁺/CaMKII/MEK1/ERK pathway induced by stress. Appropriate levels contribute modulating signaling.

Язык: Английский

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Mitochondria- and endoplasmic reticulum-localizing iridium(III) complexes induce immunogenic cell death of 143B cells

Journal of Inorganic Biochemistry, Год журнала: 2024, Номер 259, С. 112655 - 112655

Опубликована: Июнь 27, 2024

Язык: Английский

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Tp53 Mutation-Specific Dysregulation of Store-Operated Calcium Entry and Apoptotic Sensitivity in Triple-Negative Breast Cancer

Опубликована: Янв. 1, 2025

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors, associated with poor prognosis limited treatments. TNBC often harbours TP53 mutations, disrupting p53's roles in apoptosis cell cycle regulation. Beyond transcriptional functions, p53 regulates through non-transcriptional mechanisms, including modulation of calcium homeostasis via store-operated current (SOC), a key regulator proliferation survival. This study explores the relationship between channel expression, SOC, potential restoring function to enhance apoptotic sensitivity. Bioinformatic analysis showed significant downregulation CACNA1D (encoding CaV1.3, L-type voltage-gated channel) mutations. Functional studies revealed reduced SOC resistance thapsigargin (TG)-induced frameshift (FS) stop mutant cells compared wild-type (WT). The common R273H missense mutation similar as WT cells. Treatment reactivator COTI-2 restored expression FS lines enhanced Combined TG treatment further synergized apoptosis, highlighting therapeutic potential. These findings reveal novel link mutations disrupted signalling TNBC, showing type affects Ca2+ expression. restores function, sensitizing supporting combination therapies targeting p53. Further investigation validation preclinical models could advance translational

Язык: Английский

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