Leveraging Microneedles for Raised Scar Management

Polymers, Год журнала: 2025, Номер 17(1), С. 108 - 108

Опубликована: Янв. 2, 2025

Disruption of the molecular pathways during physiological wound healing can lead to raised scar formation, characterized by rigid, thick tissue with associated symptoms pain and pruritus. A key mechanical factor in development is excessive tension at site. Recently, microneedles (MNs) have emerged as promising tools for management they engage provide them off-loading from both internal external sources. This review explores mechanisms which physical intervention drug-free MNs alleviates on fibroblasts within tissue, thereby promoting remodeling reducing severity. Additionally, role an efficient cargo delivery system controlled sustained release a wide range therapeutic agents into highlighted. By penetrating facilitate localized drug administration modulate inflammation fibroblastic cell growth. Finally, remaining challenges future perspective field been

Язык: Английский

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Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 12, 2025

Tumors often exhibit greater stiffness compared to normal tissues, primarily due increased deposition within the tumor stroma. Collagen, proteoglycans, laminin, and fibronectin are key components of extracellular matrix (ECM), interacting facilitate ECM assembly. Enhanced fiber density cross-linking result in elevated interstitial fluid pressure, subjecting tumors significant physical stress during growth. This mechanical is transduced intracellularly via integrins, Rho signaling pathway, Hippo thereby promoting invasion. Additionally, pressure fosters glycolysis cells, boosting energy production support metastasis. Mechanical cues also regulate macrophage polarization, maintaining an inflammatory microenvironment conducive survival. In summary, signals play a crucial role growth Understanding these their involvement progression essential for advancing our knowledge biology enhancing therapeutic approaches.

Язык: Английский

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Enhancing Tumor Targeted Therapy: The Role of iRGD Peptide in Advanced Drug Delivery Systems

Cancers, Год журнала: 2024, Номер 16(22), С. 3768 - 3768

Опубликована: Ноя. 8, 2024

Chemotherapy remains the primary therapeutic approach in treating cancer. The tumor microenvironment (TME) is complex network surrounding cells, comprising various cell types, such as immune fibroblasts, and endothelial well ECM components, blood vessels, signaling molecules. often stiff dense of TME interacts dynamically with influencing cancer growth, response, metastasis, resistance to therapy. effectiveness treatment solid tumors frequently reduced due poor penetration drug, which leads attaining concentrations below levels at site. Cell-penetrating peptides (CPPs) present a promising that improves internalization agents. CPPs, are short amino acid sequences, exhibit high ability pass membranes, enabling them deliver drugs efficiently minimal toxicity. Specifically, iRGD peptide, member notable for its capacity deeply penetrate tissues by binding simultaneously integrins ανβ3/ανβ5 neuropilin receptors. Indeed, characteristically expressed allows peptide home onto cells. Notably, respective dual-receptor targeting mechanism considerably increases permeability vessels tumors, an efficient delivery co-administered or nanoparticles into mass. Therefore, facilitates deeper drug efficacy therapies. Distinctively, we will focus on action, systems their application, deliberate future perspectives developing iRGD-conjugated therapeutics. In summary, this review discusses potential overcoming barriers maximize efficiency while minimizing side effects.

Язык: Английский

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Green chemistry: Modern therapies using nanocarriers for treating rare brain cancer metastasis from colon cancer

SLAS DISCOVERY, Год журнала: 2025, Номер unknown, С. 100213 - 100213

Опубликована: Янв. 1, 2025

Brain metastasis (BM) from colon cancer is associated with a poor prognosis and restricted treatment alternatives, largely due to issues related blood-brain barrier (BBB) permeability the negative effects of standard chemotherapy. Nanotechnology improves efficacy by enabling targeted controlled drug delivery. This review article evaluates potential nanotechnology-based therapies for treating BM, emphasizing their capacity cross BBB, diminish metastatic growth, enhance overall survival rates. A multiple studies evaluated nanoparticles (NPs) as carriers chemotherapy, focusing on parameters including particle size, surface charge, drug-loading capacity. The study also reviewed that examined BBB penetration, in vitro tumor accumulation, vivo growth inhibition. In findings indicated NPs accumulate more efficiently BM tissue than healthy brain show significant penetration. vivo, nanotherapy markedly inhibited prolonged relative conventional chemotherapy or control treatments while exhibiting reduced side effects. Recent demonstrated plant extracts can effectively safely synthesize nanomaterials, positioning them viable environmentally friendly precursor nanomaterial production. Nanotechnology-based demonstrate minimizing systemic toxicity, enhancing therapeutic efficacy, facilitating Further research required confirm these implement clinical practice.

Язык: Английский

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Decoding the Nectin Interactome: Implications for Brain Development, Plasticity, and Neurological Disorders

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

The nectin family of cell adhesion molecules (CAMs) comprising nectins and nectin-like has emerged as a key regulator various pivotal neural processes, including neuronal development, migration, synapse formation, plasticity. Nectins engage in homophilic heterophilic interactions to mediate cell-cell adhesion, contributing the establishment maintenance circuits. Their extracellular domains facilitate trans-synaptic interactions, while intracellular participate signaling cascades influencing cytoskeletal dynamics synaptic function. exhibition distinct localization patterns neurons, astrocytes, blood-brain barrier underscores their diverse roles brain. dysregulation been implicated several neurological disorders, such neurodevelopmental depression, schizophrenia, Alzheimer's disease. This review examines structural functional characteristics distribution molecular mechanisms governing connectivity cognition. It further discusses experimental studies unraveling nectin-mediated pathophysiology potential therapeutic interventions targeting nectin-related pathways. Collectively, this comprehensive analysis highlights significance brain function, paving way for future research directions clinical implications.

Язык: Английский

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Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2554 - 2554

Опубликована: Март 12, 2025

Glycosaminoglycans (GAGs) are a diverse family of ancient biomolecules that evolved over millennia as key components in the glycocalyx surrounds all cells. GAGs have molecular recognition and cell instructive properties when attached to surface extracellular matrix (ECM) proteoglycans (PGs), which act effector molecules regulate cellular behavior. The perception mechanical cues arise from perturbations ECM microenvironment allow undertake appropriate biosynthetic responses maintain composition tissue function. PGs substituted with provide structural support weight-bearing tissues an ability withstand shear forces some contexts. This review outlines complexity functional they convey PGs. important roles cartilaginous fibrocartilages subject tension high also vascular neural tissues. Specific synaptic stabilization specificity plasticity regulation neurophysiological CNS/PNS control A better understanding GAG instructional behavior may be insightful for development GAG-based biotherapeutics designed treat dysfunction disease processes novel repair strategies following trauma. significant level sophistication many contexts, needs fully deciphered order achieve useful therapeutic product. offers exciting opportunities modern glycomics arena.

Язык: Английский

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Understanding Merkel Cell Carcinoma: Pathogenic Signaling, Extracellular Matrix Dynamics, and Novel Treatment Approaches

Cancers, Год журнала: 2025, Номер 17(7), С. 1212 - 1212

Опубликована: Апрель 2, 2025

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer, driven by either polyomavirus (MCPyV) integration or ultraviolet (UV)-induced mutations. In MCPyV-positive tumors, viral T antigens inactivate tumor suppressors pRb and p53, while virus-negative MCCs harbor UV-induced mutations that activate similar oncogenic pathways. Key signaling cascades, including PI3K/AKT/mTOR MAPK, support proliferation, survival, resistance to apoptosis. Histologically, MCC consists of small round blue cells with features, high mitotic rate, necrosis. The microenvironment (TME) plays central role in disease progression immune escape. It comprises mix tumor-associated macrophages, regulatory cytotoxic cells, elevated expression checkpoint molecules such as PD-L1, contributing an immunosuppressive niche. extracellular matrix (ECM) within the TME rich proteoglycans, collagens, metalloproteinases (MMPs), facilitating adhesion, invasion, interaction stromal cells. ECM remodeling integrin-mediated further promote evasion therapy resistance. Although inhibitors targeting PD-1/PD-L1 have shown promise treating MCC, remains major hurdle. Therapeutic strategies concurrently target TME-through inhibition components, MMPs, integrin signaling-may enhance responses improve clinical outcomes.

Язык: Английский

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An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 16, 2025

Intervertebral disc degeneration (IDD) remains a global healthcare challenge. Here, by analyzing clinical samples, we discover the loss of milk fat globule-EGF factor 8 (MFG-E8) from nucleus pulposus (NP) tissue-along with increased enzymatic breakdown glycosaminoglycans (GAGs)-as an overlooked for IDD development. Repairing degraded NP extracellular matrix (ECM) structurally-mimicking glycan glue to enrich MFG-E8 may counter degeneration. Accordingly, synthesize glucomannan octanoate (GMOC) robust resistance ECM-cleaving enzymes, which forms assemblies maintain healthy cell phenotype. GMOC injected into degenerated intervertebral enriches in situ, leading tissue regeneration rat and rabbit model, represent two scenarios pre-surgical intervention post-surgical IDD, respectively. In summary, report enriching ECM as mechanism promote treatment.

Язык: Английский

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Roles for TRPV4 in disease: A discussion of possible mechanisms.

Cell Calcium, Год журнала: 2024, Номер unknown, С. 102972 - 102972

Опубликована: Ноя. 1, 2024

Язык: Английский

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Mechanisms of breast cancer metastasis: the role of extracellular matrix

Molecular and Cellular Biochemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 9, 2024

Язык: Английский

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