Published: Jan. 1, 2025
Language: Английский
Advanced Materials, Journal Year: 2024, Volume and Issue: 36(24)
Published: March 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.
Language: Английский
Citations
25
Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 108 - 108
Published: Jan. 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.
Language: Английский
Citations
2
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)
Published: June 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.
Language: Английский
Citations
9
Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 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.
Language: Английский
Citations
1
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3195 - 3195
Published: March 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.
Language: Английский
Citations
1
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4968 - 4968
Published: May 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.
Language: Английский
Citations
6
Small, Journal Year: 2024, Volume and Issue: 20(43)
Published: July 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".
Language: Английский
Citations
6
Published: Jan. 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
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 20, 2025
Introduction The impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, molecular mechanisms underlying spaceflight-induced dysregulations are still unclear. Methods In this study, blood from eleven crewmembers was collected before during International Space Station (ISS) missions. Transcriptomic analysis performed in isolated peripheral mononuclear cells (PBMCs) using RNA-sequencing. Differentially expresses genes (DEG) space were determined by comparing inflight to preflight samples. Pathways statistical analyses these DEG Ingenuity Pathway Analysis (IPA) tool. Results comparison pre-flight, a total 2030 differentially expressed PBMC between 135 210 days orbit, which included significant number surface receptors. dysregulated pathways mostly involved energy oxygen metabolism, responses, cell adhesion/migration death/survival. Discussion Based associated functions, we propose that dysfunction caused constant modulation mechano-sensing receptors microgravity, triggered signaling cascade led calcium overloading mitochondria. response shares T-cell exhaustion features, likely initiated microgravity than infection. Consequences include dysregulation prolonged survival potentially explains reported findings inhibition T activation telomere lengthening astronauts. Conclusion Our study identifies upstream cause downstream consequences cells.
Language: Английский
Citations
0
Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 89 - 89
Published: Jan. 31, 2025
The contemporary approach to nutrition increasingly considers the role of non-nutritive bioactive compounds in modulating immune system and maintaining health. This article provides up-to-date insight into immunomodulatory effects selected compounds, including micro- macronutrients, vitamins, as well other health-promoting substances, such omega-3 fatty acids, probiotics, prebiotics, postbiotics (including butyric acid sodium butyrate), coenzyme Q10, lipoic acid, plant-derived components phenolic flavonoids, coumarins, alkaloids, polyacetylenes, saponins, carotenoids, terpenoids. Micro- zinc, selenium, magnesium, iron, play a pivotal regulating response protecting against oxidative stress. Vitamins, especially vitamins C, D, E, B, are vital for optimal functioning they facilitate production cytokines, differentiation immunological cells, neutralization free radicals, among functions. Omega-3 acids exhibit strong anti-inflammatory enhance cell function. Probiotics, modulate intestinal microbiota, thereby promoting integrity barrier communication between microbiota system. Coenzyme renowned its antioxidant attributes, participates protection cells from stress promotes energy processes essential Sodium butyrate regeneration epithelium, which is crucial maintenance homeostasis. emphasizes necessity an integrative that not only nutritional but also non-nutritional provide adequate support Without them, will never function properly, because it has been adapted this course evolution. data presented may serve foundation further research potential applications prevention treatment diseases associated with dysfunction.
Language: Английский
Citations
0