Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 2, 2023

Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal communication between microenvironment (TME) is observed, with TME providing supportive niche for CSC survival self-renewal, while CSCs, turn, influence polarization persistence TME, promoting an immunosuppressive state. Consequently, these interactions hinder efficacy current therapies, necessitating exploration novel therapeutic approaches modulate target CSCs. this review, we highlight intricate strategies employed by evade surveillance develop resistance therapies. Furthermore, examine dynamic interplay shedding light on how interaction impacts progression. Moreover, provide overview advanced that specifically which hold promise future clinical translational studies treatment.

Language: Английский

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Targeting aging and age-related diseases with vaccines

Nature Aging, Journal Year: 2024, Volume and Issue: 4(4), P. 464 - 482

Published: April 15, 2024

Language: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

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A high-resolution view of the heterogeneous aging endothelium

Angiogenesis, Journal Year: 2024, Volume and Issue: 27(2), P. 129 - 145

Published: Feb. 7, 2024

Vascular endothelial cell (EC) aging has a strong impact on tissue perfusion and overall cardiovascular health. While studies confined to the investigation of aging-associated vascular readouts in one or few tissues have already drastically expanded our understanding EC aging, single-cell omics other high-resolution profiling technologies started illuminate intricate molecular changes underlying across diverse beds at scale. In this review, we provide an overview recent insights into heterogeneous adaptations endothelium. We address critical questions regarding tissue-specific universal responses endothelium process, turnover dynamics throughout lifespan, differential susceptibility ECs acquiring traits. doing so, underscore transformative potential approaches advancing comprehension essential foster development future innovative therapeutic strategies for conditions.

Language: Английский

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Fully Integrated Multifunctional Flexible Ultrasonic–Electric‐Coupled Patches for Advancing Wound Care Paradigms

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Wound repair in adults lacks natural regenerative capacity seen during fetal period, frequently resulting the formation of tissue fibrosis and functional impairments. By transforming process into healing, it is possible to restore original state significantly enhance human health. Advanced treatment methods, e.g., a wearable patch with ultrasound electrical stimulation, offer promising solutions for wound regeneration by overcoming limitations traditional approaches such as skin engineering physiotherapy machines. Here, flexible ultrasonic–electric‐coupled presented which delivers noninvasive full‐space stimulation tissue, offering functionalities including anti‐inflammation, protection, repairing, continuous monitoring. Specifically, applies an electric field surface while directing toward deeper layers, effectively remodeling collagen morphology composition akin that normal skin, promoting macrophage polarization M2 phenotype, facilitating situ hair follicles. Moreover, allows real‐time monitoring prediction recovery status analyzing resistance value, thereby high‐quality healing. This technology will contribute developing future therapeutic programs clinical applications, demonstrating its significance advancing healing progress.

Language: Английский

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Andrias davidianus Derived Glycosaminoglycans Direct Diabetic Wound Repair by Reprogramming Reparative Macrophage Glucolipid Metabolism

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Harnessing cross‐species regenerative cues to direct human potential is increasingly recognized as an excellent strategy in medicine, particularly for addressing the challenges of impaired wound healing aging populations. The skin mucus Andrias davidianus plays a critical role self‐protection and tissue repair, yet fundamental factors mechanisms involved remain elusive. Here, this work presents evidence that glycosaminoglycans (GAGs) derived from secretion (SAGs) serve potent mediators angiogenesis inflammatory remodeling, facilitating efficient diabetic wounds. Mechanistic studies reveal SAGs promote macrophage polarization toward anti‐inflammatory pro‐regenerative phenotype (CD206 + /Arg1 ) via glucolipid metabolic reprogramming. This process suppresses excessive inflammation enhances expression VEGF IL‐10 create facilitative microenvironment regeneration. Additionally, develops SAGs‐GelMA composite microspheres address multiple stages healing, including rapid hemostasis, exudate control, activation endogenous processes. engineered approach significantly improves scarless wounds by recruitment reparative macrophages. findings offer new insights into highlight therapeutic application repair.

Language: Английский

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Integrative cross‐tissue analysis unveils complement‐immunoglobulin augmentation and dysbiosis‐related fatty acid metabolic remodeling during mammalian aging

iMeta, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Abstract Aging‐related decline and adaptation are complex, multifaceted processes that affect various tissues increase risk of chronic diseases. To characterize key changes in cross‐tissue aging, we performed comprehensive proteomic metabolomic analyses across 21 solid plasma samples, alongside shotgun metagenomic profiling fecal microbial communities young aged mice. Our findings revealed widespread aging‐rewired inflammation, characterized by complement system activation universal immunoglobulins accumulation multiple tissues. This inflammatory remodeling significantly enhanced vulnerability to aging‐related tissue injury. Moreover, identified organ‐specific organ‐enriched proteins with high functional specificity. Among these, were closely linked disorders arising from lipid metabolism dysfunction. Analysis multi‐tissue profiles aging disrupted inter‐tissue metabolic coupling, activities polyunsaturated fatty acids metabolism, gut microbiota homeostasis. Aged mice exhibited a marked decrease Escherichia an Helicobacter , strongly correlating alterations omega‐3 omega‐6 acid abundances. Through multi‐omics integration, molecular hubs driving organismal responses aging. Collectively, our study uncovers extensive aging‐associated tissues, emphasizing the interplay between systemic inflammation dysbiosis‐driven remodeling. These provide deeper insights into development healthy perspective.

Language: Английский

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Senescent Macrophages Promote Age‐Related Revascularization Impairment by Increasing Antiangiogenic VEGF‐A165B Expression

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

ABSTRACT Peripheral arterial disease is a common vascular in the elderly. Therapeutic revascularization, including angiogenic and arteriogenic therapy, promising treatment approach for peripheral disease. However, progress of clinical trials not ideal, possibly due to insufficiency preclinical models, such as taking into account effect aging on regeneration. Macrophages are crucial angiogenesis arteriogenesis. The microenvironment typically makes recruited monocytes macrophages more susceptible senescence. feature ischemic hindlimb muscle old individuals their underlying role remains unclear. In this study, we reveal that skeletal mice senescent proinflammatory. By transplanting following ischemia, find inhibit revascularization. Mechanistically, these induce endothelial dysfunction via increasing growth factor A‐165B (VEGF‐A165B) expression secretion, eventually impair Notably, plasma VEGF‐A165B levels elevated patients with PAD positively associated lower ankle brachial index (ABI). Our study suggests targeting presents an avenue improve age‐related revascularization damage.

Language: Английский

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Integrated-omics profiling unveils the disparities of host defense to ECM scaffolds during wound healing in aged individuals

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122685 - 122685

Published: June 27, 2024

Language: Английский

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A Nanocapsule System Combats Aging by Inhibiting Age-Related Angiogenesis Deficiency and Glucolipid Metabolism Disorders

ACS Nano, Journal Year: 2024, Volume and Issue: 18(32), P. 21061 - 21076

Published: Aug. 1, 2024

Insufficient angiogenic stimulation and dysregulated glycolipid metabolism in senescent vascular endothelial cells (VECs) constitute crucial features of aging. Concomitantly, the generation excess senescence-associated secretory phenotype (SASP) active immune-inflammatory responses propagates within injured vessels, tissues, organs. Until now, targeted therapies that efficiently rectify phenotypic abnormalities VECs have still been lacking. Here, we constructed a Pd/hCeO2–BMS309403@platelet membrane (PCBP) nanoheterostructured capsule system loaded with fatty acid-binding protein 4 (FABP4) inhibitors modified platelet membranes investigated its therapeutic role aged mice. PCBP showed significant maintenance organs demonstrated excellent biocompatibility. Through cyclic tail vein administration, extended lifespan steadily ameliorated abnormal phenotypes mice, including SASP production, immune inflammatory status, age-related metabolic disorders. In ECs, mediated activation growth factor (VEGF) signaling glycolysis inhibition FABP4 by inducing synthesis hypoxia-inducible factor-1α, thereby reawakening neovascularization restoring homeostasis. conclusion, nanocapsule provides promising avenue for interventions against aging-induced dysfunction.

Language: Английский

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